Tuesday 21 June
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01. Eposters - Brain - Malignant

00:00 - 00:00 #28839 - P001 Importance of interval between MRI and frameless Gamma Knife SRS for brain metastases with peritumoral edema under steroid treatment.
P001 Importance of interval between MRI and frameless Gamma Knife SRS for brain metastases with peritumoral edema under steroid treatment.

Purpose: For brain metastases (BM) with peritumoral edema, the tumor volume and location may change quickly. Steroid is used to reduce the edema extent, but may cause tumor shift. This study aims to evaluate the impact of time interval between planning MRI and frameless Gamma Knife (GK) stereotactic radiosurgery (SRS) on tumor size, location and isodose coverage for BM.

 

Materials and methods: Five patients who underwent frameless GK SRS for BM with peritumoral edema were reviewed retrospectively. All patients were receiving steroid during SRS. Every patient had one diagnostic MRI (median 22 days before SRS), and one planning MRI (median 7 days before SRS). There were a total of 18 lesions in this study. We contoured tumors on the contrast enhanced T1 weighted images of both diagnostic MRI and planning MRI, and assigned them as diagnostic GTV and planning GTV, respectively. Research SRS plans were generated based on diagnostic MRI, with 100% prescribed dose (PD) covering GTV, and 100% PD covering at least 95% PTV (1 mm GTV expansion), which is the same as the clinical plans. The changes in tumor volumes, centroid locations, and isodose distribution were evaluated.   

 

Results: The median of tumor volume difference was 30.8% (maximum 400%). The median of tumor shift was 0.1 mm (maximum 2.7 mm) in X-axis, 0.5 mm (maximum 2.2 mm) in Y-axis, and 0.2 mm (maximum 0.4 mm) in Z-axis. The shifting distance was 0.62 mm (maximum 3.57 mm). The variation of dose-volume histogram and Paddick conformity index (PCI) were also noted. The volumes covered by 100% PD (VPD) of planning GTVs dropped to 93.11% from 100%. The VPD of planning PTVs dropped to 79.82% from 98.31%. PCI decreased from 0.8 to 0.61, which is farther away from the ideal value. If the diagnostic MRI were used in SRS planning, instead of the planning MRI, a detrimental consequence of missing 6.89% of GTV and 18.81% of PTV would occur, and the isodose conformity would also be worse.

 

Conclusion: BM with peritumoral edema in this patient group changes rapidly despite the use of steroid. To assure the target accuracy, a short interval between MRI and SRS delivery is ideal. An alternative way is to deliver framed SRS in such cases, because it guarantees the shortest interval. In frameless GK SRS, the interval between planning MRI and SRS should be kept as short as possible to avoid marginal miss.


Kuanyin HSIAO, Huichuan WANG (Houston, USA), Ramiro PINO, E. Brian BUTLER, Bin S TEH
00:00 - 00:00 #29312 - P002 Our Experience in the Treatment of Glioblastoma with Radiosurgery, Multicentric Study, Long Term Follow-Up.
P002 Our Experience in the Treatment of Glioblastoma with Radiosurgery, Multicentric Study, Long Term Follow-Up.

The treatment of glioblastoma multiforme is a challenge for the neurosurgeons and radiation oncologohist . The current treatment include surgery, radotheraphy , imunologic treatment, virus tretment and etc. Radisorugery has been introduce in the last ten years and the recently results did not change the philosophy of treatment.  Only one prospective randomized trial has been published investigating the effect of SRS added to conventional external beam radiation therapy (EBRT) on the survival of patients with newly diagnosed GBM and found no benefit in patient outcome giving SRS as boost before standard radiotherapy and carmustine ]. Evidence regarding SRS in tumor recurrence is unconclusive for establishing SRS as standard practice 

We present a retrospective multicentric study , three  different radiosurgery centers of patients with GBM ,who were treated at tumor recurrence with SRS aiming to evaluate the efficacy of SRS as treatment modality considering treatment outcome and overall survival.

 

Materials and Methods

We retrospectively reviewed patients who received SRS for recurrent glioblastoma  between January 1992 and February  2021, a total of 48 patients were included in this study.  One center used the frame based rigid fixation stereotactic radiosurgery system 200 (SRS 200) developed by the Gainesville University of  Florida in a Precise LINAC (Linear Accelerator) developed by Elekta (Stockholm, Sweden) the second center used Cyberknife (Accuray, Sunnyvale, California, USA) and the third center in used Infini gamma ray (GR), rotating, intracranial, stereotactic radiosurgery system (Masep Medical Company, Shenzhen, China).

Patients received SRS at a median time of 10 months (1-94) after initial diagnosis. Single lesions were documented and treated in 38 (81%) patients and 11 (22.9%) patients had multiple lesions treated at the time of SRS. A group of five (10.9%) patients received a second SRS treatment session due to tumor recurrence

Median survival after SRS was compared between both time frames 1992-2011 and 2012-2020. Median OS was nine months and 20 months since diagnosis for patients treated during second time span (2012-2020). A two-month difference of median survival after SRS was found between time frames (p=0.008, X2=7.008). Median overall survival since time of diagnosis did not achieve statistical significance (25.7 versus 20 months) (p=0.947, X2=0.004) between both periods 

Based on the results presented herein, GBM patients following a STUPP regimen plus SRS at time of recurrence along with concomitant immuno-chemotherapy can anticipate a superior survival rate as opposed to what has been reported with single therapeutic modalities.


Kita SALLABANDA DAIZ, Eduardo LOVO IGLESIAS, Maria Loreto YAÑEZ SEPULVEDA, Morena SALLABANDA HAJRO, Kita SALLABANDA DAIZ (Madrid, Spain)
00:00 - 00:00 #29313 - P003 Adaptive (two session) radiosurgery for large brain tumors with high alfa/beta.
P003 Adaptive (two session) radiosurgery for large brain tumors with high alfa/beta.

Introduction

Adaptive radiosurgery implies two and sometimes three sessions of radiosurgery for large brain tumors with time spans from 30 to 15 days apart in between them. The main objectives are a safe dose scaling allowed by tumor shrinkage and thus a new adaptation of a plan to the new target volume. Originally two-session radiosurgery was described and has been mainly used for metastatic tumors afflicting the brain, nevertheless there are also primary brain tumors with suspected high alfa/beta that can benefit from this radiosurgical technique.

Method

We reviewed our case series of patients that have been treated with adaptive radiosurgery in our centers in primary and secondary brain tumors. Dosimetry comparative studies regarding healthy tissue V12, V18, and V20 comparing adaptive radiosurgery versus fractionated three consecutive session radiosurgery were done using Time Dose Fraction (TDF)

Results

33 Patients with a total of 60 tumors (46 secondary and 14 primary) were identified. Mean tumor volume for primary tumors were 15 cc, the mean prescription dose was 13 Gy, during the second session, tumor volume was reduced to 73.6% of the original dimension, mean tumor volume was 5cc, mean prescription dose for the second session was also 13 Gy, 8 tumors were in the pineal region, 4 in the hypothalamic region and 2 else were. For secondary tumors mean tumor volume was 11.7cc mean prescription dose during the first session was 12 Gy, for the second session mean tumor volume was 5.5cc with a 66.6% reduction and the prescription dose was 15 Gy. Tumor response, tumor reduction between sessions was documented in 55 tumors (92%) local control at one year for the whole series was 92%, 4 patients with metastatic tumors required surgery, 1 patient with a primary tumor passed away from tumor progression. Potential healthy tissue sparing favored adaptive radiosurgery V12 versus fractionated radiosurgery V18 and V20 427% and 338% respectively

Conclusions

Adaptive radiosurgery is an effective technique in large tumors or those located in critical areas expected to have a high alfa/beta. It achieves rapid symptom alleviation and thus reducing the need for surgery. The potential of healthy tissue sparing due to tumor volume shrinkage and replanning is substantially higher than a traditional fractionated radiosurgery approach.


Eduardo LOVO (San Salvador, El Salvador), Kaory BARAHONA, Victor CACEROS, Fidel CAMPOS, Alejandro BLANCO, Julio ARGUELLO
00:00 - 00:00 #29327 - P005 CyberKnife for recurrent malignant gliomas: a systematic review and meta-analysis.
P005 CyberKnife for recurrent malignant gliomas: a systematic review and meta-analysis.

 

Background and Objective: Possible treatment strategies for recurrent malignant gliomas include surgery, chemotherapy, radiotherapy, and combined treatments.  Among different reirradiation modalities, the CyberKnife System has shown promising results.  We conducted a systematic review of the literature and a meta-analysis to establish the efficacy and safety of CyberKnife treatment for recurrent malignant gliomas. 

Methods: We searched PubMed, MEDLINE, and EMBASE from 2000 to 2021 for studies evaluating the safety and efficacy of CyberKnife treatment for recurrent WHO grade III and grade IV gliomas of the brain.  Two independent reviewers selected studies and abstracted data.  Missing information was requested from the authors via email correspondence.  The primary outcomes were median Overall Survival, median Time To Progression, and median Progression-Free Survival.  We performed subgroup analyses regarding WHO grade and chemotherapy.  Besides, we analyzed the relationship between median Time To Recurrence and median Overall Survival from CyberKnife treatment.  The secondary outcomes were complications, local response, and recurrence.  Data were analyzed using random-effects meta-analysis. 

Results: Thirteen studies reporting on 398 patients were included.  Median Overall Survival from initial diagnosis and CyberKnife treatment was 22.6 months and 8.6 months.  Median Time To Progression and median Progression-Free Survival from CyberKnife treatment were 6.7 months and 7.1 months.  Median Overall Survival from CyberKnife treatment was 8.4 months for WHO grade IV gliomas, compared to 11 months for WHO grade III gliomas.  Median Overall Survival from CyberKnife treatment was 4.4 months for patients who underwent CyberKnife treatment alone, compared to 9.5 months for patients who underwent CyberKnife treatment plus chemotherapy.  We did not observe a correlation between median Time To Recurrence and median Overall Survival from CyberKnife.  Rates of acute neurological and acute non-neurological side effects were 3.6% and 13%.  Rates of corticosteroid dependency and radiation necrosis were 18.8% and 4.3%. 

Conclusions: Reirradiation of recurrent malignant gliomas with the CyberKnife System provides encouraging survival rates.  There is a better survival trend for WHO grade III gliomas and for patients who undergo combined treatment with CyberKnife plus chemotherapy.  Rates of complications are low.  Larger prospective studies are warranted to provide more accurate results. 


Lucio DE MARIA (Brescia, Italy), Lodovico TERZI DI BERGAMO, Alfredo CONTI, Kazuhiko HAYASHI, Valentina PINZI, Taro MURAI, Rachelle LANCIANO, Sigita BURNEIKIENE, Michela BUGLIONE DI MONALE, Stefano Maria MAGRINI, Marco Maria FONTANELLA
00:00 - 00:00 #29351 - P006 Evaluation of biological effective dose for Gamma Knife staged stereotactic radiosurgery for large brain metastases.
P006 Evaluation of biological effective dose for Gamma Knife staged stereotactic radiosurgery for large brain metastases.

Objective: Gammaknife (GK) staged stereotactic radiosurgery (Staged-SRS) has emerged as an effective treatment option for large brain metastases (BMs) (> 2cm in diameter or > 4 cc in volume) with encouraging clinical results. However, because of the tumor shrinkage observed between two sessions of Staged-SRS, it has been challenging to evaluate the overall total composite treatment dose. This study aims to develop a novel workflow to evaluate the total biological effective dose (BED) delivered to both the tumor and normal brain tissue in Staged-SRS and to compare those in single fraction SRS (SF-SRS) and hypo-fractionated SRS (HF-SRS) treatment.

Methods: Patients treated with GK Staged-SRS at a single institution were retrospectively included. Deformable image registration was performed for MRI images acquired at each session using commercial software to account for tumor shrinkage. The dose delivered in two staged sessions was then summed based on the registration and the total BEDs to tumor/normal brain tissue of Staged-SRS were computed using the linear-quadratic model with and without considering cell repopulation during session interval. Each patient was also replanned for SF-SRS and HF-SRS where the BEDs were computed using the same formalism. Tumor BED98% ­and brain V84Gy2, which was equivalent to V12Gy commonly assessed in SF-SRS, were compared between SF-SRS, HF-SRS, and Staged-SRS plans with the Wilcoxon Rank Sum test.

Results: Twelve patients with a total of 24 BMs treated with GK Staged-SRS were retrospectively identified. We observed significant differences (p<0.05) in tumor BE­D98% but comparable brain V84Gy2 (p=0.677) between the Staged-SRS and SF-SRS plans. No dosimetric advantages of Staged-SRS over HF-SRS were observed. Tumor BED98% in the HF-SRS plans were significantly higher than those in the Staged-SRS plans (p<0.05). Despite the additional 1-mm setup margin added to the tumor with resultant larger PTV, brain V84Gy2 in the HF-SRS plans remained lower (p< 0.05).

Conclusion: We presented a novel approach to calculate the composite BEDs delivered to both tumor and normal brain tissue for Staged-SRS. Compared to SF-SRS, Staged-SRS delivers a higher dose to tumor but comparable dose to normal brain tissue. In addition, our results didn’t show any dosimetric advantages of Staged-SRS over HF-SRS.


Taoran CUI (New Brunswick, USA), Joseph WEINER, Shabbar DANISH, Anupama CHUNDURY, Nisha OHRI, Ning YUE, Xiao WANG, Ke NIE
00:00 - 00:00 #29385 - P007 Adaptive staged-dose Gamma Knife Radiosurgery for the treatment of large brain metastases. Report of 40 consecutive cases and review of literature.
P007 Adaptive staged-dose Gamma Knife Radiosurgery for the treatment of large brain metastases. Report of 40 consecutive cases and review of literature.

BACKGROUND: Brain metastases are the most common brain tumors, being one of the most frequent neurological complications of systemic cancer and an important cause of morbidity and mortality. Stereotactic Radiosurgery is efficacious and safe in treatment of brain metastases, with good local control rates and low adverse effects rate. Large brain metastases present some issues in balancing local control and treatment-related toxicity. Adaptive staged-dose GammaKnife Radiosurgery (ASD-GKRS) has shown to be a safe and effective treatment for large brain metastases.

METHODS: We retrospectively analyzed  and compared with data from  review of literature our series of patients treated with Adaptive staged-dose GammaKnife Radiosurgery for large brain metastases in ASST Grande Ospedale Metropolitano Niguarda, Milan - Italy, between February 2018 and May 2020.

RESULTS: Forty patients with  large brain metastases underwent Adaptive staged-dose GammaKnife Radiosurgery, with median prescription dose of 12Gy and a median interval between stages of 30 days. At 3-months follow-up the survival rate was 75,0% with a local control rate of 100%. At 6-months follow-up the survival rate was 75,0% with a local control rate of 96.7%. The mean volume reduction was 21.81 cm3 ( 16.76 - 26.86; IC95%). The difference between baseline volume and 6-months follow-up volume was statistically significant.

CONCLUSIONS: Adaptive staged-dose GammaKnife Radiosurgery is a safe, non invasive and effective treatment for brain metastases, with a low rate of side effects. Large prospective trials are needed to strengthen data obtained about the effectiveness and safety of this technique in managing large brain metastases.


Crisà FRANCESCO MARIA, Leocata FILIPPO, Arienti VIRGINIA MARIA, Picano MARCO, Berta LUCA, Brambilla MARIA GRAZIA, Mainardi HAE SONG, Monti ANGELO FILIPPO, Cenzato MARCO, Palazzi MAURO, La Camera ALESSANDRO (Milan, Italy)
00:00 - 00:00 #29397 - P008 Genetic algorithm and neural networks in radiosurgery for multiple metastases.
P008 Genetic algorithm and neural networks in radiosurgery for multiple metastases.

Purpose: To evaluate the optimization of PTV margins in multiple metastases radiosurgery (SRS) with single isocenter technique by the use of bio-inspired algorithms and neural networks.

Method: 10 plans were created and optimized with Elements Multiple Mets SRS v2.0 (Brainlab AG, Munchen, Germany). The mean number of metastases per plan was 5 ± 2 [3,9] and the mean volume of GTV was 1.1 ± 1.3 cc [0.02, 5.1]. The total number of metastases was 55. Considering all possible combinations of rotational and translational movements (6!x26=46080), the maximum displacement (roll, pitch, yaw, x, y, z) was optimized by a genetic algorithm (GA). By the use of a multilayer perceptron, the PTV margin (2 mm, 1 mm or 0.5 mm) was determined considering the target distance to isocenter and the volume of the lesion. The original plans were re-calculated using the PTV optimized margin and new dosimetric variations were obtained. The Paddick conformity index (PCI) and gradient index (GI) were analyzed.

Results: The GA parameters such as number of parents, cross-over point and mutation rate were optimized to reduce the computation time and to obtain global optimization points. Considering the maximum effective displacements due to rotations and translations, it is necessary to define larger and optimized PTV margins to reduce dosimetric variations on PCI and GI. The multilayer perceptron neural networks hyperparameters (learning rate, activation function, inner layers, number of neurons) were optimized for reducing the computation time and to obtain better loss functions.

Conclusion: The GA and neural networks are tools to facilitate the PTV margin decision on SRS for multiple metastases with single isocenter. These computational tools based on artificial intelligence consider a complete dosimetrical and geometrical study of the mechanical uncertainties due to rotations and translations in these treatments.


José Alejandro ROJAS-LÓPEZ (Argentina, Argentina), Daniel VENENCIA, Miguel Ángel CHESTA, Francisco TAMARIT
00:00 - 00:00 #29404 - P009 Contrast clearance analysis has direct impact on the survival of patients with brain metastasis treated with Gamma Knife.
P009 Contrast clearance analysis has direct impact on the survival of patients with brain metastasis treated with Gamma Knife.

Purpose

Pseudoprogression is a well-characterized toxicity associated with radiation for intracranial lesions which can be difficult to differentiate from tumor progression on follow-up MRI, making treatment decisions challenging. Serial MRIs can lead to delay of the treatment and allows tumor growth. This study shows that the clinical application of the contrast clearance for early differentiation has a direct impact on patient’s survival.

Methods

Fifty-seven consecutive patients diagnosed with brain metastasis and treated with Gamma Knife Radiosurgery (GKRS) who had presented suspicious lesion growth on their follow-up were submitted to contrast clearance analysis to distinguish between treatment effect from tumor progression. Lesions considered to have recurrence were retreated with GKRS. Kaplan-Meir Survival Analyses was used at the end of the follow-up period.

Results

The most common primary disease was non-small cell lung cancer (40%), followed by breast (12%) and melanoma (11%). The use of contrast clear analysis suggested 24 lesions to be tumor recurrence and 35 to be pseudoprogressions. Total follow-up period was of 72 months. Kaplan-Meir Survival Analyses showed that retreated patients had greater survival with p< .05 according to Wilcoxon test.

Conclusion

The use of contrast clearance imaging is a promising tool to distinguish tumor progression from radiation necrosis in the setting of radiosurgical treatment. Early differentiation allows early retreatment and improvement of the patient survival. Further studies are needed to clearly show its sensitivity and positive predictive value in metastatic disease.


Victor GOULENKO, Matthew RECKER, Dheerendra PRASAD (Buffalo, NY, USA), Robert PLUNKETT
00:00 - 00:00 #29418 - P010 Single isocenter radiosurgical treatments for multiple brain metastases.
P010 Single isocenter radiosurgical treatments for multiple brain metastases.

Purpose/Objective(s):

To communicate our institutional experience with single isocenter radiosurgery treatments for multiple brain metastases, including challenges with determining planning target volume (PTV) margins and resulting consequences, image-guidance translational and rotational tolerances, intra-fraction patient motion, and prescription considerations with larger PTV margins. 

Materials/Methods:

Eight patient treatments with 51 targets were planned with various margins using Elements Multiple Brain Mets SRS treatment planning software (Brainlab, Munich, Germany). Forty-eight plans with 0mm, 1mm and 2mm margins were created, including plans with variable margins, where targets more than 6cm away from the isocenter were planned with larger margins. The dosimetric impact of the margins were analyzed with V5Gy, V8Gy, V10Gy, V12Gy values. Additionally, 12 patient motion data were analyzed to determine both the impact of the repositioning threshold and the distributions of the patient translational and rotational movements. 

Results:

The V5Gy, V8Gy, V10Gy, V12Gy volumes approximately doubled when margins change from  0mm to 1mm and tripled when change from 0mm to 2mm. With variable margins, the aggregated results are similar to results from plans using the lower of two margins, since only 12.2% of the targets were more than 6cm away from the isocenter.

With 0.5mm re-positioning threshold, 57.4% of the time the patients are repositioned.  Reducing the threshold to 0.25mm results in 91.7% repositioning rate, due to limitations of the fusion algorithm and actual patient motion. 

The 90th percentile of translational movements in all directions is 0.7mm, while the 90th percentile of rotational movements in all directions is 0.6 degrees. Median translations and rotations are 0.2mm and 0.2 degrees, respectively.

Conclusions:

Based on the data presented, we have switched our modus operandi from 2mm to 1mm PTV margins, with an eventual goal of using 0.5 and 1.0mm variable margins when an automated margin assignment method becomes available. The 0.5mm and 0.5 degrees repositioning thresholds are clinically appropriate with small residual patient movements.


Nzhde AGAZARYAN (Los Angeles, USA), Steve TENN, Tania KAPREALIAN
00:00 - 00:00 #29425 - P011 Efficacy of a biweekly 3-Stage stereotactic radiosurgery for large brain metastases: The effect of EGFR tyrosine-kinase inhibitor on tumor response and clinical outcomes.
P011 Efficacy of a biweekly 3-Stage stereotactic radiosurgery for large brain metastases: The effect of EGFR tyrosine-kinase inhibitor on tumor response and clinical outcomes.

Stereotactic radiosurgery(SRS) is one of the primary treatment modalities for brain metastases. However, radiosurgical control of large brain metastases(LBM) remains challenging and shows suboptimal local control rates and an increased risk of radiation injury. To overcome these limitations, fractionated or staged SRS has been used. This study was performed to evaluate the clinical outcomes of a biweekly 3-stage SRS for LBM.

A total of 53 patients were treated with a biweekly 3-stage SRS for 62 LBM. Female was 27, and the mean age was 63.7years. The mean Karnofsky Performance Score(KPS) was 79.2. Non-small cell lung cancer(NSCLC) was the most common primary cancer in 31 patients, the others include 6 patients of small cell lung cancer(SCLC), 9 patients of gastro-intestinal tract cancer, 5 gynecological cancer patients, and so on. Epidermal growth factor receptor(EGFR) mutation was identified in 13 patients, and EGFR tyrosine-kinase inhibitor(TKI) was used in 10 patients during and/or after the staged SRS. The mean tumor volume was 19.1cm3. The mean marginal dose of 11.7Gy was delivered to the 50% isodose line based on a new treatment planning every two weeks. 

Among 53 patients, 6 patients were dropped from the treatment. The tumor volume gradually decreased with each treatment stage. The mean tumor volume at the second and third stage was 14.8cm3 and 11.0cm3, respectively. The lesions from squamous cell of NSCLC decreased most rapidly, and followed by gynecological cancer, SCLC and adenocarcinoma of NSCLC (the volume ratio at the third stage was 0.39, 0.53, 0.56, and 0.64, respectively). However, the lesions from gastro-intestinal tract cancer were slow to respond, and only reduced to 83.2% of the initial volume at the 3rd stage. The most significant factor related with tumor volume reduction by the 3rd stage was usage of EGFR-TKI(p=0.016). The mean overall survival was 15.3 months, and the estimated overall survival rates were 62% and 46% at 6 and 12 months, respectively. In the multivariate analysis, KPS(p=0.002) and usage of EGFR-TKI(p=0.021) were significantly associated with overall survival. The mean overall survival of the group of usage of EGFR-TKI was significantly longer than that of the others(20.7 and 13.1months, respectively).

The biweekly 3-stage SRS seems to be effective treatment for patients with LBM, especially in patients who were treated with EGFR-TKI during and/or after SRS. However, patients were selected cautiously considering the primary tumor site and possible treatment options for their systemic tumor control.


Ji-Eyon KWON (Seoul, Korea), So Young JI, Jung Ho HAN
00:00 - 00:00 #29426 - P012 Analysis of the metastases brain tumor to predict the overall survival within three-months for non-small cell lung cancer using machine learning algorithms.
P012 Analysis of the metastases brain tumor to predict the overall survival within three-months for non-small cell lung cancer using machine learning algorithms.

Purpose: Gamma knife radiosurgery (GKRS) is commonly employed in patients with brain metastases, but the predictions of overall survival within 3 months after GKRS are inaccurate. ­All patients with brain metastases do not share the same prognosis and should not receive the same treatment. Especially, non-small cell lung cancer (NSCLC) patients revealed more than 10% of the treated patients died within 8 weeks [1]. The early death could denote overtreatment and questionable to treat. The purpose of this study was to predict the overall survival with machine learning algorithms including decision-tree and random forest modeling in NSCLC patients. And we also investigated the important features for overall survival. 

Methods: We randomly selected 120 NSCLC patients treated the GKRS at Chungbuk National University Hospital. The patients were randomly divided into 80 training groups and 40 testing groups with 14 features. The categorical variable was executed to preprocessing using one-hot encoding methods. Root mean squared logarithmic error is used to find out differences between prediction and actual values. And all data was verified by the three neurosurgeons and two medical physicists. To predict overall survival, we used to machine learning algorithms and extracted important features. 

Results: Accuracy of algorithms to predict overall survival was 77.5%, 72.5%, and 73.68 %, decision-tree, random forest, and boosted tree classifier. The important features commonly showed age, chemotherapy, and pre-operation each algorithm. And permutation features commonly showed the age, which is important variable for predicting overall survival in NSCLC patients. 

Conclusions: These results suggest that machine learning algorithms are a useful tool for predicting the overall survival and finding important variables in NSCLC patients. Among of algorithms, decision-tree showed high accuracy, and considering to age, volume size, and number of lesions in sequence when make a treatment planning in patients with NSCLC. 


Hyeong Cheol MOON, Dong Suk JANG, Young Seok PARK (Cheongju, Korea)
00:00 - 00:00 #29465 - P014 Viable tumor recurrence is a major cause of local failure after bevacizumab therapy for radiation necrosis in brain metastases treated with stereotactic radiosurgery.
P014 Viable tumor recurrence is a major cause of local failure after bevacizumab therapy for radiation necrosis in brain metastases treated with stereotactic radiosurgery.

Background

Bevacizumab (BVZ) is known to be effective to control radiation necrosis (RN) following stereotactic radiosurgery (SRS) for brain metastases (BMs), although treatment failure may occur. Here, we investigated the incidence and pattern of local failure after BVZ therapy for RN and its underlying biological mechanism.

 

Methods

We conducted a retrospective analysis on 17 patients who had been treated with BVZ for RN following SRS for BMs between 2016 and 2021. In each patient, the diagnosis of RN was made based on the conventional and advanced MR with or without positron emission tomography. Median 5 cycles (range, 2-10 cycles) of BVZ (5 mg/kg) were administered at 2-week intervals. Treatment response was assessed by volumetric changes of the lesions on MR and patients’ neurological status.

 

Results

Treatment response was typically brisk and substantial. Best MR response was seen at median 13 weeks (range, 3-56 weeks) after the start of BVZ with a median volume decrease of 84.5% (range, 38.7-100%) of perilesional brain edema on T2WI and of 54% (range, 2.9-100%) of contrast enhancing lesions on T1WI. Patients’ neurological status improved in 16 patients (94.1%) and was stationary in 1 (5.9%). During the median follow-up of 12 months (range, 2-60 months), delayed local failure was observed in 6 patients (35.3%) at median 10 months (range, 6-14 months) after starting BVZ treatment, where viable tumor recurrence was demonstrated in all of them. No reconstitution of RN without viable tumor was observed during the follow-up.

 

Conclusions

Although BVZ was highly effective to control RN following SRS for BMs, delayed local failure frequently occurs owing to viable tumor recurrence. This may imply that much predominant vascular stabilizing effect of BVZ over anti-tumor effect transiently obscures the presence of potential viable tumor cells but does not prevent them from eventual recurrence.


Young Hyun CHO, Kyoungjun YOON, Do Hee LEE, Young-Hoon KIM (Seoul, Korea), Sang Woo SONG
00:00 - 00:00 #29466 - P015 Validation of lexicographic optimisation-based planning for brain metastasis radiosurgery with coplanar arcs.
P015 Validation of lexicographic optimisation-based planning for brain metastasis radiosurgery with coplanar arcs.

Purpose: Recent advances in automated treatment planning demonstrated improved plan quality and best practice reducing routine planning workload. In this study, a not yet commercially available fully-automated lexicographic optimisation planning, called mCycle (Elekta AB, Stockholm), was validated for intracranial stereotactic radiosurgery (SRS).

Material and Methods: Twenty-one single-lesion SRS treatment plans (21 Gy/1 fx) delivered between November 2019 and December 2021 were retrospectively selected and re-planned by mCycle (Monaco 5.59.13). Constraints and objectives were sequentially optimized by multi-criterial optimization (MCO) according to an a-priori assigned priority list, a so-called Wish List (WL). Four patient sets were used to achieve a robust WL. All plans were optimized with 2 coplanar 140°-arcs and calculated with the Monte Carlo algorithm (1 mm-dose grid, 0.5%-statistical uncertainty). The main criteria for planning approval was a brain volume receiving more than 12 Gy less than 10 cm3 (V12Gy < 10 cm3). A target coverage as high as possible was requested, with at least the 80% of the prescription dose covering the 99% of the PTV. Manual plans (MP) and mCycle plans (mCP) were compared in terms of dose-volume constraints and monitor units (MUs). Statistical significance was assessed performing the Wilcoxon Mann Whitney test with Bonferroni correction for multiple tests (alpha=0.05). Plan deliverability was verified by pre-treatment QA.

Results: The 21 mCP re-planning took only 5 working days. Dose statistic comparison is reported in Table 1. Plan comparison showed a statistically significant increase in target dose coverage, both for CTVs and PTVs, without significantly increasing the near-maximum doses. The PTV Paddick’s conformity index (CI) was equally improved and the brain V12Gy in mCP was comparable to the one in MP. Other organs at risk (OARs) were never significantly interested by clinically relevant doses. These results were obtained with a lower median number of MU (-11.6%) even if this difference was not statistically significant and plans registered a comparable gamma analysis (local 2%/2mm).

Conclusions: The novel mCycle autoplanning produced high-quality clinically acceptable radiosurgery plans with coplanar arcs significantly reducing the overall planning time: the planning of one MP and one mCP took about 1 working day and 2 hours, respectively. While the OAR sparing was comparable between MP and mCP, the target coverage was significantly increased, reducing the MU number and preserving the plan deliverability. The validation showed the mCycle capability to generate high-quality deliverable plans according to institutional-specific planning protocols.


Sara TRIVELLATO (Monza, Italy), Paolo CARICATO, Paolo CARICATO, Roberto PELLEGRINI, Gianluca MONTANARI, Denis PANIZZA, Denis PANIZZA, Valeria FACCENDA, Valeria FACCENDA, Stefano ARCANGELI, Stefano ARCANGELI, Elena DE PONTI, Elena DE PONTI
00:00 - 00:00 #29555 - P016 Radiosurgery for recurrent glioblastoma.
P016 Radiosurgery for recurrent glioblastoma.

Abstract Background. Despite the combined treatment in accordance with modern standards, recurrent glioblastoma usually occurs with in several months after resection and causes low relapse-free and overall survival. One of the most effective methods for malignant glioma progression is repeated radiotherapy. Indications for this approach have expanded after introduction of stereotactic irradiation into routine clinical practice.

Objective. To evaluate the results of radiosurgery in patients with recurrent glioblastoma and to identify the factors determining its effectiveness. Material and methods. Radiosurgery has been carried out in 168 patients with relapses of glioblastoma between 2005 and 2021. This study enrolled 88 patients with 180 foci of local and distant progression. Mean age of patients was 42.8±2.1 years (range 4—73). Mean period between diagnosis and repeated irradiation was 12.7 months. Mean volume of focus was 2.4 cm3, mean dose — 20 Gy. Median follow-up period after radiosurgery was 11.2 months.

Results. Repeated irradiation with correction of systemic therapy improved progression-free survival and overall survival with significant radiation-induced toxicity (CTCAEv4.0, Grade 3 - 8.4%). Annual overall survival was 62.2%, median of overall survival after radiosurgery — 15.1 months. Significant factors of local control were marginal dose of at least 18 Gy and distant relapse. Median of progression-free survival in the group of distant progression of glioblastoma was only 3.6 months vs. 9.1 months in patients with local recurrence.

Conclusion. Repeated irradiation in radiosurgery mode with a dose of 18 Gy and higher is an effective option for local treatment increasing progression-free and overall survival in patients with progression of glioblastoma.


Ivan OSINOV, Andrey GOLANOV (Moscow, Russia), Valery KOSTYUCHENKO, Sergey BANOV, Anjelika ARTEMENKOVA
00:00 - 00:00 #29556 - P017 Dose-staged radiosurgery in the treatment of patients with large (>4cc) brain metastasis.
P017 Dose-staged radiosurgery in the treatment of patients with large (>4cc) brain metastasis.

Background: Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2,5 cm in maximum diameter remains challenging. The SRS possibilities in the treatment of such patients are limited by the high risks of developing post-radiation complications. The use of dose-staged SRS (DSSRS) allows delivering of high dose to the lesions in several treatment sessions with minimize radiation exposure to normal brain tissues.

Objective: The article presents the results of dose-stage radiosurgery using Leksell Gamma Knife to patients with metastatic brain lesions >4,0 cc.

Methods: Volumetric measurements were performed at the moment of first and second stages of treatment and on follow-up. Outcome was evaluated using methods for binary data, PFS and OS - using conventional time-to-event methods.

Results: Data from 42 patients (pts) with 203 lesions were analyzed. The median age was 56.6 years (24-77). 42 lesions >4,0 cc, were treated in 2 stages DSSRS, other 161 lesions treated in one fraction. Median tumor volume at first stage was 11,4 cc (4,5–22,5 cc) and at second stage - 8,0 cc (1,7–20,8 cc). The median prescription dose at first and second stages were 12,0 Gy (10–15 Gy) and 15,0 Gy (10–18 Gy) respectively. The median duration between stages was 23 days. Three month follow-up imaging results were available for 42 lesions: the median volume was 1.3 cc (0,01-26,0 cc), local control (LC) at 3, 6, 12 month was 96,9%, 93,3%, 78,6% respectively. Median PFS was 8,7 month, 17 pts (40,4%) had new metastasis at 12 month after DSSRS. PFS at 6 and 12 month was 71,0±8,8%, and – 36,7±10,5% respectively. In univariate analyzes pts receiving systemic drugs therapy after DSSRS had significantly better PFS rate (p=0,03). Estimated OS rates at 6 and 12 months were 58,3±8,1% and 42,6±8,4% respectively. In multivariate analyze KPS>80 and systemic drugs therapy had significant impact to OS (p=0,01). Grade 2-3 adverse radiation effects (ARE) appeared at 16.6% with median 4,0 month (1,5-12,0).

Conclusion: DSSRS is an effective treatment modality that resulted in significant reduction of brain metastases >4,0 cc, with excellent 6-month (93,3%) and 12-month (78,6%) LC rates and an overall grade 2-3 ARE rate of 16,6%. Prospective studies with larger cohorts and longer follow-up are necessary to assess long-range durability and toxicities of DSSRS.


Ivan OSINOV, Andrey GOLANOV (Moscow, Russia), Sergey BANOV, Aleksandr SAVATEEV, Valery KOSTYUCHENKO
00:00 - 00:00 #29807 - P018 Distinguishing tumor progression from adverse radiation effects after brain metastasis radiosurgery: the longitudinal GRASP imaging experience.
P018 Distinguishing tumor progression from adverse radiation effects after brain metastasis radiosurgery: the longitudinal GRASP imaging experience.

Abstract

We investigated the utility of a novel imaging technique, golden-angle radial sparse parallel (GRASP) dynamic contrast-enhanced permeability MRI, in distinguishing brain metastasis progression and treatment-induced adverse radiation effects (ARE) following stereotactic radiosurgery (SRS).

 

Methods:

We retrospectively analyzed patients with brain metastases treated with gamma-knife SRS at our institution from 2013-2020 who had GRASP MRI before and at least once after SRS. The contrast-enhanced GRASP sequence, a single acquisition of about 6 minutes, is obtained in routine MRI. For each scan, three non-overlapping regions of interest (ROIs) in the maximally enhancing tumoral components and a control ROI in the superior sagittal sinus (SSS) were drawn. Analysis was limited to the first 100 seconds of acquisition. Slopes of the ROIs’ signal intensity-time curves during wash-in (period of maximally increasing SSS signal intensity) and wash-out (period of monotonically decreasing signal intensity after peak SSS enhancement). Tumor ROIs’ wash-in slope (nWin) and wash-out slope (nWout) normalized to the SSS were compared between tumor progression and ARE groups. Tumor progression was pathologically confirmed from post-GK surgically resected lesions. ARE was diagnosed on either surgically resected tissue with no signs of tumor or on lesion resolution on imaging follow-up. Two-sample t-tests with significance level p<0.05 and receiver-operating characteristic (ROC) analysis with optimal threshold identification by Youden’s index were performed.

 

Results:

32 patients comprised this study population: 16 had tumor progression and 16 had ARE. Seventeen patients underwent surgical resection of their lesion, with 16 (94%) showing pathology-confirmed recurrences and 1 (6%) showing ARE. Fifteen patients were followed closely and their imaging and clinical outcomes were consistent with ARE. Primary cancer types included lung (31%), melanoma (31%) and breast (19%).

Post-SRS, ARE had significantly lower nWin than tumor progression on all three follow-up scans (scan 1: 0.17±0.08 vs. 0.26±0.14, p=.03; scan 2:  0.18±0.09 vs. 0.34±0.15, p=.001; scan 3: 0.17±0.07 vs. 0.32±0.11, p<.001). No significant differences were found in pre-SRS nWin or pre- or post-SRS nWout (p>.05). Post-SRS nWin differentiated ARE and tumor progression with area under the ROC curve of 0.82 on scan 1, 0.86 on scan 2, and 0.88 on scan 3. Optimal threshold 0.18 yielded sensitivity of 75% and specificity of 69% on scan 1 and sensitivity of 92% and specificity of 69% on scan 2. Threshold 0.28 on scan 3 yielded sensitivity of 67% and specificity of 100%.

 

Conclusions:

Longitudinal GRASP MRI may help differentiate brain metastasis progression from adverse radiation effects.


Assaf BERGER (New York, USA), Matthew LEE, Eyal LOTAN, Girish FATTERPEKAR, Douglas KONDZIOLKA
00:00 - 00:00 #29810 - P019 Can lung cancer with brain metastases be cured in the current era?
P019 Can lung cancer with brain metastases be cured in the current era?

Background

Metastatic brain cancer has been considered a terminal condition with the goal of long term palliation but little hope for cure. Use of brain radiosurgery and/or resection, in addition to advanced systemic immunological and targeted therapies have enabled improvements in overall and progression free survival, often after systemic therapy is stopped. This study aimed to explore the possibility of curing patients with non-small cell lung cancer (NSCLC) brain metastases in the current era. 

 

Methods

During the years 2008-2016, 236 NSCLC patients underwent their first gamma knife radiosurgery (GKS) for brain metastases at our institution. Of these, using a prospective registry, we found 22 (9%) lung cancer patients that had an overall survival of at least 5 years from the initial GKS.  Demographic, clinical and histological data were collected, including GKS parameters, systemic treatments and survival analysis.

 

Results

In the lung cancer population, all patients (aged 58±9, 73% female) had non-small cell lung cancer, of which 9% and 27% were EGFR and ALK mutation positive, respectively. Overall survival from the first GKS was 113 months (95% CI, 101-125) and 43% (95% CI, 9-76) had at least 10 years survival. Five patients (23%) required no active treatment by the end of their follow-up for a period of 29 months, 7-118. Brain metastases locations included lobar hemispheres (100%), cerebellum (59%) and brainstem (18%) with the median largest treated tumor measuring 1.05 (0.14-17.81).

The median total number of treated metastases was 10 (range 1-29) and the median number of procedures was 4 (1-13). Spread to sites other than CNS was evident in 36%, and therapeutic regimens included immunotherapy, biological targeted therapy and chemotherapy in 18%, 55% and 55% of patients respectively.

 

Conclusions

Long-term survival in patients with NSCLC and brain metastases is feasible in the current era of radiosurgery combined with targeted systemic therapeutics. Of those living more than 5 years, the chance for living with stable disease and no need for active treatment for at least 2 years was 18%.  With modern multimodality therapy, perhaps there is now potential for eventual cure.


Assaf BERGER (New York, USA), Reed MULLEN, Kenneth BERNSTEIN, Joshua.s SILVERMAN, Erik SULMAN, Bernadine R. DONAHUE, Elaine SHUM, Joshua SABARI, Abraham CHACHOUA, John G. GOLFINOS, Douglas KONDZIOLKA
00:00 - 00:00 #29910 - P020 Re-irradiation of recurrent anaplastic ependymoma using radiosurgery.
P020 Re-irradiation of recurrent anaplastic ependymoma using radiosurgery.

Introduction:  anaplastic ependymomas are quite rare tumors that often relapse after preliminary removal with subsequent conventional radiation therapy, while often the optimal tactics for treating relapses has not been precisely determined

OBJECT: To evaluate the role stereotactic radiosurgery with GammaKnife (GKRS) in patients with recurrent or residual intracranial anaplastic ependymomas after resection and fractionated radiation therapy (RT).

METHODS: From April 2005 till January 2022 at “Moscow GammaKnife Center”, which affiliated with Burdenko Neurosurgical Institute (National scientific research Center of neurosurgery named after N.N. Burdenko) 114 patients (65 males and 49 female) with anaplastic ependymoma was treated at 214 procedures (13 – hypofractionated with LGK Icon, other – radiosurgicaly (2005-2011 – LGK C, 2011-2018 – PFX; 2018-2022 – Icon). Most patients were younger than 19 years – 96 vs 18 pts. Median age at first GK procedure was 9 years (from 2 to 59). 44 patients had 2 and more GK treatment (up to 10) (additionally to surgeries and RT with other units). All patients underwent resection of an ependymoma followed by cranial or neuraxis (if spinal metastases were confirmed) RT and adjuvant chemotherapy. The median time from initial treatment to GKRS was 17.5 months.

RESULTS: The median radiosurgical target volume was 1.2 (from 0.002 to 33 cc) and the median dose to the tumor margin was 18 Gy (range 15-24 Gy). Total number of irradiated targets is 712 (72% supratentorial, 28% – subtentorial). Median number of tumors treated in one session was 2 (from 1 to 23). 43 tumors (6%) treated with GK more than once (up to 4 times). Average 83 patients followed at least 1 year (max 15 years). Progression-free survival after the initial GKRS was 68.4%, at 1 year. The distant tumor relapse rate despite RT and GKRS was 20.6% at 6 months and 45.0% at 12 months, respectively. Overall survival (OS) after GKRS was 89.5% at 1 year, and 5-year OS reaches 69.0%, respectively. Adverse radiation effects developed in 10 patients (8.7%).

CONCLUSIONS: Stereotactic radiosurgery in different modes is the treatment of choice, along with reoperation, in patients with residual or recurrent ependymomas after initial combine  treatment.


Ivan OSINOV, Valery KOSTYUCHENKO, Aleksandr SAVATEEV, Andrey GOLANOV (Moscow, Russia)
00:00 - 00:00 #29913 - P021 Experience of preoperative Gamma Knife radiosurgery for recurrent brain metastases.
P021 Experience of preoperative Gamma Knife radiosurgery for recurrent brain metastases.

Introduction Resection of brain metastases (BM) without additional radiation therapy yields a high local failure rate. Drawbacks of postoperative stereotactic radiosurgery (SRS) include uncertainty in target delineation, potential delay in the administration of SRS and intraoperative risk of tumor spillage. Preoperative SRS might address these potential drawbacks. We present our experience with preoperative Gamma Knife radiosurgery (GKRS) for recurrent BM.

 

Methods Data of patients with recurrent BM treated with GKRS followed by surgical resection between June 2019 and June 2021 at the Elisabeth-TweeSteden Hospital Tilburg were retrospectively collected. Surgery was performed because of mass effect, a symptomatic lesion or a large tumor volume not eligible for salvage stereotactic radiosurgery. Pre-operative SRS was performed with GKRS followed by surgery within 24 hours. All patients had follow-up appointments with MRI scan as long as clinical meaningful. In case of new intracranial disease new treatment was offered if appropriate. Descriptive analyses were used to give an overview of the patient characteristics. Kaplan-Meier curves were used to analyze overall survival.

 

Results 25 patients (male 8, female 17; median age 64 years (range 20-79 years)) underwent preoperative GKRS for recurrent brain metastases. Most patients were previously treated with GKRS (68%). Most patients had non-small cell lung cancer (44%), followed by breast (12%), small cell lung cancer (12%) and melanoma (12%). The median total tumor volume of the index lesion was 22.2cc (range 6.4cc - 73.6cc). A dose of 18-22 Gy, was prescribed to the isodoseline (mean 45%; range 40-53%) covering 99-100% of the target. The median overall survival was 18.5 months (95% CI, 4.9 to 32.1 months). Eight patients (32%) had (multiple) surgical complications, three of these patients died due to these complications. Twelve patients (48%) developed a local recurrence. The median time to local recurrence was 6.9 months (95% CI, 4.7 to 9.1 months). Of the 16 patients with a subtotal resection, 10 patients developed a local recurrence, with 6 recurrences at the place of the macroscopic residual tumor. Two patients (8%) developed leptomeningeal disease at 2.8 months and 3.9 months and two patients (8%) developed new brain metastases (distant failure) at 5.4 months and 23.8 months, respectively.

 

Discussion Pre-operative radiosurgery was well tolerated in a group of patients with recurrent BM who were eligible for surgery. Larger series are needed to perform multivariate analyses on predictors of local recurrence in order to evaluate for which patients this treatment option is best suited.


Eline VERHAAK, Tom VAN SEETERS, Hilko ARDON, Liselotte LAMERS, Suan Te LIE, Hazem AL-KHAWAJA, Jeroen VERHEUL, Wouter VERFAILLIE, Bart BROUWERS, Bart DE BOER, Bram VAN DER POL, Wim DE JONG, Jannie SCHASFOORT - VAN DEN TILLAART, Diana GROOTENBOERS, Patrick HANSSENS (Tilburg, The Netherlands)
00:00 - 00:00 #29925 - P022 Stereotactic radiosurgery of local recurrences of brain metastases.
P022 Stereotactic radiosurgery of local recurrences of brain metastases.

Brain metastases (BM) are the most frequent tumors of the central nervous system. Nowadays stereotactic radiosurgery (SRS) is treatment of choice  for BM in many situations.  Local recurrences after radiosurgery seriously complicate the course of cancer diseases and worse the prognosis of life duration, neurological status and quality of life in patients with BM. Currently, there are no standards of treatment for recurrent BM.

The purpose of the study to evaluate the efficacy and safety of repeated radiosurgical (rRS) procedures for local relapses (LR)  in patients with brain metastases after prior stereotaxic surgery.

Materials and methods.

An analysis of the re-irradiation local treatment of 59 patients were carried out. There were 110 lesions of LR detected after the previously performed SRS with Gamma Knife (GK). Primary cancer was: non-small cell lung cancer in 10 (17%), breast cancer in 29 (49%), melanoma in 13 (22%), renal cell carcinoma in 5 (8.5%) and colorectal cancer in 2 (3.5%) patients. All patients underwent repeated radiosurgery with median marginal dose 22 Gy (15 to 24 Gy).

Results.

The local control of repeated irradiated BM for the 6- and 12-month periods was 95.5% and 83.9%, respectively. Statistically significant prediction factors for lower risk of LR after rRS were: the volume of the lesion  ≤1 cc (p=0.0241) and dose >20Gy/D99% (p=0,031), according to multifactorial analysis. The frequency of local radionecrosis after repeated radiosurgery was higher than after first SRS: 28.2% vs. 13.3%. The volume of LR ≤1 cc was a significant predictor of lower risk of post-radiation edema (p=0.01) and radio necrosis (p=0.0224) according to multifactorial analysis.

Conclusions:

The SRS of LR is an effective treatment for controlling tumor growth of repeated irradiated BM with acceptable post-radiation toxicity. Repeated stereotactic radiosurgery (SRS) of local recurrences (LR) of GM is designed to improve treatment outcomes, maintain quality of life and prolong it in patients with brain metastases who relapse after prior radiosurgery. The volume of the LR focus can change the treatment tactics: it is possible that with a metastasis recurrence size of more than 1 cm3, it is preferable to use surgical treatment or stereotactic radiation in the hypofractionation mode, which needs to be confirmed in further studies.


Amayak DURGARYAN, Andrey GOLANOV (Moscow, Russia), Sergey BANOV, Elena VETLOVA, Valeriy KOSTYUCHENKO, Ivan OSINOV, Elena IGOSHINA
00:00 - 00:00 #29927 - P023 Re-irradiation of relapsed intracranic lesions with stereotactic radiotherapy: a monoinstitutional experience.
P023 Re-irradiation of relapsed intracranic lesions with stereotactic radiotherapy: a monoinstitutional experience.

Purpose: The treatment of relapses of already irradiated primary brain tumors and metastases is difficult, given the limited effectiveness of systemic therapy and the risks of surgery or re-irradiation. Here we present the results of salvage Stereotactic Radiotherapy (SRT) for the treatment of recurrent primary brain tumors and metastases (mts) after previous radiotherapy (RT).

Material/Methods: From January 2018 to October 2021, 137 intracranial lesions (33 patients) were re-irradiated with robotic SRT. Primary histology was: NSCLC (n=10), breast cancer (n=9), glioblastoma (n=4), meningioma (n=2), oligodendroglioma (n=2), hemangiopericytoma (n=2), pituitary adenoma (n=2), prostate cancer (n=1), and melanoma (1). Previous RT on the same volume were performed with: GammaKnife (n=11), CyberKnife (n=8), Whole-Brain RT (n=8), post-operative IMRT/Helical IMRT (n=8), VMAT-SRT (n=5), post-operative 3D-CRT (n=3). Eight patients had multiple previous treatments. Median time from the previous radiotherapy was 13 (3-377) months. Gross Tumor Volume (GTV) was delineated on computed tomography and contrast-enhanced T1 magnetic resonance. Median GTV was 5.24 (0.22-78.32) cc. Planning Target Volume (PTV) was obtained adding an expansion to GTV of 1 mm (for brain metastases), or 3 mm (for glioblastoma). Median PTV was 10.19 (0.43-136.9) cc. Median prescribed dose was 30 (24-37.5) Gy in 1-5 fractions (median number of fractions was 5), at a median isodose of 76% (67-80%).The patients were followed up with contrast-enhanced MRI performed every three months.

Results: SRT was delivered on a median number of 2 (1-24) lesions; 7 patients were treated on 5 lesions simultaneously (from 5 to 24 lesions). Acute toxicity was G2 headache in three patients (GTV>1cc or >3 lesions), controlled by increasing the dose of steroids.

Median follow-up after re-irradiation in 20 evaluable patients was 9 (1-37) months. Radionecrosis occurred in only one patient (GTV>1cc). He underwent two previous VMAT SRT (prescribed dose 30 Gy in 5 fractions and 21 Gy in 3 fractions) and presented seizures. He was treated with steroids and levetiracetam. Six-, 12-, 18-month overall survival (OS) was 79.2%, 51.7%, 37.7% respectively. Six-, 12-, 18-month local relapse free survival was 70.7%, 64.8%, 48.6% respectively (see Figure 1).

Conclusions: SRT for re-irradiation is feasible, with only one case of radionecrosis registered. The treatment is effective with 12-month local control registered in 65% of pts. An accurate patient selection is warranted in order to avoid toxicity and a longer follow-up is needed to confirm the low radionecrosis rate.


Stefano Lorenzo VILLA (Milan, Italy), Chiara Lucrezia DEANTONI, Andrei FODOR, Roberta TUMMINERI, Flavia ZERBETTO, Sara BROGGI, Jessica SADDI, Barbara LONGOBARDI, Antonella DEL VECCHIO, Italo DELL'OCA, Nadia Gisella DI MUZIO
00:00 - 00:00 #29932 - P024 Pre-operative Stereotactic Radiosurgery Followed by Surgical Resection of Local Recurrence Brain Metastasis.
P024 Pre-operative Stereotactic Radiosurgery Followed by Surgical Resection of Local Recurrence Brain Metastasis.

Salvage-therapy of local recurrence brain metastasis (LRBMs) after previous treatment (surgical or stereotactic radiotherapy) is a seriously problem due to combination of local re-growth of a metastatic tumor and radiation necrosis. Re-irradiation deteriorates the radiation necrosis. Surgical resection is often the only reasonable solution. However, according to the multivariate analysis of Cagney DN at al. 2019, surgical resection followed by stereotactic radiation of previously irradiated LRBMs was complicated by leptomeningeal disease (LMD) in 32.7% (HR, 2.39; 95% CI, 1.25-4.57; P = .008). It is necessary to search for new modalities for the treatment of LRBMs.

Objectives:   The goal of this study is to analyze the effectiveness of pre-operative stereotactic radiosurgery (PreSRS) followed by surgical resection (SR) of LRBMs.

Methods: Between December 2015 and June 2021, 25 patients of 26 LRBMs (Me=10.1 ccm (range 2.9-59) in volume) after previous treatment (SR n=5 or stereotactic radiotherapy n=20) were undergone PreSRS followed by SR. Radiation dose the median (Me) = 19.35 Gy (range 17.3-24), and was determined by tolerance of intact brain tissues. SR was performed on the same day after PreSRS in 5 cases, on the next day - 10, on the second day - 8, 3-5 day - in 2 cases.

Results: 25 patients (Me=57 years (range 30-71 )) were observed with Me = 11.5 months. Primary tumor site was the breast in 10 cases, lung in 5, melanoma in 5, kidney in 3, and other in 3. LRBMs occurred after 14 months - Me(range 4-62 ) after the first line of therapy.

12-months OS was 52% after PreSRS followed by SR of LRBMs. New metastases were observed in 48 % (n=12), Me = 9 months (range 2-35).  Local re-recurrence was in 4 cases (15%), at 5/6/10/17 months respectively and was independent of the primary tumor. 4 patients (15%) had symptomatic radiation necrosis.  One year LMD was observed in 4 cases (16%).

Conclusion: PreSRS  followed by SR for LRBMs reduces the rates of  re-recurrences brain metastasis and  LMD compared with the  surgery followed by stereotactic radiotherapy. PreSRS followed by SR of LRBMs could be reasonable decision that is necessary to confirm during further studies.


Elena VETLOVA, Andrey GOLANOV (Moscow, Russia), Natalia ANTIPINA, Elena IGOSHINA, Valeriy KOSTJUCHENKO, Ivan OSINOV, Vasiliy LUKSHIN, Dmitriy USACHEV
00:00 - 00:00 #29938 - P025 Intra-fraction error analysis of homemade mouth-bite masks in linac-based SRS for brain metastases.
P025 Intra-fraction error analysis of homemade mouth-bite masks in linac-based SRS for brain metastases.

Purpose

This study aims to evaluate the intra-fraction accuracy of stereotactic linac-based radiosurgery (SRS) for brain metastases (BM) using a frameless homemade mouth-bite thermoplastic mask in combination with cone-beam computed tomography (CBCT) and six-degrees of freedom (6-DOF) couchtop.

 

Methods 

A frameless approach using a homemade mouth-bite thermoplastic mask (figure 1) was implemented during Covid-19 pandemic emergency period to offer BM SRS under conditions of limited mobility. All patients were treated at a single institution with single-isocenter coplanar 6 MV flattening filter free (FFF) volumetric modulated arc therapy (VMAT) radiosurgery, with a 2 mm isotropic expansion from the gross tumor volume (GTV) to the planning target volume (PTV). Before treatment delivery, patients underwent a low-dose CBCT to check position accuracy. Through image co-registration, translational (x, y, z) and rotational errors (pitch, roll, and yaw) were determined and validated by experienced radiation oncologists. The 6-DOF couchtop was used to automatically relocate the patient with sub-millimetric precision. Immediately after irradiation, patients underwent a second CBCT to evaluate the intra-fraction motion, and data were collected and analyzed.

 

Results 

From February 2020 to November 2021, 40 patients (74 lesions) received BM SRS (14-21 Gy). The whole procedure, from the pre-treatment CBCT scan to the end of irradiation and subsequent CBCT, required a median time of 11 minutes [8-19]. Mean translational error was 0.1 mm ± 0.4 mm [-0.7; 1.4] in lateral direction, and 0.0 mm ± 0.4 mm [-1.4; 1.0] in longitudinal direction. A 2.2 mm maximum shift was recorded on the vertical axis, although the mean translation error was 0.1 mm ± 0.4 mm. Pitch, roll and yaw registered a mean value of 0.0° ± 0.3° [-0.8°; 0.7°], 0.0° ± 0.2° [-0.8°; 0.6°], and 0.0° ± 0.3° [-0.9°; 0.9°], respectively. The results are summarized in figure 2.

 

Conclusion 

This study demonstrates that homemade mouth-bite thermoplastic masks provide a steady patient fixation and, combined with CBCT, 6-DOF couchtop, and fast FFF coplanar treatment delivery allow minimal intra-fraction uncertainties in BM SRS. These results, coupled with the study of the dosimetric impact of residual rotational and translational errors, might lead to a reduction of the PTV margin in this setting.


Valerio PISONI (Monza, Italy), Valerio PISONI, Sara TRIVELLATO, Valeria FACCENDA, Valeria FACCENDA, Paolo CARICATO, Paolo CARICATO, Raffaella LUCCHINI, Raffaella LUCCHINI, Denis PANIZZA, Denis PANIZZA, Stefano ARCANGELI, Stefano ARCANGELI
00:00 - 00:00 #29939 - P026 Fractionated Stereotactic Radiosurgery (fSRS) for patients with recurrent high grade gliomas. A retrospective study of Hellenic Neuro-Oncology Society (HeNOS) investigating independent prognostic factors prolonging overall survival.
P026 Fractionated Stereotactic Radiosurgery (fSRS) for patients with recurrent high grade gliomas. A retrospective study of Hellenic Neuro-Oncology Society (HeNOS) investigating independent prognostic factors prolonging overall survival.

Fractionated Stereotactic Radiosurgery (fSRS) for patients with recurrent high grade gliomas.

A retrospective study of Hellenic Neuro-Oncology Society (HeNOS) investigating independent prognostic factors

prolonging overall survival

Boskos Christos, MD, PhD, Tsioukis Vasileios, MD, Korovila Alexandra, MD, Baziotis Ioannis, MD, Kapsalis Panagiotis, MD, Paschalis Theodoros, PhD, Katsaros Vasileios, MD, PhD, Liouta Evangelia, PhD, Koutsarnakis Christos, MD, PhD, Stranjalis George, MD, PhD, (Hellenic NeuroOncology Society- HeNOS)

PURPOSE: To evaluate the efficacy of fractionated Stereotactic Radiosurgery (fSRS) as reirradiation, combined with surgery and systemic therapy for patients with recurrent high grade gliomas.

METHODS AND MATERIALS: Between April 2015 and November 2021, 48 patients with recurrent malignant glioma received fractionated Stereotactic Radiosurgery (fSRS), 30 Gy in 6-Gy/5 fractions) plus systemic therapy with rechallenge Temozolomide or lomustine/bevacizumab. For fSRS we used a Linac and a Robotic Radiosurgery system. Re-operation was opted before fSRS for 11 patients with locally recurrent or progressive malignant glioma. All patients had a Karnofsky performance score (KPS) ≥ 60 and were previously treated with standard chemoradiotherapy (Temozolomide). Thirty-three patients had a GBM, 10 had an anaplastic astrocytoma (AA) and 5 an anaplastic oligodendroglioma (AO), according to WHO 2016 classification. No grade III+ side effects were observed.

RESULTS: Median overall survival (OS) and median Progression Free Survival (PFS) was 9,43 months and 7,83 months respectively. 6- and 12-month OS rates after fSRS was 71% and 37% respectively, while 6- and 12-months PFS rates were 58% and 24% respectively. Surgical resection (p = 0.013). higher KPS (p = 0.001) and AO histology proven with 1p19q co-deletion (p=0.028) were independent favοrable prognostic factors for OS after multivariate analyses.

CONCLUSION: In general, fSRS treatment may be a safe and effective option for patients with recurrent malignant gliomas in combination with/without surgical resection and systemic therapy. Re-operation, high KPS and AO histology (1p19q co-deletion) positively affected the results of fSRS treatment.


Christos BOSKOS (ATHENS, Greece), Vasileios TSIOUKIS, Alexandra KOROVILA, Ioannis BAZIOTIS, Panagiotis KAPSALIS, Theodoros PASCHALIS, Vasileios KATSAROS, Evangelia LIOUTA, Christos KOUTSARNAKIS, George STRANJALIS
00:00 - 00:00 #29948 - P027 Re-irradiation with SRS on recurrent high grade astrocytoma.
P027 Re-irradiation with SRS on recurrent high grade astrocytoma.

Introduction:

High-grade gliomas account for about half of all brain tumors in adults. Re-irradiation in combination with systemic bevacizumab therapy has been shown to be a meaningful option for patients with recurrent high-grade glioma.
The aim of this report was to present a case of irradiation and re-irradiation of astrocytoma with SRS, with excellent tolerance and response to treatment.

Case:

56-year-old patient. In October 2017 the woman began with headache and dysarthria.
CNS MRI: 26x17mm lesion in the left cerebral hemisphere, with post-contrast enhancement.
In December 2017, surgery was performed, anatomical pathology: Astrocytoma WHO Grade IV.  

June/2018 she presents dyslalia, photophobia, headache, abulia, amnesia.
CNS MRI: in surgical bed, polylobulated image with 52x41mm post-contrast enhancement, recurrence of previous lesion. Biopsy: WHO Grade IV Pleomorphic Astrocytoma

October/2018 SRS is performed in 5 fractions. She was prescribed  temozolamide.
(a/b: 6)
GTV:                       DT:36Gy DD:7Gy EQD2:59.4Gy
CTV: Edema            DT:25Gy DD:5Gy EQD2:34.37Gy

February/2019 presents expressive aphasia, photophobia, altered right eye campimetry, headache, mild ataxia and decreased visual acuity.
CNS MRI with high resolution treatment response assessment maps post contrast injection (TRAMS) reports persistence of a known lesion with an inflammatory component, radionecrosis, and disease progression.

May/2019 re-irradiation and bevacizumab treatment were decided. 

May/2019 SRS 5 fractions.
GTV  (tumor volume delimited by TRAMS)      DT:36Gy DD:7Gy EQD2:59.4Gy
CTV: 5mm expansion of tumor volume           DT:25Gy DD:5Gy EQD2:34.37Gy

August/2019 TRAMS shows a notable decrease in tumor volume. Improvement of previous symptoms.
July/2020 MRI CNS: no regrowth or signs of radionecrosis are observed.
February/2022 the patient is in good general condition, presents mild expressive aphasia, dyslexia and ataxia. She continues in systemic treatment.

Discussion and conclusion:

The patient presented good tolerance to both SRS. Control with TRAMS  was decisive in defining the volume to be treated, since it allowed radionecrosis to be differentiated from disease progression.
With a follow-up of 4 years after the initial diagnosis and after 2 years and 9 months after re-irradiation, the patient continues to have an excellent quality of life.
SRS seams to be a safe and effective treatment option for re-irradiation in recurrent high-grade glioma.


Maria Milla GALETTO (Cordoba, Argentina), Daniela Mariel ANGEL SCHUTTE, Oscar Ariel MURIANO, Veronica VERA, Agustin GIRAUDO, Valentina GREGORAT, Agostina VILLEGAS, Mercedes CHIBAN, Silvia ZUNINO
00:00 - 00:00 #29973 - P028 Radiosurgery and Stereotactic brain Radiotherapy with systemic therapy in recurrent high grade gliomas: is it feasible?
P028 Radiosurgery and Stereotactic brain Radiotherapy with systemic therapy in recurrent high grade gliomas: is it feasible?

Purpose. For recurrent high-grade gliomas (HGG) no standard therapeutic approach has been reported thus surgery, chemotherapy and reirradiation (re-RT) may all be proposed. The aim of the present study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG.

Material/Methods. We included retrospectively all patients with histological diagnosis of HGG that, in the study period, suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT. Median dose was 24 Gy (range 18-36 Gy) and median number of fractions was 5 (range 1-6). Outcome was evaluated by clinical neurological examination and brain MRI performed 1 month after re-RT and then every 2-3 months.

Results. From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median time between primary/adjuvant RT and disease recurrence was 8 months (range 2-27). In 6 cases (20%) reoperation was performed and, in most cases, (84%), a second line of systemic therapy was administrated. Median OS after recurrence was 12.1 months (95%CI 7.1-23.5). Six-month and 1-year OS were, respectively, 81% (95%CI 57-93%) and 51% (95%CI 26-72%). Median PFS after recurrence was 11.2 months (95%CI 6.2-23.1). Six-month and 1-year PFS were, respectively, 70% (95%CI 48-84%) and 32% (95%CI 13.12-52.8%). Regarding SRS/FSRT, no acute or late neurological side effects grade ≥ 2 were reported. No case of radio-necrosis was detected.

Conclusion. Re-RT with SRT/FSRT in association with second line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. However, validation of these results by prospective studies is needed.


Alessia SURGO (Acquaviva Delle Fonti, Italy), Fabiana GREGUCCI, Roberta CARBONARA, Letizia LAERA, Maria Paola CILIBERTI, Morena CALIANDRO, Ilaria BONAPARTE, Alba FIORENTINO
00:00 - 00:00 #29993 - P029 TTF-1 and napsin A predict local failure and survival after Gamma-knife radiosurgery in patients with brain metastases from lung adenocarcinoma.
P029 TTF-1 and napsin A predict local failure and survival after Gamma-knife radiosurgery in patients with brain metastases from lung adenocarcinoma.

Objectives

 

Gamma-knife radiosurgery (GKRS), combined with contemporary targeted therapies and immunotherapies, has improved the overall survival of patients with lung adenocarcinoma (ADC). Given that histological subtypes reflect prognosis in primary ADC, it is important to integrate pathological biomarkers to predict clinical outcomes after GKRS in patients with brain metastases from lung ADC. Therefore, we investigated the prognostic relevance of various biomarkers of primary lung ADC for clinical outcomes after GKRS.

 

Materials and Methods

 

A total of 95 patients with 136 brain metastases (1–4 oligometastases) treated with GKRS between January 2017 and December 2020 were enrolled. The Kaplan–Meier method and univariate and multivariate analyses using Cox proportional hazard regression models were used to identify prognostic factors for local control, survival, and distant brain control.

 

Results

 

Multivariate analysis revealed thyroid transcription factor-1 as an independent prognostic factor for local control (hazard ratio [HR] = 0.098, confidence interval [CI] = 0.014–0.698, P = 0.0203) and napsin A as a significant predictor of overall survival after GKRS (HR = 0080, CI = 0.017–0.386, P < 0.01). In EGFR mutation subset analysis, patients with EGFR exon 19 mutations showed better distant brain control than those with EGFR exon 21 mutations (P < 0.01).

 

Conclusion

 

Pathological biomarkers of primary cancer should be considered to predict clinical outcomes after GKRS in patients with lung ADC. Using such biomarkers can also help provide personalized treatment to each patient, improving clinical outcomes after stereotactic radiosurgery.


Roh HAEWON, Jong Hyun KIM (Seoul, Korea), Lee SUNG YOUNG
00:00 - 00:00 #29999 - P030 Number fractionated radiosurgery for numerous small brain metastases.
P030 Number fractionated radiosurgery for numerous small brain metastases.

Background:

Treatment of multiple brain metastases more than 10 is challenging and has been controversial. Whole brain radiotherapy (WBRT) is generally believed to be the first treatment choice. However, this is not always adequate because of the inconsistent effects and combined adverse effects such as dementia which may be resulted afterward. In order to escape from mental deterioration, WBRT has to be replaced by the other treatment methods like radiosurgery. We have performed such a treatment for numerous small brain metastases by Gamma Knife stereotactic radiosurgery (GKS).

Methods:

Twelve cases of numerous (more than 30) brain metastases were treated by GKS retrospectively during a period from July, 2016 to June, 2021. They were seven males and five females with the mean age of 63.4 years. All of them were with lung cancers. Mean total session number was 5.42 times, ranging 2 to 17. Each tumor was treated with the margin dose between 14 to 20 Gy. The tumor number treated in whole sessions was ranged from 31 to 144 (mean, 70.8).

Results:

Almost all the irradiated tumors either disappeared or shrank at the patient’s death or at the last follow-up, though new metastatic tumors were subsequently developed in some cases which required an additional treatment with GKS. At the last follow-up (3 to 51 months after GKS), nine cases were alive and well and three were dead. As adverse effects, two cases demonstrated seizures by radiation brain injury and another showed a gait disturvance. No apparent mental deterioration was observed during follow-up.

Conclusions:

Local tumor control without any severe side effects including mental deterioration was achieved, which seemed to be consistent with radiosurgery in cases with 10 or less brain metastases. Radiosurgery for numerous small brain metastases may be preferable rather than whole brain irradiation.


Yoshimasa MORI (Kawasaki, Japan), Yasuhiro MATSUSHITA, Yoshihisa KIDA
00:00 - 00:00 #30002 - P031 Upfront GKS in combination with high-dose MTX and Rituximab for primary CNS lymphoma in elderly patients: A single-center pilot study.
P031 Upfront GKS in combination with high-dose MTX and Rituximab for primary CNS lymphoma in elderly patients: A single-center pilot study.

OBJECTIVES 

Primary central nerve system lymphoma (PCNSL) is rare aggressive non-Hodgkin lymphoma. Current standard of care for PCNSL typically includes high-dose methotrexate (MTX), rituximab, radiotherapy, and chemotherapy with autologous stem cell rescue. These treatment strategies have improved the prognosis but still eluded half of the patients, that is, immunocompetent elderly patients. Given the risk of neurologic and hematologic toxicity, these patients may be poor candidates for whole-brain radiotherapy or myeloablative chemotherapy. We offered stereotactic radiosurgery (SRS) for upfront regimen followed by high-dose MTX and rituximab in elderly patients of newly diagnosed PCNSL.

 

MATERIAL AND METHODS 
The author conducted the retrospective review of 13 immunocompetent patients >60 years with PCNSL who underwent gamma knife radiosurgery (GKS) as first-line therapy in combination with the standard chemotherapy based on high-dose MTX and rituximab. Local recurrence (LR) was defined as tumor progression expanding more than 20% in the prescribed isodose line. The progression-free survival (PFS) was measured starting from first-line treatment completion. Overall survival (OS) was calculated from the date of the histologic diagnosis of PCNSL to the date of death or last follow-up.

 

RESULTS

Overall, 13 patients received GKS for 14 lesions with a median volume of 8.59cm3 (range 2.95-120.89cm3). The median age at GKS was 71 (range 60-86) and the median KPS was 80. GKS was given via single fraction to the median dose of 17 Gy (range 12-22Gy) in 10 patients and 3 or 4 fractionations with a cumulative dose of 24 Gy at 50% isodose line in 3 patients. During the follow-up period (median 16.3 months; range 5.3-31.3 months), 2 patients had LR and 3 patients developed distant recurrence with a median 9.1 months of the time to progression. 2 patients were expired due to hematologic complications after chemotherapy. In terms of GKS, no major complication or radiation necrosis was observed. 6-month and 12-month PFS were 83.1% and 60.6%, respectively, and OS were 92.3% and 82.1%, respectively. The median values of both PFS and OS were not reached.

 

CONCLUSION

With favorable local control, SRS may have a role as the first-line treatment of elderly patients in newly diagnosed PCNSL. The comparative efficacy of such an approach should be examined in prospective trials.


Jeong-Hwa KIM (Seoul, Korea), Jung-Won CHOI, Doo-Sik KONG, Ho Jun SEOL, Do-Hyun NAM, Jung-Il LEE
00:00 - 00:00 #30033 - P032 Radiosurgery for brain metastases from breast cancer.
P032 Radiosurgery for brain metastases from breast cancer.

Background: Brain metastasis (BM) occur in approximately 15% of patients affected by advanced breast cancer (BC). In the last two decades, overall prognosis of metastatic BC patients has improved with the introduction of new target therapies. Integration of systemic therapy of local ablative therapy may represent an effective, non-invasive approach to control intracranial metastasis, in particular in oligometastatic patients. This report analyzes clinical outcome of BM from BC treated with GammaKnifeRadiosurgery (GKRS).

Materials and Methods: Data of 58 consecutive BC patientstreated with GKRS from November 2012 to August 2020, accounting for 149 metastases, were retrospectively examined. We assessed the correlation between clinical-pathological factors and outcome. Overall survival (OS), local control (LC) and distant brain control (DBC) were calculated from the date of GKRS using the Kaplan-Meier method.

Results: Medianage was 56 years (range: 31-80). RPA class was 1 in 28 out of 57 patients. Estrogen receptor positive, HER-2 positive and triple negative BC was found in 42%, 44% and 16% of   patients.  In 19 (34%) patients the brain was the only metastatic site. At the time of GKRS all patients had controlled extracranial disease. Ten patients (17%) had an history of surgical BM excission and 5 (9%) patients had a prior WBRT.  Mean number of brain metastasis treated with GKRS was 2 (range:1-11). Mean prescription dose was 21 Gy (15-24): 9 patients underwent a second radiosurgery course. At the time of BM diagnosis 41 (72%) patients received GKRS and continuation of the same chemotherapy schedule. Fifteen radiological radio necrosis were reported: however, 3 patients had symptomatic radionecrosis, two treated with steroids and one with surgery. Local control was 95%, 92% and 86% at 6, 12 and 24 months, respectively. Median distant brain control after GKRS was 47months (95%CI:20-60 months), DBC was 85%, 72% and 63% at 6, 12 and 24months, respectively. Median overall survival was 24months (95% CI:15-45 months). Overall survival was 85% at 6months, 68% and 48% at 1 and 2 years. Patients with RPA class I had improved survival (median 45 versus 18 months, p=0.036,  HR 2 C95% 1.1-3.9).

Conclusions: Our study showed that GKRS is associated with high local control rates and rare severe side effects. Use of GKRS for progressive BMs allowed for continuation of the same chemotherapy line in the majority of patients. This may be of particular in RPA I patients that show longer survival and may draw the higher benefit from GKRS.

 


Daniela GRETO, Manuele ROGHI, Chiara BELLINI, Isacco DESIDERI, Mauro LOI, Emanuela OLMETTO, Icro MEATTINI, Luca VISANI, Viola SALVESTRINI (Florence, Italy)
00:00 - 00:00 #30037 - P033 Single versus multiples shorts dose planning for Gamma Knife Radiosurgery of brain metastases.
P033 Single versus multiples shorts dose planning for Gamma Knife Radiosurgery of brain metastases.

Aims. Brain metastases (BMs) represent a significant medical concern in cancer patients. A valuable treatment option in selected patients with BMs is radiosurgery (RS), in particular using dedicated platforms such as the GammaKnife (GK). However, the impact on treatment response of different technical solutions, in particular use of multiple or single isocenters (shots), has not been established. The aim of our study is to evaluate differences in dosimetric parameters and clinical outcome among patients receiving multiple or single shot GammaKnife radiosurgery (GKRS)  for BMs measuring less than 1 cm .

Methods: Demographic, disease- and treatment-related features of 86 consecutive patients treated with the Leksell Gamma Knife® Perfexion™ for a total of 282 BMs were retrospectively collected. Each lesion was irradiated using one or two shots with a diameter of 4 and/or 8 mm. Selectivity Coverage and Gradient Index (GI) were examined for each lesion. Radiological response to RS treatment was observed according to RANO (Response Assessment in Neuro Oncology) criteria with MRI at 1, 3, 6 and 9 months.

Results:  Mean volume of metastases was 103.1 mm3 (2.4-721 mm3). Among treated BMs, 210 (74%) and 72 (25%) BMs were treated with one or two shots, respectively.  Mean coverage of the plans executed with one shot was 99.9% (range: 92-100%) while it was 99.7% (range: 95-100%) using two shots. Mean selectivity and mean gradient were respectively 0,25 (range: 0.001-0.63) and  3.2 (range: 0.85-8.10)  in single shot plans,  and 0.35 (range: 0.07-0.78) and  3.2 (range: 2.11-9.8) in two shots plans. A statistically significant improvement in coverage was found in one shot plans (0.9995 vs 0.9968, p=0.0001), while selectivity was significantly better using two shots (0.2494 vs 0.3546, p=0.0001).

Considering patient and disease-related characteristics, breast histology correlated with a poorer local control (p=0.0001) at 3 and 6months MRI, while a GPA (Graded Prognostic Assessment) < 3 was predictive of local failure (p=0.018) at 9months MRI. Concerning local control, overall local control rate at 1 month was 96%: patients treated with one shot had an improved local control at 1 (1.0% vs 11.6% p=0.0001) and 6months (5.9% vs 20.7%, p=0.026) as to two shots.

 Conclusion: Our study suggested that, in BMs with a diameter inferior to 1 cm receiving GKRS, the use of a single shot resulted in a better coverage and a better local control at one and three months. However, GPA score and histology affect clinical outcome of patients with BMs. 


Daniela GRETO, Manuele ROGHI, Maria Grazia CARNEVALE, Isacco DESIDERI, Giulio FROSINI, Barbara GUERRIERI, Viola SALVESTRINI (Florence, Italy)
00:00 - 00:00 #30051 - P034 Stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) as adjuvant treatment for resected brain metastases (BMs): a single-center series.
P034 Stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) as adjuvant treatment for resected brain metastases (BMs): a single-center series.

Post-operative SRS and fSRS are effective and safe approaches commonly used to treat BMs. In our series, 71 patients (pts) who underwent partial or total resection for BM and adjuvant SRS or fSRS with Cyberknife (CK) were retrospectively analyzed. Pts with prior whole brain irradiation (WBRT) or leptomeningeal disease (LMD) were excluded. The main represented histologies were breast and non-small cell lung cancers. Almost all pts had no ongoing systemic therapies at the moment of CK. Twenty-nine pts underwent SRS (14-20 Gy in single fraction), 42 fSRS (21-24 Gy in 3 fractions). They all had a Karnofsky performance status ≥ 70. The cumulative 1-year local control (LC) rate and progression free survival (PFS) were 78.5% and 87%, respectively. The cavity recurrence rate was 38% versus (vs) 17% for SRS and fSRS group, respectively (p=0.15), with a median time to progression of 17 months vs 12. Only 4 events of late brain radiation necrosis (RN) were registered, all G2 graded according to CTCAE v.5. No other G2 toxicities were reported. The median overall survival (OS) was 47 months, with a 12-months OS rate of 83%. A 20% rate of LMD was reported; the type of surgical resection of the BM (piecemeal vs en-bloc), and the inclusion or exclusion of the surgical corridor leading to the cavity in PTV volume did not show a statistically significant correlation with the onset of LMD. A better trend for PFS emerged for pts with a waiting time from surgery to treatment ≤ 45 days vs > 45 days (p=0.07). PTV volume, dose prescription, fractionation and histology seemed not to affect LC, nor OS. A DS-GPA score ≥ 3 vs < 3, an extracranic (EXC) disease absent or oligometastatic vs present not oligometastatic, and an EXC disease at last follow-up stable vs in progression were found to be significantly correlated with a better OS (p=0.0000, p=0.02, p=0.0009, respectively). We can confirm that both SRS and fSRS are effective and safe approaches in the adjuvant setting of resected BMs; dose prescription and fractionation must be selected according to PTV volume. With regards to OS, they are a valid alternative to WBRT. Further data are needed to better assess the role of target delineation, waiting time from surgery to irradiation, and systemic therapies to improve pts outcomes.


Valentina PINZI (Milan, Italy), Anna ROMEO, Marcello MARCHETTI, Sara MORLINO, Irene TRAMACERE, Laura FARISELLI
00:00 - 00:00 #30081 - P035 The ghost lesion: delayed post GK brain metastasis recurrent enhancement between 8 and 36 months as a manifestation of benign radiation change mimicking recurrent malignancy.
P035 The ghost lesion: delayed post GK brain metastasis recurrent enhancement between 8 and 36 months as a manifestation of benign radiation change mimicking recurrent malignancy.

Successful Gamma Knife brain metastasis treatement, with complete lesion resolution, can be followed by delayed post SRS recurrent MRI enhancement at the treatment site, up to 36+ months after treatement, but as a manifestation of benign post treatment delayed radiation change and not recurrent malignancy. This enhancment can then be persistent for many months and even enlarge subsequently, and also with elevated choline using Magnetic Resonance Spectroscopy. These are usually reported as recurrent malignancy by the radiologist but needs to be correlated with the pre Gamma Knige SRS plan and then observed rather than re-treated by radiation or chemotherapy. I have many of these "Ghost Lesions" which have been confirmed as delayed radiation change to validate this important concept.


Stephen HOLMES (honolulu, USA)
00:00 - 00:00 #30084 - P036 The interval between surgery and stereotactic radiosurgery is critical for local control of resected brain metastases.
P036 The interval between surgery and stereotactic radiosurgery is critical for local control of resected brain metastases.

Purpose: Stereotactic radiosurgery (SRS) is commonly employed for resected brain metastases. Because of uncertainty about the optimal timing of SRS delivery after surgery, we retrospectively evaluated local control (LC) at the site of postoperative SRS to study this question.

Materials & Methods: We identified a consecutive series of 133 patients with surgically managed BM who received SRS or fractionated SRS at our institution from 2012 to 2018. We assessed the interval between surgery and SRS with LC, local recurrence-free survival, distant recurrence, distant recurrence-free survival, and overall survival.

Results: The median age of our cohort was 64.5 years. 72 patients (54.1%) had a single BM, and the median BM diameter was 2.9 cm. Postoperative MRI showed a gross total resection was achieved in 111 patients (83.5%). 123 patients (92.5%) received fractionated SRS. The median time from resection to SRS was 37.0 days, and the overall LC rate was 83.6%. The interval between surgery and SRS was predictive of LC. For patients with LC at the surgical site, the median time from surgery to SRS was 34.0 days. For patients without LC, the median time from surgery to SRS was 61.0 days (p<0.01). The LC rate was 97.7% when SRS was administered ≤4 weeks postoperatively, compared with 76.4% if SRS was administered after an interval >4 weeks (p<0.01). Local recurrence-free survival was improved for patients who underwent SRS at ≤4 weeks (P = .02). Delayed SRS was also predictive of distant recurrence (p=0.02) but not overall survival.

Conclusions: In this retrospective study, LC after postoperative SRS for BM was most strongly predicted by time to SRS, and a cutoff of 4 weeks was a reliable predictor of recurrence. These findings merit investigation in a prospective, randomized trial.


Diana ROTH O'BRIEN, Sydney M. KAYE, Philip POPPAS, Sean E. MAHASE, Anjile AN, Paul J. CHRISTOS, Benjamin L. LIECHTY, David J. PISAPIA, Rohan RAMAKRISHNA, A. Gabriella WERNICKE, Susan C. PANNULLO, Jonathan P.s. KNISELY (New York, USA), Theodore E. SCHWARTZ
00:00 - 00:00 #30087 - P037 A Simple Temporal Empirical Model Application for Fractionated SRS Boost Post Whole Brain Irradiation.
P037 A Simple Temporal Empirical Model Application for Fractionated SRS Boost Post Whole Brain Irradiation.

Introduction: The dose prescription for radiotherapy is based on the phenomenon linear-quadratic model which was originally developed for the experimental result in cellular scale. And a biologically effective dose (BED) concept was defined. This empirical model was applied to clinical practice by adjusting the time and amplitude of fractionated dose. Another empirical model was through direct collecting of clinical outcomes or tolerance in actual patients with exponential power index fitting, and a nominal standard dose (NSD) concept was defined.  In this study, the combination of both analytical empirical models was applied to estimate the approximate dose level in fractionated SRS post whole brain irradiation situation, and the practical goal is to develop accurate dose prescriptions for SRS retreat patients.

Methods and Materials: A patient was under the treatment of whole brain with prescription at 30Gy in 10 fractions and the procedure elapsed in 13 days.  This whole brain treatment covered the whole brain volume at 1483.01cc and equivalent spherical diameter at 14.1cm.  The coverage the brain is 97.4% with conformity index at 1.30.  After 222 days, the follow-up imaging showed that more lesions were shown up, so a 5 factions SBRT treatment with 6Gyx5 was delivered with elapsing in 10 days. One of the lesions was 17.66cc in 3.5cm diameter. A two single ARC method was employed to deliver the prescription dose to the target and reached the coverage at 98.8% with conformity index at 1.12. Two methods were employed to compute the dose in NSD, and BED.  First is a direct computation, the second is considering the residual dose due to temporal effect.  Finally, the two results were compared to those of a single fraction SRS volume-based prescription. 

Results:  Given the alpha beta ratio at 10, the total NSD and BED were 39.5Gy and 59.3Gy when both temporal effect and 5 fraction SRS being considered. Without considering the temporal effect, the total NSD and BED for 5 fraction SRS post whole brain irradiation were 60Gy and 87.0Gy; And for the single fraction volume-based SRS situation, the total NSD and BED were 48Gy and 89.4Gy. 

Conclusion and discussion: Temporal empirical model could be used for high precise dose estimation for post whole brain irradiation with SRS and SBRT. And the temporal effect could generate significant variation in dose prescription. Moreover, the efficacy in multiple lesion SRS prescription could be further analysis and dose energy delivery pattern effect could be explored.


Kaile LI (Hagerstown, MD, USA), Cengiz AYGUN
00:00 - 00:00 #30088 - P038 Stereotactic radiosurgery for treatment of lung cancer patients with brain metastasis before and after the era of targeted therapy.
P038 Stereotactic radiosurgery for treatment of lung cancer patients with brain metastasis before and after the era of targeted therapy.

Introduction: Radiosurgery has been an important part of treating lung cancer patients who develop brain metastasis. The timing and utilization of radiosurgery is not as clear in more recent years with the availability of targeted agents and discovery of druggable mutations for treatment of these patients. We examine our experience with these patients over a period of time before and after the routine of testing for known lung cancer mutations and use of agents that target these mutations. 

 

Methods: We retrospectively reviewed the charts of 267 (133 female, average age 64, range 34-86) patients with brain metastases from lung cancer patient treated with stereotactic radiosurgery over a 20-year period of time. We report a median follow up of 25 months after first radiosurgery for patients with non-small cell carcinoma (182 adenocarcinoma, 32 squamous, 6 large cell, and 19 unknown subtype) as well as, 28 small cell carcinomas that failed initial whole brain radiotherapy. We examine the number and timing of radiosurgical treatments, outcomes of the treated lesions including suspected treatment related imaging changes, and the use and type of targeted therapy for these patients. 

 

Results: Of the 265 patients examined, 80 patients were never smokers, 76 had brain surgery sometime during their course of which 45 patients had radiosurgery performed to a postop resection cavity. We treated an average number of 2 lesions with a range 1-12. 191 patients required only one SRS treatment while 77 had two radiosurgery sessions, 22 with three sessions, 7 with four sessions, and 2 with 5 sessions. We found 34 (13%) cases of confirmed radiation necrosis within this group. PD-1 mutation data was available on 151 patients with 30 (20%) with PD-1 expression greater than 10% and 43 (28%) greater than 1%. We are currently exploring ALK and EGFr mutational status in a similar manner The majority (87%) of our patients, including those with unknown mutational status were treated with some form of targeted therapy. The average number of targeted agents were 2 with a range of 1-6. The effect on overall survival and local control is also under examination for factors to predict these patient outcomes. 

 

Conclusion: The treatment algorithms for lung cancer patients with brain metastasis is evolving, the results of our study can help guide future best practices for management of these patients. 


Randy L. JENSEN (Salt Lake City, USA), Lindsay BURT, Don CANNON, Dennis C. SHRIEVE
00:00 - 00:00 #30091 - P039 Bio-inspired algorithms on multiple metastases single isocenter radiosurgery for PTV margin optimization.
P039 Bio-inspired algorithms on multiple metastases single isocenter radiosurgery for PTV margin optimization.

Purpose: To compare the genetic operators (mutation, crossover and number of individuals in the population) between genetic algorithm (GA) and differential evolution (DE) to determine the optimization-efficiency for the maximum displacement produced by the combined effect of rotations and translations in single isocenter multiple metastases radiosurgery (SIMM-SRS).

Method: The order and direction of rotational/translational displacements for 144 targets (21 SIMM-SRS plans) was studied for the 0.5º/0.5 mm case using GA and DE. To determine the maximum displacement produced, in-house software was performed. It allowed the handling of the DICOM files of the plans. The relationship between genetic operators such as mutation rate (m), crossover point (p) and population size (n) with respect to the search for maximum global displacements was studied.

Results: The GA showed better benefits with respect to DE. By the selection of a low mutation rate, crossover point equals to 6 and medium population size, the GA reached global maxima displacements in low computation time without the problem of fall into local maxima. The mean maximum displacement produced by the combination of rotations and translations is 2.2 ± 0.6 mm with a mean distance to isocenter of 53 ± 11 mm.

Conclusion: The implementation of GA is feasible in SIMM-SRS for the determination of the maximum displacements produced by rotations and translations.


José Alejandro ROJAS-LÓPEZ (Argentina, Argentina), Daniel VENENCIA, Miguel Ángel CHESTA, Francisco TAMARIT
00:00 - 00:00 #30116 - P040 Large brain metastasis treated with adaptive staged-dose Gamma Knife radiosurgery: preliminary results of a single centre retrospective analysis of 76 patients.
P040 Large brain metastasis treated with adaptive staged-dose Gamma Knife radiosurgery: preliminary results of a single centre retrospective analysis of 76 patients.

Purpose: to retrospectively analyse plans of patients with large brain metastasis (BM) treated with adaptive staged-dose gamma knife radiosurgery in two stages.

Material and Methods: since 2018, 76 patients with large BM  (>10 cm3) has been treated with a two-stages radiosurgery protocol using a dose prescription of 12 Gy at 50% of maximum of the dose distribution and planned time interval of 1 months between the two stages. The plans were elaborated with Gammaplan v.11.1.1 treatment planning system and delivered on a Gamma knife Perfexion unit. MR T1 weighted images, dose distribution and structures were exported to MIM software v. 7.1.4 for subsequent analysis. A rigid deformation between MR images of the two stages was calculated and the two dose distributions of the two plans were linearly summed up on the MR image of the second sessions. The initial tumour volume, its change after the time interval Δt between the two stages  (ΔVol%), and the volume of surrounding healthy tissues receiving 12Gy in the summed dose distribution (V12GyHTacc) were calculated.  The volume of treated BM and the presence of side effects will be considered and analysed as follow-up parameters at 3, 6, and 12 months after the second stage.

Results: Two distinct BM were treated simultaneously in 5 patients using the same prescription of 12 Gy in both stages. For 33 patients one or more smaller BM with higher dose prescription were treated during one of the two stages. The tumour volume at the first stage was (24.±15.4)cm3 and the shrinkage ΔVol% resulted in (-32±29)% after a Δt of (31.3±5.5) days. In only 9 patients out of 76 (11.8%) the tumour increased volume during the time interval between the two stages and in one of these cases (1.3%) ΔVol% was greater than 30%. The dose accumulated to the healthy tissues surrounding tumours resulted in V12HTGyacc of (48.7±31.5)cm3. No acute treatment-related toxicity was recorded between the two fractions. We reported the preliminary data about the volume of treated BM and the presence of side effects, collected and analysed as follow-up parameters at 3, 6, and 12 months after the second stage.

Conclusions: adaptive staged-dose gamma knife radiosurgery in two session for brain metastases is highly effective on local control with a low rate of complications due to low dose irradiation to surrounding brain tissue. Further information will come from the analysis of follow-up data taking accumulated dose distribution into account.


Luca BERTA, Hae Song MAINARDI, Maria Grazia BRAMBILLA, Angelo Filippo MONTI, Paola Enrica COLOMBO, Alberto TORRESIN, Filippo LEOCATA, Marco PICANO, Alessandro POZZA, Virginia Maria ARIENTI, Mauro PALAZZI, Alessandro LA CAMERA (MILAN, Italy)
00:00 - 00:00 #30127 - P041 A prospective single arm phase II study to evaluate safety and efficacy of silibinin in patients with brain metastases treated with stereotactic radiotherapy: preliminary results from SUSTAIN TRIAL.
P041 A prospective single arm phase II study to evaluate safety and efficacy of silibinin in patients with brain metastases treated with stereotactic radiotherapy: preliminary results from SUSTAIN TRIAL.

Purpose

Brain metastases (BMs) accounts for more than one-half of all intracranial tumors. Survival of patients (pts) with BMs has increased in recent years with the entry of stereotactic radiosurgery (SRS), providing excellent rates of local disease control. Silibinin or silybin, a natural polyphenolic flavonoid isolated from milk thistle seed extracts, showed promising antitumor activity in preclinical studies. Furthermore, the use of a silibinin-based nutraceutical has resulted in significant clinical and radiological improvement of BMs in pts with progressive non-small cell lung cancer (NSCLC) after whole brain radiotherapy and chemotherapy. The aim of our exploratory study is to evaluate whether the use of a silibinin-based nutraceutical significantly reduces distant-brain failure (DBF) at 6 months in pts with first-diagnosed BMs treated with SRS with or without surgery. Here a preliminary analysis on the first 18 pts enrolled is reported. 

 

Methods

SUSTAIN is a prospective, single arm, phase II study. A total of 80 pts with newly diagnosed BMs treated in our center and complying with the entry criteria are planned to be enrolled. Pts receive 2 capsules (cps) of SILLBRAIN® per day for the first month after SRS and 1 cp per day thereafter. The 6-month DBF rate is assessed according to RANO criteria for brain metastases (RANO-BM). Contrast-enhanced magnetic resonance (MRI) of the brain is performed at baseline and every 12 weeks after SRS. Validated health-related quality of life questionnaires (EORTC QLQ-C30 and BN20) are administered at baseline and every 12 weeks after SRS.

 

Results

Eighteen pts had been enrolled at the time of this primary analysis. NSCLC and breast cancer were the prevalent histologies, with 9 and 4 cases respectively. Ten pts had metachronous BMs onset, and 8 pts synchronous. Nine pts received at least 1 line of systemic therapy and 17 pts reported a controlled extracranial disease at BMs diagnosis. The overall number of BMs was 55. All BMs were treated with SRS, with a median prescription dose and median prescription isodose of 24Gy and 80%, respectively. According to RANO-BM criteria, 2 pts reported distant intracranial failure with 3 and 19 months of DBF. One pts discontinued SILLBRAIN® assumption due to grade 1 nausea (CTCAE v5.0). No other adverse events were reported.

 

Conclusion

The use of silibinin-based nutraceuticals after SRS might prolong distant brain failure-free survival in BMs pts, with a favorable safety profile. Final results from SUSTAIN trial are awaited to confirm these encouraging findings.


Isacco DESIDERI, Maria Grazia CARNEVALE (Florence, Italy), Luca VISANI, Viola SALVESTRINI, Ilaria BONAPARTE, Ludovica ZISCA, Lorenzo LIVI
00:00 - 00:00 #30129 - P042 Stereotactic radiotherapy using a mask system of Leksell Gamma Knife Icon for patients with metastatic brain tumors.
P042 Stereotactic radiotherapy using a mask system of Leksell Gamma Knife Icon for patients with metastatic brain tumors.

[Objectives] Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment.

[Methods] We retrospectively analyzed 1125 patients (a total of 1572 treatments) with brain metastases who underwent Gamma Knife Icon using mask fixation for the first four years at Rakusai Shimizu Hospital. Patients with small, few, newly diagnosed, and non-eloquent area tumors were treated in a single session. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule. If the tumor number was large, we selected a multisession schedule. The most common origin was lung (734 patients), followed by breast (135), gastro-intestinal tracts (124), kidney (43), and others (88). Median tumor number was three and median cumulative tumor volume was 2.7 ml.

[Results] 433 cases were treated in a single session, 733 with fractionation, and 366 with multiple sessions. For large tumors, we selected fractionated schedules as follows; 7.0 Gy x 5Fr (5-10 ml), 4.2Gy x 10Fr (10-20ml), 3.7Gy x 10Fr (20-30ml), 3.2Gy x 10Fr (30ml-). Median survival times after Icon treatment was 20.3 months, with only 2/3/5% of neurological deaths at 6/12/24 months after treatment. Poor local control rates were 9/18/27% at 6/12/24 months post-treatment. Preservation of neurological function rates were 95/92/89% at 6/12/24 months post-treatment. Serious complications occurred in only 1/1/2% of patients at 6/12/24 months post-treatment.

[Conclusions] Although these results are limited to short periods, survival rates, local control rates and qualitative survival rated in patients unsuitable for stereotactic radiosurgery, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges.


Takuya KAWABE (Kyoto, Japan), Manabu SATO
00:00 - 00:00 #30143 - P043 Neoadjuvant stereotactic radiosurgery vs. postoperative radiosurgery for brain metastases: A Dosimetric study.
P043 Neoadjuvant stereotactic radiosurgery vs. postoperative radiosurgery for brain metastases: A Dosimetric study.

Objectives:

To investigate the potential of neoadjuvant SRS (stereotaxic radiosurgery)  versus surgical bed SRS by providing a detailed dosimetric comparison. To this end, we determined the difference of V12 Gy (Volume of the healthy brain receiving 12Gy) in neoadjuvant SRS versus posoperative SRS to the surgical bed in brain metastases.

 

Background:

Neoadjuvant SRS for brain metastases is an alternative approach that could help improve uncertainties regarding margins, targeting, and reduction of healthy irradiated brain tissue. Comparative clinical data are scarce, which is why we carried out this simulation study at the National Institute of Neurology and Neurosurgery in Mexico City.

 

Methods:

We reviewed the database of patients who underwent surgical resection of brain metastases who received SRS in the postoperative period between October 2017 and July 2020. The delimitation of the objective and the treatment planning were based on an MRI (resonance image magnetic) and computed tomography (CT). Two hypothetical treatment scenarios for the neoadjuvant tratments were created (preoperative and postoperative) and later the PTV (planning target volume) and V12 Gy were compared in the different scenarios.

 

Results: 

Fifteen patients were included, out of which the most common histologies were of pulmonary and renal origin (66.6%). The V12 Gy was larger in the postoperative setting and lower in the preoperative setting. These results had a significant difference (18.599 vs 8.013, p <0.0001).

 

Conclusion:

In our analysis, from a dosimetric point of view, the findings obtained favor the preoperative treatment and suggest that preoperative SRS may help reduce the risk of radiation necrosis due to the fact that there is better delineation of the PTV and less uncertainty regarding the delineation of the objective and therefore less exposure of healthy tissue to radiation.


Rocio MAMANI (Lima, Peru), Javier JACOBO, Jose ARROYO, Alfredo HERRERA, Carlos BARRIOS, Laura HERNANDEZ, Axayacatl GUTIERREZ, Sergio MORENO
00:00 - 00:00 #30151 - P044 Initial experience using IDENTIFY for motion monitoring during frameless VMAT radiosurgery.
P044 Initial experience using IDENTIFY for motion monitoring during frameless VMAT radiosurgery.

Purpose: We report our initial clinical experience using IDENTIFY, an optical surface guidance system, for monitoring intra-fraction motion during stereotactic radiosurgery with HyperArcTM.

Methods: The IDENTIFY system consists of three ceiling mounted camera pods. For each treatment fraction, a reference surface was captured after radiographic image guidance prior to the first beam on. Surface guidance and linear accelerator trajectory logs were used to evaluate the reported offsets relative to the reference surface. Offsets were obtained at the start of treatment (after radiographic image alignment), end of treatment, and during treatment at 4 gantry angles: 140 and 220 degrees, when all three camera pods had a clear view, and 50 and 310 degrees, when the view of one of the camera pods was obstructed.

Results: 733 fractions of 295 treatment plans were evaluated. The average treatment time was 3.35 min (range 1.87 to 7.45 min). The mean (x,y,z) translation offset at the end of treatment was (0.00, -0.01, -0.07) mm, with median magnitude 0.27 mm and 95% of magnitudes were less than 0.97 mm. The mean reported offset during treatment was (-0.40, 0.23, -0.08), (-0.25, 0.02, -0.16), and (-0.16, 0.21, -0.05) mm at table angles 45, 90, and 315 degrees, respectively. The mean change in translation when a camera pod was blocked by the gantry was (0.01, 0.14, 0.02), (0.10, 0.23, 0.07), and (-0.02, 0.15, -0.00) mm at table angles 45, 90, and 315 degrees, respectively. The fraction of offsets exceeding 1 mm was 4.4%, 6.9%, and 2.5% when all three cameras had an unobstructed view, and was 13.4%, 1.9%, and 10.6% when a camera pod was blocked at table angles 45, 90, and 315 degrees, respectively.

Conclusion: The IDENTIFY system can be used to monitor for intra-fraction motion with submillimeter accuracy; however, the accuracy is reduced when a camera is obstructed by the gantry and/or the couch is rotated. Action levels should be established accordingly to account for this behavior.


Richard A. POPPLE (Birmingham, USA), Elizabeth L. COVINGTON, Dennis N. STANLEY, John B. FIVEASH
00:00 - 00:00 #30166 - P045 Sarcopenia analysis as a tool for outcome prediction in patients with brain metastases treated with gamma knife radiosurgery.
P045 Sarcopenia analysis as a tool for outcome prediction in patients with brain metastases treated with gamma knife radiosurgery.

Introduction: 

Sarcopenia is defined as reduced muscle mass and is characterized by a significant increase in health risk and mortality. Although sarcopenia has been associated with worse outcomes in the surgical and oncological literature, its association with outcome in patients with brain metastases treated with Gamma Knife Radiosurgery (GKRS) has never been formally examined. We performed a retrospective study to determine the association of sarcopenia with survival in patients with brain metastases treated with GKRS. 

Methodology:

A single-centre cohort of 344 consecutive patients with brain metastases treated with GKRS at from 2017 to 2021 was studied retrospectively. Computed tomography images of the abdomen were acquired prior to each patient’s initial GKRS treatment, and axial sections at the third lumbar (L3) level were captured for quantification of muscle and adipose tissue using Slice-O-Matic Software® (Tomovision). Skeletal muscle index was calculated and sarcopenia was determined based on previously established literature thresholds. Chart reviews were performed to obtain patient information including age, sex, primary malignancy, quantity and total volume of brain metastases at time of treatment, and margin dose delivered. The primary outcome of interest is survival after GKRS, categorized in a binary fashion.

Results:

Metastatic tumors represented in the cohort were lung (47.1%), breast (19.5%), melanoma (10.5%) and renal (9.6%), with the remaining 13.5% being of miscellaneous primary origin. The median number of brain metastases was 2 with median tumor volume 4.7 cm3. Proportion of patients alive at 6- months and 1- year time point post-GKRS treament was 70.6% and 47.4% respectively. A preliminary Kaplan-Meier survival analysis suggests that severe muscle-depletion in male patients is associated with decreased survival after GKRS treatment. 

Conclusions:

Preliminary data suggest an association between pre-treatment muscle depletion and survival after GKRS for a subset of patients with brain metastases. Future work will need to address the value of sarcopenia analysis in patient selection for GKRS and prognostication in the setting of brain metastases.


Ryan CHRENEK (Edmonton, Canada), Vickie BARACOS, Rachel KHADAROO, Samir PATEL, Tejas SANKAR, Greg BOWDEN
00:00 - 00:00 #30168 - P046 LINAC-based stereotactic radiosurgery with co-planar beams in the treatment of brain metastases.
P046 LINAC-based stereotactic radiosurgery with co-planar beams in the treatment of brain metastases.

Aim Single-fraction radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) are established treatment options in the management of brain metastases (BM). Limited data are available using a LINAC-based approach with co-planar arcs. This study analyzed a mono-institutional series of patients treated with this technique. 

Methods From October 2019 to December 2021, 54 patients (102 BM) with different primary solid tumors were treated with SRS or fSRS delivered with single-isocenter coplanar FFF-VMAT on a Linac platform. Patients’ characteristics are summarized in Table 1. Post-treatment MRI scans were used to assess local control (LC) and disease progression (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) scale. Survival curves were calculated from the date of treatment by using the Kaplan-Meier (KM) method. 

Results Median age at diagnosis of BM was 67 years (34-85). Median follow up was 5.0 months (0.3-22.9). At the time of treatment, the median Graded Prognostic Assessment (GPA) score was 2.0 (0.5-3.5). The majority of patients (45 [83.3%]) had extracranial metastases, of whom 28 (51.9%) had visceral metastases. 83.9% and 16.1% of lesions received SRS (18-21 Gy in 1 fraction) and fSRS (27 Gy in 3 fractions), respectively. The mean GTV was 0.85 (0.08-4.97) cm3 and the mean PTV was 2.58 (0.67-11.96) cm3. Dosimetry statistics are reported in Table 1. LC and PD were observed in 19 (33.9%) and 21 (37.5%) treatments, respectively. The pattern of PD was extra-field in 12 patients (57%), in-field in 5 patients (24%) and both in- and extra-field in 4 patients (19.0%). Seven patients and 4 patients with extra-field PD were treated with whole brain radiotherapy (WBRT) or additional SRS, respectively. At the last follow-up 22 patients died and 6 patients were lost. Median OS and PFS were 7.6 months and 3.1 months, respectively. 

Conclusions Our findings show that Linac-based SRS and fSRS with co-planar beams and a single isocenter is an effective treatment modality in the management of single or multiple BM. The analysis of a larger sample size and a longer clinical follow-up are needed to confirm these preliminary results.


Sofia Paola BIANCHI, Miriam TORRISI (Milano, Italy), Sara TRIVELLATO, Raffaella LUCCHINI, Giorgio PURRELLO, Paolo CARICATO, Valeria FACCENDA, Martina Camilla DANIOTTI, Denis PANIZZA, Stefano ARCANGELI
00:00 - 00:00 #30174 - P047 Small brain metastases treated with single isocenter SRS.
P047 Small brain metastases treated with single isocenter SRS.

Purpose:

A safety and efficacy of single-isocenter SRS (SI-MM-SRS) for small brain metastases is not well defined. Our study aim was to determine response to treatment of metastatic lesions after single isocenter SRS, especially lesions with PTV volume below 0.5 cm3.

 

Materials and methods:

The analysis included a group of 36 patients treated at Department of Neurooncology and Radiosurgery at Franciszek Lukaszczyk Oncology Center beetween 02.08.2018 r. and 15.09.2020 r. due to multiple brain metastases with a follow-up MRI 6 months after treatmentA total of 195 metastatic lesions were treated, including 71 lesions with PTV volume bellow 0.5 cm3All patients were treated with the BrainLab Elements MultiMets software using single isocenter Dynamic Conformal Arcs. The ExacTrac system was used to monitor the position during SRS. MRI was analyzed in all patients 6 months after treatment.

 

Results:

The patients' median survival was 14.63 months and the median follow-up was 23.45 months. Local control was found in 93% of all metastatic lesions; in lesions below 0.5 cm3 it was 96%. Tumors with a volume below 0.5 cm3 did not have a worse response rate (p = 0.626) and there was no increased risk of radiation necrosis (p = 0.541). Symptomatic radiation necrosis was diagnosed in 1 patient (3%) after 6 months. Twelve lesions (6%) with radiation necrosis were asymptomatic. A statistical relationship was found between survival and the sum of PTV volumes of metastatic lesions (p = 0.0182; HR = 1.06 (95% 1.01; 1.10)). There was no correlation between survival and the number of tumors (p = 0.337).

 

Conclusions: 

Multiple brain metastases irradiated with a single isocenter technique show a high response rate. Tumors below 0.5 cm3 have a high response rate with low risk of radiation necrosis.


Maciej BLOK (Bydgoszcz, Poland), Tomasz WISNIEWSKI, Magdalena ADAMCZAK-SOBCZAK, Izabela ZAREBSKA, Maciej HARAT
00:00 - 00:00 #30175 - P048 Long-term results of Linac-based Single-Isocenter Multiple-Metastases Stereotactic Radiosurgery.
P048 Long-term results of Linac-based Single-Isocenter Multiple-Metastases Stereotactic Radiosurgery.

Purpose: Linac-based SRS is an optional treatment of multiple brain metastases. Our study aim was to assess the safety and efficacy of a linac-based single-isocenter SRS (SI-MM-SRS) for multiple brain metastases in relation to various clinical factors.

 

Materials and methods: The analysis included a group of 123 patients treated at the Department of Neurooncology and Radiosurgery at Franciszek Lukaszczyk Oncology Center  between 02.08.2018 r. and 15.09.2020 r. due to multiple brain metastases.  The minimum follow-up was 12 months and the median follow-up was 23 months. The median number of lesions was 4 and median sum of PTV volume was 9.95 cm3. All patients were treated with the BrainLab Elements MultiMets software using single isocenter Dynamic Conformal Arcs. The ExacTrac system was used to monitor the position during SRS.

 

Results: Sixteen percent of patients was still alive in time of analysis. The 6- and 12-months rate was 60% and 33%. In the multivariate analysis the sum of PTV volumes (p=0.0007) but not a number of lesions was related to survival. Every increase by 1 cm3 of total brain metastatic volume increased the risk of death by 2%. A diagnosis of squamous cell carcinoma of the lung was related to worst outcomes. Out of 123 patients, 95 patients presented for the first follow-up visit (median 35 days after SRS). The reported neurological symptoms were stabilized or improved in 79% of patients. There was no relationship between the neurological deterioration and the parameter V12 for whole brain (p = 0.319).

 

Conclusions:  The survival results of patients with multiple metastases are encouraging but depends on histopathology and total PTV volume. V12 parameter was not related to onset of symptoms early after SRS.


Maciej BLOK (Bydgoszcz, Poland), Tomasz WISNIEWSKI, Magdalena ADAMCZAK-SOBCZAK, Izabela ZAREBSKA, Maciej HARAT
00:00 - 00:00 #30177 - P049 Radiosurgery to 53 brain metastases with complete response.
P049 Radiosurgery to 53 brain metastases with complete response.

Radiosurgery (SRS) is a stereotactic radiotherapy technique in a few fractions (1-5) in the central nervous system. Is a non-invasive, high-precision technique that enables the administration of a high dose of irradiation per fraction to one or multiple targets, with an ablative effect and low doses in healthy organs

The aim of this case report is to share the experience of a clinical case of a patient with brain metastases who received SRS twice. First SRS was in 2019 in 13 metastases and a second SRS 13 months later in 53 new metastases with excellent tolerance and complete response.

43-year-old woman with a history of breast cancer in 2014, underwent neoadjuvant chemotherapy, mastectomy and axillary dissection

2017 Local recurrence, performed surgery + radiotherapy

2018 Liver metastases, underwent chemotherapy

August/2019 MRI of the brain shows 13 metastases

        SRS in 1 fraction of 21 Gy in 13 brain metastases

Thirteen months free of symptoms with normal work activity

September/2020 MRI shows 53 new brain metastases

          SRS in 1 fraction of 21 Gy in each of the metastases

Continues in controls with MRI every 3 months

July/2021 MRI of the brain shows all the treated lesions, in both SRS, controlled, 4 new millimetric lesions appear that it is decided to control

September/2021 Clinical control patient in good general condition, performs normal work activities, no headache or cognitive impairment

Metastatic spread in the CNS is frequent in patients with primary breast, lung, kidney cancer or melanoma, with a 10-30% risk of developing brain metastases

Historically, these patients have been treated with whole brain radiotherapy (WBRT), with cognitive deficit as a chronic consequence

However, a select group of patients with brain metastases can now achieve longer survival with the maintenance of good neurological function if their brain metastases are controlled.

Radiosurgery with dedicated linear accelerator and mask (Frameless) is a safe and non-invasive technique capable of controlling brain metastatic disease

SRS in patients with good performance status and controlled systemic disease is an effective therapeutic approach with less toxicity than total brain irradiation

Low doses to the healthy irradiated brain, allows normal cognitive activity and better quality of life

 


Agostina VILLEGAS FRUGONI (Cordoba, Argentina, Argentina), Oscar Ariel MURIANO, Maria Milla GALETTO, Daniela Mariel ANGEL SCHUTTE, Veronica VERA, Agustin GIRAUDO, Valentina GREGORAT, Mercedes CHIBAN
00:00 - 00:00 #30178 - P050 Is still a challenge the treatment of large brain metastases as well as the treatment of metastases closed to critical areas? Our experience with Gamma Knife Icon and review of the literature.
P050 Is still a challenge the treatment of large brain metastases as well as the treatment of metastases closed to critical areas? Our experience with Gamma Knife Icon and review of the literature.

This study reports the experience of a single institute concerning the treatment of brain metastases in fractional mode (frame modality and frameless) with a review of the literature. We preferred fractionation for metastases close to critical structures or with a large volume.

We used two modalities of fractionation: hypofractionated stereotactic radiosurgery (HSRS), which consists of three or five consecutive days of treatment and staged stereotactic radiosurgery (SSRS), which consists of two fractions delivered with an interval of about four / five weeks.  All procedures were performed with  Gamma Knife Icon.

Seven patients were treated with HSRS and five patients with SSRS. In the HSRS group two patients have metastases close to critical organs; median volume was 6,441 cm3(range 0,815 – 17,357 cm3) and median total marginal dose was 25 Gy at 50% (range 21 – 32,5 Gy) in three or five days. For the SSRS group median volume at the first treatment was 11,214 cm3 (range 8,1 – 26,777 cm3) and 7,627 cm3 (range 3,757 – 18,46 cm3) at the second treatment; the median total marginal dose was 12 Gy for both first and second fraction. Follow up (FU): At 12 months 7 patients were alive and 4 deceased (extracranial disease progression), one patient was lost to FU. At 18 months 3 patients were alive and 7 deceased (in one case for cerebral progression, the other cases extracranial disease progression) while 2 patients were lost to FU. Complications: we observed one case of radionecrosis in a patient previously radiotherapy and one case of seizure. From the literature review it emerged that positive predictive factors are: controlled extracranial tumor, prolonged fractionation days in HSRS and decrease of the tumor volume between fractions in SSRS. Our experience partly reflects these results: the patients undergoing surgery post Gamma Knife surgery had not experienced a reduction in volume between the first and second fractions, while the patients with less favorable clinical course up to death presented extracranial metastates and poor control of the disease. We didn’t observe significant difference in survival in patients undergoing treatments lasting 3 days compared to 5 days.

Fractionated radiosurgery with Gamma Knife offers a slightly or non-invasive therapeutic alternative for treating more fragile patients and without long-term healing chances with large brain metastases or metastases closed to critical organs.


Alberto FRANZIN (Brescia, Italy), Lodoviga GIUDICE, Karol MIGLIORATI, Giorgio SPATOLA, Cesare GIORGI, Chiara BASSETTI, Corrado D'ARRIGO, Oscar VIVALDI, Mario BIGNARDI
00:00 - 00:00 #30179 - P051 Impact of molecular biomarkers in non-small cell lung cancer on local control of brain metastases treated with radiosurgery.
P051 Impact of molecular biomarkers in non-small cell lung cancer on local control of brain metastases treated with radiosurgery.

As the oncology treatment paradigm shifted from a palliative one-for-all treatment towards individually tailored patient-adapted therapy, stereotactic radiosurgery (SRS) is a gold standard in treatment of brain metastases (BM). Lung and bronchus cancer is the third most common cancer diagnosis in the world. At the time of diagnosis, approximately 10% of patients with advanced non-small cell lung cancer (NSCLC) already have BM. Using targeted therapy and immunotherapy increases the number of patients with BM eligible for SRS. 

We present a retrospective analysis of local control after SRS of BM depending on histology and molecular subtype of primary lung cancer.

Methods:

We analyzed patients with BM from NSCLC treated with SRS in our institution from 2017 till 2021. A total of 68 patients are reported, median age 66 (35-80) years. All patients had known status of molecular biomarkers EGFR, ALK, ROS1 and PD-L1. At least one positive biomarker was found in 45% of patients. A total of 186 targets were treated (173 BM and 13 resection cavities). Most of the patients (93%) were diagnosed with adenocarcinoma and 7% with squamous cell carcinoma.   For a final evaluation, there were 49 (72%) patients eligible. The patients were treated by the Varian Edge radiosurgery system. The planning and follow-up imaging was done on a Siemens Skyra 3T MRI system, the image data was analyzed using Syngo.via software suite. The pretreatment and posttreatment images were compared using RANO-BM criteria for target and non-target lesions. 

Results:

Stable disease had 67% of patients, 29% of patients had partial response and 4% had disease progression by RANO-BM.  There were no patients with a complete response, although some of the lesions were undetectable in follow-up images. A total of 7 patients were treated by whole brain radiotherapy prior to SRS, five of them showed stable disease and the rest fitted the criteria for partial response.The response pattern mostly consisted of lesions shrinking in volume with central necrosis and/or central hemosiderin deposits, indicating hemorrhage within the lesion. One of the lesions showed severe intralesional hemorrhage which caused enlargement of the lesion. The perilesional vasogenic edema was reduced in most of the patients. No irradiation necrosis of the surrounding normal brain tissue was observed.

Conclusion:

SRS is a valuable tool in treating BM of lung cancer, providing  therapy with favorable results visible in a relatively short time. No significant difference in response was observed in patients with positive biomarkers. 


Ana MISIR KRPAN (Zagreb, Croatia), Hrvoje VAVRO, Josip PALADINO, Matea LEKIC, Hrvoje KAUCIC, Hrvoje SOBAT, Asmir AVDICEVIC, Domagoj KOSMINA, Vanda LEIPOLD, Adlan CEHOBASIC, Ivo PEDISIC, Dragan SCHWARZ
00:00 - 00:00 #30182 - P052 THE IMPACT OF NEUTROPHILS TO LYMPHOCYTES RATIO ON SURVIVAL IN PATIENTS AFFECTED BY BRAIN METASTASES AND TREATED WITH GAMMA-KNIFE RADIOSURGERY.
P052 THE IMPACT OF NEUTROPHILS TO LYMPHOCYTES RATIO ON SURVIVAL IN PATIENTS AFFECTED BY BRAIN METASTASES AND TREATED WITH GAMMA-KNIFE RADIOSURGERY.

Purpose: Several studies investigated the correlation between neutrophil-to-lymphocyte ratio (NLR) in peripheral blood and the prognosis in different diseases including various cancers.However, little is known about the impact of NLR on the prognosis of patients with brain metastases. We aim to evaluate the predictive value of NLR in patients with brain metastasis from non-small lung cancer (NSCLC) and melanoma candidates to gamma knife (GK) radiosurgery. 

Methods: We retrospectively examined 111 consecutive patients with brain metastases (BMs) from NSCLC and melanoma treated with GK radiosurgery. NLR was calculated using N/L, where N and L, respectively, refer to peripheral blood neutrophils (N) and lymphocyte (L) counts. Kaplan-Meier curves depicted the time to survival according to NLR. Univariable and multivariable Cox regression analyses were used to confirm the impact of NLR on overall survival. 

Results: 

Median (IQR) age at diagnosis of brain metastases was 64 yrs. (55;70). Median (IQR) NLR was 7.25 (4.18;12.4). Median (IQR) overall survival was 5.0 months (2.0;11.5). 

At univariable Cox-regression analyses, NLR was associated with improved overall survival (HR: 1.05; p=0.004). On the other hand, total number of lymphocytes, neutrophils and monocytes were not associated with improved overall survival (all p>0.1). At multivariable Cox regression analyses, after adjusting for patient age, sex and the use of DEX therapy, NLR represented an independent predictor of overall survival (HR: 1.06; p=0.003).

Conclusion: NLR represents an independent prognostic factor in patients affected by brain metastases  from NSCLC and melanoma. Inflammation and immunity may play a critical role in these patients. Further analysis examining more specific neutrophils or lympocytes subsets may increase our understanding of cancer etiology and progression.


Filippo GAGLIARDI, Silvia SNIDER, Francesca RONCELLI (Milan, Italy), Edoardo POMPEO, Lina Raffaella BARZAGHI, Alessandra BULOTTA, Chiara LAZZARI, Antonella DEL VECCHIO, Pietro MORTINI
00:00 - 00:00 #30194 - P053 Impact of the neuro-radiologist and neuro-surgeon in contouring with the neuro-oncologist on local relapse rates for brain metastases treated with stereotactic radiosurgery.
P053 Impact of the neuro-radiologist and neuro-surgeon in contouring with the neuro-oncologist on local relapse rates for brain metastases treated with stereotactic radiosurgery.

Background:  The audit evaluates the value of MDT, including neuro-radiologist and neuro-surgeon, review of contouring carried out by a clinical oncologist in stereotactic radiosurgery (SRS).

Methods: A sequential audit was conducted of all patients receiving intracranial SRS at our local institution for the first 22 months of a new SRS service. Lesions were contoured first by clinical oncologist then reviewed/edited by MDT. The initial contour was compared with final using Jaccard conformity and geographical miss indices. The dosimetric impact of a contouring change was assessed using plan metrics to both original and final contour. The impact of the contouring review on local relapse, overall survival and radio necrosis rate was evaluated with at least 24 months follow up (24-46 months).

Results: 113 patients and 142 lesions treated over 22 months were identified. Mean JCI was 0.92 (0.32-1.00) and 38% needed significant editing (JCI<0.95). Mean GMI was 0.03 (0.0-0.65) and 17% showed significant miss (GMI>0.05). Resection cavities showed more changes, with lower JCI and higher GMI (p<0.05). There was no significant improvement on JCI or GMI shown over time. Dosimetric analysis indicated a strong association of conformity metrics with PTV dose metrics; a 0.1 change in GTV conformity metric association with 6-17% change in dose to 95% of resulting PTV. Greater association was seen in resection cavity suggesting the geographical nature of a typical contouring error gives rise to greater potential change in dose. Clinical outcomes compared well with published series. Median survival was 20 months and local relapse free rate in the treated areas of 0.89 (0.8-0.94) at 40 months, and 0.9 (0.83-0.95) radio-necrosis free rate at 40 months with a median 17 months to developing radionecrosis for those that did.

Conclusions: This work highlights that a MDT contour review adds significant value to SRS and the approach translates into reduced local recurrence rates at our local institution compared with previously published data. No improvement in clinical oncologist contouring over time was shown indicating a collaborative approach is needed regardless of experience of clinical oncologist. MDT input is recommended in particular in contouring of resection cavities.


K SAYAL, M ROBINSON, C TUNSTALL, S PADMANABAN, R WATSON, P PRETORIUS, R JOSEPH, S JEYARETNA (Oxford, United Kingdom), C HOBBS
00:00 - 00:00 #30198 - P054 Immediate response to Boswellia serrata extract of steroid-refractory, symptomatic edema after radiosurgery to 31 brain metastases.
P054 Immediate response to Boswellia serrata extract of steroid-refractory, symptomatic edema after radiosurgery to 31 brain metastases.

INTRODUCTION:

Both immediate and delayed peri-lesional post-treatment vasogenic edema is a commonly encountered phenomenon after intracranial metastases are treated with stereotactic radiosurgery. When the effect is symptomatic, steroids are usually employed as first-line management. In some cases, however, patient symptoms are refractory to steroids, even at escalated doses. Indian frankincense is an herbal extract from the sap of the Boswellia serrata tree which has been touted in Ayurvedic medicine for many years as a means of managing various inflammatory conditions. It was successfully tested in a small, pilot randomized clinical trial for cerebral edema associated with large volume of irradiated brain


Evan THOMAS (Columbus, OH, USA), Josh PALMER
00:00 - 00:00 #30199 - P055 Cranial Outcomes from Postoperative and Preoperative Stereotactic Radiosurgery in Large Brain Metastases: A meta-analysis.
P055 Cranial Outcomes from Postoperative and Preoperative Stereotactic Radiosurgery in Large Brain Metastases: A meta-analysis.

Purpose: Postoperative stereotactic radiosurgery (SRS) is currently the standard of care for adjuvant radiation treatment after surgical resection of a brain metastasis. Preoperative SRS might represent a more beneficial therapeutic option by decreasing leptomeningeal recurrence and radionecrosis (RN) risk without compromising local control (LC) rates or introducing delays in systemic therapy after craniotomy; however, results of phase 3 randomized control trials comparing both approaches are still underway. We analyzed the current level of evidence regarding intracranial outcomes in each setting for patients with large metastases.

 

Methods and Materials: A systematic search was conducted on PubMed, Cochrane and Embase from inception to April 2020 (update to be performed prior to meeting to maximize timeliness). PRISMA guidelines were used to select articles where patients with “large” brain metastases (>4 cm3 or >2 cm in diameter) received postoperative or preoperative SRS as treatment. Random effects meta-analyses using timing of SRS relative to surgery as covariates were conducted.

 

Results: Through search methods 1,235 studies were identified. After assessment for eligibility we included a total of 14 studies, 7 studies evaluating multi fraction postoperative SRS, 4 studies on single fraction postoperative SRS, and 3 studies on single fraction preoperative SRS. In the postoperative SRS group 608 patients were included, and 148 in the preoperative SRS group. The total number of metastatic lesions was 819; 660 in the postoperative SRS group and 159 in the preoperative SRS group. Median age for all patients was 58 years, with a median follow-up of 13.1 months [5.2-24 months] for postoperative SRS and 10.5 months [6.3-13 months] for preoperative SRS group. Median total radiation dose in the postoperative SRS group was 23 Gy [12-39 Gy], and 16 Gy [15-18 Gy] in the preoperative SRS group. Median overall survival was 13.1 months [5.5-28.1 months] for postoperative SRS and 15.1 months [13-17.2 months] for preoperative SRS groups. The 1-year local control (LC) random effects estimate was 79.0% (95% CI: 56-95.0%) for preoperative SRS and 78.8% (95% CI: 67.1-88.5%) for postoperative SRS (p=0.98). Radiation necrosis (RN) random effects estimate was 4.5% (95% CI: 0.4-12.5%) and 7.0% (95% CI: 1.9-15.0%) for preoperative and postoperative SRS respectively (p=0.63).  

 

Conclusions:  Rates of local control and radiation necrosis were similar in preoperative and postoperative SRS groups. Ongoing prospective clinical trials will further investigate the relative safety and efficacy of these two treatments.  


Henry RUIZ GARCIA, Eric LEHRER, Lina MARENCO-HILLEMBRAND, Jennifer PETERSON, Kaisorn CHAICHANA, Alfredo QUINONES-HINOJOSA, Daniel TRIFILETTI (Jacksonville, USA)
00:00 - 00:00 #30201 - P056 Estimation of the Maximum Number of Lesions Able to be Treated with Single Session Stereotactic Radiosurgery with Contemporary Planning Systems.
P056 Estimation of the Maximum Number of Lesions Able to be Treated with Single Session Stereotactic Radiosurgery with Contemporary Planning Systems.

Purpose: Emerging evidence supports the role of stereotactic radiosurgery alone in patients with up to 15 brain metastases. As modern technology and evidence develops to allow treatment to numerous brain metastases, a re-evaluation of the capability of modern radiosurgery treatment planning systems is warranted. The objective of this study is to explore the number and volume of lesions that can be treated with the latest Gamma Knife(GK) and CyberKnife(CK) treatment modalities in a single treatment setting.

Methods: 200 target contours with volumes varying from 0.001 cc to 1.1 cc were simulated on a model MRI scan of a normal brain. Target volumes were derived from clinically treated contours superimposed on the model brain scan. All lesions were planned to 20Gy/1 fraction with the exception of brainstem lesions planned to 15 Gy/1 fraction per institutional clinical treatment guidelines. For GK treatment plans, due to limitations in the planning system, individual plans with 52 lesions each were generated ensuring greater than 99% target coverage and maximizing conformity. Subsequently, number of lesions were progressively increased until the threshold mean dose to the brain (including target volumes) of 8Gy was reached. Similarly, CK plans were generated with 11-30 lesions each using fixed cones and prescribed such that at least 99.6% of the target volume received prescription dose. Composite dose distribution was generated to calculate the dose metrics from all plans.

Results: The maximum number of target lesions and total tumor volume (TTV) corresponding to a mean brain dose to a pre-specified threshold of 8 Gy for GK treatment plans was 156 lesions and 8.4 cc, and 66 lesions and 7.3 cc for CK plans, respectively. Corresponding V12cc to brain was 142.8 cc for GK and 225.5 cc for CK modalities.  The increase in V12cc is mainly attributed from the inability to optimize all lesions simultaneously.  

Conclusion: Approximately 156 lesions of mixed sizes can be treated on GK in a single session totaling a target volume of 8.4 cc before exceeding a brain mean dose of 8 Gy. CK plans were found to allow a fewer number of lesions (66) and target volume (7.3 cc) for the same 8Gy brain mean dose while resulting in a higher  V12Gy.  V12Gy for both technologies showed a correlation to the TTV. Proximity of the lesions may result in overlap of low dose volume resulting in increased V12Gy.


Ranjini TOLAKANAHALLI, D Jay WIECZOREK, Yongsook LEE, Matthew HALL, Martin TOM, Minesh MEHTA, Michael MCDERMOTT, Alonso GUTIERREZ, Rupesh KOTECHA (Miami, USA)
00:00 - 00:00 #30202 - P057 Association between stat3 expression and gamma-knife radiosurgery on the post-operative cavity after cerebral metastasis resection.
P057 Association between stat3 expression and gamma-knife radiosurgery on the post-operative cavity after cerebral metastasis resection.

STAT proteins (Signal Transducers and Activators of Transcription) are heterogeneous transcription factors that are known to be critically involved in cellular proliferation, growth and apoptosis process. STAT3 phosphorylated status strongly correlates also with metastasis process promotion. It represents a negative prognostic predictor both for the recurrence of tumor lesions and for their progression after surgical treatment. Considering that the addition of stereotactic radiosurgery to the surgical resection of brain metastases decreases local relapse and death from neurologic cause, we investigate the correlation between STAT3 primary tumor expression and post-resection cavity stereotactic radiosurgery response in brain metastasis in terms of local relapse, distant brain control, overall survival and local radiosurgery side effects.

Data of all patients who underwent post-operative stereotactic radiosurgery to the resection cavity following excision of brain metastases at our Department of Neurosurgery of Verona between 2009 and 2019 were reviewed.  All patients with GTR (Gross Total Resection) of single brain metastasis from variable primitive tumor and no previous radiant adjuvant therapy were included in our study. A total of 82 patients (42 women and 40 men) were enrolled. Twenty-two brain metastases cavities were cerebellar, while sixty supratentorial. The site of the primitive tumor was:  32 cases of lung cancer, 14 of breast cancer, 14 of gastro-enteric cancer, 9 of renal cancer, 6 of ovarian cancer, 4 of melanoma, 2 of uterus cancer, 1 of not better specified cancer. About stereotactic radiosurgery treatment parameters, mean volume treated was 7,82 cc (1,01-22,6); mean prescription dose was 17,52 Gy (13,0-22,0) with a 50% prescription isodose and a maximal prescription dose of  35,08 Gy, (26,0-44,0); mean shot number was 11,9 (1-29). Patients were divided into two groups based on histological examination and expression of  STAT3 activated status in the primitive tumor tissue. The response to the treatment of the two different groups based on outcomes for local relapse, distant brain control, overall survival and local radio surgery side effects was analyzed and compared. 


Roada BUCPAPAJ, Roada BUCPAPAJ (Verona, Italy), Marco GALUPPO, Serena AMMENDOLA, Giorgia BULGARELLI, Michele LONGHI, Emanuele ZIVELONGHI, Anna D'AMICO, Giuseppe Kenneth RICCIARDI, Paolo POLLONIATO, Enrico BASSO, Francesco SALA, Valeria BARRESI, Giampietro PINNA, Antonio NICOLATO
00:00 - 00:00 #30205 - P059 Increased risk for Ex-vacuo Ventriculomegaly with Leukoencephalopathy (EVL) in whole brain radiation therapy and repeat radiosurgery treated brain metastasis patients.
P059 Increased risk for Ex-vacuo Ventriculomegaly with Leukoencephalopathy (EVL) in whole brain radiation therapy and repeat radiosurgery treated brain metastasis patients.

Background:  Cerebral atrophy with leukoencephalopathy is a known morbidity after whole brain radiation therapy (WBRT), resulting in ex-vacuo ventriculomegaly with leukoencephalopathy (EVL).

Objective: Here we studied whether repeat radiosurgery contribute to the risk for EVL in WBRT treated brain metastasis patients.

Methods: In a retrospective study, we identified 195 patients (with 1,018 BM) who underwent stereotactic radiosurgery (SRS) for BM (2007-2017) and had >3 months of MRI follow-up. All patients who underwent ventriculoperitoneal shunting were excluded. Cerebral atrophy was measured by ex-vacuo-ventriculomegaly, defined based on Evan’s criteria. Demographic and clinical variables were analyzed using logistic regression models.

Results:  Ex-vacuo ventriculomegaly was observed on pre-radiosurgery imaging in 29.7% (58/195) of the study cohort. On multivariate analysis, older age was the only variable associated with pre-radiosurgery ventriculomegaly. Of the 137 patients with normal ventricular size before radiosurgery, 27 (19.7 %) developed ex-vacuo ventriculomegaly and leukoencephalopathy (EVL) post-SRS. In univariate analysis, previous whole brain radiation therapy was the only factor associated with increased risk for developing EVL (OR = 5.08; P<0.001). In bivariate models that included prior receipt of WBRT, the number of SRS treatments was the only radiosurgery parameter that independently increased EVL risk (OR = 1.499, P = 0.025).

Conclusions: While repeat radiosurgery contributes to the risk of EVL in BM patients, this risk is ~ 50 fold lower than that associated with WBRT.


Clark CHEN (Minneapolis, USA)

"Tuesday 21 June"

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02. Eposters - Brain - Benign

00:00 - 00:00 #29322 - P060 VESTIBULAR SCHWANNOMAS TREATED WITH CYBERKNIFE RADIOSURGERY IN 3 SESSIONS: CLINICAL RESULTS.
P060 VESTIBULAR SCHWANNOMAS TREATED WITH CYBERKNIFE RADIOSURGERY IN 3 SESSIONS: CLINICAL RESULTS.

Vestibular schwannomas are benign tumors that arise from the vestibulocochlear nerve. In multiple studies, radiosurgery in the treatment of these lesions has shown excellent local control results at 10 years, with little toxicity. However, the strict dose limitation in the brainstem and the relationship that exists between the dose received by the cochlea and the preservation of useful hearing, supposes a challenge for single-dose radiosurgery in large lesions (> 10cc), Koos 4-5, or lessions located <1 mm from the cochlea. In this study, 33 patientes with vestibular schwannomas that, due to the proximity to the cochlea (<1mm),  size > 10cc or relationship with the brainstem (Koos 4), did not meet dose restrictions in a single session, were retrospectively included. These patients were treated between November 2012 and April 2019 with Cyberknife radiosurgery in 3 sessions, administering a total dose of 18 Gy (6 Gy per fraction). 7 patients had previously undergone surgery, but none of them had previously received irradiation. The median volume treated was 2.17 cc (range 0.11-25 cc). The median tumor coverage with the prescription isodose was 98.5% and the median conformity and homogeneity index were 1.14 and 1.25, respectively. The median follow-up was 39 months (7-76 months). Two of the patients progressed after treatment, both Koos 4, with a statistically significant relationship (p 0.049). The 3-year progression-free survival was 91%. 21 patients (64%) preserved useful pretreatment hearing (Gardner-Robertson I-II), 8 patients (24%) had moderate to severe dysfunction (GR III-IV) and 4 patients (12%) had completely lost their hearing (GR 5). 81% of the patients who retained useful hearing maintained it after treatment. Except for one patient who started with useful hearing and lost it completely, those who worsened with respect to their baseline situation, did so only in 1 point on the GR scale. A statistically significant relationship between the maximum dose in the cochlea and other dosimetric parameters (V15, V10, V6) with worsening of hearing was not found. Conclusions: Radiosurgery in 3 sessions constitutes an effective alternative, with acceptable preservation of useful hearing in patients with vestibular schwannomas who are not candidates for radiosurgery in a single session. However, it is necessary to prolong the follow-up to assess the long-term efficacy and toxicity.


Morena SALLABANDA (Madrid, Spain), Kita SALLABANDA
00:00 - 00:00 #29352 - P061 Long-term results of gamma knife radiosurgery for treatment of intracranial glomus jugulare tumors.
P061 Long-term results of gamma knife radiosurgery for treatment of intracranial glomus jugulare tumors.

Introduction: Glomus Jugulare tumors are benign but locally aggressive ones that represent a therapeutic challenge. Previous studies about the use of Gamma Knife Radiosurgery (GRS) in those tumors have documented good results that needed larger number of patients and longer follow up periods to be confirmed.

 

Patients and Methods: Between August 2001 and December 2017, 70 patients with glomus jugulare tumors were treated at the Gamma Knife Center, Cairo. They were 46 females and 24 males. The mean age was 48 years (16-71 years). Nineteen of these patients were previously operated, 5 were partially embolized, 3 underwent embolization and subsequent surgery and 43 had gamma knife as their primary treatment. Volume-staged gamma knife radiosurgery was used in 10 patients and single-session in 60 patients, with a total of 86 sessions. The mean target volume was 12.7 cm3 (range 0.2 to 34.5 cm3). The mean tumor volume was 15.5 cm3 (range 0.2 to 105 cm3). The mean prescription dose was 14.5 Gy (range 12 to 18 Gy).

 

Results: The mean follow up period was 60 months (range 18 to 206 months), and by the time of the data analysis, two of the patients were dead (66 and 24 months after GK treatment). The tumor control was 98.6% (69/70). Thirty-two tumors became smaller and 37 were unchanged. The symptoms improved in 36 patients, were stable in 32 patients, and worsened in 2 patients who developed a transient facial palsy and worsened hearing. Symptomatic improvement began before any reduction in tumor volume could be detected, where the mean time to clinical improvement was 7 months whereas the mean time to tumor shrinkage was 18 months.

 

Conclusions: This study about the long term follow up of the GKR for the intracranial glomus jugulare tumors confirmed that this is a highly effective and safe treatment. This data shows that the clinical improvement is not correlated with the radiological volume reduction.


Reem EMAD (Cairo, Egypt, Egypt), Khaled ABDEL KARIM, Amr ELSHEHABY, Wael REDA, Ahmed NABEEL, Sameh ROSHDY
00:00 - 00:00 #29358 - P062 Gamma Knife treatment for acoustic neuromas: how homogeneous can it be?
P062 Gamma Knife treatment for acoustic neuromas: how homogeneous can it be?

Purpose

Stereotactic radiosurgery represents one of the main treatment options for acoustic neuromas. At our institution, patients suffering from these tumors are either treated with linear accelerators (linacs) or Leksell Gamma Knife® (LGK, Elekta AB, Sweden). Although a single LGK fraction is preferred, in cases where the tumor is involving or abutting the brainstem, cranial nerves or cochlea, homogeneous normofractionated treatments are usually adopted. In this study, we investigated the range of homogeneity and organ at risk (OAR) sparing that can be achieved using a non-clinical alpha version of LGK Lightning enabling higher homogeneity.

Methods

The data sets of six patients treated for acoustic neuromas at our institution were retrospectively analyzed. All tumors were either abutting and/or compressing the brainstem and/or the cochlea. For each patient, four treatment plans were generated (54Gy,1.8Gy/fx): one linac plan using Monaco (Elekta AB, Sweden) treatment planning system, one LGK Lightning plan (LGK) using the clinical version 11.3 and two LGK Lightning plans using the alpha version. Each plan was normalized to D95% of the target volume and the metrics Dmean and D2% for OAR were determined. Gradient Index (GI), Paddick Conformity Index (PCI) and Homogeneity Index (HI) were calculated, beam-on-times (BOT) reported and a mean dose-volume-histogram was generated (figure 1).

Results

The linac and LGK clinical plans show the highest and lowest possible homogeneity and OAR doses, respectively. The two alpha plans represent the possible homogeneity range in-between: one plan gives the highest achievable homogeneity (LGK Hom) while the other promotes OAR sparing (LGK OAR). The median values were: GI 7.25 (linac), 3.5 (LGK Hom), 3.46 (LGK OAR) and 2.81 (LGK); PCI 0.74 (linac), 0.71 (LGK Hom), 0.7 (LGK OAR) and 0.79 (LGK); HI 1.1 (linac), 1.23 (LGK Hom), 1.33 (LGK OAR) and 1.6 (LGK). D2%,median brainstem was reduced from 30.3 Gy (linac) to 23.9 Gy (LGK Hom), 21.6 Gy (LGK OAR) and 16.3 Gy (LGK). Median Dmean cochlea decreased from 33.6 Gy (linac) to 26.3 Gy (LGK Hom), 22.7 Gy (LGK OAR) and 21.2 Gy (LGK). The median BOT per fraction was 73s (linac), 300s (LGK Hom), 330s (LGK OAR) and 600s (LGK).

Conclusion

In this study we showed that the homogeneity of the LGK plans can be enhanced towards linac homogeneity while maintaining low OAR doses. Besides the reduction of BOT by up to half, higher dose gradients were observed.


Manon SPANIOL (Mannheim, Germany), Yasser ABO-MADYAN, Sabine MAI, Michael EHMANN, Florian STIELER
00:00 - 00:00 #29378 - P063 Stereotactic radiosurgery for Cushing's disease: A single center report and meta-analysis of clinical outcomes.
P063 Stereotactic radiosurgery for Cushing's disease: A single center report and meta-analysis of clinical outcomes.

Objective:

To analysis the safety and efficacy of stereotactic radiosurgery (SRS) in Cushing's disease (CD) and provide stronger evidence, we perform a single-center study and a meta-analysis.

Materials and Methods:

We retrospectively analyzed patients with CD underwent gamma knife radiosurgery (GKRS) at West China Hospital of Sichuan University from March 2010 to December 2018. The definition of endocrine remission were (1) normalization of 24h-urinary free cortiso (UFC) or serum cortisol50nmol/L after 1-mg dexamethasone suppression test (1-mg DST) and (2) off of all medications affecting 24h-UFC or serum cortisol production for at least 4 weeks. Studies related to SRS for Cushing's disease were included via searching PubMed and EMBASE through December 1, 2021. Studies were included when normalization of 24h-UFC was defined as endocrine remission. The results of our center were pooled with those of the included studies to analyze the clinical outcomes of SRS for Cushing's disease using Stata 15.0.

Results:

  This single-center study included 25 patients with Cushing's disease received GKRS. 18 patients underwent primary GKRS (72.00%), 5 patients received GKRS for residual tumor postoperatively (20.00%), 2 patients underwent GKRS for postoperative recurrence (8.00%). The median marginal dose and maximum dose was 28.00Gy and 58.00Gy. The durable endocrine remission rate was 44.00% after a median follow-up time of 15.00 months, and the mean interval from GKRS to endocrine remission was 20.73 months. Actuarial rates of durable endocrine remission at 1, 3 year was 24.10% and 68.40% respectively. The new hypopituitary rate was 24.00% and none suffered new visual disturbance. 

  We included 16 studies (15 from literature and 1 from our center) with 744 patients in Meta-analysis. Of 16 studies, GKRS was applied in 9 studies, Linear accelerator (LINAC) was applied in 4 studies, Cyber knife radiosurgery (CKRS) was applied in 1 study, proton stereotactic radiosurgery (PSRS) was applied in 1 study and 1 study applies GKRS and CKRS. Meta-analysis results showed that the estimated endocrine remission rate, local control rate and new hypopituitary rate were 51.00%, 94.00% and 25.00% after receiving SRS.

Conclusions:

SRS is a safe and effective alternative treatment for patients with Cushing's disease who suffer postoperative residual or recurrence, cannot tolerate surgery or the side effects of medications.


Meng-Qi WANG, Wei WANG (Chengdu, China)
00:00 - 00:00 #29393 - P064 Stereotactic radiosurgery for skull base meningiomas: the effectiveness of treatment of 117 patients.
P064 Stereotactic radiosurgery for skull base meningiomas: the effectiveness of treatment of 117 patients.

Introduction. Interest in the treatment of meningiomas, as one of the most common primary brain tumors, and the widespread introduction of innovative and high-tech treatments, such as stereotactic radiosurgery, have improved the treatment of skull base meningiomas. Optimization of radiosurgical methods of irradiation and determination of optimal doses of treatment aims to improve the effectiveness of treatment of these tumors.

Aim. To analyze the results of radiosurgical treatment of 117 patients with skull base meningiomas on the linear accelerator Trilogy to achieve local control of tumor growth and to evaluate the effectiveness of radiosurgical treatment in achieving local control of tumor growth when using method of combining radiation with intensity modulation and conformal dynamic rotation (IMRT + MLC Dyn Arc).

Materials. The average value of the volume of the target was 7.4 cm3 (0.85-22.1 cm3), the average prescribed dose (PD) - 12.6 Gy, the maximum dose in the range from 12.3 to 20.0 Gy. The technique of combining radiation with intensity modulation and conformal dynamic rotation (IMRT + MLC Dyn Arc) was used in 40 (34%) cases.The observation period ranged from 12 to 84 months.

Results. The study of local control of tumor growth after SRS by the univariate Kaplan-Meier method revealed 90% of cases with a median follow-up of 43 months. The Kaplan-Meier method revealed a predictor effect of the combined IMRT + MLC Dyn Arc irradiation technique, which determines a greater number of cases of achieving local control in a shorter period (p = 0.041,Fig. 1). Analysis of the effect of the combination of IMRT + MLC Dyn Arc irradiation on local control (according to the Cox proportional hazards model) found that the technique increases the intensity of local control by 1.61 times compared to standard methods of radiosurgical irradiation (HR = 1.61).

Conclusions. SRS is a method that provides high rates of local control of the growth of skull base meningiomas (90% of cases with a median follow-up of 43 months). The technique of combining radiation with intensity modulation and conformal dynamic rotation is a predictor of local control of tumor growth (p = 0.041).


Chuvashova OLGA (Kyiv, Ukraine)
00:00 - 00:00 #29410 - P065 Expected volumetric variation of Vestibular Schwannoma after Gamma Knife Radiosurgery.
P065 Expected volumetric variation of Vestibular Schwannoma after Gamma Knife Radiosurgery.

Introduction

Vestibular schwannomas (VS) are benign tumors that can be treated with observation, surgical resection, or radiation therapy. Following SRS, the time to volumetric response can vary and serial MRI should be done for proper assessment.

 

Method

 

382 consecutive patients over 20 years treated with GKRS, all treatments were delivered in a single session. Typical follow-up includes contrasted MRI brain imaging at 3, 6, and 12 months following treatment, after which patient would be transitioned to annual imaging. Initial tumor volume was obtained based on target volume using GammaPlan. Follow up MRIs were imported into GammaPlan, overlaid with the treatment MRI, and residual tumor volumes measured.

 

Results:

 

There was a statistically significant relative reduction in tumor volume starting at 12-months post-treatment which continued through subsequent imaging (Figure 1). At 76 months, the median reduction in tumor volume was 60.6% [IQR 46.4-72.9%]. Of these patients, 69 (39.4%) had pseudoprogression of their tumor. In 34 (49.3%) patients, pseudoprogression was first observed at 3-months followed by 29 (42.0%) occurring at 6 months post-treatment. The maximum median increase in tumor volume was 36.1% [IQR 23.5-62.0%]. The median volume of pseudoprogressed tumors remained elevated compared to pretreatment values for nearly 24 months. As compared to tumors without pseudoprogression, pseudoprogressed tumors remained significantly elevated for at least 36 months, with relative median tumor volumes approximating each other at 76 months (Figure 2). The tumors of 11 patients with pseudoprogression were still elevated beyond 36 months however none required retreatment. Other treatment variables, such as age, sex, Koos grade, prior surgery, dose, isodose line, gradient index, and tumor volume were not associated with the development of pseudoprogression on Pearson’s correlation.

 

Conclusions

Following SRS for vestibular schwannoma, tumor reduction can be seen within 12 months with a median volumetric decrease of over 60% with long term follow up. Approximately 40% of patients experience pseudoprogression following SRS. Most pseudoprogressed tumors shrink below pretreatment values by 24 months and pseudoprogression is not associated with treatment failure. 


Mark FARRUGIA, Victor GOULENKO, Patrick JOWDY, Dheerendra PRASAD (Buffalo, NY, USA)
00:00 - 00:00 #29412 - P066 Radiosurgery for pituitary adenomas: monoinstitutional analysis.
P066 Radiosurgery for pituitary adenomas: monoinstitutional analysis.

Introduction. Pituitary adenomas (PA) represent one of the most common intracranial pathologies, accounting for 10-20% of intracranial tumors. Although PA are histologically benign, the neurological and physiological consequences can be devastating, particularly if these tumors involve the anterior optic pathways. Surgery is the first line treatment in many cases. However, about 30% of patients require additional treatment after microsurgery for recurrent or residual tumors. Radiosurgery (RS) represents a viable option as adjuvant treatment following incomplete surgical resection, tumor recurrence, or failure of medical therapy. The RS literature data report tumor control rate higher than 90% at 10 years. However, the concern about the optic neuropathy may limit the single session radiosurgery (sRS) indications.

The aim of this study is to retrospectively evaluate the efficacy and safety of multi-session radiosurgery (mSRS) for such cases.

Materials and Methods. Forty-two patients treated by means of mRS between 2011 and 2019 have been analyzed. All patients have at least a post RS radiological (MRI), endocrinological and ophthalmological follow-up.

Results. The median age at the time of mSRS was 54 years. Twenty-six (62%) patients had evidence of partial or total hypopituitarism before mSRS. Visual defects were present in 66.7% of patients. The median follow-up was 29.5 months (range 6-110 months). The median tumour volume pre-mSRS was 7070 mm3 (range, 1339 - 74530 mm3). The mean prescription dose was 25 Gy in 5 fractions.

After the treatment, 33 patients (78,6 %) have stable disease, 7 (16.6 %) showed partial response; one patient (2.4%) had a complete response; one patient (2.4) experienced a tumor progression. One patient (2.4 %) developed mild visual worsening. None of the analyzed patients developed new or worsened hypopituitarism.

Conclusion. Our results suggest that mRS can be proposed as a safe and effective treatment modality for patients suffering from recurrent or residual pituitary adenomas.


Marcello MARCHETTI (Milano, Italy), Valentina PINZI, Maria Luisa FUMAGALLI, Elena DE MARTIN, Sara MORLINO, Cecilia IEZZONI, Laura FARISELLI
00:00 - 00:00 #29808 - P067 Hearing Preservation in Vestibular Schwannoma Radiosurgery.
P067 Hearing Preservation in Vestibular Schwannoma Radiosurgery.

Background

Our aim was to evaluate hearing outcomes in vestibular schwannoma (VS) patients treated by stereotactic radiosurgery (SRS) in the modern era of cochlear-dose restriction, providing information about patient and tumor characteristics, radiosurgery dosimetry, and effects on functional preservation.

Methods

During the years 2013-2018, 353 patients underwent Gamma-knife SRS for VS at our institution. We followed 175 VS patients with pre-SRS serviceable hearing (Gardner-Robertson Score, GR 1 and 2) and at least 3 years of follow-up. Volumetric and dosimetry data were collected at SRS and 6 months later, Biological Effective Dose (BED), integral doses (ID) of total and intra-canalicular (IC) tumor components, cochlear doses and hearing outcomes.

Results

Mean age was 56 years and 74 (42%) had baseline GR of 2. The majority of cases were Koos 2 (47%), and 15% were Koos 3-4. Mean cochlear dose was 3.5 Gy.

Overall, median time to hearing deterioration of at least 1 level in the GR scale was 31 months (95% CI 23,42), with 72% keeping their baseline GR level in the 1st year, 55% in the 2nd year, and 46% in the 3rd year. In a multivariable analysis, the risk for hearing deterioration at any time point was significantly higher in patients with baseline GR of 2 (OR=2.24, p=0.025). Predictors of lower risk for hearing deterioration included tumor volume <0.43 cc (OR=0.43, p=0.027) and BED < 61 (OR=0.44, p=0.047). The risk for earlier hearing deterioration was significantly reduced by age< 58 (HR=0.54, p=0.009), mean cochlear dose <3.1 Gy, (HR=0.56, p=0.002) and BED <61 (HR=0.45, p=0.002), while it was higher when the tumor-free canal space was <0.041cc (HR=1.88, p=0.008). Median time to serviceable hearing loss (GR 3-4) was 38 months (95% CI, 26-46), with 77% hearing preservation in the 1st year, 62% in the 2nd year, and 50% in the 3rd year. Patients optimal for the best hearing outcomes would be younger than 58 with baseline GR of 1, free canal space  0.041 cc (diameter of 4.5 mm) and mean cochlear dose <3.1 Gy. For such patients, serviceable hearing preservation rates were 92% by 12 months and 81% by 2 years, staying stable for more than 5 years post-SRS.

 

Conclusion

Hearing preservation after SRS for VS patients with pre-treatment serviceable hearing is correlated in the current era to the specific baseline GR score (1 or 2), age, cochlear dose and BED. Increased baseline tumor-free canal space correlates with better hearing outcomes. 

 


Assaf BERGER (New York, USA), Juan Diego ALZATE, Kenneth BERNSTEIN, Reed MULLEN, Sean MCMENOMEY, David FRIEDMANN, Eric SMOUHA, Erik SULMAN, Joshua.s SILVERMAN, J. Thomas ROLAND, John G. GOLFINOS, Douglas KONDZIOLKA
00:00 - 00:00 #29837 - P068 Jugular Foramen Schwannoma: A rare tumor treated by Stereotactic Radiosurgery at our Institution.
P068 Jugular Foramen Schwannoma: A rare tumor treated by Stereotactic Radiosurgery at our Institution.

Introduction

Juglar foramen schwannomas are a rare type of benign tumors located in jugular foramen, accounting for 2-4 % of all intracranial schwannomas. They can arise from cranial nerves IX, X or XI, with IX being the most commonJugular foramen schwannomas (JFS), can present with various symptoms depending on the size and the anatomic location of the tumor.

Surgical resection has been considered as the primary treatment option for JFS. However, complete resection is often difficult because of the anatomical location of the tumor and its relationship to adjacent structures. Stereotactic radiation therapy has been considered as an equally good and safer alternative to surgery, especially for small volume tumors. 

 

Case Study

In June 2021, a 59 year old male presented with hoarseness of voice and difficulty in speaking. Contrast MRI of the brain revealed a well-defined lobulated extra axial lesion measuring 13.7 x 9.8 x 10.0 mm, seen within the left jugular foramen, expanding it and projecting into the left cerebello- medullary cistern. It was causing compression on the IX, X and XI cranial nerves. Radiologically, the features were suggestive of jugular foramen schwannoma.

The patient was given the option of surgery vs stereotactic radiosurgery (SRS). Patient chose (SRS) in view of non-invasive technique. He was immobilized using stereotactic head thermoplastic cast with rigid mouth and head fixation. Then CECT scans were acquired at 1mm slice thickness and imported in Monaco TM treatment planning system for planning. The CECT images were fused with MRI images for delineation of the tumor and other critical structures. He underwent SRS treatment on 6MV Linear Accelerator using micro multileaf collimator to the localized portal. The tumor volume was 1.01cc. The prescribed dose to tumor was 15 Gy in single fraction. The 80% isodose line coverage to tumor was ensured to 98.7% volume. In addition, dose received by nearby critical organs such as cochlea, brain stem, left optic nerve, right optic nerve and optic chiasm were found well within the tolerance level. As of now, patient is improving clinically. This is the first case of our institution since we started the radiation facility in 2014.

 

Conclusion

Stereotactic radiation therapy has a high tumor control rate, high rate of cranial nerve preservation and low morbidity in small Jugular Foramen Schwannomas.


Manishi BANSAL (Mohali, India), Mohandass P, Ankush JINDAL, Manoharan M
00:00 - 00:00 #29881 - P069 Post surgical management of who grade II meningiomas: our experience, role of gamma knife and review of literature.
P069 Post surgical management of who grade II meningiomas: our experience, role of gamma knife and review of literature.

Grade II  meningiomas have a higher tendency to local recurrence despite gross total resection (GTR). In patients with GTR options for radiotherapy or active monitoring are  still under debate. Gamma Knife radiosurgery (GKRS) is a current method used to treat  residue, but the effectiveness of this treatment on WHO grade II meningiomas is not  clearly reported. Primary aim  of the study is to retrospectively analyze the different post-surgical management of grade II  meningiomas. Secondary endpoint of the study was to evaluate the role of adjuvant stereotaxic radiosurgery with GKRS in the treatment of any residuals or relapses.

Retrospective study was conducted at the Neurosurgery Unit of Fondazione Poliambulanza of Brescia for all patients who were discharged with histological diagnosis of grade II meningiomas, from November 2016 to November 2020. Follow-ups with seriate MRI were analyzed , in order to classify patients as stable, with local recurrence or distal recurrence and based on post surgical management (wait and see, conventional adjuvant radiotherapy or stereotaxic radiosurgery using GKRS). For patients undergoing GKRS, both as an adjuvant treatment and as a relapse treatment, radiological follow up were analyzed. Kaplan-Meier analysis was used to estimate disease control (presence or absence of relapse) and PFS. A total of 47 meningiomas were examined: 33 underwent wait and see strategy, 6 underwent adjuvant radiotherapy treatment, while adjuvant GKRS treatment was performed in 8 patients. Follow up was possible in 43 meningiomas, with 17 stable patients, 24 with focal recurrence and 2 with relapsed distally. 3 out of 10 patients with Simpson I undergoing wait and see had recurrence, while the percentage of recurrence for Simpson grade II/III undergoing wait and see was higher (12/20). GKRS was carried out on 19 patients, with a total of 24 meningiomas;  8 received it as adjuvant treatment while in 16 patients, GKRS was carried out on relapse. 3 out of 24 meningiomas treated with GKRS relapsed during follow up.

Grade II  meningiomas with GTR Simpson II and III have a significantly different outcome than those with GTR Simpson I, and  absence of adjuvant treatment leads to a significant worsening in the disease progression curve, with a lower PFS than meningiomas treated with STR but undergoing with adjuvant radiotherapy treatment. Stereotactic radiosurgery using GKRS allows  good local control of the disease, both on residues and possible relapses, but does not prevent any distant relapse.


Karol MIGLIORATI (BRESCIA, Italy), Giorgio SPATOLA, Lodoviga GIUDICE, Chiara BASSETTI, Mario BIGNARDI, Cesare GIORGI, Oscar VIVALDI, Alberto FRANZIN
00:00 - 00:00 #29897 - P070 Gamma knife radiosurgery for brainstem cavernous malformations: Clinical series.
P070 Gamma knife radiosurgery for brainstem cavernous malformations: Clinical series.

Objective

The purpose of this study is to investigate the efficacy of gamma knife radiosurgery for brainstem CMs in preventing bleeding, as well as, assess safety with regards to radiation-induced complications. Additionally, we aimed to evaluate the feasibility and safety of volume-staged gamma knife radiosurgery for larger CMs in the brainstem.

Patients and methods

Between September 2007 and August 2017, 32 patients with brainstem cavernous malformations (CMs) were treated by gamma knife. A total of 33 lesions were treated (one patient had two brainstem CMs) There were 16 males and 16 females. The mean age at the time of treatment was 25 years (3-51 years). Twenty-eight patients had at least one hemorrhagic event before radiosurgery. The patients underwent 40 gamma knife sessions. These included 28 single sessions (including two sessions for same patient for 2 different lesions in pons). Five patients had volume-staged gamma knife treatments due to the large size of the CM. The mean total CM volume/lesion was 2.2 cc (0.1-30.4 cc), while the mean target volume/session was 1.8 cc (0.1-11.5 cc). The mean prescription dose was 12 Gy (10-14 Gy) and the mean 12 Gy volume was 1.2 cc (0.1-10.8 cc).

Results

The mean follow up after treatment was 44 months (12-134 months). One patient died during follow up. The annual hemorrhage rate (AHR) before gamma knife radiosurgery was 25.5%. After treatment there were a total of 5 hemorrhagic events with an overall AHR of 3.8%. Three hemorrhagic events occurred in the first 2 years after treatment with an AHR of 5.2% and 2 events more than 2 years after treatment with an AHR of 1.7%. No hemorrhagic events occurred among the patients treated by volume-staged radiosurgery. Clinical improvement was observed in 15 (46.9%) patients, was stable in 16 (50%) and worsened in 1 (3.1%). Temporary adverse radiation events developed in 3 patients (9%).

Conclusion

GKS for brainstem cavernomas has an acceptable safety profile. The annual hemorrhage rate after GKS appears to be reduced. Nonetheless, to better assess efficacy of GKS for brainstem cavernomas, prospective trials are needed. Volume-staged gamma knife radiosurgery for large brainstem CM appears to be a viable treatment option.


Wael A REDA (cairo, Egypt), Amr ELSHEHABY, Khaled ABDEL KARIM, Ahmed NABEEL, Sameh ROSHDY, Reem EMAD ELDIN
00:00 - 00:00 #29906 - P071 A prospective longitudinal cohort study of progressing incidental meningiomas treated with gamma knife surgery.
P071 A prospective longitudinal cohort study of progressing incidental meningiomas treated with gamma knife surgery.

Objective

Incidental meningiomas are frequent findings. It remains unclear whether proactive treatment or surveillance is the optimal management. We aimed to compare longitudinal tumor volume changes and its clinical impact during active monitoring prior to and post intervention with gamma knife surgery (GKS).  

 

Methods

In a prospective study of the natural history of incidental meningiomas 31 (50 %) out of 62 patients with 33 (48.5 %) of 68 tumors (31 WHO I and 2 Grade II) were treated with GKS between 2010 and 2021 due to tumor growth. Clinical and radiological data was obtained every 6 months for two years, then annually during active monitoring and following GKS. Study end-points were changes in tumor volume, development of tumor related symptoms and GKS-related morbidity and mortality.

 

Results

Mean age at diagnosis was 60.5 y (range 34-79) for GKS treated vs. 68.4 y (range 42-85) for untreated patients (p = 0.027) and tumor volume was 3.5 (range 0.03-26.0) cm3 for treated tumors vs. 6.4 (range 0.07-35) for untreated tumors (p = 0.016). The mean prescription dose was 12 Gy. Mean follow-up time prior to and after intervention was 27.6 months (range 5-131) and 82.2 (range 0.5 - 127) months. Tumor growth was 0.17 cm3/year prior to GKS (p <0.001) and decelerated to 0.05 cm3/year (p = 0.303) post GKS. Neurological deficits were seen in 3 (9.6 %) of which two had atypical tumors and later succumbed to the disease, one were transient due to pseudoprogression following GKS. Four patients (12 %) treated with GKS died from unrelated disease.

 

Conclusion

Growth trajectories of incidental meningiomas were different and more stable after GKS. However, the clinical significance of volume stabilization of asymptomatic meningiomas is unknown. Most incidental meningiomas are detected in elderly patients and although the incidence of SRS induced neurological deficits was low at 3.2 % there was considerable unrelated mortality. We believe our data supports active surveillance as initial management. The optimal timing of interventions remains to be illuminated.


Torbjørn Austveg STRØMSNES (Bergen, Norway), Bente Sandvei SKEIE
00:00 - 00:00 #29911 - P072 Dosimetric plan comparison between the novel ZAP-X radiosurgery device and the CyberKnife System for vestibular schwannomas.
P072 Dosimetric plan comparison between the novel ZAP-X radiosurgery device and the CyberKnife System for vestibular schwannomas.

Introduction

Stereotactic Radiosurgery is a well established treatment modality for vestibular schwannomas. Its excellent local control rate and the low toxicity profile were proven by several clinical trials. Nevertheless, an increased risk of hearing loss was reported for single fraction SRS for patients receiving more than 4 Gy to the cochlea. Especially in the case of intrameatal lesions located close to the inner ear, achieving the proposed constraints for the cochlea might be challenging.

ZAP-X is a novel radiosurgery device using 3 MV X-rays for the treatment of intracranial lesions. Although the ZAP-X is becoming increasingly popular in radiosurgery robust dosimetric comparative data with other established dedicated radiosurgery devices is still lacking. In our study we aim to perform a dosimetric plan comparison between CyberKnife (CK) Robotic Radiosurgery  and the ZAP-X for 5 vestibular schwannomas and report on the differences concerning the most important plan parameters.

Material and methods

Five intrameatal vestibular schwannoma lesions of Koos grade 1 and grade 2 within a volume range between 0.06 ccm and 1.21 ccm were chosen for the dosimetric comparison.

The treatment planning was carried out independently, based on the same structure sets including the PTV and the OARs, by trained medical physicists on the CK System and on the ZAPX

Since the conventional chosen prescription isodose varies significantly between the two devices - typically 70-80 % for CK and 40-60 % for ZAP-X - planners were free to choose the prescription isodose which ensured optimal target coverage with the given prescribed dose while respecting the OARs constraints.

For the comparison of the plans the target-specific parameters (Coverage, New Conformity Index (nCI), gradient index (GI)) and the doses received by the OARs were evaluated.

Results:

The most significant difference between ZAP-X (average 3.33) and CK (average 5.51) showed up in the GI.The nCI varied between 1.17 and 1.53 for ZAP-X and 1.07 and 1.55 for CK. An excellent coverage above 99 % for all cases was achieved by both modalities.

The cochlea maximum dose was significantly better for ZAPX (average 3.2 Gy) than for CK (average 6.3 Gy), as well as the cochlea mean dose (1.63 Gy vs 3 Gy) 

Conclusion

The novel ZAP-X radiosurgery device convinces with a high conformity and steep dose fall off, which is at least comparable to the plan parameters published for the CK.In terms of sparing the OAR, the ZAP-X plans delivered better results compared to CK

 


Cristina PICARDI (Switzerland, Switzerland)
00:00 - 00:00 #29931 - P073 Treatment of vestibular schwannoma with stereotactic radiosurgery.
P073 Treatment of vestibular schwannoma with stereotactic radiosurgery.

Treatment of vestibular schwannoma with stereotactic radiosurgery

Angel Daniela; Muriano Oscar; Murina Patricia; Vera Veronica; Zunino Silvia; Venencia Daniel.

Instituto Zunino, Fundación Marie Curie. Córdoba, Argentina.

Abstract

Introduction: vestibular schwannoma (VS) is a benign tumor that grows in the vestibular portion of the VIII cranial nerve. Stereotactic radiosurgery (SRS) is accurate and safe for small tumors and larger ones that are not operable.

Objectives: The primary endpoint was to define fractionation related to tumor size and dose-limiting flexibility in 94 patients diagnosed with VS. Secondary endpoints were: evolution of initial symptoms after radiosurgery, and toxicity associated with treatment, as well as tumor control, and progression-free survival.

Methods: A retrospective analysis of 94 patients who received SRS 2010-2020. Tumor diameter, volume and proximity to risk organs was obtained directly from the planner. SRS was applied in 1 (13Gy) 3 (18Gy) or 5 (20-30 Gy) fractions. Treatment planning was performed with dynamic arc modality in TPS iPlan v4.5 (Brainlab) and VMAT, Elements Cranial SRS v1.5 (Brainlab). Hearing and symptoms were evaluated before SRS and during follow-up.

Results: 94 patients, mean age 58 years [21-86 years], 57 women (60.6%) and 37 men (39.4%) were irradiated; 95 SV; 6, 57, 25 and 7 were classified as Koos I, II, III and IV respectively; the mean diameter was 18.9mm [6.3-50.5mm] and the mean volume 2.58cc [0.01-21.78cc]. The fractionation was decided according to the tumor size and relationship with OARS. As initial symptoms, 19 patients had anacusis (20.2%), 61 hearing loss (64.9%), 56 tinnitus (59.6%), 41 dizziness (43.6%), 4 mild facial paresis (4.3%), 3 spasms (3.2%) and 3 trigeminal nerve pain (3.2%). Follow-up of 75/94 patients was 61 months [10-133 months] showed significant improvement in dizziness (p<0.036). Symptom intensity worsened in 13 patients (2 anacusis, 6 tinnitus, 2 dizziness, 2 facial spasm, and 1 trigeminal pain) but improved in 29 (11 tinnitus, 15 dizziness, 1 paresis, and 2 spasms). Tumor control was evaluated in 70/94 patients with magnetic resonance imaging, with 67/70 (95.7%) showed stability or tumor reduction. There were no patients with SV progression during follow-up.

Conclusions: we can suggest that SRS is a treatment suitable for small neurinomas and a therapeutic possibility for larger tumors with fractionated stereotactic radiotherapy. The number of fractions to be used is decided according to the tumor volume to respect the organs at risk.

Key words: Fractionation, VIII cranial nerve neuroma, Radiosurgery, Schwannoma, SRS with Novalis accelerator.


Daniela ANGEL (Cordoba, Argentina)
00:00 - 00:00 #29949 - P074 - WITHDRAWN - Safety and Efficacy of Primary Multisession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas.
P074 - WITHDRAWN - Safety and Efficacy of Primary Multisession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas.

Background

While multisession dose fractionated gamma knife radiosurgery (DF GKS) is common, its use has never been described for jugular paragangliomas (JP), which are notoriously difficult to treat.

Objective

To define the efficacy, safety, and complication profile of dose-fractionated GKS in two or three consecutive sessions for the treatment of a cohort of ten cases of JP.

 

Methods

Between 2012 and 2017, ten patients of JP were treated with dose-fractionated GKS in 2 or 3 sessions, as it was not safe to treat the lesion in a single session because of the large volume or proximity to organs at risk. The small to medium sized JP are treated with 16-22 Gy radiation but the large volume JP were treated with 23-25 Gy radiation dose. The Leksell-G frame was kept in situ during the whole procedure. The tumor volumes on pre- and posttreatment imaging were compared utilizing the Leksell Gamma Plan treatment plan software to assess tumor progression. The patients were regularly evaluated for their clinical outcome with radiologic correlation. 

 

Results

The mean radiological follow up was 39 months (range: 12 – 78 months).The mean marginal dose for three fractions and two fractions was 7.64 Gy @ 50% and 11.2 Gy @ 50% respectively.The mean tumor size was 29.9cc (range: 9.95 – 47.63cc) at treatment and 21.9cc (range,8.83-37.5 cc) at follow-up (suggestive of 26.7% reduction).Tumor control was achieved in all patients (100%).Out of 110 potential neurological problems (signs/ symptoms) evaluated (11 in each patient), 56 (50.9%) were present preoperatively.Of them, 27 (48.2%) improved and 29 (51.8%) stabilized after treatment.There were two new-onset neurological problems (out of 110, 1.8%) attributable to treatment (new onset headache, spinal accessory paresis).No patient suffered any permanent neurological deterioration.

Conclusion

Dose-fractionated GKS for large volume JP leads to acceptable progression-free survival, tumor control rate and symptomatic improvement. It may be preferred to surgery or fractionated radiotherapy in view of better safety, efficacy, and complication profile. 


Manjul TRIPATHI (Chandigarh, India), Kanchan MUKHERJEE
00:00 - 00:00 #29957 - P075 Stereotactic irradiation of sporadic and vhl-associated hemangioblastomas of the cns.
P075 Stereotactic irradiation of sporadic and vhl-associated hemangioblastomas of the cns.

Hemangioblastomas are rare, benign, highly vascular tumors most frequently arising in the cerebellum, brainstem, or upper cervical cord, and account for 2-6% of all brain and spinal cord tumors. These lesions are sporadic or seen in association with von Hippel-Lindau (VHL) disease, an inherited autosomal dominant disorder caused by mutation in the VHL tumor suppressor gene. In sporadic hemangioblastomas, the prognosis is relatively favorable. In the presence of a germline VHL mutation, on the contrary, they are characterized by the occurrence of relapses, synchronous and asynchronous multiple hemangioblastomas. Thus, the diagnosis of Hippel-Lindau syndrome is an important part of the examination of patients with hemangioblastomas, especially those under the age of 50. However, within the group of sporadic and hereditary hemangioblastomas, there are differences in the growth rate, recurrence, sensitivity to radiotherapy of inoperable tumors, as well as in the profiles of molecular genetic structural and expression changes in the genome of tumor cells.

From 2005 to 2021, at the National Scientific and Medical   Center of Neurosurgery named after N.N. Burdenko 108 patients with hemangioblastomas received stereotactic irradiation (95 patients with VHL syndrome). Sporadic forms hemangioblastomas is characterized the solitary nature of the lesion, mostly  localized in the posterior cranial fossa or cervical spinal cord. All cases of multiple hemangioblastomas were associated with VHL syndrome. The average age of the patient is 30.2 years (median 14-76 years). 805 of brain and spinal cord tumors were treated. 627 tumors (78%) were treated in the radiosurgery (16-20 Gy). 138 (17%) in the hypofractionation (22,5-24 Gy in 3 fractions; 27,5-30 Gy in 5 fractions), and 40 (5%) tumors 45-54 Gy in 25-30 fractions. Median follow-up was 40.3 months (range 1-182 months). 5-year PFS was 86%.

Our results are  confirming that stereotactic radiosurgery and radiotherapy are effective and relatively safe methods of radiation treatment of patients with hemangioblastomas. However, the choice of fractionation regimen and doses, depending on the association with the VHL syndrome, requires further research, the long-term efficacy of radiotherapy for hemangioblastomas still needs to be investigated. Also very  important  to conduct  studies in which  exploring the role of radiotherapy for early treatment of asymptomatic lesions. Perhaps, the study of combinations of germline and somatic VHL mutations and mutations in minor candidate genes of hemangioblastomas will reveal new diagnostic and prognostic criteria of course and treatment including stereotactic irradiation  for different forms of hemangioblastomas of the central nervous system.

 


Arina LESTROVAYA, Natalia ANTIPINA, Andrey GOLANOV (Moscow, Russia), Elena VETLOVA, Svetlana ZOLOTOVA
00:00 - 00:00 #29959 - P076 Radiolobiological Behavior Of Cystic Vestibular Schwannoma Following Gammaknife Radiosurgery: A Series Of 14 Cases.
P076 Radiolobiological Behavior Of Cystic Vestibular Schwannoma Following Gammaknife Radiosurgery: A Series Of 14 Cases.

Introduction

Cystic component within the vestibular schwannoma (CVS) is long believed to be a negative predictor of tumor response to GKRS. Lesser is discussed about the radiobiological behavior of CVS. Here we present our experience of treating CVS with upfront GKRS.

Materials and methods

Total 14 cases (8 males and 6 females) of non syndromic intra tumoral CVS with mean age of 47.71 years (range 30 – 65 years) underwent GKRS between March 2011 and December 2020. CVS was defined on CEMRI when the cystic component occupies at least 30% of the total volume of tumor. The volume of solid and the cystic components were calculated separately. CVS were sub grouped as predominantly cystic (cyst volume more than 50% of the total tumor volume) or predominantly solid (solid portion constitutes more than 50% of the total tumor volume).

Follow up radiology were carefully evaluated for reduction in tumor sizes both solid and cystic component. Radiosurgical treatment success was considered if the tumor size remained same or there was a reduction on follow up MRI. Patient undergoing additional treatment (surgery/ GKRS) was considered as treatment failure.

 

Result (Table 1)

The mean tumor volume and marginal dose was 5.8cc and 12.32Gy respectively. There were 6 patients with predominantly solid CVS and 8 with predominantly cystic CVS. Twelve of them had Koos grade 3 tumor and two had Koos grade 4 tumor.

One patient (predominantly cystic CVS with multiple cysts) became symptomatic and underwent surgical decompression. Rest all 13 patients showed reduction in tumor size.  The average tumor volume reduction was 32.82% at a mean follow up of 82.38 months. The cystic portion regressed earlier than the solid portion. The radiosurgical response was best seen in patients with predominantly cystic CVS with single intra tumoral cyst (average tumor volume reduction of 78% at a mean follow up of 59.75 months, Figure -1) followed by predominantly solid CVS with single intra tumoral cyst (average tumor volume reduction of 37.6% at a mean follow up of 60 months, Figure 2), predominantly solid CVS with multiple cysts (average volume reduction of 11.5% at mean follow up of 102.5 months) and lastly predominantly cystic CVS with multiple cysts (average volume reduction of 9.8% at mean follow up of 100.6 months).

Conclusion

GKRS can be considered as a safe and effective upfront therapy for CVS. The cystic component regresses earlier than the solid component following GKRS.

 


Sushant SAHOO (Chandigarh, India)
00:00 - 00:00 #29966 - P077 A comparison of dosimetric characteristics and cochlear doses between Varian Edge and Accuray CyberKnife for stereotactic radiosurgery for vestibular schwannoma.
P077 A comparison of dosimetric characteristics and cochlear doses between Varian Edge and Accuray CyberKnife for stereotactic radiosurgery for vestibular schwannoma.

Goals: The goal of this study was to compare dosimetric characteristics of fixed conus based Accuray CyberKnife (CK) system and multileaf collimator (MLC) based Varian Edge (Edge) system for stereotactic radiosurgery (SRS) of vestibular schwannoma (VS) with special emphasis on cochlear dose, the leading contributor to hearing impairment after SRS. 

Methods: Six patients with relatively small vestibular Schwannoma (mean PTV 0,9 ccm, range 0,2ccm to 3,2ccm) were chosen for this study. For each patient two SRS plans were made - one using CK system, and one using EDGE system. Same simulation planning CTs, contours, and dose constraints were used in both plans. 

In all plans, 95% of the PTV received a dose of 12 Gy in a single fraction. During optimization of each plan, cochlear dose and homogeneity indexes were reduced as low as possible without compromising dose coverage.

CK plans were generated using VOLO optimizer, with two fixed collimators chosen for dose homogeneity.

EDGE plans were generated using Eclipse photon optimizer for RapidArc with multiple non-coplanar arcs and HD MLC, for purposes of achieving better dose conformity.

Dosimetric values used for comparison were new conformity index (nCI), homogeneity index (HI),  maximum cochlear dose (Dmax ) and mean cochlear dose (Dmean ).

Results: Both systems yielded comparable results in terms of nCI.
(nCI for CK = 1,3 +/- 0,2; nCI for Edge = 1,6+/-0,4) (p = 0,1).

HI were significantly higher for EDGE, making CK more effective at keeping the dose homogeneous.
(HI for CK = 1,11+/-0,01;  HI for EDGE = 1,13+/-0,02) (p=0,005), 

Significant differences were also observed between cochlear doses, with CK achieving better results
Dmax for CK = (6,8+/-1,8) Gy;  Dmax for Edge = (7,5 +/-2,2)Gy, (p=0,03)
Dmean for CK = (2,3+/-0,5) Gy;  Dmean for Edge = (3 +/-1)Gy, (p=0,02) 

Conclusions: In this specific case of relatively small VS both systems yielded highly conformal plans due to non-coplanar, multiple focal beam entries.

Edge achieved less homogeneous dose distributions than CyberKnife.

CK was more efficient in cochlea sparing. In all CK plans dose coverage for PTV was achieved with Dmean to cochlea being well below the 4Gy limit. This was not the case for one of the EDGE plans, where Dmean to cochlea exceeded 4 Gy.

Our results indicate that CK could be a better option than EDGE when it comes to dose homogeneity and cochlea sparing for SRS for relatively small VS.

 

 


Vanda LEIPOLD (Zagreb, Croatia), Ivana ALERIĆ, Hrvoje KAUCIC, Adlan ČEHOBAŠIĆ, Domagoj KOSMINA, Mihaela MLINARIĆ, Sofija ANTIĆ, Mladen KASABAŠIĆ, Ana MISIR KRPAN, Jelena TRAJKOVIĆ, Dragan SCHWARZ
00:00 - 00:00 #30027 - P079 Linear accelerator radiosurgery for petro-clival meningiomas.
P079 Linear accelerator radiosurgery for petro-clival meningiomas.

Introduction:

Meningiomas of the Petro-Clival area are frequently treated by radiosurgery. The purpose of this study was to assess the efficacy and side effects of radiosurgery in our institution.

Methods:

From 1993 to 2016, 138 patients with Petro-Clival meningiomas were treated with linear accelerator radiosurgery (RS). The median prescribed dose was 13 Gy. Mean tumor volume was 3.76 cm3 (range 0.19 cm3-12.5 cm3, SD 2.68 cm3). In 93 patients (67.4%), RS was the primary treatment (no previous surgical intervention) and 45 patients (32.6%) had undergone previous surgery. Follow up (minimum 2 years, maximum 23 years, median 5 years) was done with annual MRI, neurological and neuro-ophthalmological examinations.   

Results:

131 tumors (94.9 %) were controlled at end of follow up, of which 32.1 % were unchanged and 67.9 % experienced a reduction in size. 25 treated patients (18.1%) had functional improvements in cranial nerve deficits [ CN-II though CN-VIII, n=23] or non-specific neurological symptoms including headache and imbalance (n=2). Twelve patients (8.7%) developed new cranial nerve deficits including CN-III, IV, and VI presenting as diplopia (n=2), CN-V (n=5), and CN-VIII (hearing loss n=5). Post-treatment visual field deficits (related to optic tract radiation injury) occurred in 3 patients (2.2 %), of which 2 completely recovered. Worsening of pre-existing deficits occurred in 6 patients (4.3%) affecting CN-V (n=3) and CN-VIII (n=3). Hydrocephalus occurred in 4 patients (2.9%) requiring shunting.

Conclusion:

Single session Linear Accelerator (LINAC) radiosurgery was a safe and highly effective treatment for Petro-Clival meningiomas in our series, achieving high tumor control rates and low incidence of morbidity over long term follow up.


Michael CHODAKIEWITZ (Los Angeles / Tel Aviv, USA), Roberto SPIEGELMANN
00:00 - 00:00 #30031 - P080 Gamma knife radiosurgery for rathke's cleft cysts: a multicenter survey.
P080 Gamma knife radiosurgery for rathke's cleft cysts: a multicenter survey.

Background

Rathke’s cleft cysts (RCCs) are benign cystic sellar lesions, often incidentally diagnosed but sometimes presenting with visual and/or endocrine disorders. These lesions arise from remnants of the embryologic Rathke’s pouch. They may account for 6-10% of symptomatic sellar and suprasellar lesions and growth rates ranges from 5% to 30% in the different series. Normally asymptomatic cysts are followed by serial imaging, otherwise symptomatic RCCs are managed by surgical decompression. Recurrence of RCCs after surgery, has been described up to 30%, leading occasionally to multiple surgical procedures that increase morbidity.

Objective

To evaluate a multicenter experience in the treatment of RCCs with Gamma Knife radiosurgery (GKRS).

Methods

We retrospectively analyzed 6 patients (2 male and 4 female) that underwent GKRS for RCCs in three centers (Ospedale Civile Maggiore – Verona, Ospedale Niguarda and Ospedale San Raffaele – Milano) between 2007 and 2017. Presenting symptoms included headache, memory loss, lipothymia, visual field deficit, endocrine disorders till panhypopituitarism. Five patients underwent previous surgery while one patient had a neuroradiological diagnosis of RCC. The radiosurgical technique has already been described in previous reports. After GKRS, follow-up protocol (with some differences among the centers) included MRIs between 3 and 6 months, then annually, visual field testing, and endocrine evaluations.

Results

All surgically treated patients (five), were closely followed by clinical and radiological examinations; one patient required a redrainage for cyst’s recurrence after three years. The rationale of treating RCCs with GKRS is based on the observation that these can be considered benign neoplastic lesions with a close relationship with craniopharyngioma, since they share a common histological origin from remnants of the squamous epithelium from Rathke’s cleft. The mean age at time of GKRS was 61 years old; mean prescription dose was 11.4 Gy (range 6,5 – 15 Gy) normalized to the 50% isodose line, and mean follow-up period was 90 months (range 36 – 156 months). No patient required further surgery or developed new visual/endocrine deficit after GKRS. In 5 patients we observed a > 50% volume reduction of the cyst, while in one patient the lesion was stabilized. There are only few previous reports regarding usage of radiation therapy for RCCs, and our series confirm the safety and efficacy of stereotactic radiosurgery.

Conclusions

The clinical and radiological findings of our series, with a long follow-up period, suggest that GKRS could be considered a feasible and safe adjuvant treatment for recurrent RCCs.


Riccardo LAVEZZO (Verona, Italy), Michele LONGHI, Valeria BARRESI, Emanuele ZIVELONGHI, Giuseppe Kenneth RICCIARDI, Anna D'AMICO, Giorgia BULGARELLI, Paolo Maria POLLONIATO, Giampietro PINNA, Francesco SALA, Andrea MANZONI, Filippo LEOCATA, Marco PICANO, Virginia Maria ARIENTI, Hae Song MAINARDI, Marco CENZATO, Roberto STEFINI, Alessandro LA CAMERA, Lina Raffaella BARZAGHI, Marco LOSA, Enrico GARBIN, Pietro MORTINI, Piero PICOZZI, Antonio NICOLATO
00:00 - 00:00 #30093 - P081 Gamma Knife Radiosurgery in the treatment of Glomus jugulare tumours - the Vienna series.
P081 Gamma Knife Radiosurgery in the treatment of Glomus jugulare tumours - the Vienna series.

Objective:

Glomus jugulare tumour (GJT) is considered a slowly growing, benign lesion located in the skull base. The tumour is frequently highly vascular and surgical removal is rarely radical. Consequently, radiosurgery became a relevant role in the treatment of these tumours.

Methods:

A retrospective analysis identified 42 patients with GJT treated with Gamma Knife Radiosurgery (GKRS). 19 out of 42 patients underwent surgery before GKRS. 23 patients had GKRS as primary treatment. Five patients were lost to follow up (FU).

Results:

The mean total FU was 64 months (range 11-212m). The mean dose to the tumour margin was 13 Gy (range 9-16 Gy). The mean tumour size was 10.1 cc (1.2-74.0 cc)

In MRI controls 13 tumours decreased (35.1%), 22 remained stable (59.5%) and two (5.4%) showed a progression and were managed conservatively. Treatment failures received a marginal tumour dose of 13 and 15 Gy, respectively.

Conclusion:

GKRS is an effective treatment option for GJTs even after prior surgical resection and provides a tumour control of nearly 95%.


Brigitte GATTERBAUER (Vienna, Austria)
00:00 - 00:00 #30098 - P082 The longitudinal volumetric response of vestibular schwannomas after gamma knife radiosurgery.
P082 The longitudinal volumetric response of vestibular schwannomas after gamma knife radiosurgery.

Introduction:

Gamma Knife radiosurgery (GKRS) is an effective treatment for vestibular schwannomas (VS) and has been used in > 100,000 patients worldwide. The present study seeks to define the serial volumetric tumor response of Koos Grades I-IV VS after radiosurgery.

Methods:

201 consecutive VS patients underwent GKRS in a single institution during a five-year interval. All patients had a minimum follow-up ≥18 months and at least 2 interval post-procedure MRI follow-up scans. The gross tumor volumes (GTV) were contoured and serially compared between GKRS planning and follow-up MRIs. Change over time of the GTVs were assessed with linear models using time as a continuous variable. A test for linear trend was evaluated according to the initial Koos classification of tumor.

Results:

The most common Koos grade was II (n = 74, 36.8%), followed by grade III (n = 57, 28.4%), grade I (n = 41, 20.4%) and grade IV (n = 29, 14.4%). The mean tumor volume at the time of GKRS was 2.12 ± 2.82 cm3 (range, 0.12 - 18.77 cm3) and the median margin dose was 12 Gy. Early follow-up (up to 18 months) revealed that tumor volume transiently increased in 54.8% of patients regardless of Koos grade. Koos grade II, III and IV tumors thereafter decreased significantly in volume on long-term longitudinal analysis (up to 54 months, p < 0.05). Patients with larger Koos grade III and IV tumors showed a trend toward delayed radiographical decrease 18 months after treatment. At last follow-up (mean 40.50 ± 10.11 months), only 19 patients (9.4%) showed a persistent increase of tumor volume.

Conclusions:

Although VS patients may have an early measurable volumetric increase after GKRS, over an additional observational interval of up to five years, >90% of patients have stable or gradually reducing tumor volumes. Volumetric regression is recognized most often in Koos Grade III and IV tumors and may not be fully detectable until 3-4 years after GKRS.


Luigi ALBANO (Milan, Italy), Hansen DENG, Zhishuo WEI, Ajay NIRANJAN, Lawrence Dade LUNSFORD
00:00 - 00:00 #30101 - P083 What is the role of radiosurgery in the management of neurofibromatosis type 2 associated vestibular schwannoma?
P083 What is the role of radiosurgery in the management of neurofibromatosis type 2 associated vestibular schwannoma?

Introduction: Type-2 Neurofibromatosis (NF2) is characterized by the appearance of bilateral vestibular schwannomas (VS). Those lesions deteriorate patients quality of life over time. Because its development can be traced back to genetic causes, it occurs cumulatively in some families. For controlling these tumors, among others, stereotaxic radiosurgery may have a beneficial role. The aim of this work was to evaluate the long-term management of members of an NF2-family followed and treated. Based on these cases, we try to answer the question of what conditions for the ideal radiosurgery treatment could be. 

Material and Method: Data were collected from 29 members of a family, affected by NF2. The information was obtained from previous medical records of follow-ups and examinations and treatments, and during conversations by patients and relatives. Based on this information, we were able to use data from 11 patients with the NF2-phenotype and 18 other individuals with no signs of the disease. If treatment was necessary, surgery or gamma radiosurgery, or a combination of those was performed.

Results: A total of 6 open skull surgeries were performed in 4 NF2-patients to reduce VS size. One patient had three operations. Tumor progression was common after surgery and several iatrogenic complications worsened the quality of life. Due to further increase in size, 1 patient of the surgically treated group also underwent radiosurgery on the same side. This intervention prevented further tumor growth so far. Gamma radiosurgery was performed 4 times in 3 patients. One patient had irradiation at both sides. Using low radiation doses (12-13Gy@50%marginal dose), the increase in tumor size stopped in all cases, however, the hearing performance of patients deteriorated slowly. Other complications were rare. 

Conclusion: We can conclude that if the NF2-associated VS is recognized in time and the individual has a follow-up with adequate regularity, radiosurgery is likely to provide a good quality of life. Audiological follow-up is also required to determine the timing of radiosurgery. In case of good hearing values, it is advisable to postpone the radiosurgery treatment until the tumor growth allows it. So tumor size and growth are not the only indications of further treatment. Finally, it can be concluded that radiosurgery is a safe and effective treatment tool in these cases. Using locally delivered irradiation techniques, good tumor growth control, longer life expectancy, and adequate quality of life can be provided, although complete healing is not expected.


József Gábor DOBAI (Debrecen, Hungary), Bernadett SZŰCS, Mihály SIMON, Árpád KOVÁCS
00:00 - 00:00 #30104 - P084 Gamma-Knife Stereotactic Radiosurgery for Giant Intracranial Tumors – A Series of 70 Patients.
P084 Gamma-Knife Stereotactic Radiosurgery for Giant Intracranial Tumors – A Series of 70 Patients.

Background – Although surgery remains the primary option in large intracranial tumors, there are significant number of patients who either refuse or are not amenable for surgery. We explored the role of stereotactic radiosurgery as an alternative to External Beam Radiation Therapy (EBRT) in such patients.

 

Objective - To assess the radiological and clinical outcomes of giant intracranial tumors (volume ≥ 20 cc) managed with Gamma Knife Stereotactic Radiosurgery (GKSRS)

 

Material and Methods – This retrospective study was carried out in a single centre over 8 years (from January 2012 - December 2019). Patients with intracranial tumor volume ≥ 20 cm3, who received GKRS and had a minimum of 12 months of follow up were included in the study. Vascular lesions like AVM’s were excluded. GKRS was done on Perfexion system® (Elekta AB, Stockholm, Sweden). Demographic profile, clinical presentation, functional status, radiological details, Gamma-knife parameters as well as follow-up clinico-radiological findings were acquired and analysed.

 

Results – A total of 70 patients had pre GKRS tumor volume ≥ 20 cm3 with >12 months of follow up were included in the study. The mean age of the patients was 42.54 ± 14.47 (range 11-75) years. Majority (97.1%) received GKSRS in single fraction. Two patients received staged treatment. Mean target volume at the time of radiosurgery was 34.2±16.4 cm3 and mean radiation dose to the target margin was 16.5 ± 5.0 Gy. At a mean follow up of 34.3±15.6 months, tumor control was achieved in 91.4% (n=64) of the patients with tumor progression occurring in 6 (8.6%) patients. Post radiation Imaging (PRI) changes were observed in 11 (15.7%) patients but were symptomatic in only 2 (2.8%) patients.

 

Conclusions - The present series defines ‘giant intracranial lesions’ for GKRS and demonstrates excellent radiological and clinical outcomes in these patients. GKRS may therefore be considered as the primary option in such giant intracranial lesions in which surgery carries significant risk based on patient related factors.

 


Deepak AGRAWAL, Satish VERMA, Deepak AGRAWAL (New Delhi, India)
00:00 - 00:00 #30110 - P085 Clinical outcomes after stereotactic radiosurgery for meningiomas involving Meckel’s cave: the difference in outcomes according to the direction of invasion into the cave.
P085 Clinical outcomes after stereotactic radiosurgery for meningiomas involving Meckel’s cave: the difference in outcomes according to the direction of invasion into the cave.

Objective We analyzed the clinical and radiological outcomes of patients with Meckel's cave meningioma after stereotactic radiosurgery (SRS).

Method Between 2009 and 2020, 190 patients with para-Meckel’s cave meningiomas were treated with SRS. Patients who were treated with SRS and whose clinical and radiological follow-up was longer than 3 months were eligible for study inclusion. Meckel's cave meningiomas were defined as meningiomas invading any part of the ipsilateral Meckel’s cave from the porus trigeminus to the anterior end of Meckel’s cave.

Result Seventy-six patients (57 females and 19 males, with a median age of 55.5 years) met the study inclusion criteria. The median follow-up was 37 months (range, 3 - 128). The medial tumor volume was 3.22 cc (range, 0.163 – 56.3). The median margin dose was 14.0 Gy (range, 7 - 18). The presenting symptoms were diplopia in 21 (27.6%) patients, trigeminal nerve-related symptoms such as neuralgia and/or hypesthesia in 30 (39.5%). In 25 (32.9%) patients, Meckel’s cave MNG was diagnosed incidentally. In terms of tumor location, tumors in which tumor epicenter was located close to the porus trigeminus (retro-gasserian-ganglion type) were related with trigeminal nerve-related symptoms (57%), but, pre-gasserian ganglion type tumors caused more often diplopia (50%) (p < 0.005). At the last clinical follow-up after SRS, 47.4% of tumors were stable, 48.7% had regressed, and 3.9% had progressed. Fifty-five percent of symptomatic patients noted clinical improvement. Symptoms improved in 71% of patients with diplopia, but only 27% of patients with trigeminal neuralgia showed improvement.

Conclusion SRS is a good alternative treatment for MNGs invading Meckel's cave. However, tumor-related trigeminal neuralgia tends to be poorly improved.


So Young JI (Seoul, Korea), Hwang KIHWAN, Chae-Yong KIM, Juh RAHYEONG, Jung Ho HAN
00:00 - 00:00 #30114 - P086 Outcomes Of Gamma-Knife Radiosurgery In Partially Embolized Arterio-Venous Malformations.
P086 Outcomes Of Gamma-Knife Radiosurgery In Partially Embolized Arterio-Venous Malformations.

Background:

The role of gamma knife radiosurgery(GKRS) in partially embolized AVMs has always remained subject of debate.

Objective:

To evaluate the efficacy of GKRS in partially embolized AVMs and to analyze factors influencing obliteration.

Methods and Material:

This is a retrospective study from a single institute performed over a period of 12 years(2005-2017). It included all the patients who underwent GKRS for partially embolized AVMs. Demographic characteristics, treatment profiles, clinical and radiological follow ups of minimum one year were obtained. This study assumes that every AVM that shows obliteration on MRI would be completely obliterated if DSA were done on them.

Results:

A total of 46 patients with a mean age of 30 years(range: 9-60 years) were included in the study. Follow up imaging was available for 35 patients either by DSA or MRI, out of which, 21 had complete obliteration(100% obliteration), one had near total obliteration(> 90% obliteration), 13 had subtotal obliteration(<90%) and one had no change in the volume following GKRS. Mean duration for complete obliteration was found to be 3.45 years(range: 1-10 years). An obliteration rate of 79% was noted in our study. The factors analyzed were not found to be significantly influencing obliteration. Six out of nine patients(66%) presenting with seizures, were seizure free after the treatment. Hemorrhage was noted in three patients following combined treatment. All of these cases were managed non-surgically.

Conclusion:

Obliteration rates by GKRS in partially embolized AVM when compared to the obliteration rates, in the literature of non-embolized AVMs, are lesser. However, due to the more complicated nature and the higher grade of some of these AVMs, embolization followed by GKRS is a valid modality of management when chosen carefully. Nidus volume and SM grade had no role, interval between embolization and GKRS had negative impact on obliteration rates.

 


Dwarakanath SRINIVAS, Arivazhagan ARI (Bangalore, India), Somanna SAMPATH
00:00 - 00:00 #30117 - P087 Hypofractionated stereotactic radiosurgery for intracranial meningiomas.
P087 Hypofractionated stereotactic radiosurgery for intracranial meningiomas.

Background
Stereotactic radiosurgery (SRS) is nowadays a recognized therapeutic option for the treatment of intracranial meningiomas, but a single session SRS may lead to a higher risk of treatment-related toxicities in larger meningiomas (more than 3 cm) or in meningiomas located close to critical structures, like the optic chiasm or the brainstem.
The purpose of this study was to evaluate the possible role of hypofractionated multisession SRS (hSRS) for the management of meningiomas of large size or those located near critical structures.
Methods
From May 2012 to October 2021, 84 consecutive patients were treated at our Institution with hSRS in either exclusive or adjuvant setting. Efficacy was evaluated in terms of both local control and clinical outcomes.  Acute and late toxicities were registered too.
Results
Median age at hSRS was 70 years (range 35-88). 48 patients (57.1%) had a meningioma of the convexity while 36 patients (42.9%) of the skull base.
Surgery was performed in only 40 cases (47.6%), thus providing the histological grading (20 patients G1, 20 patients G2). Treatment was delivered with a Linear Accelerator with Volumetric Modulated Arc Therapy, using two different fractionation schedules, 25 Gy in 5 fractions (66%) or 30 Gy in 5 fractions (34%).
With a median follow-up of 36 months, local control was 94.05% (median not reached). None of the variable analyzed (sex, age, previous surgery, histological grade, site) was correlated to a better local control at univariate analysis.
Regarding the clinical outcomes, 33 patients (39.2%) remained asymptomatic after treatment, 23 patients (27.3%) had a worsening of their initial symptoms, 22 patients (26.1%) had stable symptoms and 6 patients (7.14%) had a clinical relief.
A local relapse occurred in 5/84 patients suffering from meningioma of the convexity, three of which were grade 2 atypical meningioma. 
Treatment was well tolerated in most cases, with only 3/84 patients registering a late toxicity: one symptomatic radionecrosis, one generalized seizure due to increased edema and one hypofunction of the hypothalamic-pituitary axis.
Conclusions
In patients affected by large intracranial meningiomas or meningiomas located close to critical structures, hSRS can lead to a good local control rate with an acceptable toxicity profile. Prospective trials with a larger cohort of patients are needed to confirm these promising results.

 


Antonio Marco MARZO (Milano, Italy), Pierina NAVARRIA, Elena CLERICI, Luisa BELLU, Sara LILLO, Sofia Paola BIANCHI, Federico PESSINA, Letterio Salvatore POLITI, Marta SCORSETTI
00:00 - 00:00 #30118 - P088 Dosimetric comparison between Varian EDGE™ and CyberKnife® systems using single fraction stereotactic radiosurgery treatment for peripheral brain meningiomas.
P088 Dosimetric comparison between Varian EDGE™ and CyberKnife® systems using single fraction stereotactic radiosurgery treatment for peripheral brain meningiomas.

Goals:

The goal of this study was to compare the dose distributions to the brain between two systems for stereotactic radiosurgery: CyberKnife® (CK) and MLC based Varian EDGE (EDGE). 

 

Material and methods:

Seven patients with peripheral brain meningiomas treated on Varian EDGE were studied. Additional treatment plans were made on the CK system using VOLO optimizer in order to evaluate differences between two systems. The dosimetric characteristics were compared in the non-target brain tissue; Brain - Planning target volume (PTV) with mean PTV size (15±13) ccm and prescribed dose of 14Gy in a single fraction. 

 

EDGE treatments were delivered using RapidArc® non-coplanar arcs with multileaf collimator (MLC), while CK treatments were delivered using fixed collimators. For both optimization systems normal tissue objective (NTO) was used.

Analyzed characteristics were: maximum dose Dmax, volume of 12Gy, 10Gy and 2Gy isodose line (V12Gy, V10Gy, V2Gy), conformality index (CI), and dose gradient index (DGI). 

 

Results:

Dmax on non-target brain tissue was slightly lower on EDGE planning system (17±2)Gy than on CK ((18±3)Gy, p=0.08). Brain-PTV volume of (3±2)ccm received 12Gy on EDGE, and  (6±4)ccm on CK (p=0.05). For the 10Gy isodose line isodose volume on EDGE was smaller compared to CK: (6±3)ccm and (9±5)ccm, respectively (p=0.04).  For low doses of 2Gy no significant difference in isodose volumes was observed with a tendency for lower doses to occupy  larger volumes on EDGE plans (110±50)ccm as opposed to CK (100±60)ccm. In terms of CI, EDGE proved to be considerably more conformal (1.17±0.17) than CK system (1.24±0.19, p=0.002). DGI showed to be similar (p=0.13), although EDGE  seemed to have steeper dose decline (76±8) than CK (72±9).

 

Discussion:

Results of our study indicated that both systems yielded comparable results. Better conformity and the dose fall-off on Varian EDGE treatment plans were a result of multi-leaf collimator and non-coplanar arcs that enabled more detailed coverage and dose control. CyberKnife® appeared to be more suitable for low dose control, most likely due to fixed conus collimators and absence of dose leakage. Therefore, CK could be adequate for multiple small targets in the brain.


Ivana ALERIĆ (Sveta Nedelja, Croatia), Vanda LEIPOLD, Hrvoje KAUČIĆ, Adlan ČEHOBAŠIĆ, Mihaela MLINARIĆ, Sofija ANTIĆ, Domagoj KOSMINA, Sanja BREZOVEC, Ana MIŠIR KRPAN, Dragan SCHWARTZ
00:00 - 00:00 #30128 - P089 Long term results in stereotactic radiosurgery for craniopharyngioma: monoistitutional experience.
P089 Long term results in stereotactic radiosurgery for craniopharyngioma: monoistitutional experience.

Aim: the use of radiosurgical treatment (SRS) in patients with craniopharyngioma has been documented, but long-term follow-up reports are rare.The purpose of this study was to analyze the long-term outcomes of the SRS in patients with craniopharyngioma, reviewing a series of patients consecutively treated in a single institution.

Materials: 27 patients were treated for residual or recurrent craniopharyngioma between 2008 and 2018 with CyberKnife SRS.

Patients underwent magnetic resonance imaging, visual and neuroendocrine evaluations before and after SRS at regular intervals. Both a multisession treatment regimen and a single fraction were used. A non-isocentric treatment plan was developed for each patient.

The radiological response to treatment was assessed using RECIST guidelines (vers 1.1).

Results: of 27 patients, 16 were males and 11 females.

The average age at treatment was 46 years old, and the follow-up period was 20 to 160 months (90 mean, 48 median). The treatment was delivered to 10 patients with single fraction (median dose 13 Gy), to 17 pts with multiple fractions (median dose 25 Gy). The maximum dose of anterior optic pathway is 24Gy for stereotactic fractionated radiosurgery.

16 patients were treated for relapse after radical surgery and 11 patients received treatment after non-radical surgery.

A partial reduction of the disease was observed in 8 of 27 patients (mean response 5,5 months).

3 patients achieved total tumour regression. Only 1 patient underwent new surgery due to disease progression. 15 patients maintained disease stability after treatment.

No patient showed deterioration of visual or neuroendocrine function after SRS.

Conclusions: SRS has proven safe and effective, with no evidence of long-term complications.

The use of SRS will be increasingly evaluated in the future, also in combination with conservative surgical resection.


Sara MORLINO (Milano, Italy), Marcello MARCHETTI, Valentina PINZI, Irene CANE, Maria Luisa FUMAGALLI, Laura FARISELLI
00:00 - 00:00 #30145 - P090 Radiosurgical versus conservative management in cerebral cavernous malformations - a retrospective analysis.
P090 Radiosurgical versus conservative management in cerebral cavernous malformations - a retrospective analysis.

Objective: We compare the clinical and radiological outcome in patients with cerebral cavernous malformations (CCMs), treated with Gamma Knife radiosurgery to the natural course / conservative management.

 

Methods: A retrospective analysis of all patients with CCMs, who had been treated conservatively or radiosurgically between 1980 and 2019 at the Medical University of Vienna, was performed.

 

Results: In total, 102 patients were treated radiosurgically, while 536 patients were managed conservatively. We present clinical and radiological data. Clinical data, hemorrhage risk and clinical outcome of the radiosurgery group is compared to the natural course / conservative management.

 

Conclusion: Gamma Knife radiosurgery represents a safe and effective treatment option for CCM.


Anna CHO (Vienna, Austria), Paul KRACHSBERGER, Shivam PALIWAL, Olga CIOBANU-CARAUS, Philipp GOEBL, Dorian HIRSCHMANN, Brigitte GATTERBAUER, Christian DORFER, Josa M. FRISCHER
00:00 - 00:00 #30159 - P091 Dose-staged radiosurgery for large arteriovenous malformations.
P091 Dose-staged radiosurgery for large arteriovenous malformations.

Objective: The modern tactic of treatment of cerebral arteriovenous malformations (AVMs) involves an integrated approach with the use of methods of microsurgery, embolization, and stereotactic radiosurgery (SRS). Single fractional SRS is the standard for radiosurgical treatment of AVMs. However, in cases of large AVMs (>10 cc), especially those located in eloquent areas of the brain, the high single doses (18-24 Gy) required to obliterate the AVM may not always be delivered safely. Dose-Staged radiosurgery for large AVMs can reduce radiation exposure to critical structures while maintaining a high level of AVM obliteration after radiosurgery. The work aims to evaluate the safety and efficacy of dose-staged SRS for large AVM based on our clinical experience.

 

Methods: We prospectively followed 8 patients (3 women and 5 men) with large AVM (>10 cc) who underwent dose-staged hypofractinated radiosurgery using the CyberKnife M6 (Accuray Inc., Sunnyvale, CA) at the Sigulda Hospital Centre of Stereotactic Radiosurgery since 2016. The mean age of the study group was 36,6 [range 30,1 - 50 years], 6 patients had a history of the previous hemorrhage from AVM. 6 patients had endovascular obliteration of AVM before SRS using ethylene-vinyl alcohol copolymer Onyx, but an incomplete shutdown of the nidus or recanalization was further determined. 7 patients had headaches, 6 - seizures, 4 patients had sensory and motor deficiency. Hypofractinated SRS in dose 22-27 Gy (71-80% isodose) was administered. 6 patients had a total dose 24 Gy in 2 fractions, 1 patient had a total dose 22 Gy in 2 fractions and 1 patient had 27 Gy in 3 fractions.

 Results: All patients undergo magnetic resonance imaging (MRI) and MRI angiography in 6, 12, 24 months after the treatment. Digital subtraction angiography (DSA) was performed for 6 patients, who were more than 24 months after SRS. 4 patients after dose-staged hypofractinated SRS had signs of obliteration of AVM. The clinical condition of all patients was stable, no one had signs of post-radiation toxicity grade 2-3. 1 patient had signs of repeated bleeding from AVM 6 months after treatment.

Conclusions: Dose-staged SRS for large AVMs, especially located in eloquent zones is safe, in terms of post-radiation toxicity. However, the assessment of statistically reliable levels of obliteration requires further observation and research.

 


Vladyslav BURYK (Sigulda, Latvia), Maris MEZECKIS, Sandra LEDINA
00:00 - 00:00 #30161 - P092 Dose to the trigeminal nerve predicts risk of trigeminal neuropathy in patients receiving gamma knife stereotactic radiosurgery for vestibular schwannoma.
P092 Dose to the trigeminal nerve predicts risk of trigeminal neuropathy in patients receiving gamma knife stereotactic radiosurgery for vestibular schwannoma.

Objectives 

To validate dosimetric and clinical predictors of the development of trigeminal neuropathy (TN) in patients treated with stereotactic radiosurgery (SRS) for a diagnosis of vestibular schwannoma (VS). 

Methods

Prospective data collection on all patients treated at a single centre with SRS for VS between April 2013-June 2020, with 3 month then annual follow up year 1-3 then at year 5 and 10.  Subjective and objective parasthesia and pain were recorded at each clinical review.  Excluded those with less than 1 year of follow up or pre-existing TN. Treatment plan dosimetry relating to dose to cisternal part of trigeminal nerve, brainstem and tumour volume were recorded. Mann U Whitney was used to evaluate the link between the variables and the risk of TN at time of last follow up. Receiver operating characteristics were plotted and threshold analysis performed.

Results

301 patients were treated during the time frame.  97 were excluded due to trigeminal symptoms at time of SRS or insufficient follow up. 204 patients treated with average 12.5GY to 50% isodose with gamma knife perfexion/Icon, had an average follow up of 3.01 years with 25% >5 years follow up. 24 developed symptoms of TN developed after SRS, transitory in 7 cases. 

The volume of the Vth nerve receiving at least 11Gy, the maximum dose to the cisternal portion of the Vth nerve and tumour volume are predictive factors in development of TN with p values of 0.020, 0.011 and 0.041 respectively (see table).

Threshold analysis showed a maximum dose to the Vth nerve of 11.15Gy (see figure) and of 1.5mm3 for the volume receiving ≥11Gy, beyond which trigeminal neuropathy is more likely.

Conclusions

To minimise the risk of development of TN the maximum dose to the Vth nerve should be kept <11Gy. In cases where this is not achievable minimising the volume of the nerve receiving ≥11Gy is important. To reduce the risk of this side effect we advocate treating vestibular schwannomas when there is still a gap to the trigeminal nerve in order to achieve these dosimetric parameters. 


Louise WADE, Rachael WAIN, Alison L CAMERON (Bristol, United Kingdom)
00:00 - 00:00 #30172 - P093 Paragangliomas: Results of 32 patients submitted to radiosurgery and followed for a minumun of 60 months.
P093 Paragangliomas: Results of 32 patients submitted to radiosurgery and followed for a minumun of 60 months.

Paragangliomas, also called glomus tumors, are rare neuroendocrine tumors arising from paraganglia, and given the morbidity and mortality associated with surgical treatment, is a great challenge for Neurosurgery. The use of Radiosurgery has gained a lot of space in recent years, with excellent results, but the lack of long-term follow-up still left in doubt its effectivenes.

OBJECTIVE: To present the results of local lesion control and toxicity in a series of patients undergoing treatment with exclusive use of focal ionizing radiation, be it Radiosurgery (RS), Fractionated Stereotactic Radiotherapy (FSRxT) or Hypofractionated Stereotactic Radiotherapy (HFSRxT) and who were followed for a minimum of 60 months after treatment.


MATERIAL AND METHODS: A retrospective analysis in the medical records of our hospital, selecting patients with intracranial Paragangliomas who underwent SR, FSRxT or HSRxT) between 2000 and 2017. A Linear Accelerator (LINAC) was used associated with Micro-Multileaf collimators and dedicated software. To enter the study, these patients had a minimum follow-up of 60 months. We evaluated local control as well as treatment toxicity.

RESULTS: Among 2758 patients treated, 32 patients were selected. With a mean follow-up of 85 months, 68% of patients had a reduction of the lesion when compared to treatment and 32% maintained stability of the lesion. No patient followed had progression of the disease, but 1,  that had bilateral lesion, and the untreated lesion progressed 3 years later, when it was treated there and subsequently reduced its volume. No patient presented clinical worsening associated with toxicity in the brain tissue or cranial nerves involved.

CONCLUSION: Treatment with the use of focal ionizing radiation, whether SR, FSRxT or HSRxT, is an extremely safe and effective procedure in the management of paragangliomas regardless of their volume. Even in giant tumors should be the first therapeutic option and surgery should be limited to selected cases


Alice Jardim ZACCARIOTTI, Vladimir ZACCARIOTTI (GOIÂNIA, Brazil), João ARRUDA, Nilceana AIRES, Jean PAIVA, Flamarion GOULART
00:00 - 00:00 #30173 - P094 Automatic planning (Lightning) evaluation for Gamma Knife radiosurgery for AVMs: Comparison with Manual planning and IntuitivePlan inverse planning.
P094 Automatic planning (Lightning) evaluation for Gamma Knife radiosurgery for AVMs: Comparison with Manual planning and IntuitivePlan inverse planning.

Introduction

Lightning is a novel optimizer based on a linear programming solution for Gamma Knife treatment planning. We wanted to compare planning results between manual plans created by expert users, a competing commercial optimiser (IntuitivePlan) and Lightning for a series of arteriovenous malformations (AVMs).

 

Methods and Materials

20 consecutively treated AVM patients were selected and their manually created clinical treatment plans were used as the basis of this study. Replanning was performed using IntuitivePlan1 and Lightning. Lightning plans were optimised by varying low dose/beam on time weighting. Plan quality indices including coverage, selectivity, Paddick conformity index (PCI). Gradient Index (GI) and Efficiency Indices (EI) were compared and analysed to determine if a superior method of planning existed. Planning, beam on times and the number of isocentres were also noted. The difference in each parameter between one method over another was determined by a two-tailed t-test and was considered significant for p-values of <0.05. 

 

Results

Planning time was significantly lower when using the Lightning optimizer than other techniques, 1.0 vs 11.6 min, P<10-6 (Lightning vs Manual) and 1.0 vs 3.8 min, P<10-6 (Lightning vs IP). Lightning plans had higher Selectivity, PCI and lower GI than manual plans but these differences were not statistically significant.

 

Conclusion

Lightning can produce high quality plans for AVMs in a significantly shorter time and in some cases the quality metrics are better compared to manual plans created by expert planners.

 

References

1.     I Paddick, D Grishchuk, A Dimitriadis: IntuitivePlan inverse planning performance evaluation for Gamma Knife radiosurgery of AVMs. Journal of Applied Clinical Medical Physics 21 (9), 90-95


Ian PADDICK (London, United Kingdom), Diana GRISHCHUK, Anna KARANATSIOU
00:00 - 00:00 #30176 - P095 Hypofractionated Gamma Knife Icon radiosurgery for tumors close to the optic pathways: preliminary experience.
P095 Hypofractionated Gamma Knife Icon radiosurgery for tumors close to the optic pathways: preliminary experience.

Gamma Knife radiosurgery (GKRS) is the standard of single fraction high-dose irradiation of relatively small brain lesion. Despite the steep radiation dose gradient inherent to the GKRS treatment, eloquent structures that lie within 2 mm of the traditional single-session high-dose radiation target are at risk. This may represent a problem for the treatment of large benign tumor close to the optic pathways. Hypofractionation has the advantage of achieving a desired therapeutic effect with a tolerable dose of radiation to the optic apparatus, but it’s not very comfortable for the patient to perform a multisession treatment with the stereotaxic frame. Leksell Gamma Knife Icon makes it possible to overcome the problem of holding the frame, without however the accuracy of the latter.

In order to evaluating the efficacy and safety of treatment by repositioning with Gamma Knife Icon, we reviewed our case series, analyzing the clinical and radiological outcome of all patients treated in a frameless modality from September 2017 to December 2020.

Patients with benign perioptic lesion, including skull base meningiomas, pituitary adenomas and craniopharingioma treated with Gamma Knife Icon were included. For each patient we collected demographic and clinical data, as well as radiological imaging. Pre- treatment volumes have been calculated using the Leksell Gamma Plan Treatment Planning System, as well as the treatment plan. For clinical follow up we evaluated the onset of visual disturbances (both of the visual and of the visual field); moreover we evaluate radiological follow up.

We collected a total of 78 patients (59 female and 19 male) with a mean age of 60,8 years (from 38 yrs to 85 yrs). The most frequent lesion are meningiomas (64 patients), followed by 11 patients with pituitary adenomas, 2 patients with craniopharingiomas and 1 patient with solitary fibrous tumor. The average tumor volume was 5,136 cm3. 27 patients (34,6 %) presesented neurological symptoms at the time of treatment and pre-existing disorders mainly included diplopia and visual disturbance. Of these 27 patients, only 3 had a worsening of previous symptoms, in particular in one case there was a worsening of diplopia and in two patients a slight worsening of campimetric deficit. None of the asymptomatic patients developed post GKRS neurological disorders. At a mean follow-up of two years, all patients presented radiological stability of the treated lesions.

In this preliminary report, hypofractionation with Gamma Knife Icon represents a good option for tumors close to the optic pathway.


Alberto FRANZIN (Brescia, Italy), Karol MIGLIORATI, Lodoviga GIUDICE, Giorgio SPATOLA, Chiara BASSETTI, Cesare GIORGI, Corrado D'ARRIGO, Oscar VIVALDI, Mario BIGNARDI
00:00 - 00:00 #30186 - P096 Linear accelerator- based radiosurgery results for Von Hippel-Lindau associated central nervous system hemangioblastomas.
P096 Linear accelerator- based radiosurgery results for Von Hippel-Lindau associated central nervous system hemangioblastomas.

Introduction: Hemangioblastomas are benign slow-growth vascular tumors that may appear sporadic or in association with von Hippel-Lindau disease. Sporadic forms are described as solitary tumors, while multi-tumor presentation is a suspicion criterion for VHL. Surgery is the gold standard treatment, nevertheless, in situations of multiple disease as in VHL, the optimal timing of procedure for hemangioblastoma patients is uncertain. Due to the multiple lesions and diverse location of VHL associated hemangioblastomas, the high morbidity of surgical reinterventions and the difficult location of the lesions, the use of stereotactic radiosurgery has been proposed as an effective strategy during the multimodal management of hemangioblastomas, considered as a safe alternative, when recurrent surgery represents high morbidity, for lesions located at inaccessible structures, or in multiple lesions. The purpose of the study is to describe the clinical results of VHL associated CNS hemangioblastomas treated with Linear accelerator-based radiosurgery, with the relevance up of being the first study using exclusively a Linear accelerator platform.

Methods: Case series nested in a retrospective cohort of patients diagnosed with CNS hemangioblastomas treated with radiosurgery at Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez with LINAC The data base was reviewed from January 2016 to December 2020. We included 21 patients with the diagnosis of SNC hemangioblastoma associated to VHL disease. Those patients without MRI follow-up were eliminated. We studied the characteristics of the hemangioblastomas including the location, volume, number of lesions, the clinical response according to RECIST criteria, and the performance status according to Karnofsky Performance Status Scale.

Results: After the exclusion, 19 patients were studied, 13 women and 6 men with a mean age of 37.2 years and a total cumulated tumoral lesions of 43 which 85.7% were located on cerebellum. The mean tumoral size was 2.68 cm3. The median radiosurgery dose was 18 Gy for VHL patients and 16 Gys for sporadic hemangioblastomas. A complete clinical response was observed in 11.4%, a partial clinical response was registered in 13.6%, 68.2% noted a stable disease, and 6.8% had disease progression of the irradiated lesions.

Conclusion: Radiosurgery treatment represents a safe option with an impact in the disease statism and free-progression survival.

 


Gabriel Alejandro CONTRERAS PALAFOX (Ciudad de Mexico, Mexico), Juan Carlos HEREDIA GUTIÉRREZ, Alejandro RODRIGUEZ - CAMACHO, Sergio MORENO JIMENEZ, Guillermo Axayacalt GUTIÉRREZ ACEVES
00:00 - 00:00 #30207 - P097 Long-term tumor control of benign intracranial meningiomas after radiosurgery in a series of 4565 patients.
P097 Long-term tumor control of benign intracranial meningiomas after radiosurgery in a series of 4565 patients.

OBJECTIVE: Radiosurgery is the main alternative to microsurgical resection for benign meningiomas. Aim is to assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published.

METHODS: From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author

RESULTS: Median tumor volume was 4.8 cm3, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up < 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P< .001), for female vs male patients (P < .001), for sporadic vs multiple meningiomas (P< .001), and for skull base vs convexity tumors (P < .001). Permanent morbidity rate was 6.6% at the last follow-up. 

CONCLUSION: Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.

 


Santacroce ANTONIO (Munich, Germany)
00:00 - 00:00 #30209 - P098 Primary Gamma Knife Radiosurgery for Cystic Vestibular Schwannomas: Myths busted.
P098 Primary Gamma Knife Radiosurgery for Cystic Vestibular Schwannomas: Myths busted.

Cystic Vestibular Schwannomas (VSc) have shown variable response to Gamma knife Radiosurgery (GKRS). Despite few papers in the recent past, there is a reluctance in offering GKRS to these VSc as a first line of treatment. We aimed to review our patients of VSc who had been treated primarily with GKRS and analyse the factors helpful in predicting better response. Methodology: The patients of VSc who were treated primarily with GKRS from the years 2014-2019 with a minimum follow up of 2 years were assessed and divided into 2 groups based on the relative cyst diameter with respect to the total tumor Diameter. All the factors pertaining to tumor character and GKRS delivered were analysed and appropriate statistical analysis carried out. The Artificial Neural Network analysis was run to find out the factors which support better tumor outcome post GKRS. Results will be discussed.

Conclusion: VSc form a heterogenous group of tumors who respond differently with GKRS. They are surgically very challenging when compared to predominantly solid tumors because of the adherence of the 7th and 8th neural complex. Analysing the factors that influence the outcome will help us select appropriate patients for surgery versus GKRS procedure.


Sunder KRISHNA, Shweta KEDIA (New Delhi, India), Shashank KALE, Rajinder THAYLLING, Manmohan SINGH, Deepak AGARWAL

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03. Eposters - Brain - Functional & Others

00:00 - 00:00 #28912 - P099 Radioneuromodulation for pain.
P099 Radioneuromodulation for pain.

Introduction.

In refractory pain especially patients experimenting a severe pain crisis, treatment to time response is of an essence. Typically, intracranial radiosurgery for functional indications is though to function in most patients in a delayed fashion taking as much as 3 months.  

Radioneuromodulation could explain the immediate pain relief experienced by a subgroup of patients after stereotactic radiosurgery (SRS) for trigeminal neuralgia or pain derived from extensive bone metastases in terminally ill oncological patients.

Ideally radioneuromodulation would be consistent, prompt in alleviating pain, and a long-lasting alteration of neuronal activity achieved by a precisely targeted sub-necrotic dose in pain centers or pathways in the brain.

Methods.

We reviewed our case series of patients experimenting pain crisis (10/10) in refractory trigeminal neuralgia treated with multitarget radiosurgery by irradiation of the affected nerve and contralateral centromedian nucleus (CM) and perifascicular complex (Pfc) area, and our series of patients of oncological pain that received radiosurgery to the hypophysis.

Results.

For those with non-oncological pain 9 patients were treated 8 (88.8%) achieved an equal or greater than 50% pain relief at 48 hours the remaining patient achieved it at 10 days (Glossopharyngeal neuralgia). The doses for the first 7 patients were 90 Gy in the nerve and 140 Gy in the thalamus, for the last 2 patients’ doses were lowered to 80 Gy to the nerve and 120 Gy in the thalamus. At 3 months pain relief was 70% (50 to 100%). For oncological pain 16 patients were treated with irradiation of the hypophysis with 130-150 Gy, 13 (81%) had a pain relief of at least 50% or more at a mean of 2.8 days (1-5), 4 (33%) died without substantial pain, most 6 (46.1%) had substantial pain days before there death and 3 (23%) had substantial pain weeks (2) before there death. Under both protocols there were no adverse events to report.

Conclusions.

Multitarget radiosurgery for pain crisis in trigeminal pain is a proof of concept that its beneficial effect is consistent in achieving prompt pain relief (<72hrs) in most patients. Irradiation of the hypophysis for terminally ill patients with pain from bone metastases is known to be consistent in obtaining a quick pain response, irradiation of the body’s main hormonal gland might mediate a radio-endocrine-neuromodulatory effect, nevertheless radioneuromodulation possibly is a promising concept that needs to be studied to understand the doses necessary to be effective while being in the sub-necrotic ranges.


Eduardo LOVO (San Salvador, El Salvador), Alejandra MOREIRA, Fidel CAMPOS, Victor CACEROS, Juan ARIAS ROSA, Claudia CRUZ
00:00 - 00:00 #29334 - P101 Image-guided LINAC radiosurgery for hypothalamic hamartomas.
P101 Image-guided LINAC radiosurgery for hypothalamic hamartomas.

Image-guided frameless robotic LINAC radiosurgery was recently reported as an effective  early treatment option for children with catastrophic epilepsy induced by hypothalamic hamartomas.

A larger treatment cohort is presented here, including 10 HH patients treated with Cyberknife radiosurgery.All the patients received a single treatment, except one requiring a second treatment . All patients underwent single-fraction image-guided robotic radiosurgery using the Cyberknife. Mean age at the time of treatment was 26,1 y( median: 22 y). Mean treatment volume was 0,64 cc( median: 0,61 cc). Mean prescribed dose was 16,27 Gy( median 16 Gy). Mean prescription isodose was 76% ( median: 79%). Mean average dose delivered to the target was 18,89 Gy( median: 18,31 Gy). Mean Maximum dose was 21,53 Gy(median: 20,51 Gy).

 Currently, 8 patients out of 10 ( 80%) experience complete ( Engel class I) or near complete ( Engel class II) seizure freedom , one patient has a reduction of seizure burden superior to 50%( thus being in the Engel class III) and one patient has experinced no benefit ( Engel class IV) . Four patients ( average age 13,5 y, average seizure duration 6,5 years) achieved complete seizure control within 4 to 18 months after the treatment(Engel I).  Four patients( average age 40,7 y, average seizure duration 32,7 y)  achieved Engel class II outcome.This group required 12 to 36 months to develop improved seizure outcomes. One patient developed Engel class III outcome after being temporarily classified in class II . One patient experienced no seizure improvement and refused any further treatment. This failure is likely explained by the presence of a small intrahypothalamic post-surgical residual not included in the target volume. 

Two patients temporarily classified as a class I 1 year after the treatment  experienced seizure relapse (however preserving a better seizure control in comparison to baseline ). One underwent reirradiation using the same dose and volume as first treatment achieving stable Engel class I outcome. The other is currently in class II.  Major neuropsychological improvement was experienced by the 5 patients with Engel I outcome, while 4 more patients reported an improvement in the overall quality of life, daily performances and sleep. No neurological complications have been found. 

 

Overall image-guided LINAC radiosurgery using the Cyberknife proved to be safe and effective for the treatment of seizures induced by hypothalamic hamartomas.Treatment of younger patient with shorter seizure history appears to provide better seizure outcomes.

 


Pantaleo ROMANELLI, Giancarlo BELTRAMO, Livia BIANCHI, Alfredo CONTI (Bologna, Italy)
00:00 - 00:00 #29407 - P102 Hypofractionation Gamma Knife Radiosurgery for Hemangioma.
P102 Hypofractionation Gamma Knife Radiosurgery for Hemangioma.

Objective:

Demonstrate the efficacy and safety of hypofractionated treatment with maximum dose of 50Gy for adequate hemangioma volume reduction with optic apparatus protection.

 

Method:

Retrospective analysis of 3 cases of hemangiomas treated with multiple session GKRS and evaluation of maximal tumor and optic apparatus doses, volume response and symptomatology.

 

Case 1:

64 yo man with progressive left vision loss, MRI showing a 2.157cm3 mass at posterior medial intra-orbital extending to the apex. A 5 fraction GKRS with total of 25Gy, at 50% isodose line, and gradient index of 2.8. Maximum optic dose was 22Gy with a mean of 9.1Gy. Follow-up scans at two, five, ten and sixteen months showed a volumetric decrease of 16, 25, 47 and 72,5% respectively, with no evidence of adverse radiation effect and stabilization of the visual acuity.

 

 

Case 2:

40 yo woman with scotomas and blurry vision. MRI showed a right sided intraorbital, extra-ocular mass with total entrapment of the optic nerve. Biopsy confirmed cavernous hemangioma. Patient progressed with right amaurosis. GKRS with 25 Gy at 54% isodose line in 5 fractions. Maximal tumor dose was 46.3Gy, due to tumoral involvement to the nerve, no optic protection was possible. Follow-up scans at 2, 4, 12 and 15 months showed a volumetric reduction of 59%, 76%, 90% and 89%, respectively, with the patient reporting identification of luminous stimulus, but no functional vision.

 

Case 3:

77 yo woman with worsening proptosis presented on MRI an enhancing lesion on the lateral orbital wall without compression of the optic nerve. Single session GKRS was performed prescribing 12 Gy of marginal dose at 51% isodose line, with maximal tumor dose of 23.5Gy and gradient index of 2.49. Maximum optic dose was 3.9 Gy with mean of 1.5. The 1-month follow-up scan showed a 3% increase in volume and the 5-month FU had 8% increase. A new GKRS treatment was performed in a single session with 15 Gy at 56% isodose line. Cumulative total tumor dose was 50.2 Gy, and a maximal cumulative dose to the optic nerve of 7.2Gy with mean of 4.3. The lesion presented at 6 and 9 months 17.4 and 24% decrease. Patient had no visual complains during the folow-up and proptosis completely resolved.

 

Conclusion:

 

The maximal dose < 25Gy was insufficient to treat this kind of lesion, but a maximum dose close to 50Gy in multiple session had adequate tumor reduction and optic apparatus protection.


Victor GOULENKO, Dheerendra PRASAD (Buffalo, NY, USA), Robert PLUNKETT, Kenneth SNYDER
00:00 - 00:00 #29474 - P103 Leksell gamma knife hypophysectomy impact on cancer-related intractable pain.
P103 Leksell gamma knife hypophysectomy impact on cancer-related intractable pain.

Introduction:

Hypophysectomy is a method used in analgesia in patients with painfull bone metastases. The pain relief after this procedure is not pathophysiologically fully understood but the stimulation of hypothalamic non-opioid pain suppression system is prefered theory nowadays. Firstly this procedure was performed by classical transsphenoidal surgical approach or stereotactic thermocoagulation. In only a few studies Leksell gamma knife (LGK) was used for radiosurgical hypophysectomy. This single-centre study aimed to evaluate the effect and safety of the LGK hypophysectomy in a patient with malignant disease suffering from intractable cancer-related pain.

 

Methods:

From 1996 to 2019 we enrolled 19 patients (11F), mean age 59,4 years with the diagnosis of disseminated carcinoma included breast cancer (41%), prostate cancer (23%), lung cancer(18%), kidney cancer (6%), laryngeal cancer (6%) and rectal cancer (6%). All patients underwent radiosurgical hypophysectomy on LGK (model C and Perfexion). The prescription dose was 75-100Gy on 50% isodose line, the maximal dose on the optic pathways was 8-12Gy. 

 

Results:

The effect of radiosurgical hypophysectomy on pain relief was evaluated in nine patients. In the rest 10 patients, the evaluation was not possible due to bad clinical status (Karnofsky < 60%), they did not come for a visit or they died in consequence of the malignant disease before the effect onset which was from 2 to 4 weeks. In all evaluated patients pain relief was achieved (0-60% of pre-procedural pain). The effect of the hypophysectomy was lasting for the rest of their lives (the mean follow-up period was 14 months). In two patients we observed a side effect - hypocortisolism and diabetes insipidus with good response on substitutional therapy. No other adverse events were observed.

 

Conclusion:

Our results suggest that the LGK hypophysectomy is permanently effective and safe procedure to reduce a cancer-related intractable pain especially in bone metastases of hormonally active tumours.


Jaromir MAY (Prague, Czech Republic), Dusan URGOSIK, Roman LISCAK
00:00 - 00:00 #29896 - P104 Gamma knife Radiosurgery for Third Ventricular Colloid Cysts.
P104 Gamma knife Radiosurgery for Third Ventricular Colloid Cysts.

Background: Colloid cysts often occur in the third ventricle, and they are considered benign slowly growing lesions. They commonly present with symptoms of intracranial hypertension and rarely sudden death due to acute hydrocephalus. Management options include cerebrospinal fluid diversion procedure by shunt, endoscopic or transcranial surgical excision and stereotactic aspiration. Complications associated with excisional procedures make them undesirable to some patients. Stereotactic radiosurgery has emerged as a non-invasive less risky treatment option. To date, there is no clinical series in literature reporting on this treatment modality.

 

Objective: To determine the efficacy and safety of gamma knife radiosurgery in the treatment of third ventricular colloid cysts.

 

Patients and methods

This is a retrospective study involving eleven patients with third ventricular colloid cysts that underwent gamma knife radiosurgery. Gamma knife radiosurgery was used as a primary treatment in all the patients.  The median prescription dose was 12 Gy (11-12 Gy). The tumor volumes ranged from 0.2 to 10 cc (median 1.6 cc).

 

Results

The median follow up was 50 months (18-108 months). Tumor control was achieved in 100% of the patients. Complete or partial response was observed in 10 patients (91%). Six patients (55%) had hydrocephalus on imaging at initial diagnosis. Four of these patients had VP shunt insertion before GK. Two patients required shunt insertion after GK.

 

Conclusion

GK for third ventricular colloid cysts is a promising treatment, as regards efficacy and safety, to be added to other treatment options. A longer follow up is required to confirm long-term control.


Khaled ABDEL KARIM (Cairo, Egypt), Amr ELSHEHABY, Wael A REDA, Reem EMAD ELDIN, Ahmed NABEEL, Sameh ROSHDY
00:00 - 00:00 #29901 - P105 Epileptic encephalopathies secondary to hypothalamic hamartomas treated with radiosurgery: case series.
P105 Epileptic encephalopathies secondary to hypothalamic hamartomas treated with radiosurgery: case series.

Introduction:

Hypothalamic hamartomas are congenital lesions that typically present with gelastic seizures, refractory epilepsy, neurodevelopmental delay and severe cognitive impairment. Open/endoscopic surgical procedures to remove/disconnect the hamartoma have been reported to be effective, but are associated with significant morbimortality, therefore not considered as a therapeutic modality. Robotic radiosurgery (CyberKnife®) is an emerging alternative with few side effects in the management of these lesions. 

Patients & methods:

Five patients with refractory epilepsy and epileptic encephalopathies secondary to hypothalamic hamartomas who completed radiosurgery (CyberKnife®) are presented. Describing lesional characteristics, seizure semiology, antiepileptic treatments, radiation protocols, electroencephalographic abnormalities, seizure control and neurocognitive outcomes. 

Results:

Hypothalamic hamartomas were defined based on neuroimaging studies. In one patient a biopsy reported gliotic white and gray matter with disorganized mature-looking neurons with thick-walled vessels. Semiology revealed predominantly non-motor focal onset aware emotional (gelastic) seizures. All patients met pharmacoresistance criteria. All patients received ~17 Gy as a single fraction except in one requiring 5 fractions. Electroencephalography revealed severe abnormalities including high voltage delta activity and interictal focal epileptiform discharges. After 24 months of follow-up, one patient remained free of disabling seizures with convulsions with antiepileptics discontinuation only (Engel class Id) and one patient persisted only with rare disabling seizures (Engel Class IIa). After 16 months, one patient remained free of disabling seizures with convulsions with antiepileptics discontinuation only. After 12 months, one patient was seizure free and after 8 months one patient remained free of disabling seizures with convulsions with antiepileptics discontinuation only. All patients exhibited generalized cognitive alterations in attention, memory, language, praxis, gnosis, executive functions, with poor adaptive skills and marked behavioral difficulties, Four patients presented moderate cognitive disability and one had a borderline cognitive ability.  In patients evaluated before and after radiosurgery, one presented improvement in gnostic-practical abilities, slight improvement in language, attention and memory. Another patient presented a slight improvement in his adaptive abilities.

Discussion:

The cases described are consistent with previous reports showing favorable results with the use of radiosurgery regarding seizure frequency reduction. However, no marked improvement in neurocognitive function was observed, thus further studies are required.

Conclusion:

Radiosurgery (Cyberknife®) should be considered as the first line non-invasive treatment for epileptogenic hypothalamic hamartomas not amenable to microsurgical resection due to an adequate seizure control, a requirement of lower doses of antiepileptics and few side effects related to this procedure. Although more studies are still required, this may be a good management option.


Esteban JARAMILLO-JIMÉNEZ, Esteban JARAMILLO-JIMÉNEZ (Medellín, Colombia), Juliana SANDOVAL-BARRIOS, Fergus John WALSH, Maria Clara JARAMILLO-JIMÉNEZ, Simón PÉREZ-LÓPEZ, Juan David ECHEVERRI-SÁNCHEZ, Hernán Darío BARRIENTOS-MONTOYA, José Luis ASCENCIO-LANCHEROS, John Freddy GIRALDO-PALACIO, Iván Manuel SIERRA-ARRIETA, David Ignacio GÓMEZ-DUQUE, Iader Alfonso RODRÍGUEZ-MÁRQUEZ
00:00 - 00:00 #29947 - P106 Choroid plexus papilloma in a adult: case report.
P106 Choroid plexus papilloma in a adult: case report.

Objetive: Chroroid plexus tumors are a rare intraventricular neoplasm originating from choroid plexus that account for only 0.3-0.6% of all intracranial tumors. These tumors are seen more frequently in children, especially in first two years of life with an incidence of 1.5-4% in this age group. The mayority of the tumors are benign choroid plexus papilloma WHO grade I. Here we report a case of choroid plexus papilloma in an adult patient and his treatment.

Methods: A 39-year-old man was admitted to the neurosurgery department of his hospital for a headache, gaze shift to the left, and disorientation. By computed tomography and magnetic resonance imaging in January / 2020, a tumor in the third ventricle directed to the mesencephalon with a cystic component was reported compatible with choroid plexus papilloma of 21x26x22mm. Due to the location and restriction of surgical treatments due to the COVID19 pandemic, he was sent for radiotherapy evaluation. Treatment with stereotactic radiosurgery was decided in our department 12 Gy in 1 fraction in a volume at PTV of 11.25cc with a prescription at 100% of the dose, coverage of 98.3% at GTV in 31th July 2020. Surveillance was maintained through imaging studies.

Results: By magnetic resonance imaging of July 23, 2021, 12 months after having indicated the treatment, no tumor data was reported, although clinically even with mild persistence of dizziness, achieving a complete answer.

Conclusion: Choroid plexus papillomas are rare, benign tumors originating from choroid plexus. Although its initial treatment has been established surgical resection, it cannot always be achieved due to the location, conditions of the patient, or in this case indirect reasons such as space limitation due to Pandemic. In this case, radiosurgery was indicated as initial treatment, achieving a complete response at 12 months, so we verified that radiosurgery can be used as initial treatment in early stages and in locations that are not susceptible to resection.


Victor Javier VAZQUEZ ZAMORA (puebla, Mexico)
00:00 - 00:00 #29950 - P107 - WITHDRAWN - Immobilizing The Jaw During Stereotactic Radiosurgery For Lesions Extending Beyond Temporomandibular Joint: An Avant-Grade Approach For A Quick, Reversible, Non-Invasive, Radiolucent And Reliable Fixation.
P107 - WITHDRAWN - Immobilizing The Jaw During Stereotactic Radiosurgery For Lesions Extending Beyond Temporomandibular Joint: An Avant-Grade Approach For A Quick, Reversible, Non-Invasive, Radiolucent And Reliable Fixation.

Background: Jaw immobilization is required for patients undergoing Gamma Knife Radiosurgery (GKRS) for extracranial lesions involving potentially mobile regions such as the temporomandibular joints (TMJ), the parapharyngeal spaces, and the craniocervical junction. Literature reports intermaxillary fixation with titanium screws in the maxilla and mandible to immobilize TMJ. But the invasive nature of the procedure and the metal artifacts are often a deterrent. 

Methods: The authors describe a novel method of jaw immobilization with intermaxillary elastics on non-metallic aesthetics brackets while maintaining precision and accuracy in a patient of trigeminal schwannoma extending beyond TMJ. 12 brackets were applied on incisors and premolars of both upper and lower jaw. Orthodontic elastics generated sufficient tension for jaw immobilization. The lesion was treated in two fractions with hypofractionated GKRS.

Results: The two fraction treatment could be performed without need of any anesthesia. The patient remained comfortable throughout the procedure and could take food in the interfraction period. 

Conclusion:  Orthodontic brackets and elastics are a quick, reversible, non-Invasive, radiolucent, repeatable,  and reliable fixation to facilitate lesions extending beyond TMJ while maintaining the precision and accuracy of GKRS. 


Manjul TRIPATHI (Chandigarh, India)
00:00 - 00:00 #29951 - P108 - WITHDRAWN - Safety and Efficacy of Primary Hypofractionated Gamma Knife Radiosurgery for Giant Hypothalamic Hamartoma in Pediatric Population.
P108 - WITHDRAWN - Safety and Efficacy of Primary Hypofractionated Gamma Knife Radiosurgery for Giant Hypothalamic Hamartoma in Pediatric Population.

Background: Giant hypothalamic hamartoma (HH) is a difficult to manage disorder with neurological, developmental, endocrinological, psychological, and social implications. 

Objective: Authors present outcome in three patients of giant HH, who underwent primary hypofractionated GKRS at a single institution, as a part of multidisciplinary management. Hypofractionated GKRS was chosen because of large size of the lesion (>Regis III), proximity to the optic apparatus, intractable seizures, and reluctance for any invasive surgical intervention.

Methods: In this prospective analysis, three pediatric patients (age range 17-65 months) were treated with primary hypofractionated GKRS in 2-3 consecutive days with interfraction interval of 24 hours. All patients had precocious puberty and were on GnRH analogue. Preoperative work up included neurological, endocrinological, and neuropsychological assessment. We treated patients with frame based GKRS with 8.1-9.2 Gy radiation per fraction at 50% isodose in 2-3 fractions. We targeted the entire hamartoma volume similar to tumor radiosurgery. The mean target volume was 5.67 cc (4.45-7.39 cc). The mean maximum point dose to the optic apparatus was 9.5 Gy (8.05-9.5Gy). We followed these patients for clinical and endocrinological assessment at every 6 months interval. We followed with repeat MRI at 6 months, one, two, and three years duration. The seizure outcome analysis was performed using seizure subtype and response to treatment evolving with the time with Engel scale. The patients were prospectively followed on pre-decided parameters. A comparison is done with contemporary alternative techniques. 

Results: At a mean follow up of 27 months (24-30), 2 patients became Engel class 3 while one achieved Engel class 1 control. 2 patients showed halted pubertal growth with no hormonal aberration. 2 patients showed significant volumetric reduction (48% and 32%) and patchy necrosis inside the HH. There was no deficit in visual function, memory, cognition, or any other complication. All patients showed shrinkage of hamartoma from optic chiasma. One patient showed reduction in aggressiveness.

Conclusion: Giant HH are exceptionally difficult neurological diseases. Primary hypofractionated GKRS may be an alternative approach as mono/multitherapy with promising results and minimal complication. 


Manjul TRIPATHI (Chandigarh, India)
00:00 - 00:00 #29998 - P109 Gamma Knife radiosurgery for trigeminal autonomic cephalalgias: preliminary results of a single-center study.
P109 Gamma Knife radiosurgery for trigeminal autonomic cephalalgias: preliminary results of a single-center study.

Background: Gamma Knife radiosurgery (GKRS) has been used for trigeminal autonomic cephalalgias (TACs). However, the outcomes of studies investigating GKRS for TACs in the literature are inconsistent, and the ideal target and treatment parameters remain unclear. The aim of this study is to investigate the safety and the efficacy of GKRS for the treatment of drug-resistant TACs.

 

Objective: To report on 9 patients who underwent GKRS-mediated ablation of the cisternal part of the trigeminal nerve and of the sphenopalatine ganglion for TACs.

 

Methods: We assessed 9 patients with TACs who were treated with GKRS ablation of the cisternal part of the trigeminal nerve and of the sphenopalatine ganglion. We recorded characteristics including facial pain distribution and autonomic features, changes in pain scores and complications.

 

Results: Patients were followed up for a median of 6 months (mean 11, range 3-44 months). Three patients with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), five patients with chronic cluster headache (CH) and one patient with paroxysmal hemicrania were treated with GKRS. All patients with SUNCT had complete pain relief. Four patients with CCH had considerable pain reduction; pain recurred in one at the 3-month follow-up assessment, and one patient developed bothersome facial paresthesia. The patient with paroxysmal hemicrania had complete pain relief. Autonomic features were improved in all patients except one with CCH.

 

Conclusions: GKRS is an effective treatment in patients with SUNCT and in some patients with chronic CH and paroxysmal hemicrania. Trigeminal sensory disturbances may occur over time in a subset of patients. Studies in larger groups of patients and with longer follow-up assessments are warranted.

 


Andrea FRANZINI, Elena CLERICI (, Italy), Pierina NAVARRIA, Pessina FEDERICO, Piero PICOZZI
00:00 - 00:00 #30022 - P110 Individualized options for surgery and gamma knife treatment of primary trigeminal neuralgia.
P110 Individualized options for surgery and gamma knife treatment of primary trigeminal neuralgia.

Objective To evaluate the efficacy and safety of microvascular decompression (MVD), MVD combined with partial sensory rhizotomy (PSR) and gamma knife surgery (GKS) for primary trigeminal neuralgia (PTN) as to explore the individualized surgical treatment of PTN. Methods A retrospective analysis was conducted to the pain-relief rate and complications of 187 PTN patients. Patients in MVD, MVD+PSR and GKS group were followed up for 36.84±12.06 months, 32.18±13.99 months and 32.97±12.79 months respectively. Results  The 187 patients were divided in three groups as 135 patients in MVD group, 30 in GKS group and 22 cases in MVD+PSR group. The efficacy latency in MVD was 1.4±0.8 days and 42.7±4.0 days in GKS group (P0.01). At the end-points, the effective rate of pain-relief was 95.45% (21/22) in MVD+PSR, 93.33% (126/135) in MVD and 90.00% (27/30) in GKS group without significant difference. The complete pain-free rates were 86.36% (19/22) in MVD+PSR, 73.33% (99/135) in MVD and 43.33% (13/30) in GKS group. That in MVD and MVD+PSR group were higher than in GKS (P<0.0167, 0.001). The sensory dysfunction was much higher in MVD+PSR group (100.00% : 20.00%, 14.07%; P<0.001, 0.001). Other complications was also more common in MVD+PSR group (36.36% : 6.67%, 4.44%; P <0.0167, <0.001). The recurrent pain occurred in 28 (14.97%) patients without significant difference. After adjustment, 89.28% patients achieved definite pain-relief. The satisfaction rate of patients was 85.93% in MVD, 80.00% in GKS and 68.18% in MVD+PSR group without significant difference. MVD group had higher full satisfaction rate (P<0.001, 0.001). Conclusion Both surgery and GKS are effective and similar for PTN. The GKS has a latency time anyway. Surgery has a higher rate of postoperative pain-free for PTN than GKS. The recurrence rate of surgery and GKS is low, and also similar in the mid-term follow-up, yet with a high pain-relief rate after medicine adjustment. ④The incidence of complications after MVD and GKS is low. MVD is preferred for those with definite neurovascular compression (NVC). GKS is preferred for those without NVC or obvious NVC, in older ages, intolerance, refuse invasive therapy, or select GKS. ⑦Because MVD+PSR have a high incidence of complication and low patient satisfaction, PSR is seldom recommended. And careful evaluation of the NVC is essential before operation.


Xiaoyue LI, Dongdong ZHAO, Bing LU, Liang CHEN, Haipeng PAN, Wen FENG, Yongsheng HE, Yongsheng HE (Chengdu, China)
00:00 - 00:00 #30042 - P111 Posterior cranial fossa myopericytoma treated with a combined microsurgery and stereotactic radiosurgery approach: case report and literature review.
P111 Posterior cranial fossa myopericytoma treated with a combined microsurgery and stereotactic radiosurgery approach: case report and literature review.

Background

Myopericytoma is a rare tumor deriving from the perivascular myoid cellular environment, it’s usually described in soft tissues of the extremities and closed to vascular structures; intracranial localization is even more unusual with only nine cases reported in literature. We describe the first combined treatment of a myopericytoma involving the central nervous system with microsurgery and Gamma Knife radiosurgery.

Case report

A 19 year-old female presented with worsening nuchal headache started one week before hospitalization. Computed tomography scan and subsequent magnetic resonance imaging showed a posterior cranial fossa well-circumscribed enhancing lesion attached to the right tentorial edge, radiologically suggestive for meningioma. She underwent gross total surgical excision through a retrosigmoid approach. Histopathology revealed a myopericytoma. At 3 months follow-up a tumor regrowth was found, with also supratentorial extension. In order to minimize the risks of a second surgical operation, Gamma Knife radiosurgery was performed obtaining a remarkable response, with no radiological evidence of residual tumor or recurrence 2 years after radiosurgery. The patient is neurologically asymptomatic.

Conclusions

Myopericytoma is a novel class of perivascular tumors, it has mostly a benign course and based on the actual literature, a gross total resection should be the mainstay of treatment, when achievable. Nowadays, no preoperative study can allow to myopericytoma diagnosis that depends on histological examination, since it can mimic meningioma or cerebrovascular malformations on imaging. Surgical resection combined with Gamma Knife radiosurgery may be considered for high-risk surgical residual or recurrent intracranial myopericytomas.


Riccardo LAVEZZO (Verona, Italy), Salima MAGRINI, Marta ROSSETTO, Irene COATI, Angelo Paolo DEI TOS, Matilde CAZZAGON, Nicola CAVASIN, Paolo Maria POLLONIATO, Anna D'AMICO, Michele LONGHI, Francesco SALA, Antonio NICOLATO
00:00 - 00:00 #30078 - P112 Stereotactic Ablative Radiotherapy (SABR) in pediatric patients: pioneering in Mexico.
P112 Stereotactic Ablative Radiotherapy (SABR) in pediatric patients: pioneering in Mexico.

INTRODUCTION

Pediatric cancer in Mexico continues to be a health problem with an average 5-year global survival rate of 60%. Solid tumors take third place behind leukemias/lymphomas and brain tumors, with localized advance staging found at the time of diagnosis in 2/3 of cases. The incidence of metastasis to the lung in this group of patients is found in 25% of the cases. Traditionally, surgery is the treatment of choice. However, we find patients with several resections or whose localization calls for pneumonectomy, which impacts on quality of life. 

The use of radiotherapy in general is omitted as far as possible in the pediatric population which is the reason that SBRT case reports is scarce.  

HYPOTHESIS

Pioneering institutional experience in SABR management of oligometastatic illness in pediatric populations in Mexico

MATERIAL AND METHODS

At the ABC Medical Center, between May 2019 and November 2021, we have treated 6 patients with diagnosis of stage IV oligometastatic sarcoma with a total of 8 treated lesions: lung (4), spine (4).  All were treated with SABR, Novalis Tx equipment with 18-60Gy/1-8 (fr) fractions.

RESULTS

Follow-up has been 6.5 months The average age of our population was 12 years (range 6-14), two female and 4 males.  The diagnoses were:  Ewing Sarcoma (3), adrenal carcinoma (1), Triton Tumor (1), carcinoid tumor (1).  The total doses used were 30Gy:  SRS technique 18 Gy/1fr. or 27Gy/3fr. and SBRT technique 30-50Gy/5fr. and 60 Gy/8fr. fractioning.  Tolerance of the treatment was good: no patient presented toxicity greater than 3-4 toxicity >grade 3-4.  Treatment response: 1 complete response, 4 partial response, 2 stables, 1 progression. Mean survival time was 17.3 months.

CONCLUSIONS

The use of SBRT is feasible and able to be reproduced in pediatric patients.  It is well tolerated, allows for less invasive management and has a positive impact on the quality of life of patients with oligometastatic tumors.


Dolores DE LA MATA (MEXICO CITY, Mexico), Catalina TENORIO, Guillermo A. GUTIERREZ ACEVES, Mariana HERNANDEZ-BOJORQUEZ, Sergio MORENO JIMENEZ
00:00 - 00:00 #30090 - P113 The safety and efficacy of vestibular schwannoma radiosurgery in patients with neurofibromatosis.
P113 The safety and efficacy of vestibular schwannoma radiosurgery in patients with neurofibromatosis.

Neurofibromatosis type 2 (NF-2) is a rare autosomal dominant genetic condition that predisposes to the development of neuroectodermal neoplasms among which bilateral vestibular schwannomas (VS). Radiosurgery is one of the possible treatment options in patient with  sporadic vestibular schwannoma (VS), though  it safety and efficacy in VS associated with NF-2 is unknown. In addition, the possible influence of radiosurgery on the development of deafness is discussed. In total, 56 patients with suspected NF-2, 23 males and 33 females, were enrolled into the study. The patients underwent clinical assessment and neuroimaging at Burdenko Neurosurgery Institute. DNA-diagnostic was included sequence analysis of NF2 gene and multiplex ligation-dependent probe amplification (MLPA) analysis for deletion and duplication detection. Age of patients at onset ranged from 2 to 32 years (MED = 18 years, IQR = 8.5).

Vestibular schwannoma was first symptomatic tumour in 28 cases, non-vestibular schwannoma, including spinal tumour in 8 cases, meningioma in 17 cases, ependymoma in 3 cases. Radiosurgery was provided in 20 VS, in most cases (83) were provided radiotherapy treatment, in 1 case in patient with mosaic form was developed only one schwannoma at the time of examination and in 1 case and in one case, a child with bilateral VS was started bevacizumab treatment. In 9 cases was found CNV mutations, in 45 cases – SNV, in 2 cases pathogenic genetic variant was not detected by either NGS or MLPA. The type of radiation treatment was chosen depending on the size of the tumor and the preservation of hearing. The radiosurgery was performed on the CyberKnife or Novalis. No significant differences were found between the radiotherapy and radiosurgery groups in terms of the effectiveness of radiation and treatment and the development of post-radiation reactions. Also, no significant differences were found between the level of useful hearing and the type of pathogenic mutation. However, the most severe phenotype was observed in patients with nonsense and frameshift mutations. In this patient, an earlier start of radiotherapy treatment was required. No  significant differences between initial level of hearing and neurological symptoms before and after radiosurgery.
Conclusion

Radiosurgery could be possible treatment option in patients with neurofibromatosis-2, In our case series wasn’t detected any serious complications.  However, is needed improvement of early diagnosis in this group of patients so the level of neurological symptoms satisfactory depend on initial level.


Golanov ANDREY (Moscow, Russia), Elizaveta MAKASHOVA, Zolotova SVETLANA, Karandasheva KRISTINA, Mishael GALKIN, Kirill ANOSHKIN
00:00 - 00:00 #30092 - P114 STEREOTACTIC RADIOSURGERY IN TREATMENT OF PSYCHIATRIC CONDITIONS: SHOULD IT BE A PREFERRED APPROACH?
P114 STEREOTACTIC RADIOSURGERY IN TREATMENT OF PSYCHIATRIC CONDITIONS: SHOULD IT BE A PREFERRED APPROACH?

Introduction: For the last 70 years, stereotactic radiosurgery (SRS) has been a rarely used option in management of intractable psychiatric conditions. Since its introduction in 1950-s, SRS was used in multiple centers worldwide with >100 cases of SRS for psychiatric indications described in the published literature. Currently, it is considered one of several options along with radiofrequency (RF) lesioning (capsulotomy, cingulotomy, subcaudate tractotomy and limbic leucotomy) and deep brain stimulation (DBS) targeting ventral striatum, anterior limb of the internal capsule, nucleus accumbens, subcallosal cingulum, etc.

Methods: We reviewed recent literature on psychiatric surgery (lesioning, DBS and SRS) and determined relative advantages/disadvantages of each approach.

Results: There is a growing body of literature documenting successful treatment of certain psychiatric conditions with precise surgical interventions. Despite overall DBS attractiveness due to its non-destructive nature, testability, adjustability and reversibility, there are multiple limitations, including invasiveness of surgical intervention, high energy requirements, hardware-related risks, need for settings adjustment over time, non-negligible implant costs, etc.  

SRS, on the other hand, although initially designed for treatment of functional disorders, is significantly underused for psychiatric conditions. Several unique SRS features may be particularly useful in psychiatric applications – high degree of precision, minimal invasiveness, absence of implanted hardware, feasibility of same-session bilateral interventions, excellent patient tolerance and satisfaction profiles, etc. Blind comparative sham-controlled studies are much likely with SRS than open destructive/modulative surgeries. In addition, linking the targeting to metabolic or physiological imaging modalities may be specifically applied to SRS. Moreover, unique SRS advantages include lack of incisions, no immediate dramatic changes in the patient’s condition (as it takes weeks-to-months for clinical effects to appear), no procedure-related confusion, no need in anesthesia/sedation, painless nature of the treatment, minimal infection/hemorrhage risk, permanent treatment effects, predictable effect and lesion size, and lack of additional expenses for disposable or implantable equipment.

Conclusion: Initially designed for functional stereotactic procedures, radiosurgery may present a set of benefits that are not available with other techniques; it may turn out to be the best modality for treatment of medically intractable psychiatric disorders.  As our ability to predict treatment success and individualize approach to each patient with medically intractable mental disorders becomes more refined and sophisticated, radiosurgery may become a premier tool for such interventions with clear advantages over standard stereotactic interventions, perhaps even DBS. Presented rationale of SRS use should stimulate further research and clinical applications of SRS in psychiatric indications.


Konstantin V. SLAVIN (Chicago, USA)
00:00 - 00:00 #30111 - P115 Gamma Knife® (GK) Practice Pattern Trends Over a 10 Year Period (2011-2021): A Single Institutional Experience.
P115 Gamma Knife® (GK) Practice Pattern Trends Over a 10 Year Period (2011-2021): A Single Institutional Experience.

We reviewed our Gamma Knife® Radiosurgery case mix to evaluate practice pattern changes across a 10 year period of time. In 2011 we completed 384 procedures with 782 lesions targeted. The majority of the treatments were for malignant disease with metastases representing the largest subgroup (n=245; 63.8%), A total of 117 (30.4%) benign pathologies were treated with benign tumors (n=63; 16.4%), functional cases and AVMs (each n=27; 7%) representing the most common cases treated with the remainder of cases represented by a variety of other pathologies. All treatments were completed using the Perfexion™ system. By 2021, we doubled our case volume completing (n=778) procedures, however, nearly tripled the number of targets treated (n=2317).  Metastases again represented the largest cohort (n= 617 cases;79.3%), 84 (10.8%) benign tumors, 19 (2.4%) functional cases and 15 (1.9%) AVMs. In 2021, all cases were completed using the GK ICON™ System and 193 cases (24.8%) were performed using mask-based immobilization.  There were also 16 anesthesia cases. Approximately 50% of the treated patients were from Ohio and 50% came from out of state.

The above data demonstrates a growing volume of cases treated with GK at a single institution across a decade, with metastases representing the dominant and expanding cohort of cases treated (63.8% vs 79.3%). The associated nearly tripling of lesions treated likely reflects a willingness to treat patient with a greater number of brain metastases per session. Further, 24.8% in 2021 were treated with mask-based immobilization reflecting a work-flow change and expanded capabilities compared to treatments in the previous decade.


Glen STEVENS (Cleveland, USA), Gene BARNETT, Alireza MOHAMMADI, Sam CHAO, Erin MURPHY, John SUH, Gennady NEYMAN, Lilyana ANGELOV
00:00 - 00:00 #30121 - P116 GAMMA KNIFE RADIOSURGERY FOR SYMPTOMATIC TRIGEMINAL NEURALGIA -STRATEGY OF THE TREATMENT -.
P116 GAMMA KNIFE RADIOSURGERY FOR SYMPTOMATIC TRIGEMINAL NEURALGIA -STRATEGY OF THE TREATMENT -.

 Introduction

For the treatment of essential trigeminal neuralgia(TN), Gamma Knife radiosurgery(GKRS) is widely adopted now. But there are few reports about GKRS for symptomatic TN caused by a tumor, arteriovenous malformation, etc. Generally, pain of symptomatic TN is controlled by GKRS of targeting the lesion earlier than that of essential TN. We also have experienced some cases of symptomatic TN. Here, we summarize the results of our cases and reviewed the strategy of GKRS for symptomatic TN.

Methods

From January 2001 to December 2019, 30 patients suffering from symptomatic TN were treated by GKRS at our institution. Of them, 24 patients that could be followed up for a minimum of 6 months were retrospectively examined.

Results

In 19 of the 24 cases, pain could be controlled by GKRS targeting only the lesion. But in some cases, pain could not be controlled in spite of the lesion control by GKRS. In these cases, the pain could be controlled by an additional GKRS directly targeting the fifth cranial nerve, using for treating essential TN. And, in cases of emergency or in cases where GKRS was not suitable for treatment of the lesion, from the first, adding or using the same GKRS for treating essential TN was effective.

Conclusions

We reviewed the strategy of performing GKRS for symptomatic TN from our experienced cases. In some symptomatic TN cases, pain could not be controlled only through lesion control by GKRS. Although GKRS for symptomatic TN should be directed to the lesion rather than the trigeminal root originally, in such cases, it was indicated that adding or using the same GKRS for treating essential TN was effective and safe for the treatment of symptomatic TN. Thus, we recommend that GKRS should be directed to the trigeminal root in the following cases: 1. when GKRS targeted at the lesion has not been effective. 2. if there is an emergency. 3. if the lesion is deemed not amenable to GKRS.


Hiroyuki KENAI (OITA, Japan), Hisato NAKAYAMA, Seiji UESUGI, Takashi KARUKAYA, Hirofumi NAGATOMI
00:00 - 00:00 #30126 - P117 The use of 3D printing model for brain arteriovenous malformations radiosurgery – case report.
P117 The use of 3D printing model for brain arteriovenous malformations radiosurgery – case report.

The treatment of brain arteriovenous malformations (bAVM) continues to be challenging even with radiosurgery chosen as the first treatment option in selected cases. The correct definition of the radiosurgical target is one of the most important factors for the obliteration of these malformations. The current imaging protocol usually provides images in two dimensions, which makes it difficult to completely understand the anatomical complexity of the lesions. This case report proposes a realistic 3D model as a tool for better delineation of arteriovenous malformations submitted to radiosurgery. A 32-year-old woman presented to the clinic for evaluation of a bAVM detected on imaging studies post stroke associated with intraventricular hemorrhage in April 2011. Angiography revealed an bAVM in the right insular lobe with feeding vessels from the medial lenticulostriate artery. The medical team decided to pursue interventional endovascular treatment in sessions, final one in December 2018 (four sessions in total). The last digital subtraction angiography (DSA) demonstrated 90% of occlusion but still a nidus that received an arterial supply from the branches of the right posterior cerebral artery. The patient was counseled to treat the medial and deep portions of the AVM with radiosurgery. During the CT scan a AngioCT (DICOM files, slices 1,5 mm) was recalled and used for 3D printing. One bAVM printing model was previously obtained. For prototype generation, file format stereolithography (*.stl) were obtained from the combination of CT scan and AngioCT of the patient from the software Materialise Mimics Research™. We adopted that magenta color for patent blood vessels and white resin for embolized vessels. Utilizing all of this information a single target was designed in two steps by the same neurosurgeon. Initially, a bAVM volume (V1) using just the protocol images (CT, MRI and DSA) was created. After this, other contouring (V2) was designed using the CT, MRI, DSA plus the 3D model like a real image to understand the lesion and two different plans were created.  In the first one (V1) the volume was 16.17 cm3 while the second (V2) was 13.85 cm3. The difference between the two volumes (V1 – V2) was 2.32 cm3 that represents 14.34% of the V1 volume (V1-V2/V1). The treatment was performed in June 2019 using V2 as a target, receiving a radiation dose of 15Gy. At this moment, she is being followed with control images without complaints.


Renato SILVA CAMPOS (Brasília, Brazil), Luis Gustavo GUIMARAES, Luciano COELHO DE FREITAS, Leonardo BICUDO DOS SANTOS, Joao Elias SANTANA GONCALVES
00:00 - 00:00 #30147 - P118 Gamma Knife Radiosurgery for a brain metastasis of a ghost cell carcinoma.
P118 Gamma Knife Radiosurgery for a brain metastasis of a ghost cell carcinoma.

Background: Besides microsurgical resection, radiosurgery has been established as the primary treatment option for many patients with brain metastases (BM) in recent years. For the first time, we report on the radiosurgical treatment of a patient with a brain metastasis from a ghost cell carcinoma of the mouth.

Case description: We report on a 56 year old male patient with a salivary ghost cell carcinoma of the mouth. Lymph node and pulmonary metastases were present. Thirty-four months after initial diagnosis of the primary tumor, the patient noticed difficulties with tying his shoes and a gait disturbance due to a weakness of his left leg. Consequently, a BM was diagnosed and treated by Gamma Knife radiosurgery (GKRS) with a marginal dose of 16Gy at the 50% isodose line. At 3- and 6-month follow-up after GKRS, the radiated BM was significantly reduced in tumor volume and showed almost no surrounding edema. In addition, at 6-month follow-up, the patient was completely free of neurological symptoms. Two months later, the patient suffered from a severe clinical deterioration, including acute kidney failure and seizures. Imaging showed oncological disease progression in the liver and potential progression of the radiated BM in comparison to the last follow-up MRI. The patient succumbed to his disease in the same month, 43 months after initial tumor diagnosis.

Conclusion: Radiosurgery for a BM of a ghost cell carcinoma seems to be an effective treatment option. A slightly higher prescription dose than 16Gy might be advisable.


Helena UNTERSTEINER, Anna CHO, Farjad KHALAVEH, Dorian HIRSCHMANN, Thorsten FUEREDER, Josa Maria FRISCHER (Vienna, Austria)
00:00 - 00:00 #30158 - P119 - In-vivo accuracy of frameless, MLC-based LINAC SRS thalamotomy for essential tremor.
P119 - In-vivo accuracy of frameless, MLC-based LINAC SRS thalamotomy for essential tremor.

BACKGROUND: For many years, the standard of care for radiosurgical thalamotomy has been a frame-based treatment, either on Gamma Knife or a linear accelerator with cones. Our institution has recently completed enrollment of phase I/II prospective clinical evaluating the safety and efficacy of a linear-accelerator based treatment with thermoplastic mask utilizing the linear accelerator’s native high-definition collimator to generate a similar rapid-falloff spherical dose distribution. In this study, we assessed the in-vivo accuracy of our treatments.

METHODS: We treated patients on an IRB-approved clinical trial (ClinicalTrials.gov Identifier: NCT03305588) using a Varian Edge™ (Palo Alto, CA) linear accelerator equipped with high-definition multi-leaf collimator and 10MV flattening-filter free beam using our previously described virtual-cone approach. Optical surface guidance was used to monitor the patient position during treatment. For 15 patients having follow-up imaging, the planned dose distribution was exported in the pre-treatment MPRAGE image space. The pre-treatment MPRAGE was co-registered to the 6-month post-treatment post-contrast T1 SPACE image using a two-stage linear registration (rigid followed by affine). The lesion was segmented using a semi-automated, threshold-based method. The center-of-gravity (COG) of the lesion and of the planned 65 Gy isodose volume were calculated.

RESULTS: The mean distances between the center coordinates of the lesion and target were less than 0.5 mm in all axes (mean ± standard deviation between lesion and target: x = -0.1 ± 0.3; y = -0.1 ± 0.5; z = -0.3 ± 0.7 mm). The mean Euclidean distance between the target and lesion COG was 0.86 mm (95% confidence interval 0.58 to 1.13 mm).  The distance was significantly correlated with imaging signal-to-noise ratio (SNR), suggesting patients with greater head motion and poorer quality imaging resulted in a greater discrepancy between target and lesion.

CONCLUSION: The distance between the target position and lesion position is consistent with sub-millimeter accuracy for frameless SRS thalamotomy. Imaging quality is a limiting factor when assessing the targeting accuracy.


Richard A. POPPLE (Birmingham, USA), Erik H. MIDDLEBROOKS, Evan M. THOMAS, Harrison C. WALKER, Benjamin A. MCCULLOUGH, Barton L. GUTHRIE, Markus BREDEL
00:00 - 00:00 #30187 - P120 Neuromodulatory Effect and Dose Response of Functional Radiosurgery on Cortical Neurons.
P120 Neuromodulatory Effect and Dose Response of Functional Radiosurgery on Cortical Neurons.

Purpose: The effects of functional radiosurgery on neuronal circuits remain poorly understood. Neurons of the prefrontal cortex communicate via precisely-timed action potentials that control decision making, working memory, and executive control. Here, we examined the dose response of ablative radiation dose on the patterns of communication of neural circuits in prefrontal acute slices. Materials and Methods: Serially escalating doses from 20 Gy to 100 Gy of ablative radiation were applied to population of rodent cortical neurons using the robotic Radiosurgery device (CyberKnife(R) G4) at a standard dose rate (SDR) of 10 Gy/min. Neuronal communication within irradiated prefrontal slices were compared to control slices (sham radiation); and assessed by plating slices on a multielectrode array that captured high-resolution (18 kHz) extracellular activity across 4,096 channels simultaneously. Comparisons also with recordings of slices treated with a pro-epileptiform solution containing a potassium channel blocker, 4-AP, reduced extracellular magnesium, and increased extracellular potassium and finally, correlated with staining for cell death. Results: Compared to control slices (mean rate of 0.06 Hz), the post-radiosurgery slices yielded a 40-fold increase in discharge rates (mean rate of 2.87 Hz for 20 Gy, 2.44 Hz for 50 Gy, and 1.95 Hz for 100 Gy radiation). Pearson cross-correlations were computed across all pairs of channels, yielding a matrix of 4,096-by-4,096 interactions. Radiated slices exhibited decreased correlations relative to control slices. A total of 7,446 neuronal interactions were above a threshold correlation of 0.5 in control slices, compared to none following a 20 Gy dose, 50 interactions following a 50 Gy dose and 28 interactions following a 100 Gy dose.  Slices treated with pro-epileptiform solution slices yielded large seizure-like events characterized by increased discharge rates and increased pairwise correlations. Conclusion: Post-radiosurgery slices yielded a unique signature of neuronal activity with increased rates; but with a pronounced decrease in correlations; suggesting diminished communication across neurons to create a neuro-modulatory effect on target tissue; or result in cognitive toxicity on organ-at-risk respectively. We speculate on an interaction between two competing mechanisms: (i) widespread neuronal disinhibition leading to an increase in neuronal firing; and (ii) dose-dependent cell death and synaptic dysfunction accounting for a decrease in firing in elevated doses. These preliminary results offer a promising tool for high-resolution assays that study interactions with druggable targets for synergy or radioprotection. Analysis of the dose response with Very-high Dose rate (VHDR) will be completed in the near future. 


Megan BOUCHER-ROUTHIER, Janos SZANTO, Jean-Philippe THIVIERGE, Vimoj JANARDANAN NAIR (OTTAWA, CANADA, Canada)
00:00 - 00:00 #30188 - P121 Centro-lateral gamma knife thalamotomy for intractable pain.
P121 Centro-lateral gamma knife thalamotomy for intractable pain.

Objective: Ablative procedures in the treatment of intractable pain are   experiencing a renaissance despite the frequent overuse of neuromodulation techniques. Here we present the results of  centro-lateral thalamotomy (CLT) in  the facial and thalamic pain. 

Methods and Patients: Between 2018 and 2021, we performed unilateral CLT  in 16 patients but  for the short follow-up we present here 9 of them (F:M=7:2; median age 65 years [range 49–79]) suffering from various severe pain syndromes (4 trigeminal deafferenation pain, 2 trigeminal neuropathic pain,  2 postherpetic trigeminal neuralgia, 1thalamic pain), in whom previous treatment had failed. The median follow up period was 24 months (range 6–28 months). The Leksell Stereotactic Frame, GammaPlan Software (Elekta) and T1- and T2-weighted sequences of magnetic resonance imaging acquired at 1.5 T were used for localization of the targeted central lateral posterior thalamus (CLp). The CLp was localized 6–8 mm lateral to the wall of the 3rd ventricle, 1 mm anterior to the posterior commissure and 5-6 mm superior to the intercommissural line. The CLT was performed by Leksell Gamma Knife with an applied dose ranging from 138 to 145 Gy; single shot, 4 mm collimator. In 7  patients, radiofrequency thermolesion (80°C/60s) at the same target was performed before or after gamma knife CLT to improve the pain relief. Decreased pain intensity to less than 50 - 60% of the previous level was considered as the successful treatment.

Results: Initial successful results were achieved in 5 (55.5 %) of the patients. The relief  has been achieved after a median latency of 4 - 6 months (range 2–12 months). No neurological deficits were observed. 

Conclusions: Our results suggest that centro-lateral thalamotomy in patients suffering from severe pain syndromes is a relatively successful and safe method that can be used even in severely affected patients.

„Supported by MH CZ - DRO (Nemocnice Na Homolce – NNH, 00023884)“ 


Dusan URGOSIK (Prague, Czech Republic), Jaromir MAY, Roman LISCAK
00:00 - 00:00 #30189 - P122 linear accelerator -Based Radiosurgery for seizure control in hypothalamic hamartomas: a single-institution case series.
P122 linear accelerator -Based Radiosurgery for seizure control in hypothalamic hamartomas: a single-institution case series.

Objective: To report the seizure control in patients with hypothalamic hamartomas (HH) treated in a single medical institution with Linear Accelerator (LINAC)-based Stereotactic Radiosurgery (SRS).

Methods: Retrospective study of eleven patients with HHs treated between 2007-2019 with LINAC-based SRS in the Radiosurgery Unit of the National Institute of Neurology and Neurosurgery “Manuel Velasco Suarez” located in Mexico City. The primary objective was to determine the difference between the number of seizures before and after the SRS treatment. Secondary objectives were to determine the latency period, to report the transitory increase in the frequency of seizures and its duration, the number of Antiepileptic Drugs (AEDs) used before and after the treatment, the control of endocrine and cognitive disorders, and to report treatment complications.

Results:  The median follow-up was 37 months and the median age at SRS treatment was 27 years. Pretreatment monthly seizure median number was 60 per month (IQR 168). The mean prescription dose to 95% of the volume was 16.9 Gray (Gy). Post-SRS median monthly seizure number was one (IQR 11), resulting in a statistically significant reduction (p=0.005). No difference was found in the number of AEDs used before and after SRS (p=0.51). There were no severe treatment related complications.

Conclusion: LINAC-based SRS is an effective treatment for seizure control in patients with hypothalamic hamartomas.


Alejandro RODRIGUEZ - CAMACHO (Ciudad de México, Mexico), Gabriel Alejandro CONTRERAS PALAFOX, Guillermo Axayacalt GUTIÉRREZ ACEVES, Juan Carlos HEREDIA GUTIÉRREZ, Sergio MORENO JIMENEZ
00:00 - 00:00 #30190 - P123 - Frameless, coneless stereotactic radiosurgery on the modern linear accelerator is safe, efficient, and effective: Results of Phase I/II Prospective Clinical Trial.
P123 - Frameless, coneless stereotactic radiosurgery on the modern linear accelerator is safe, efficient, and effective: Results of Phase I/II Prospective Clinical Trial.

Purpose/Objective(s): Stereotactic radiosurgery (SRS) to ventral intermediate nucleus (VIM) is a storied & successful yet underutilized technique for tremor. High doses & small targets have historically necessitated treatment with stereotactic frame & either a GK platform or cone-mounted  linear accelerator. We developed a coneless technique to replicate the dose distributions previously only attributable to GK on a linear accelerator (LINAC). We deployed this technique & tested it in a prospective clinical trial of safety & efficacy of SRS thalamotomy for non-DBS candidate patients with medically refractory essential or Parkinsonian tremor.

Materials/Methods: We assessed tremor pre- & post-treatment & QOL FTM/PROMIS scores. We obtained  MPRAGE, FGATIR, diffusion-weighted tractographic, & resting-state fMRI sequences. We identified the VIM via both thalamic parcellation & classical stereotactic reference location, & targeted  to 130Gy dmax dosimetrically equivalently to 4 mm GK shot with static MLC’s. We ensured 25Gy isodose line did not overlap the posterior limb of capsule. We delivered treatment on a LINAC with high-definition HDMLC & intrafraction optical surface monitoring (OSMS) to ensure patient immobility. We surveilled post-treatment imaging & tremor scores.

Results: We accrued 43 patients. 1 withdrew & 1 elected to pursue previously declined DBS. At submission, 40 patients had been treated & 35 patients had ≥6 month follow-up. Median total treatment time was 32 minute. 31/35 (89%) exhibited meaningful tremor reduction (≥20% FTM reduction). Median maximum pre- & post-tremor reduction was 59.6% (range: 9.8 - 100%). Time to tremor improvement ranged from 0.3 to 15 months. 1 patient experienced Grade 2 and 1 experienced reversible Grade 3 toxicity.

Conclusion: Frameless, coneless MLC-based SRS thalamotomy on the LINAC is a safe, effective alternative workflow that may be preferable for some patients due to its efficient delivery. Data continue to mature, but current results are congruent to those of historical gamma knife & cone-based linac treatments. We have expanded the trial, and are beginning to integrate tractographic & functional imaging into target selection for future patients.


Evan THOMAS (Columbus, OH, USA), John FIVEASH, Harrison WALKER, Richard POPPLE, Erik MIDDLEBROOKS, Markus BREDEL
00:00 - 00:00 #30200 - P124 Quality of life in Parkinson’s Disease (PD) results after Functional Radiosurgery with GammaKnife (FGKRS).
P124 Quality of life in Parkinson’s Disease (PD) results after Functional Radiosurgery with GammaKnife (FGKRS).

Quality of life in Parkinson’s Disease (PD) results after Functional Radiosurgery with GammaKnife (FGKRS)

 

E. Larrachea1, F. Jimenez2, E. Figueroa3, F.A. Bova4, C. Lühr5.

1Neurology, Centro Gamma Knife Santiago, Santiago, Chile and Universidad Mayor, Santiago, Chile

2Neurology Resident, Universidad Mayor, Santiago, Chile

3Psychologist, Military Hospital, Santiago, Chile

4Medical Physicist, Centro Gamma Knife Santiago, Santiago, Chile.

5Neurosurgery, Medical Director, Centro Gamma Knife Santiago, Santiago, Chile.

 BACKGROUND

 

PD in its evolution severely affects the quality of life. Parkinson’s Disease Questionnaire 39 (PDQ 39) is one of the most used scales to measure physical, mental and social effects of Parkinson’s disease.

Despite the current safety of the procedure, there is still little experience worldwide in the use of FGKRS as an alternative surgical treatment for PD.

 

OBJECTIVE

 

to evaluate the FGKRS postoperative quality of life of patients with PD by using PDQ 39

 

PATIENTS AND METHODS / MATERIAL and METHODS

 

Twenty-one PD patients underwent FGKRS. (n=21). Male=15, Female=6. Mean Age=66 yr.  Mean Evolution time of PD = 5 yr. Ten Typical PD patients (n1=10) and Eleven Tremor predominant PD patients (n2=11). High Resolution Magnetic resonance imaging guidance was used for Subthalamic Nucleus (STN) targeting (n1 group) and Thalamic Ventral Intermediate Thalamic Nucleus (VIM) targeting (n2 group). A single 4-mm isocenter was used to target a maximum dose of 120 Gray (Gy) to the STN and 130 Gray (Gy) to the VIM. Pre and post treatment clinical evaluation was performed using PDQ 39.

 

RESULTS

 

With an average follow-up of 15 months, an overall improvement in quality of life of 37% (PDQ39 preoperative versus postoperative) was observed, however, the group of patients with typical PD showed a lower improvement of 33% versus the group of patients with trembling PD, which showed a higher improvement of 41%. This was also coincident with the choice of Target: STN in typical PD (group n1) and VIM in Tremor Variants (group n2) Observing the best results in n2.

 

CONCLUSION

 

Although the sample size is small, the conclusions of our study suggest that the use of FGKRS in PD gives better results in quality of life in patients with tremor-predominant PD variants (41%) than in those patients with typical presentations (33%) when using unilateral target FGKRS


Eduardo LARRACHEA (Santiago de Chile, Chile), Fernanda JIMÉNEZ, Eduardo FIGUEROA, Francisco A. BOVA, Claudio LÜHR

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04. Eposters - Extracranial - Head & Neck / Spine

00:00 - 00:00 #29383 - P125 Quantitative evaluation of metastatic spine tumors local control following spinal radiosurgery: The Cleveland Clinic experience of 96 lesions.
P125 Quantitative evaluation of metastatic spine tumors local control following spinal radiosurgery: The Cleveland Clinic experience of 96 lesions.

Purpose

Spine radiosurgery (SRS) is a precise and conformal treatment modality for the management of metastatic spine tumors. Multiple studies have demonstrated its safety and efficacy for pain and tumor control. However, no uniform quantitative imaging methodology exists to evaluate treatment response in these patients. This study presents post-SRS radiographic local control rates and systematically compares measurements acquired according to the World Health Organization (WHO) and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria exploring the relationship to patient outcome.

Patients and Methods

A prospective cohort of 66 patients undergoing spinal metastases SRS was followed by serial MRI scans. The studies were read by a neuroradiologist blinded to the patients' clinical course. Local control status was determined according to both the WHO and RECIST criteria, and the agreement between the measuring methodology was calculated and reported.

Results

Ninety-six metastatic spine tumors treated with SRS were evaluated in this study. The mean treatment dose was 13.96 Gy and the median follow-up duration was 10.8 months, during which the total number of MRI scans evaluated was 408. For patients with imaging follow-up (n= 81 lesions), the mean uni-dimensional size decreased by 0.2 cm and the mean area-size decreased by 0.99 cm2 (p=0.14 and p=0.03, respectively). Although 88% of the cases classifications were concordant and the agreement was significant, the WHO criteria were found to be more sensitive to tumor size change. The local control rate according to WHO and RECIST was 95% and 98%, respectively.

Conclusion

Although the WHO criteria are superior for tumor size measurement, the RECIST criteria are simpler, reproducible, and comparable to the WHO criteria, which is a novel finding. Thus, the use of RECIST method is recommended for evaluating spinal SRS treatment efficacy and standardization purposes. SRS local control rate in either method is greater than 90%.


Ran HAREL, Tehila KAISMAN-ELBAZ, Todd EMCH, Paul ELSON, Sam CHAO, John SUH, Lilyana ANGELOV (Cleveland, USA)
00:00 - 00:00 #29488 - P126 Optimal Timing of Postoperative Magnetic Resonance Imaging (MRI) in Patients with Extradural Spinal Tumors - a Pilot Prospective Study.
P126 Optimal Timing of Postoperative Magnetic Resonance Imaging (MRI) in Patients with Extradural Spinal Tumors - a Pilot Prospective Study.

Background: Postoperative MR imaging for patients with metastatic spine tumors is indicated to evaluate the extent of resection and guide further therapy.There are no clear recommendations supporting the appropriate/optimal MR image acquisition timing. We hypothesize that early MRI(eMRI) and routine MRI(rMRI) yield similar information to guide clinical decision-making.

Methods: Prospective study with patients who had debulking, decompression or separation surgery for the management of metastatic extradural spinal tumors. An MRI was performed within 72 hours of surgery(eMRI) and in 2-3 weeks post-op(rMRI). Differences between the scans were evaluated by comparing: bone marrow changes, presence and extent of fluid collection, Spine Oncology Study Group(SOSG) Score and tumor progression. Descriptive statistics and Kaplan-Meier estimator were performed.

Results:

Eight patients were enrolled(7M,1F), mean age was 62 years(± 9.7) with median follow-up of 11.5 months.Two patients underwent one level corpectomy; six underwent decompression/separation surgery (5 of 6 undergoing posterior instrumented fusion). Pathologies included Renal Cell Carcinoma(n=3), NSCLC(n=2), Breast, Tongue and undifferentiated carcinoma(each n=1). In 7 patients, extent of bone marrow change was stable between MRIs, but in one patient it went from 51-75%compromise to 76-100%. There were no significant changes in cord edema or SOSG score between eMRI and rMRI. Four patients had no signs of fluid collection after surgery, one patient had a fluid collection stable between images, one improved and two had worse fluid collection in the late MRI.Seven patients underwent SBRT after surgery, and in six the late MRI was used for treatment planning.One patient required new imaging before SBRT due to discomfort during the previous scan. Median PFS was 12 months(95%CI 7.9-20) and median OS was 14 months(95%CI 2.9-25).

Conclusion

Our cohort suggests rMRI is sufficient and appropriate to evaluate spine tumor post-resection patients and defer imaging evaluation until patient are further out from surgery. These preliminary results can potentially guide clinicians’ imaging protocols.


Dhiego Chaves De Almeida Bastos BASTOSD, Todd EMCH, Sam CHAO, Steven COLLIER, Edward BENZEL, Lilyana ANGELOV (Cleveland, USA)
00:00 - 00:00 #29774 - P127 A meta-analysis of low dose (< 55 Gy) vs. high dose (  55 Gy) adjuvant radiotherapy effects on survival for intracranial atypical meningiomas.
P127 A meta-analysis of low dose (< 55 Gy) vs. high dose (  55 Gy) adjuvant radiotherapy effects on survival for intracranial atypical meningiomas.

Background: Atypical meningiomas (AMs) can have an aggressive clinical course, exhibiting a higher recurrence rate, and portending a worse prognosis than benign meningiomas (BMs). Currently, there remains controversy as to the optimal treatment course for AMs, including the utilization of post-operative radiotherapy. Moreover, the dependence of post-operative adjuvant radiotherapy (ART) dose and its impact on survival is unclear.

 

Objective: In this meta-analysis, we investigate the effect of lower-dose (<55 Gy) vs. higher-dose (³55 Gy) ART following surgical resection on progression free survival (PFS), overall survival (OS), and treatment toxicity complications in AM patients.   

 

Methods: In accordance with PRISMA guidelines we queried PubMed, Web of Science, Cochrane, and Scopus databases for studies reporting PFS, OS, and treatment toxicity for intracranial, primary AMs treated with higher- or lower-dose ART.

 

Results: Mean 5-year PFS for patients with AM was 73.5% for higher-dose and 70.0% for lower-dose treatments, while 5-year OS was 84.9% and 71.4%, respectively. Only one study reported 5-year OS for a low-dose ART group. ART-induced toxicity incidence for grades III or higher ranged from 0.7% to 19.6% for all AM patients.

 

Conclusion: Our analysis demonstrates no significant difference in 5-year PFS when comparing higher- to lower-dose ART in atypical meningiomas. Importantly, lower radiotherapy dosages may reduce radiation associated complications. Future studies examining surgery + ART should be conducted to more completely elucidate the ideal radiotherapy candidate, modality, and dosage.


Ansley UNTERBERGER, Anjali PRADHAN, Audree EVANS, Mahlet MEKONNEN, John SHEPPARD, Khashayar MOZAFFARI, Courtney DUONG, John HEGDE, Isaac YANG (Los Angeles, USA)
00:00 - 00:00 #30000 - P128 Stereotactic radiotherapy for intramedullary spinal lesions.
P128 Stereotactic radiotherapy for intramedullary spinal lesions.

The role of stereotactic radiotherapy (SRT) for intramedullary spinal lesions was reviewed. Intramedullary spinal vascular disorders include arteriovenous malformation (AVM) and cavernous malformation (CM). Neoplasms include hemangioblastoma, gliomas (i.e., ependymoma and astrocytoma), lymphoma, and metastases. Some studies including ours have reported favorable treatment results in AVMs, though the patient numbers in each study were small. Regarding CMs, there have been no reports showing treatment results of SRT. SRT even for brain CMs is controversial. In contrast, not a few reports have been published showing good results of surgical resection. Some studies including ours have reported good results of small isolated intramedullary spinal metastases treated by SRT. Some papers have reported good results of SRT for hemangioblastoma. Though good results have been published showing surgical resection, SRT may be a good option for small hemangioblastoma in certain situations as well. Intensity-modulated radiation therapy with a wide field including peritumoral margin area, other than small localized field SRT, is thought to be better for infiltrating gliomas and lymphomas.


Yoshimasa MORI (Kawasaki, Japan)
00:00 - 00:00 #30053 - P129 Fractionated stereotactic radiotherapy in patients with locally persistent and recurrent nasopharyngeal cancer.
P129 Fractionated stereotactic radiotherapy in patients with locally persistent and recurrent nasopharyngeal cancer.

INTRODUCTION:

Radiotherapy (RT) is the mainstay of treatment for nasopharyngeal carcinoma (NPC), although chemo irradiation has also been commonly used as primary treatment in advanced-stage disease. Salvage treatment for local failure of NPC is usually difficult because of the deep-seated location, proximity to critical structures, and the high radiation dose received during primary treatment. Despite these limitations, a significant proportion of patients with local failure can still be successfully salvaged, and aggressive treatments should be considered whenever possible. Stereotactic radiosurgery (SRS) has evolved as a treatment option of recurrent tumor in the head and neck.

METHODS AND MATERIALS:

We did an extensive search of MEDLINE and PubMed for English-language articles published until January 2022. The search prioritized large, current clinical trials or studies for selection.

RESULTS

Several series reported satisfactory local control: gain of 57.5% -82.6% in disease-specific survival and 54.5% to 72.9% in progression-free survival with low incidence of complication when SRS was used to treat persistent or recurrent NPC. Fractionated stereotactic RT (FSRT) is a modification of SRS, which enables fractionated irradiation to be given without losing the advantage of the mechanical precision and accuracy as well as dose conformity of SRS. Compared with SRS using single fraction of high-dose irradiation, FSRT may be superior in terms of tumor control 40% to 77% for SRS vs 69% to 92% for FSRT and protection of normal tissues and organs surrounding the target from radiobiologic principle. SRT has the characteristics of three highs and one low, that is, high precision, high dose, high therapeutic gain ratio and low normal tissue dose. It uses three­ dimensional framework for positioning, location and treatment, with high ­dose region mainly in the target volume that will help to protect the surrounding normal tissue.

CONCLUSION:

Multiple medical institutions have used FSRT since 1999 as salvage treatment for persistent and recurrent NPC and they have shown that FSRT is effective with improved local control and decreased complications. Actually, Studies are in perspective to prove that FSRT plus an immune checkpoint inhibitor may provide a new treatment option for locally recurrent NPC.


Alia MOUSLI, Hayfa CHAHDOURA (Tunis, Tunisia), Safia YAHYAOUI, Ghaiet El Fida NOUBIGH, Rim ABIDI, Chiraz NASR
00:00 - 00:00 #30089 - P130 Increasing complexity of HN SBRT plans from neck to base of skull.
P130 Increasing complexity of HN SBRT plans from neck to base of skull.

Objectives

To characterize the complexity of HN SBRT plans at common sites. In addition, we evaluated potential dose calculation uncertainties associated with plan complexity and assessed the ability of patient QA methods in detecting the variance in treatment planning system (TPS) dose calculations.

Methods and Materials

Neck, larynx, mucosal and base of skull (BOS) are the common subsites of our HN SBRT practice. For each subsites, we identified 10 latest cases and characterized the complexity with a set of metrics, including the plan averaged MLC opening area (PA), jaw opening area (JA), plan modulation (PM), and plan normalized monitor unit (PMU). Smaller PA and higher PM and PMU reflect more challenge MLC configurations, which demand more on TPS beam modeling accuracy. To evaluate potential dose calculation uncertainties from beam modeling, we calculated dose on the same plan using a newly commissioned RayStation beam model and a legacy Pinnacle beam model commissioned for spine SBRT. Patient specific IMRT QA were also performed on 6 cases using both ArcCHECK and Octavius.  Gamma index analysis (2% and 2 mm gamma criteria) was performed on both TPS calculation of each measurement.  The passing rate difference between Pinnacle and RayStation calculation of each device was analyzed against the plan dose calculation difference in target.

Results

BOS cases had the most complex plans. The PA and its ratio to JA was the lowest at 3.29 ± 1.94 cm2 and 0.07 ± 0.03 respectively. This corresponded to the highest PMU and PM at 3.53 ± 1.10 MU/cGy and 0.88 ± 0.04 respectively. Mucosal, neck and larynx had comparable plan complexity. The average PA to JA ratio and PM were ~0.13 and 0.81 for all 3 sites. The PMU for mucosal was slightly higher than neck and larynx. The average percentage value of mean target dose difference between 2 TPS calculations were 2.83%, 1.93% and 1.80% for mucosal, neck and larynx respectively. It reached 4.67% for BOS. Octavius was sensitive to the dose calculation difference as its gamma index passing rate differed > 10% when the variance in mean target dose was > 3%.

Conclusion

HN SBRT demands highly complicated plan to spare many critical organs nearby. This is especially true for BOS cases, which are most likely to expose the variance in beam modeling. 3D dose measurement based IMRT QA system can be a great tool for verifying/fine turning the beam model for SBRT planning.


Xin WANG (Houston, USA), Congjun WANG, He WANG, Dershan LUO, Weiliang DU, Jack PHAN
00:00 - 00:00 #30109 - P131 Impact of fractionated stereotactic radiotherapy on activity of daily living and performance status in progressive/recurrent glioblastoma: a retrospective study.
P131 Impact of fractionated stereotactic radiotherapy on activity of daily living and performance status in progressive/recurrent glioblastoma: a retrospective study.

Background: The prognosis of recurrent glioblastoma (GBM) is poor, with limited options of palliative localized or systemic treatments. Survival can be improved by a second localized treatment; however, it is not currently possible to identify which patients would benefit from this approach. This study aims to evaluate which factors lead to a lower Karnofsky Performance Status (KPS) score after fractionated stereotactic body reirradiation (fSBReRT).

Methods: We retrospectively collected data from patients treated with fSRT for recurrent GBM at the Institut de Cancérologie de Lorraine between October 2010 and November 2017 and analyzed which factors were associated with a lower KPS score.

            Results: 59 patients received a dose of 25 Gy in 5 sessions spread over 5-7 days (80% isodose). The median time from the end of primary radiotherapy to the initiation of fSRT was 10.7 months. The median follow-up after fSRT initiation was 8.8 months. The median overall survival time was 25.8 months, the median overall survival time after fSRT was 8.8 months, and median progression-free survival and institutionalization-free survival times were 3.9 and 7.7 months, respectively. Initial surgery was associated with better progression-free survival (Hazard ratio (HR) = 0.48 [95%-CI, 0.27-0.86], p = 0.013).  A larger planning target volume (PTV) was associated with a lower KPS score (HR = 1.57 [95%-CI, 1.19-2.08], p = 0.028).  Only two patients showed early grade 3 toxicity and none showed grade 4 or late toxicity.

            Conclusions: A larger PTV predicts lower KPS in the treatment of recurrent GBM using fSBReRT.


Nicolas DEMOGEOT (Vandœuvre les Nancy)
00:00 - 00:00 #30192 - P132 Hybrid-arc fractionated radiosurgery of spine metastases.
P132 Hybrid-arc fractionated radiosurgery of spine metastases.

Background:

Fractionated image-guided radiosurgery (fSRS) is an effective treatment of spine
metastases. This treatment can be performed on Truebeam linear accelerator with dedicated
equipment using isocentric modulated arc therapy (Hybrid Arc). Additional advantage of using
dedicated system is the possibility of flexible fusion of CT and MRI images. Our aim was to present
the results of hybrid-arc fSRS of spine metastases using dedicated system.


Material and method:

The patient selection criteria were: age  >18  years, diagnosis of spinal
metastases (n ≤ 3), life expectancy >3  months, ESCC <3. Delineation was based on CT and MRI
+/- PET elastic fusion, Exactrac™ system was used for treatment verification and Elements Spine
Software® Brainlab™ Germany was used for dose planning. All radiation target volumes were
defined based on MRI. If tumor border was hard to define a PET images or margins of involved
part of the vertebrae were used. Dose prescription of 21 Gy- 30 Gy in 3 fractions and 25-30Gy in 5
fractions. Local control was assessed using MRI or/and PET and pain control was based on patient
assessment. Response was defined as partial or complete tumor regression in MRI. Five patients
were controlled with PET. Local control rates were defined in all patients at 3 months and in 20
patients (available data) at 6 months. Sixteen patients had at least one year of follow up. RT
toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE)
v4.0.


Results:

From 2019 to 2021, 47 spinal metastases in 34 recruited patients were treated with
Hybrid-arc fSRS. In a median follow up of 10 months (range 3-32) response in MRI and PET was
observed in 23% and 60% of treated lesions. The local control rates at 3- and 6- months were 96%
and 95%, respectively. One-year overall survival rate was 85%. Pain decreased in 60%, was
stable in 37% and not reported in 3% of cases. No adverse events ≥2 grade were observed.

Conclusions:

Our experience shows that hybrid-Arc spine fSRS provide very high local and pain
control with low toxicity. Regression assessment in the spine using MRI is limited and may
underdiagnose true response to treatment.


Magdalena ADAMCZAK-SOBCZAK, Zarębska IZABELA, Blok MACIEJ, Wisniewski TOMASZ (Bydgoszcz, Poland), Szymański PAWEŁ, Maciej HARAT

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05. Eposters - Extracranial - Ocular

00:00 - 00:00 #30005 - P133 Outcomes of GammaKnife radiosurgery of posterior uveal melanoma unsuitable for other eye-sparing treatment: 10-year single center experience.
P133 Outcomes of GammaKnife radiosurgery of posterior uveal melanoma unsuitable for other eye-sparing treatment: 10-year single center experience.

Background: Currently a wide spectrum of eye-sparing treatment modalities for posterior uveal melanoma (PUM) are in use but they have limited indications.

Purpose: to present the results of GammaKnife radiosurgery (GKRS) of PUM unsuitable for other eye-sparing treatment modalities.

Methods: Since 2012 37 consecutive patients aged from 14 to 78 years with PUM were treated with GKRS. These tumours were not indicated to other eye-sparing modalities available in our clinic – ruthenium-106 brachytherapy, transretinal excision, transscleral excision, or laser treatment, because of the tumour size or/and location. Three patients had the only seeing eye. Majority of patients refused to remove the eye. Tumour thickness was from 5.5 to 10.8 mm, mean 8.4 mm, basal diameter from 9.4 to 21.4 mm, mean 14.3 mm. Retinal detachment height was up to 8.5mm. Four tumours touched or covered the optic disc. GKRS irradiation doses were 30-40Gy on 50% marginal isodose curve. Currently doses higher 30Gy are not in use. Maximum doses on critical structures were calculated – lens (2.1-35.5 Gy, mean 10.7), ciliary body (5.1-53.0 Gy, mean 21.4), optic disc (3.4-62 Gy, mean 21.2 Gy), central retina (3.5-65 Gy, mean 24.8 Gy). Irradiation plans will be presented. Mean treatment time was 128 min (from 50 to 216). The follow up was from 6 to 96 months, mean 43 months.

Results: Complete tumour regression was achieved in 7 cases. Mean tumour regression was 53%. Regression after GKRS was much slower than after brachytherapy. Retina reattached in all but 4 patients. Two tumours around the optic disc progressed and the eyes were enucleated.  Two patients underwent surgical excision of the tumor 2 years after GKRS because of very limited response to the treatment. Radiation complications included retinopathy (38%), optic neuropathy (26%), cataract (8%), vitreal and subretinal hemorrhages (11%), glaucoma (5%). One eye was removed because of phthisis bulbi. Thirty-four eyes (92%) were preserved. Vision increased in 13% of patients, unchanged in 31%, decreased in 56%. Two patients developed liver metastasis and died in 2 years after treatment, one patient died because of the second cancer.

Conclusion: GKRS is an effective alternative for removing the eye in patients with PUM when brachytherapy or surgical excision are not indicated.  GKRS can save vision in selective cases. Radiation complications were associated with large irradiated tumor volume and may be reduced by planning optimization.

 


Andrey YAROVOY, Andrey GOLANOV (Moscow, Russia), Valery KOSTJUCHENKO, Vera YAROVAYA
00:00 - 00:00 #30150 - P134 Fractionated stereotactic radiotherapy for uveal melanoma: early results.
P134 Fractionated stereotactic radiotherapy for uveal melanoma: early results.

Aim: We report our clinical experience of a hypofractionated Cyberknife radiotherapy treatment for uveal melanoma.

Methods: We retrospectively evaluated 47 patients (pts), mean age 68 years (range 36 - 90 years) suffering from uveal melanoma treated by Cyberknife, Centro Diagnostico Italiano, Milan, Italy, between April 2014 and December 2020. All of the pts had received a diagnosis and referral from an ophthalmologist. Cyberknife robot-controlled LINAC radiosurgery was performed delivering a total dose of 54 - 60 Gy given in 3 fractions of 18 - 20 Gy prescribed to the 79 - 82% isodose surface. All pts underwent orbit MRI with gadolinium (slices thickness 1 mm) for coregistration with the planning CT scans. The planning target volume (PTV) included the contrast-enhancing lesion on MRI (GTV = CTV) plus a 2.5 mm margins in all directions. All pts were irradiated eyelids closed, with a bandage on eye, using a contention with a thermoplastic mask. For 9 pts tantalium markers were sutured to the sclera around the tumor. At presentation the mean PTV volume was 1857 mm³ (range 100 – 5792 mm³), mean tumor base measured ultrasonographically 11.7 mm (range 6-20 mm) and mean thickness 4.8 mm (range 2-10 mm).

Results: After a mean follow-up of  37 months (range 8 – 84 months) local control was achieved in 100% of pts. We observed a reduction of 7% in mean base and of 41% in mean thickness that were respectively 10.9 mm (range 4 – 20 mm) and 2.8 mm (range 0.5 – 9 mm) at follow-up. The most common side effects were radiation maculopathy in 27 pts (57%), cataract in 15 pts (32%), choroidal ischemia in 16 pts (34%). 9 pts (19%) suffered from radiation neuropathy, 10 pts (21%) from retinal detachment and 5 pts (10%) from neovascular glaucoma which required enucleation in 4 pts (8%). To reduce toxicity intravitreal anti-VEGF (+/- photodynamic terapy) and steroids 4 months after the treatment were performed to the most of patients (72%). Visual acuity was reduced in 34 pts (72%), increased in 4 pts (7%) while in the others 10 pts (21%) no change was found.

Conclusions: Our results are consistent with data in literature and show a safe, minimally invasive and well tolerated method for treating uveal melanoma. The main limitation is that it is a retrospective study. Continued accrual and follow-up are required to confirm long term results.


Isa BOSSI ZANETTI (Milano, Italy), Marco PELLEGRINI, Giancarlo BELTRAMO, Chiara PREZIOSA, Anna Stefania MARTINOTTI, Irene REDAELLI, Chiara SPADAVECCHIA, Francesco MORETTI, Livia Corinna BIANCHI, Sergio PAPA, Giovanni STAURENGHI
00:00 - 00:00 #30160 - P135 Robotic radiosurgery for primary and relapsed uveal melanoma.
P135 Robotic radiosurgery for primary and relapsed uveal melanoma.

Objectives: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and arises from melanocytes within the uvea part of the eye. Treatment of UM aims to local control of the tumour, avoidance of metastatic dissemination and preservation of the eye, therefore eye sparing radiotherapy techniques are often preferred to enucleation. Robotic radiosurgery is the form of precision distant photon irradiation with steep dose gradients that is suitable for most patients with low- and medium sized UM even located in eloquent areas of the eye (optic disc, iris). The aim of the study was to analyse  the local control rate for primary and relapsed uveal melanoma treated with robotic radiosurgery (RRS). 

Material and methods: We prospectively followed 24 patients with primary and relapsed UM who underwent RRS with CyberKnife M6 system. The mean age of the study group was 60.5 [range 31-74 years], 14 male patients, and 10 females. 50% of the patients had primary tumours, others had relapse after brachytherapy treatment. Patients did not have extrascleral growth or distant metastases. The median tumour volume before treatment was 0.67 cm3 [0.38-1.37 cm3]. The treatment plan was determined considering the size, features of the tumour configuration and the proximity of critical structures. Retrobulbar anaesthesia to achieve akinesia of the eye prior CT topometry and radiosurgery procedure.  1-3mm PTV was applied around the target to compensate for possible uncertainties caused by edema after infiltration anaesthetic. A single dose was administered to all patients with a mean dose 23.6 Gy [21-25 Gy](75-80% isodose).  

Results: Patients were followed for a median 9.5 months [6-34]. The study group showed no case of tumour progression. Tumour volume decreased by median 58.4% [0-90%]. No cases of radiation toxicity grade 2-3 were observed, except 1 patient with phthisis bulbi who had RRS for relapsed UM after brachytherapy. 2 patients had mild conjunctivitis, which was improved after prescribing medications.  

Results show that robotic radiosurgery has good local control rate and it is a safe eye preserving treatment method for both primary and relapsed uveal melanoma patients. 

Conclusion: In uveal melanoma patients who had radiosurgery, the study revealed tumour volume reduction after RRS treatment with low rates of postradiation toxicity. The stereotactic radiosurgery is a good alternative to brachytherapy for treating uveal melanoma especial in eloquent eye areas, with protection quality of life and no significant side effects.


Sandra LEDINA (Sigulda, Latvia), Maris MEZECKIS, Vladyslav BURYK

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06. Eposters - Extracranial - Body

00:00 - 00:00 #29348 - P136 Stereotactic Body RadioTherapy (SBRT) as an ablative local treatment option in patients with Oligometastatic Prostate Cancer (PCa).
P136 Stereotactic Body RadioTherapy (SBRT) as an ablative local treatment option in patients with Oligometastatic Prostate Cancer (PCa).

Backround: There is an increasing amount of data that support prostate-directed radiation therapy in selected PCa patients with metastatic disease. HORRAD and STAMPEDE trials have showed a survival advantage to prostate-directed radiotherapy in patients with “oligometastatic” disease, (per CHAARTED criteria) in addition to systemic androgen deprivation therapy (ADT). Moreover, recent technological advances in radiotherapy have led to the application of innovative techniques such as SBRT, which allows delivery of high ablative radiation doses towards improved clinical outcomes. As a result, there is a growing interest to treat this group of patients with “curative” intent using local metastasis-directed SBRT at all sites, while sparing ADT or other systemic treatments.

Methods: In our multi-institutional study, we present a case-series of oligometastatic prostate cancer (6 bone-only, 2 lymph node only and 2 bone plus lymph node metastases) between 2019-2021. All patients experienced biochemical relapse after radical/salvage radiotherapy ± ADT and remained ADT-free for at least 12 months. They underwent 68Ga-PSMA PET/CT for detection of oligometastatic disease, and the pathological site(s) that should be irradiated. The dose SBRT delivery was heterogeneous depending on metastases location (lymph node or bone), with a predominance of those 3-5 fractions, with a dosing range of 24 Gy/3 fraction, 30Gy/5fraction, to 40Gy/5 fractions. ADT-free survival (ADT-FS) was calculated as the time from completion of treatment for oligometastatic disease to initiation of ADT. Follow up with clinical review and PSA was undertaken at four weeks, then three-monthly, with PSMA PET/CT restaging as indicated.

Results: Ten oligometastatic patients received SBRT. Median time from primary treatment to oligometastatic relapse was 61.8 months. Median PSA doubling time was 5.2 months. At a median follow up of 24.7 months, 80% (8) remained ADT-free. Median ADT-free survival was 29 months (95% CI: 11 - 36 months). After SBRT, new relapses frequently occur outside the treated field, accounting for 60% of all relapse cases and there were no local failures. Incidence of grade 1 and 2 CTCAE toxicity was 29% (6) and 5% (1), respectively, limited to gastrointestinal and genitourinary side effects, such as nausea and cystitis. No toxicity of grade 3 or above was observed.

Conclusions: Treating oligometastatic prostate disease with SBRT is a feasible treatment option. It provides significant local control rates with a significant number of patients remaining ADT-free for more than 2 years, while maintaining their quality of life.


Georgios KRITSELIS (ATHENS, Greece), Georgios KOLLIAS, Chryssa PARASKEVOPOULOU, Nikolaos GIAKOUMAKIS, Konstantinos KARALIS, Marinos TSIATAS
00:00 - 00:00 #29377 - P137 Impact of pneumatic compression belt in reducing intrafractional motion during liver tumor radiotherapy.
P137 Impact of pneumatic compression belt in reducing intrafractional motion during liver tumor radiotherapy.

Purpose: To determine the impact of abdominal compression with compact and lightweight rail system (EAMIS Lite Macromedics)  in reducing inter - and intrafractional motion.

Materials and methods: This study included 29 patients with 41 liver tumors treated stereotactic body radiotherapy in 2021 in a single center. Tumor motion was assessed to every lesion. Compressed patients were supine, arms up with kneefix and abdominal compression equipment. All patients received daily online-matched cone beam computer tomography (CBCT) before treatment and during radiotherapy. Initial setup error and intrafraction motion were determined for all patients and all fraction dose. Significant intrafractional changes in liver tumor motion were defined as a change of >4 mm. The statistical analysis was performed using Statistica ver 13.3software.

Results: Total 127 measurments of set up error and intrafracion tumor movements were recorded. The mean (± SD) set up error in CBCT before treatment was 4.0 ± 4.9 mm, 5.1 ± 4.5 mm, and 4.5 ± 3.6 mm, in the LR, AP, and SI directions, respectively. The mean (± SD) liver tumor motion in CBCT during radiotherapy  was 2.1 ± 2.2 mm, 2.6 ± 2.0 mm, and 3.2 ± 2.9 mm, in the LR, AP, and SI directions, respectively. Significant intrafractional changes in liver tumor motion were observed in 6 (4%)  LR measurments , 15 (11%) AP measurments and  12 (9%) SI measurments.

Conclusions: Abdominal compression is an effective and accepted method for reducing motion during radiotherapy, All patients who had abdominal compression were able to tolerate this treatment position for all delivered fractions.


Tomasz WISNIEWSKI (Bydgoszcz, Poland), Maciej BLOK, Magdalena ADAMCZAK-SOBCZAK, Paweł SZYMAŃSKI, Maciej HARAT
00:00 - 00:00 #29416 - P138 SBRT after neoadjuvant chemotherapy (NAC) for Borderline Resectable (BRPC) and Locally Advanced Pancreatic Cancer (LAPC): Preliminary institutional results.
P138 SBRT after neoadjuvant chemotherapy (NAC) for Borderline Resectable (BRPC) and Locally Advanced Pancreatic Cancer (LAPC): Preliminary institutional results.

 

Background

NAC for tumor downstaging, better local/distal disease control, and higher R0 resection rate, followed by pancreatectomy are the two pillars of the management of BRPC and LAPC. The potential additional role of SBRT remains controversial.  

Materials and Methods

In our tertiary referral center, patients with BRPC and LAPC undergo a complete course of NAC (mostly FOLFIRINOX), cross-sectional imaging reevaluation in 2 weeks and exploration for possible resection when the tumor looks resectable, en-block with the involved major vascular structure(s). Recently, when such a resection did not look feasible and there was no disease progression, radiotherapy was delivered through SBRT technique 5fr/ 8Gy/ 40Gy total dose, with no concurrent chemotherapy. Treatment was performed using FFF arc therapy, patient was immobilized with abdominal compression and breathing motion was tracked with surface guidance. Irradiation was limited to specific breathing phases. CBCT was performed prior and at the end of each fraction. A month after SBRT, patients were restaged (CT with pancreatic protocol) for possible resection.

Results

Eleven patients (6 males/ 5 females, median age: 59, ECOG-PS score: 0-1) with BRPC (3) and LAPC (8) underwent SBRT a median of 3 weeks following NAC (Aug. 2019 - Oct. 2021). No SBRT related side effects occurred. Follow-up was complete with a median of 17 months. Five patients (45%) were subsequently explored for possible resection, a median of 2 months after SBRT, but in only 2 of them (40%, or 18% of the total) a pancreatectomy was actually performed. R0 resection was achieved in both (100%). One patient (ypT2N0) died 22 months since diagnosis and the other (ypT1cN0) is alive and well at 36 months. The 3 patients explored, but not resected, had complete encasement of the common and proper hepatic artery from its origin to its bifurcation (2 patients), or micrometastatic liver disease (1 patient). The 9 patients not subjected to pancreatectomy were followed closely and received further chemotherapy when appropriate. They had a median survival of 21 months since diagnosis. Local control was achieved in 7 (78%). Four patients are alive for 10, 13, 21 and 23 months and 5 patients died at 10, 13, 17, 20 and 21 months.

Conclusions

Our initial experience shows that SBRT following NAC for BRPC or LAPC is safe, is associated with a high rate of local control and may render resectable about one fifth of patients considered unresectable after NAC alone.


Georgios KRITSELIS (ATHENS, Greece), Grigorios TSIOTOS, Nikiforos BALLIAN, Flora STAVRIDI, Ilias ATHANASIADIS, Alexios STRIMPAKOS, Nikolaos GIAKOUMAKIS
00:00 - 00:00 #29419 - P139 Planning study of inhomogeneous dose-escalated SBRT in pancreatic cancer.
P139 Planning study of inhomogeneous dose-escalated SBRT in pancreatic cancer.

Purpose

Stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option to improve outcome of

patients with locally advanced pancreatic cancer (LAPC). More intensive schedules are often challenging

due to proximity of organs at risks (OARs). Local control is closely related to a biologically effective dose

(BED) of 100 Gy10, corresponding to a dose of 50 Gy in 5 fractions. An in-silico study was performed to

evaluate the feasibility of dose escalation in SBRT treatments of LAPC through inhomogeneous dose

prescription, and to identify patients suitable for this strategy, based on anatomical proximity between

target volumes and OARs.

Materials and Methods

We collected dosimetric data from 14 patients treated at our center for LAPC. For each patient, a

CyberKnife (CK) Synchrony re-planning for fiducial-guided pancreatic SBRT treatment was developed for a

planned dose of 50 Gy and 40 Gy in 5 fractions to gross tumor volume (GTV) and target volume planning

(PTV), respectively. Priority was given to OAR constraints. Criteria for acceptable coverage of the target

were: a) 50 Gy and 47.5 Gy to ≥90% and ≥95% of the GTV, respectively, and b) 40 Gy to ≥95% of the PTV.

For each plan, a Expansion-Intersection Volume (EIV), corresponding to the intersection volume between

PTV and OARs expanded by 5 mm, was calculated. The planned doses to the target volumes and the OARs

were evaluated and statistically analyzed.

Results

Median GTV and PTV sizes were 40.8 (range 22.3-205.3) cc and 73.7 (range 36.1-266.7) cc, respectively.

Treatment plans have been optimized to keep a V35 in the duodenum, stomach and intestines below 0.5cc

in all cases. Median V50 and V47.5 for GTV was 91.0% (range 82.4% -97.8%) and 96.8% (range 92.5% -

99.9%), respectively: GTV coverage was acceptable in 10 out of 14 cases. Median V40Gy for PTV was 96.8%

(range 90.0% -99.8%): PTV coverage was acceptable in 11 of 14 cases. Median EIV was 12.9 (3.9-25.1) cc.

Spearman correlation showed a significant association between EIV and V47.5Gy for GTV (rho -0.77228, p

<0.001) and V40Gyfor PTV (rho -0.68352, p <0.001), respectively (Figure 1).

Conclusions

Inhomogenous dose escalated prescription to a BED≥100Gy10 is a feasible treatment strategy in selected

patients with LAPC (Figure 2). EIV represents a simple tool to identify suitable patients for this approach


Sara LUCIDI, Mauro LOI (Firenze, Italy), Vanessa DI CATALDO, Andrea Gaetano ALLEGRA, Ilaria MORELLI, Chiara MATTIOLI, Michele AQUILANO, Andrea ROMEI, Raffaella DORO, Laura MASI, Lorenzo LIVI
00:00 - 00:00 #29622 - P140 A 3d-printed personalized immobilization device for breast SBRT in prone position.
P140 A 3d-printed personalized immobilization device for breast SBRT in prone position.

Introduction

Prone radiotherapy (RT) is consistently associated with reduced heart and lung doses, yet its application remains limited because of the difficulty of proper patient set-up, insufficient reproducibility and being uncomfortable. To overcome these issues, Geneva University Hospital has developed a personalized 3D-printed, MRI-compatible, breast device:  Venus Shell™.

We report the interim analysis results (10 out of 20 foreseen) of an ongoing proof-of-concept study. The main objectives were to determine if the shells could improve patient comfort and reduce time required for prone pre-positioning, while maintaining at least the same pre-positioning accuracy as without the shell.

Methods

Inclusion criteria: age18 years; undergo adjuvant RT; and WHO performance status≤2. Exclusion criteria: known cutaneous allergies to medical plasters or plastic substances; body weight > 90kg; current pregnancy; or having had a mastectomy without breast reconstruction.

For all patients, a body-surface scan was taken for the shell production and 6 ultra-low dose CT scans on the prone board were made, 3 with and 3 without shell. The time to position the patient before each CT was recorded. Patients filled comfort surveys after the surface scan and the CT imaging session. Automatic image registration between the first CT (reference) and the verification CTs (second and third) were used to evaluate the pre-positioning accuracy.

 

Results

Total breast cancer patients analysed: 6 left-sided and 4 right-sided. Median (range) age was 58 years (45-80), median body-mass-index was 23 (17-28), and breast cup size from 70A to 85D. Patients scored positively the surface scan experience with median 6 out of 7 (5-7). They also reported significantly lower pain (P=0.025) and a less unpleasant experience (P= 0.034) with the shell. No difference was found in the patient’s “feeling/urge to move” (P=0.10).

No significant difference was detected (P=0.22) for the time to pre-position with a mean±std.dev. of 1.8±0.6 with and 2.25±1 minutes without shell. However, the pre-position accuracy wearing the shell was significantly better with a mean±std.dev translation distance of 1±0.7 mm versus 24±17 mm (P<<0.001) and similar for the maximum of pitch, yaw and roll angles of 0.03±0.06° versus 1.0±0.93° (P<0.001).

Discussion

These results suggest that Venus shell™ could increase comfort and accuracy in prone breast RT and eliminate time-consuming patient position corrections following pre-positioning.  Accurate prone positioning would permit use of MRI (which can include the shell) for target delineation and allow the development of high-precision SBRT protocols in the adjuvant or neoadjuvant setting of breast cancer treatments.


Giovanna DIPASQUALE (Geneva, Switzerland), Johannes Wilhelmus Edmond UITERWIJK, Filip KASSÁK, Melpomeni KOUNTOURI, Mariagrazia DI MARCO, Matteo DELL’OMODARME, Nikolaos KOUTSOUVELIS, Pelagia TSOUTSOU, Pelagia TSOUTSOU
00:00 - 00:00 #29702 - P141 Stereotactic body radiotherapy for pulmonary oligometastases: a mono-institutional analysis of clinical outcomes and potential prognostic factors.
P141 Stereotactic body radiotherapy for pulmonary oligometastases: a mono-institutional analysis of clinical outcomes and potential prognostic factors.

Purpose We report the retrospective data of a cohort of patients who received stereotactic body radiotherapy for pulmonary oligometastases aiming to assess the clinical factors potentially affecting the clinical outcomes.

Methods The present series reports the outcomes of a cohort of 71 patients with pulmonary oligometastases. All patients were treated with SBRT performed with VMAT-IGRT, up to 5 secondary lesions. Survival estimates were performed using Kaplan-Meier method.

Results A total of 98 lesions in 71 patients were treated from February 2014 to August 2020. The most frequent histologies were: colo-rectal in 37.7%, lung cancer in 44.8%, head and neck cancer in 8.1%, other in 9.4%. Median age was 71 (range, 32-93 years). Concurrent systemic therapy was administered in 32.3%. SBRT was delivered for a median total dose of 60 Gy (range, 55-70 Gy) in 3-10 fractions for a median BED10=105 Gy (range, 96-180 Gy). Median follow-up was 29.5 months (range, 6-81), with no acute or late G>2 adverse event. Our LC rates at 2 and 4-years were 92.4% and 89.8%. DPFS rates at 2- and 4- years were 45.3% and 27.2%. A second SBRT course was proposed in 21 cases (29.5%) who developed an oligoprogression, resulting in median time to second progression of 9 months (range, 2-44) and 2-year PFS2 rate of 42.4%. At univariate analysis, patients with sequential oligometastases reported better OS rates (p=0.002), also confirmed at multivariate analysis, where also distant progression related with worse OS (p=0.022). Higher local control rates relate to better PFS (p=0.04). The 2- and 4- OS rates were 61% and 39.7%

Conclusions SBRT is feasible for pulmonary oligometastases with favorable outcomes and toxicity. At multivariate analysis, patients with sequential oligometastatic progression maintain a survival advantage. Also, local control was found to be related to improved PFS rates. 


Francesco CUCCIA, Rosario MAZZOLA (Verona, Italy), Vanessa FIGLIA, Niccolò GIAJ-LEVRA, Luca NICOSIA, Francesco RICCHETTI, Michele RIGO, Giorgio ATTINÀ, Edoardo PASTORELLO, Claudio VITALE, Ruggero RUGGIERI, Filippo ALONGI
00:00 - 00:00 #29788 - P142 Assessing the dosimetric impact of intrafraction prostate motion in dose-escalated linac-based SBRT.
P142 Assessing the dosimetric impact of intrafraction prostate motion in dose-escalated linac-based SBRT.

Purpose

The aim of this study was to investigate the impact of intrafraction prostate motion on dose metrics and the effect of beam gating and motion correction in dose-escalated linac-based SBRT.

 

Material and Methods

Fifty-six fractions from 13 patients treated with dose-escalated SBRT using FFF-VMAT technique were examined. Real-time 3D prostate motion data were acquired using a novel electromagnetic tracking device. Beam delivery was interrupted whenever the prostate trespassed a 2-mm safety tolerance in any of the three spatial directions and table couch position corrected unless the offset was transient. Prostate trajectories with and without beam gating and motion correction events were reconstructed with in-house C++ code. Both actually delivered treatments (case A) and non-gated treatments (case B) were simulated by incorporating the prostate motion for each fraction into the patient original treatment plan with an isocenter shift method. Dosimetric parameters of the two motion-inclusive plans, re-calculated with Monaco Monte Carlo TPS, were compared to planned values and with protocol dose constraints. A Wilcoxon-Mann-Whitney test (alpha=0.05) was performed to assess statistical significance.

 

Results

Average values of mean prostate displacements in case A were -0.2 mm [-1.5–0.8], 0.1 mm [-1.4–1.5], and -0.3 mm [-1.7–1.4] in lateral, longitudinal, and vertical directions, respectively. The same values in case B were -0.3 mm [-3.1–0.8], 0.0 mm [-4.2–3.7], and -0.6 mm [-3.5–1.9]. Mean relative dose differences were -0.1% [-1.8–1.0] for CTVD99% and -0.2% [-1.6–0.7] for PTVD95% in case A, and -1.2% [-8.8–0.8] and -1.2% [-5.9–0.7] in case B. Urethra planning organ at risk volume (uPRV) was slightly degraded after taking motion into account, with larger than 1% differences in uPRVD10% observed only for 1 patient in case B. The rectum and bladder dose metrics showed a favourable underexposition of rectum and an undesirable overdose to bladder in both motion-inclusive plans. Nevertheless, no protocol dose constraints violations were observed for bladder due to the posterior displacement of the prostate. In both cases, the dosimetric comparison relative to planned dose wasn’t statistically significant (p>0.05).

 

Conclusion

Current CTV-to-PTV margins, robustness of original treatment plans, and fast FFF beams delivery did not result in significant degradations of dose metrics for target and organs at risk due to intrafraction prostate motion. Anyway, beam gating and motion correction ensured superior results and are recommended in dose-escalated prostate SBRT. The dosimetric impact of daily anatomy will be also explored in future studies.


Valeria FACCENDA, Valeria FACCENDA (Monza, Italy), Denis PANIZZA, Denis PANIZZA, Martina Camilla DANIOTTI, Martina Camilla DANIOTTI, Sara TRIVELLATO, Paolo CARICATO, Paolo CARICATO, Raffaella LUCCHINI, Raffaella LUCCHINI, Stefano ARCANGELI, Stefano ARCANGELI, Elena DE PONTI, Elena DE PONTI
00:00 - 00:00 #29793 - P143 Treatment protocol in ultra-high Single-Dose Radiation Therapy for organ-confined prostate cancer.
P143 Treatment protocol in ultra-high Single-Dose Radiation Therapy for organ-confined prostate cancer.

Purpose/Objective

Great emphasis on rigorous planning and delivery techniques must be placed when using extreme hypofractionated regimens to fully exploit their potential benefits in optimizing the therapeutic ratio, thus yielding excellent clinical outcomes. The aim of this study was to report the clinical treatment planning implementation for organ-confined linac-based prostate Single-Dose Radiation Therapy (SDRT) using electromagnetic tracking for real-time intrafraction organ motion management (NCT04831983).

 

Material/Methods

Since June 2021 ten patients with localized unfavorable intermediate or selected high-risk prostate tumors were enrolled to receive an ultra-high SDRT of 24 Gy (BED 1.5 = 408 Gy). Patients were simulated with empty rectum and bladder filled by a Foley catheter. Fused CT and T2W 3D MRI image sets were used to delineate target and OARs. The PTV consisted of the CTV with a 2-mm isotropic margin. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, bladder, and urethra. Patients were planned to a minimum dose defined by the OARs dose constraints with a dose escalation to 24 Gy to the target volume away from the HDAZ. A 10MV FFF beam energy single arc from 140° to 220° was optimized using target penalties with the Monaco Monte Carlo TPS. During the treatment delivery, CBCT matching ensured patient setup alignment and target localization, and any online tracking detected motion greater than 2 mm was realigned by repeating CBCT.

 

Results

Figure 1 shows axial, sagittal, and coronal fused CT/MR slices representing the dose distribution for a patient treated with a single fraction of 24 Gy. Treatment goals and characteristics are summarized in Table1. All the predefined planning objectives were fulfilled. Median PTV volume was 68.5 cc [25.6-95.8]. Average total monitor units per plan were 6726 ± 525. All the treatment plans were quality assured using a two-dimensional silicon diode array and fulfilled the gamma (2%/2mm) passing rate >90% objective. Mean delivery time lasted 4.7 ± 0.7 minutes. Overall mean treatment time, from procedure inception to beam-off, was 17.6 ± 9.2 minutes. Intrafractional tracking was successfully carried out in all treatment sessions.

 

Conclusion

The use of an HDAZ during planning limited the volume of rectal mucosa receiving critical doses. The accomplishment of urethral sparing via negative dose-painting to minimize genitourinary toxicity is feasible through appropriate imaging procedures and online tracking during treatment delivery. Our preliminary findings offer encouraging perspectives on the feasibility and safety of 24 Gy SDRT in organ-confined prostate cancer.


Denis PANIZZA (Monza, Italy), Raffaella LUCCHINI, Valeria FACCENDA, Martina Camilla DANIOTTI, Paolo CARICATO, Sara TRIVELLATO, Elena DE PONTI, Stefano ARCANGELI
00:00 - 00:00 #29823 - P144 Efficacy of stereotactic radiotherapy in patients with oligometastatic iodine-refractory thyroid cancer.
P144 Efficacy of stereotactic radiotherapy in patients with oligometastatic iodine-refractory thyroid cancer.

Aims: 

Differentiated thyroid cancer is usually associated with a good prognosis. The development of metastases in Iodine-refractory thyroid cancer adversely affect patients' quality of life and survival. The advent of tyrosine-kinase inhibitors drugs (TKI) allowed a great improvement of patients’ outcome but, in case of oligometastatic disease, a locoregional ablative approach such as Stereotactic Radiation Therapy (SRT) could effectively control tumour progression and possibly defer the need of systemic therapies. In our study, we analysed the effectiveness of SRT in oligometastatic Iodine-refractory thyroid cancer patients. 

 

Methods:

We retrospectively analysed patients with differentiated oligometastatic thyroid cancer treated with SRT in our Radiation Oncology Unit from 2011 to 2020. 

We collected demographics and treatment-related characteristics. Local Control (LC), Progression Free Survival (PFS) and Overall Survival (OS) rates were evaluated. Patients with anaplastic histology, incomplete treatment or without follow-up information were excluded.

 

Results:

We retrospective analysed a cohort of 15 patients, aged between 47 and 72 years old (median 63,3). 8 (53,3%) patients were males and 7 (46,7%) were females. A total of 42 lesions were treated: 19 were located in bones (45,2%), 11 in lymph nodes (26,2%), 3 visceral (7.1%), 7 in the brain (16,7%) and 2 in the lungs (4,8%). SBRT was delivered in 1-8 fractions, with a median dose of 30Gy (range 14-60Gy). Median follow-up from the date of the first SRT was 47,7 months (range 14,4–105 months).

After SRT we observed a complete response in 21 lesions (50%), partial response in 13 (31%), stable disease in 7 (16,7%) and only 1 progressive lesion (2,4%). We observed 9 local recurrences (21,4%) with an actuarial LC of 95% and 89,9% at 12 and 24 months respectively, while PFS was 45.6% and 32,9% at 12 and 24 months respectively.

The OS at 12, 24, 48 months was 93,3%, 86,2% and 79%, respectively.

A total number of 10 patients (66,7%) underwent TKI treatment (4 Sunitinib and 5 Lenvatinib) for progressive disease: median time to first systemic treatment from the SBRT was 17,7 months (range 1-47,7 months).

At the end of this analysis, 5 patients (33.3%) were still without systemic therapy, showing a good disease control after a median follow-up of 50,6 months (range 35.3-57).

 

Conclusions:

In our experience, SRT yields satisfying local control rates in oligometastatic Iodine-refractory thyroid cancer, allowing for a deferral of systemic therapies.


Gabriele SIMONTACCHI (Florence, Italy), Erika SCOCCIMARRO, Marianna VALZANO, Sara LUCIDI, Monica MANGONI, Clotilde SPARANO, Lorenzo LIVI
00:00 - 00:00 #29880 - P145 Prostate Stereotactic body radiotherapy (SBRT) with a focal boost to the dominant intraprostatic nodule (DIN).
P145 Prostate Stereotactic body radiotherapy (SBRT) with a focal boost to the dominant intraprostatic nodule (DIN).

Objectives: Although localized prostate cancer (PCa) is multifocal, there is a general consensus that dominant intraprostatic nodule (DIN) is mainly responsible for disease progression after radiation therapy. We therefore assumed that stereotactic simultaneously integrated boost dose to the DIN should increase local control.

Patients and Methods: Between May 2020 and September 2021, 18 patients with clinically localized prostate cancer, having a mean age of 73 years (range 63 – 82) and with a mean PSA of 9.40 (range 4.5 – 44.7 ng/ml) underwent Cyberknife stereotactic radiotherapy treatment. According to the D’Amico definition, 5 of them (28%) had low risk, 8 (44%) intermediate risk and 5 (28%) high risk disease. All patients received 37.50 Gy in 5 consecutive fractions to the whole prostate gland, having an average volume of 71.5 cm^3 (range 44.9 – 101.9), while an integrated boost up to a total dose of 50 Gy was applied to the dominant intraprostatic nodule detected on the multiparametric MRI, having an average volume of 1.77 cm^3 (range 0.28-5.40). Ten patients (55%) had PI-RADS 5 lesions (according to the prostate imaging reporting and data System, 2nd v.) and a mean PSA density of 0.16 (range 0.06-0.81). Real time intrafractional motion tracking was used.

Results: the mean IPSS before treatment was 1/21 and no worsening was found during the acute phase. The most common GU complains were urinary urgency and aggravating nocturia, while increased stool frequency was the main GI symptom. In 1 out of the 18 patients an indwelling catheter was required for a complete bladder outlet obstruction occurred 1 week after the radiation course completion. It was the case of the higher prostate volume patient (101.9 cm^3). No urinary or rectal late grade II-III toxicity were registered. With a mean follow up of 6 months (range 3–19) no biochemical failure was observed.

Conclusions: simultaneously integrated boost dose to the DIN was well tolerated with similar acute GU and GI toxicity rates if compared with historical prostate SBRT cohorts, mainly due to the more and more proven ability of current technologies to minimize treatments’ adverse effects. Continued accrual and follow-up are required to confirm long term results.


Giancarlo BELTRAMO (Milan, Italy), Isa BOSSI ZANETTI, Sergio PAPA, Achille BERGANTIN, Francesco MORETTI, Deliu Victor MATEI
00:00 - 00:00 #29921 - P146 Predictive factors of late genitourinary toxicity after Cyberknife re-irradiation for locally recurrent prostate cancer.
P146 Predictive factors of late genitourinary toxicity after Cyberknife re-irradiation for locally recurrent prostate cancer.

Aims

Re-irradiation with stereotactic body RT (re-SBRT) is a valid treatment option for local relapse in prostate cancer after postoperative or definitive radiotherapy (RT).

However, we need predictive factors to prevent the onset of late adverse events. Here we present a retrospective analysis conducted on a cohort of patients treated with re-SBRT through Cyberknife robotic system. The correlation between dosimetric data and incidence of late genitourinary (GU) toxicity was evaluated to establish a model to predict late GU Grade >2 adverse events in this population.

Methods

We collected data of 50 consecutively  patients treated from June 2012 to February 2016. All patients were affected by biochemical relapse defined by European Urology Association Criteria after definitive or postoperative radiotherapy, and macroscopic evidence of intra-prostatic or prostate bed recurrence was detected by 18F-choline PET/CT and MRI.  Patients with metastatic or regional nodal disease were excluded. All patients underwent reSBRT using the CyberKnife robotic system, for a total dose of 30 Gy in 5 fractions every other day. Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE) toxicity scale v.5. Relationship between late GU G>2 and Gross Target Volume (ccGTV), Dose to 50% of urinary bladder volume (DB50), Maximum dose within Planning Target Volume (Dmax), urethra Dmax (UDmax) and Total Equivalent Dose (tEQD2) administered to prostate or prostate bed was explored with logistic regression. A receiver operating characteristic (ROC) curve was used to find the optimal cut-off point for continuous variables significantly predictive for late GU adverse events.

Results

After a median follow up of 48.2 months (6.4-86.3), late G> 2 GU toxicity occurred in 13 (26%) patients. At Univariate Analysis, no significant impact of ccGTV (p=0.38), DB50 (p=0.25), Dmax (p=0.88), and tEQD2 total was detected (p=0.76 ). Only UDmax showed significant association with Late G> 2 GU toxicity (p=0.02).  ROC analysis showed that UDmax >34.12 Gy best predicted GU toxicity, with a positive and negative likelihood ratio of 3.56 (95% CI 1.1-11.3) and 0.69 (95% CI 0.4-1.1), respectively (AUC 0.66, p=0.06).

 

Conclusion

These data suggest that higher urethral dose may be associated to higher risk of late G> 2 GU toxicity. Thus, due to the low number of events, larger series with long term follow up would be needed to better identify a model to predict late GU adverse events after re-SBRT.


Giulio FRANCOLINI, Cecilia CERBAI, Gabriele SIMONTACCHI (Florence, Italy), Mauro LOI, Vanessa DI CATALDO, Beatrice DETTI, Anna PERUZZI, Marco BANINI, Raffaella DORO, Laura MASI, Lorenzo LIVI
00:00 - 00:00 #29952 - P148 SBRT of oligometastatic gynecological cancer: predictors of distant progression-free survival.
P148 SBRT of oligometastatic gynecological cancer: predictors of distant progression-free survival.

Aims: This study reports the preliminary results of a monoinstitutional experience with stereotactic body radiotherapy (SBRT) performed on oligometastatic gynecological cancer patients. 

Methods: From 04/2009 to 07/2021, 85 lesions (46 patients) were treated: 5 lesions (4 patients) with Image Guided-helical Intensity Modulated Radiotherapy (IG-IMRT) at a median dose of 54 (35-63) Gy in 6 (5-10) median fractions prescribed at 95% of the Planning Target Volume (PTV), and 80 lesions (42 patients) with robotic SBRT at a median dose of 40 (18-60) Gy in 5 (1-8) fractions, prescribed at a median isodose of 80% (68-84%). Ten.6% of lesions were in the field of a previous adjuvant/salvage IG-IMRT performed at a median dose of 50.4 Gy. Primary origin was: uterine in 39.1%, ovarian/fallopian tubes in 34.8%, and cervical/vulvar/vaginal in 26.1% of patients. Metastatic site was: brain in 6.5%, liver in 4.3%, lymph-nodes in 60.9%, lung in 23.9%, and bone in 4.3% of patients. Number of concomitant lesions was 1 in 67.4%, 2 in 19.6%, 3 in 2.12%, 4 in 4.3%, and 5 in 6.5% of patients. De nuovo oligometastatic were 32.6%, induced 23.9%, and relapsed 43.5% of patients.

Results: Median age at the treatment was 67.4 years (Interquartile Range, IQR: 58.6-75.7). Median follow-up from initial diagnosis was 75.6 months (IQR:46.4–164.8). Median Biologically Effective Dose(BED) prescribed: 79.2 Gy (IQR:59.5-102.6). Twelve and 24 month local relapse-free survival(LRFS) was 88.3 and 84.3%, respectively, while 12 and 24 month distant relapse-free survival(DRFS) was 44.6 and 27.6%. Twenty-four and 36 months overall survival (OS) was 100% and 85% respectively. Acute toxicity registered was grade (G) 1 13% and G2 6.5%. Late toxicity was 2.2% G1, 2.2% G2 and 2.2% (1 patient) G3 (vertebral fracture). There were no differences in DRFS (see Fig.1) and OS between the three groups. At the multivariate analysis factors predicting distant relapse were: age at diagnosis HR=1.07 (95%CI:1.03-1.13, p=0.0021), number of lesions3 vs 1, HR= 4.16 (95%CI:1.34-12.9, p=0.0135), and induced vs de nuovo oligometastatic lesions HR=8.55 (95%CI:1.96-37.3, p=0.0043), but not relapsed vs de nuovo(p=0.067). 

Conclusion: SBRT is effective for the local control of oligometastatic disease from gynecological tumors, with low toxicity. Distant relapse remains the primary cause of failure after SBRT in oligometastatic gynecological patients, and a number of lesions≥3, age at diagnosis and induced oligometastatic lesions are predictive for distant relapse.


Andrei FODOR (Milano, Italy), Chiara BROMBIN, Giuseppina MANDURINO, Flavia ZERBETTO, Stefano VILLA, Chiara DEANTONI, Roberta CASTRICONI, Roberta TUMMINERI, Italo DELL'OCA, Anna CHIARA, Najla SLIM, Paola MANGILI, Antonella DEL VECCHIO, Nadia DI MUZIO
00:00 - 00:00 #29969 - P149 Linac-based stereotactic body radiation therapy (SBRT) in elderly prostate cancer patients.
P149 Linac-based stereotactic body radiation therapy (SBRT) in elderly prostate cancer patients.

Aim: An increasing number of literature data recommends SBRT in prostate cancer (PC) patients. A Linac-based SBRT treatment with risk-adjusted prescription dose is usually proposed to elderly patients with PC. An update of data regarding patients treated in 30 months was performed to evaluate the safety and efficacy of SBRT.

Methods: Men aged ≥70 years affected by localized PC were treated with Linac-Based SBRT. The entire prostate was irradiated up to a total dose of 35 Gy in 5 fractions.The dose was optimized to isodose line of 90% in low/favorable intermediate cases and 80% in unfavorable intermediate/high risk cases.A Volumetric Modulated Arc Therapy (VMAT) technique was used for planning and delivery.Treatment was delivered over 1 or 2 weeks based on PTV and pre-treatment urinary symptoms. Some patients also received androgen deprivation therapy (ADT) according to the risk group classification. All patients were supported by corticosteroids. Toxicity and quality of life (QoL) were assessed at baseline, after treatment and during follow-up (FU) using the Common Terminology Criteria for Adverse Events and International Prostatic Symptoms Score (IPSS). PSA values were recorded before treatment and during FU as biochemical response criteria.

Results:Between July 2019 and December 2021, 78 patients were treated.Median age was 76 years (range 61-88); 33 had low risk, 30 favorable/unfavorable intermediate risk and 15 high risk PC. Median pre-treatment PSA was 5 ng/ml (range 0,61-25).ADT was prescribed in 23 (29.5%) patients. In cases in which dose was optimized to isodose 90%, Dmax was 38,9 Gy,whereas when optimizated to isodose 80%, Dmax was 43,8 Gy. Median PTV was 109,6cc (range 75-157,7). Median baseline IPSS was 3(range 0-6). At the end of the treatment, no >G1 acute toxicity was observed. Two-three weeks after SBRT, 13(17%) patients reported G2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention) and 9 patients(12%) presented rectal tenesmus. During FU, only 3 cases of rectal bleeding were observed (related to comorbidities). No relevant deteriorations of QoL were described. At a median FU of 15 months(range 1-27), excellent biochemical disease control was achieved in all cases with a median PSA of 1,5 ng/ml (range 0,01- 7,3).No differences were observed between the two different prescription approaches.

Conclusion:Linac-based SBRT for localized PC is feasible and well tolerated, even in elderly and frail patients. Excellent biochemical disease control is associated with high compliance of very elderly patients to treatment.Longer follow-up is needed to confirm late treatment tolerance and efficacy.


Roberta CARBONARA, Fabiana GREGUCCI, Maria Paola CILIBERTI, Alessia SURGO (Acquaviva Delle Fonti, Italy), Morena CALIANDRO, Giuseppe LUDOVICO, Marcello SCARCIA, Eleonora PAULICELLI, Ilaria BONAPARTE, Alba FIORENTINO
00:00 - 00:00 #30012 - P150 Impact of pneumatic compression on reducing motion in lung SBRT.
P150 Impact of pneumatic compression on reducing motion in lung SBRT.

Purpose: To determine the impact of pneumatic abdominal compression (AC) with compact and lightweight rail system (EAMIS Lite Macromedics) on reducing inter – and intrafractional motion.

Materials and methods: This study included 11 patients with 18 lung tumors treated with stereotactic body radiotherapy in 2021 in a single center. Tumor motion was assessed in every lesion and every fraction of radiotherapy. Compressed patients were supine, arms up with kneefix and AC equipment. All patients received daily online-matched cone beam computer tomography (CBCT) before treatment and during SBRT. Initial setup error and intrafraction motion were determined for all patients and all fraction dose. Significant intrafractional changes in lung tumor motion were defined as a change of >4 mm. The statistical analysis was performed using Statistica ver 13.3software.

Results: Total 62 measurments of set up error and intrafraction tumor movements were recorded. The mean (± SD) set up error in CBCT before treatment was 4.3 ± 3.5 mm, 5.6 ± 4.0 mm, and 5.6 ± 3.7 mm, in the LR, AP, and SI directions, respectively. The mean (± SD) lung tumor motion in CBCT during radiotherapy  was 2.0 ± 1.9 mm, 2.0 ± 1.8 mm, and 2.2 ± 2.0 mm, in the LR, AP, and SI directions, respectively. Overall significant intrafractional changes were observed in at least one diameter of 16 measurments (25%), specifically in10 (16%)  LR , 5 (8%) AP and  6 (10%) SI directions. 

Conclusions: Abdominal compression is an effective and feasible technique reducing motion in lung SBRT. Residual and significant intrafractional movements occur mainly in the LR direction.


Tomasz WISNIEWSKI (Bydgoszcz, Poland), Maciej BLOK, Magdalena ADAMCZAK-SOBCZAK, Paweł SZYMAŃSKI, Szymon ZIÓŁKOWSKI, Maciej HARAT
00:00 - 00:00 #30014 - P151 Elective SBRT for iliac nodes in high risk prostate cancer.
P151 Elective SBRT for iliac nodes in high risk prostate cancer.

Elective SBRT for iliac nodes in high risk prostate cancer

 

 

Muriano Oscar; Murina Patricia; Angel Daniela; Giraudo Agustin; Villegas Frugoni Agostina; Galletto Maria Milla; Chiban Mercedes; Zunino Silvia; Venencia Daniel.

 

Instituto Zunino, Fundación Marie Curie. Córdoba, Argentina.

 

INTRODUCTION

Five-Fraction SBRT has been widely tried in low and intermediate-risk prostate cancer.

 

OBJECTIVES

To evaluate gastrointestinal (GI) and genitourinary (GU) acute toxicity (<3 months) and delayed (≥3 months), after prostate and pelvic nodes irradiation with SBRT technique.

 

MATERIALS AND METHODS

Forty-two patients underwent Five-Fraction SBRT (alternate days), they were prescribed: prostate =40 Gy (EQD2 108,6 Gy), pelvic nodes=25 Gy (EQD2 46,4 Gy), simultaneously treated volumes with Novalis Tx and TrueBeam (BrainLab-Varian). All patients underwent complete hormone blockage.

The toxicity of GU was evaluated through IPSS (International Prostate Symptom Score), dysuria (G0-G5), and GI toxicity (G0-G5), according to Common Terminology Criteria for Adverse Events (CTCAE v5.0). Patients were previously evaluated at the beginning and immediately after the treatment with a follow-up at 3, 6, 12, 18, and 24 months post SBRT.

 

 

RESULTS

Forty-two patients with a mean follow-up of 17 months were evaluated. [2-29].

Early GU toxicity: 1 patient (2%) presented G3 dysuria and 2 patients (5%) G2 dysuria.

Late GU toxicity: 1 patient (8%) presented G2 dysuria; ≥G3 dysuria was not observed.

Mean IPSS was 6 [0-19]; 9 [1-25]; 7 [1-17]; 5 [2-13]; 7 [2-18]; 6 [1-23] and 3 [1-6], prior to the treatment and 3, 6, 12, 18 and 24 months after the treatment, respectively.

Early GI toxicity: 5 patients (12%) with G2 toxicity, there was no ≥ G3 toxicity.

Late GI toxicity: 1 patient (4%) with G2 toxicity, there was no ≥ G3 toxicity.

 

CONCLUSIONS

Patients who underwent SBRT tolerated the treatment well, there was no evidence of late GI or GU ≥ G3 toxicity. Regardless of the low number of patients and short follow-up, elective external and internal iliac nodes irradiation with SBRT in high risk prostate cancer is safe and noticeably feasible. 


Oscar MURIANO (Córdoba, Argentina)
00:00 - 00:00 #30016 - P152 Prostate-Specific Antigen analysis after Stereotactic body radiation therapy.
P152 Prostate-Specific Antigen analysis after Stereotactic body radiation therapy.

Prostate-Specific Antigen (PSA) analysis after Stereotactic body radiation therapy (SBRT)

Muriano Oscar; Murina Patricia; Angel Daniela; Giraudo Agustin; Villegas Frugoni Agostina; Galletto Maria Milla; Chiban Mercedes; Zunino Silvia; Venencia Daniel.

 

Instituto Zunino, Fundación Marie Curie. Córdoba, Argentina.

 

Introduction

Five-Fraction SBRT has been widely tried in low and intermediate-risk prostate cancer, with excellent tolerance and response to PSA.

 

Objectives

The objective of the analysis was to evaluate PSA kinetics of patients with prostate cancer treated with stereotactic body radiation therapy (SBRT) without hormone blockage.

 

MATERIALS AND METHODS

A retrospective analysis of patients with localized prostate cancer treated with SBRT technique as the only and definitive treatment, from November 2013 to September 2017 was performed. Patients received 36.25 Gy to 40 Gy in five-fractions during alternate days with a Novalis Tx linear accelerator. PSA nadir, Bounce, and biochemical recurrence were evaluated.

 

Results

Ninety-nine patients were included in the analysis, with a mean follow-up of 50 months [6-81], 46 (46.5%) low risk patients, and 53 (53.5%) intermediate risk. Initial mean PSA was 7.7 ng/ml [0.42-17]. Mean PSA nadir (nPSA) was 0.48 ng/ml [0.01-4.4] and mean time to nPSA was 39 months [2-72]. Biochemical recurrence according to Phoenix criteria (≥2ng/ml) was 7%, occurring on average after 44 months [5-80]; survival rate free from biochemical recurrence was 97%, 95%, and 92% at 24, 36, and 48 months, respectively. Biochemical recurrence was not related with the age of the patient, nPSA, or the risk group (p>0.05). Bounce was observed (≥0.2 ng/ml) in PSA out of 14% of the patients, with a mean level of 0.56 ng/ml [0.2-1.42] and a mean time of 22 months appearance.

 

Conclusions

At our institutional analysis, we have observed a PSA response that coincides with the results published currently. SBRT is a safe and effective therapeutic option for patients with low and intermediate prostate cancer risk, with low nPSA and excellent survival rate free from biochemical recurrence.


Oscar MURIANO (Córdoba, Argentina)
00:00 - 00:00 #30018 - P153 Prostate/prostate bed salvage stereotactic re-irradiation.
P153 Prostate/prostate bed salvage stereotactic re-irradiation.

Objective: To evaluate toxicity and outcomes after salvage robotic stereotactic body radiotherapy-SBRT- (CyberKnife®,Accuray, Sunnyvale, Ca) re-irradiation of patients with intraprostatic/prostatic bed recurrences of pelvic malignancies. 

Methods: From 11/2018 to 10/2021, 20 patients with intraprostatic/prostatic bed recurrence after radiotherapy, diagnosed on MRI/ PET choline/PSMA and/or biopsy-proven, underwent a salvage re-irradiation with SBRT: 9 patients with prostate cancer failure after previous radical radiotherapy, and 11 patients after adjuvant/salvage radiotherapy. Median prior RT dose was 70.7 (38.25-78) Gy and the median interval to SBRT salvage therapy was 79.3 (11-208) months. Median PSA before robotic SBRT was 2.64 (1.14-26.8) ng/ml. Fiducial markers were implanted into the target in 19 of 20 patients. Median SBRT total dose was 35 (30-35) Gy in 5 fractions (EQD2=85 Gy, for α/β 1.5). Median prescription isodose was 70% (59-81%). In 12 patients, a “urethral sparing” was used. In 10 cases a precautionary therapy with steroids and alpha-lytics was prescribed during the salvage treatment. Twelve patients received neoadjuvant or concomitant/adjuvant androgen suppressive therapy during their SBRT course. Toxicity was scored in accordance with CTCAE v 5.0. 

Results: Median follow-up was 17.4 months (2.35-38.15) months. Acute genitourinary (GU) toxicity was observed in 40% of patients and was limited to grade (G)1 in 35% of patients and G2 (minimal strangury, urgency and occasional urinary incontinence) in 5%. Ten% of patients reported late GU G3 toxicity (urinary retention requiring catheterization and transurethral resection), and 5% G2 urinary toxicity. No acute and late gastrointestinal toxicity was observed. At the last follow-up 2 patients died due to a non cancer-releated cause. Twenty-four-months Kaplan Meier estimates of biochemical relapse-free survival (bRFS) was 78.2% (see Figure 1), local-relapse-free survival (LRFS) 92.3% and distant-metastases-free survival 85.1%. 

Conclusions: Prostate SBRT re-irradiation with CK is a feasible treatment option, with good short-term outcomes. Longer follow-up is necessary to assess the long-term benefits and to determine late toxicity.


Roberta TUMMINERI (MILAN, Italy), Andrei FODOR, Sara BROGGI, Chiara Lucrezia DEANTONI, Claudio FIORINO, Italo DELL'OCA, Lucia PERNA, Stefano VILLA, Flavia ZERBETTO, Paola MANGILI, Cesare COZZARINI, Antonella DEL VECCHIO, Nadia Gisella DI MUZIO
00:00 - 00:00 #30079 - P154 Stereotactic Ablative Radiotherapy (SABR) management of oligometastatic Sarcoma.
P154 Stereotactic Ablative Radiotherapy (SABR) management of oligometastatic Sarcoma.

INTRODUCTION

Radiotherapy treatment of sarcomas has not progressed greatly despite new technologies.  However, new target therapies have increased the survival rate free from progression of stage IV tumors. Sarcomas are radioresistant at standard radiotherapy fractionation doses. However, the use of high doses by fraction, for example, using intraoperative radiotherapy, has shown good results in local control (LC) of between 60-90% at 5 years. These results with SBRT can now be reproduced in the management of borderline resectable localized illness (LC 2 years-100%), non-resectable (LC 2 years-85%) and oligometastatic (LC 2 years-60-85%).

HYPOTHESIS

Institutional experience in SBRT management of oligometastasic sarcomas.

MATERIAL AND METHODS

At the ABC Medical Center, from December 2018 to September 2016, we have treated 6 patients with a diagnosis of sarcoma, and 15 lesions treated with SBRT in Novalis Tx equipment with IGRT system (CBCT y ExacTrack), with 19-60Gy/1-8fr fractioning.  Primary tumors have been treated as well as metastasis to lung, bone and brain.

RESULTS

The median follow up was 20 months. Average age was 44 years old (range 23-87), 3 men and 3 women.  The treated lesions were 3 localized non-resectable tumors and 3 oligometastatic stage IV tumors, for a total of 15 lesions: 34 in pelvis, 1 in retroperitoneal, 4 in brain, 4 in lung, 2 bone.  The total median dose used was 30Gy (1-24Gy/1fr, 30-60Gy/5fr., 60Gy/8fr.). Tolerance to treatment was good with patients, only 1 patient toxicity grade 3 (fibrosis) referred pain due to fibrosis attach to diaphragm.  Local control on treated lesions were: 6 complete response (40%), 9 partial response (60%); and mean survival time to progression was 26.5 months.  Mean overall survival was 29.6 months.

 CONCLUSIONS

The use of SBRT in oligometastatic sarcomas allows for good local control of the radiated lesions as well as improving the quality of life of the patients.

The advent of target therapies and other molecular targets allows increasing survival free from progression (SLP) and the use of combined SBRT becoming an excellent tool in integral management.

 


Dolores DE LA MATA (MEXICO CITY, Mexico), Catalina TENORIO, Mariana HERNANDEZ-BOJORQUEZ
00:00 - 00:00 #30102 - P155 Early and Late CT findings following SBRT for lung tumors: Analysis of a Mono-institutional Series.
P155 Early and Late CT findings following SBRT for lung tumors: Analysis of a Mono-institutional Series.

AIMS:

Radiological lung density changes are commonly observed in patients undergoing SBRT. Early changes include consolidation and ground glass opacities, while late changes include fibrosis, bronchiectasis, loss of lung volume and further consolidation.

This study retrospectively analyzed a mono-institutional series of patients treated with lung SBRT and correlated the CT findings with a number of clinical and dosimetric parameters.

 

METHODS:

Between December 2016 and March 2021 sixty patients with seventy primary or secondary lung lesions, were treated on a Linac platform with a VMAT technique to a BED10 ≥100 Gy. Patients, disease and treatment characteristics are summarized in Table 1.

In order to describe the radiological findings over time, the follow-up was divided into two periods: early (within 6 months) (n=70) and late (> 6 months) (n=43) time after treatment.

All the CTs were double-checked by 2 experienced radiation oncologists. Radiation-induced lung injuries were evaluated according to Ikezoe and Koening classification, respectively.

The correlation between the CT pattern and clinical and dosimetric parameters was evaluated.

 

RESULTS:

Median follow up was 9.6 months (1.5-26.8). Among the 70 CT examined at early time after SBRT, 31 had no evidence of increased density, 13 had diffuse consolidation, 11 had patchy consolidation, 8 had diffuse ground glass opacities, 6 had patchy ground

glass and 1 had signs of progression. Late lung injuries were mass like pattern (20), modified conventional pattern (5), scar-like pattern (10). Eight lesions showed signs of progression.

Neither clinical nor dosimetric characteristics were found to be significantly associated with a specific CT pattern, either in the early or late timeframe. Likewise, no significant correlation was found between early and late changes.

 

CONCLUSION:

 Lung injuries represented common radiological findings after SBRT, irrespective of clinical symptoms.

We found no correlation between radiological appearance and clinical and dosimetric parameters at any time interval. Long term results and a larger series are warranted.


Laura GIANNINI (Milan, Italy), Chiara CHISSOTTI, Jessica SADDI, Valeria FACCENDA, Paolo CARICATO, Sara TRIVELLATO, Denis PANIZZA, Elena DE PONTI, Stefano ARCANGELI
00:00 - 00:00 #30112 - P156 Stereotactic Body Radiotherapy in Patients with Lung Metastases and Primary Lung Cancer: Single Center Experience.
P156 Stereotactic Body Radiotherapy in Patients with Lung Metastases and Primary Lung Cancer: Single Center Experience.

Aim: Stereotactic Body Radiotherapy (SBRT) is an effective treatment for inoperable early stage non-small cell lung cancer and lung metastases. In this study, it was aimed to evaluate the results of patients with lung cancer and lung metastases who underwent SBRT in our clinic.

 

Methods and Materials: The data of 30 patients  who underwent lung SBRT were analyzed retrospectively. Conformity index (CI), gradient index (GI), mean lung dose (MLD),  lung V5, V20 doses, local recurrence and last status were calculated for each patient. We used combined lung minus GTV for the definition of lung volumes. The primary endpoint was radiation fibrosis (RF) after SBRT. The secondary endpoint was overall survival (OS) after SBRT. SPSS V22 was used for statistical analysis and the statistical significance limit was accepted as p≤0.05.

 

Results: Thirty patients who underwent SBRT between 01.11.2019 and 08.12.2021 in Ankara City Hospital were analyzed retrospectively. The median follow-up was 7 (1-25) months. The 38 lesions of 30 patients were irradiated. 10 (33.3%) of the patients were diagnosed with primary lung cancer and 20 (66.7%) patients had lung metastases. Primary disease was not under control in 4 (13.3%) patients in the metastatic group. The median dose of 50 Gy (35-60) in 5 (3-8) fractions. RF  was reported in 10 (33.3%) patients on control computed tomography. RF was not assosiated with gender (p=0.068); ECOG (p=0.670); primary or metastasis (p=0.417); ST before SBRT (p=0.127); ST after SBRT (p=0.981); age (p=0.663); total dose (p=0.063); total RT time (p=0.778); number of lesions (p=0.422); diameter of tumor before SBRT (p=0.828). RF was significantly associated with  fraction dose (p=0.002); number of fraction (p=0.004); total PTV volumes (p=0.030); MLD (p=0.009); V5 (p=0.008) and V20 (p=0.022). The median OS was 5.8 (1-25.1) months. The 6-month OS was  89.4% and the 1-year OS was 69.6% (Figure 1). OS was not staticaly significantly associated with gender (p=0.363); ECOG (p=0.339); primary or metastasis (p=0.593); RF (p=0.222); pre-SBRT systemic therapy (ST)  (p=0.302); post-SBRT ST (p=0.122); lesions site (peripheral vs central) (p=0.600), age (p=0.539); total dose (p=0.592); fraction dose (p=0.151); number of fraction  (p=0.196); total treatment time (p=0.582); number of lesions (p=0.891) and total planning target volume (PTV) (p=0.566).

 

Conclusion:  A significant relationship was found between PTV volume, MLD, Lung V5, V20, fraction dose, fraction number and the development of pulmonary fibrosis after SBRT.


Sedef GOKHAN ACIKGOZ, Ipek Pinar ARAL (ankara, Turkey), Yilmaz TEZCAN
00:00 - 00:00 #30136 - P157 C-PAP Breath-hold & SBRT in central and ultra-central lung cancer: a case report.
P157 C-PAP Breath-hold & SBRT in central and ultra-central lung cancer: a case report.

Clinical case: 73 years old patient, affected by COPD, diabetes, mitralic surgery in 2002 with a squamous cell lung cancer, stage cT3 N0. PET-CT in 2019 showed a centroparenchymal tumor (30 x 30 x 50 mm)  touching aortic arc, SUV 16.98. We treated the patient with SABR-SBRT combined with C-PAP as breath-holder.

C-PAP has long been safely used in patients with respiratory failure and chronic obstructive pulmonary disease to maintain airway patency. It provides a constant stream of pressurized air to the upper airways and lungs.

The physiologic effects expected during C-PAP are hyperinflation of the lungs, stabilization and  diaphragm flattening. We made frameless simulation, in supine position and Combifix immobilization, with slow CT  in axial mode, 2.5 mm thickness, 4.0 sec. time gantry rotation, without and with C-PAP.

We applied C-PAP under 10 cm H2O for 5 minutes, with a pO2 30%. Contouring phase was performed using Monaco TPS with Montecarlo alghorytm and we identified the lesion as CTV with no expansion for the PTV (0 mm). The OAR were the left and right lungs, the heart, the oesophagus and the spinal cord. The dose was specified to 95% of the PTV. All the dose constraints were respected.

We prescribed SBRT with a dose of 750 cGy/fr x 8 fractions (total dose 6000 cGy). In November 2019, the patient started the radiation treatment with VMAT and 6 MV FFF photons, to speed up the procedure. The set up was checked by daily cone beam TC.

In September 2020 a PET-TC showed that the treated lesion’s diameter was  2 mm and the SUV was 2,38 vs 7,09; there was a new paraortic lesion (diameter 15 mm, SUV 4,71) invading the left wall of aorta for a length of 4 cm. Due to the position, it wasn’t possible to biopsy it. So we planned a second radiation therapy with SBRT tecnique.

 A new TC simulation was performed with the same setting of the first treatment, except for the use of the C-PAP system, because of the COVID-19 disease. Considering the tumor ‘s site and the proximity of the descendent aorta, the dose prescribed was 400 cGy/fr x 15 fractions with a total dose of 6000 cGy.

 Actually the patient is in good clinical conditions. PET-TC showed no lesion and a mild  FDG  uptake (3,2 vs 7,5) geometrically and precisely referred to the 95% isodose volume of  the second treatment.

 


Davide DI GENNARO (Salerno, Italy, Italy), Immacolata VIVONE, Luca MASTRANDREA, Bruno CURCIO, Giuseppe SCIMONE, Diana LASLO, Arturo LOSCO, Ernesto FALCONE, Immacolata PILOTTI, Valentina SANTANGELO
00:00 - 00:00 #30144 - P158 SBRT in eldery lung cancer patients: a monocentre retrospective study.
P158 SBRT in eldery lung cancer patients: a monocentre retrospective study.

Aim

Stereotactic ablative body radiation (SABRT) for lung cancer is a validated treatment’s option for early stage and advanced or oligoprogression disease. Therapeutic strategy in lung cancer for eldery patients is limited by their comorbidities or perfomance status. 

This is a retrospective analysis to evaluate the safety and efficiency of SBRT for the treatment of lung lesions in elderly patients.

 

Material and Methods

Between April 2018 and January 2021, 44 patients (pts) with more than seventy years old affected by lung cancer in early stage or advanced disease (lung metastasis) were treated with SABRT. Only one or two lesions were irradiated in each patients (total lesions: 60) Median age was 83,5 years (range 70-91).

Patients were stratified by stage: stage IV (19), stage I (18), local relapse of previous surgery (7).

Lesions’ histology distribution was: adenocarcinoma (26), squamous cell carcinoma (7), small cell lung cancer (5) and unknown (22) - biopsy not possible for medical condition. 

Lesions were treated with four different  fractioned regimens depending on location: 50 Gy /5 fr  (19), 45 Gy/ 3 fr (23), 54 Gy/3 fr (8) and 60 Gy/ 8 fr (10), prescribed  to 80%  median isodose curve (71,8-83%).

Local control (LC) was defined by RECIST criteria, overall survival (OS) and toxicity according to CTCAE (v.4) were collected and analyzed retrospectively.

 

Results

Median follow-up was 10 months (2,2-38,2 months). Local control (LC) rate was 85,3% and 74% at 12 and 24 months respectively. Twelve and 24 months - OS was 67,2% and  57,1% respectively. Dividing patients by stage, in stage I 12 and 24 months OS was 64,9%  and  32,5%, while in stage IV 57% and 48,9%, with a difference not statistically significantly (p-value: 0,17). 

Significant lung toxicity wasn’t registered . Only two patients had G1 side effects: one, asthenia and the other thoracic wall pain .

 

Conclusion

Based on our experience, SABR for eldery patients affected by lung cancer is efficient, well tolerated with a good patient’s compliance.  In our opinion should be a valid option for the therapeutic strategy for this setting of patients. Further patients need to be treated in order to obtain a confirmation of this promising preliminary result.


Jessica SADDI (Milano, Italy), Chiara Lucrezia DEANTONI, Italo DELL'OCA, Andrei FODOR, Marcella PASETTI, Flavia ZERBETTO, Roberta TUMMINERI, Stefano Lorenzo VILLA, Sara BROGGI, Antonella DEL VECCHIO, Stefano ARCANGELI, Nadia Gisella DI MUZIO

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07. Eposters - Physics

00:00 - 00:00 #28941 - P159 Monte Carlo-based independent verification of SRS HyperArc plans.
P159 Monte Carlo-based independent verification of SRS HyperArc plans.

Purpose: To investigate the feasibility to use the free Monte Carlo PRIMO software for independent check of cranial SRS plans designed with the Varian HyperArc (HA) technique.

Materials and methods: In this study, the Monte Carlo PRIMO software v. 0.3.64.1800 was used with the phase-space files (v. 2, Feb. 27, 2013) provided by Varian for 6 MV flattening-filtered free (FFF) photon beams from a Varian TrueBeam linear accelerator (linac), equipped with a Millennium 120 multileaf collimator (MLC). This configuration was commissioned by comparing the percent depth doses (PDDs), lateral profiles and relative output factors (OFs) simulated in a water phantom against measurements for field sizes from 1×1 to 40×40 cm2. The agreement between simulated and measured relative curves was evaluated using a global (G) gamma index analysis. In addition, the accuracy of PRIMO to model the MLC was investigated (dosimetric leaf gap, tongue and groove, leaf transmission and interleaf leakage).

Thirty-five HA SRS plans computed in the Eclipse treatment planning system (TPS) were simulated in PRIMO. The Acuros XB algorithm v. 16.10 (dose to medium) was used in Eclipse. Sixty targets with diameters ranging from 6 to 33 mm were included. Agreement between the dose distributions given by Eclipse and PRIMO was evaluated in terms of 3D global gamma passing rates (GPRs) for the 2%/2 mm criteria.

Results: Average GPR greater than 95% with the 2%(G)/1 mm criteria was obtained over the PDD and profiles of each field size. Differences between PRIMO calculated and measured OFs were within 0.5% in all fields, except for the 1×1 cm2 with a discrepancy of 1.5%. Regarding the MLC modeling in PRIMO, an agreement within 3% was achieved between calculated and experimental doses. Excellent agreement between PRIMO and Eclipse was found for the 35 HA plans. The 3D global GPRs (2%/2 mm) for the targets and external patient contour were 99.6% ± 1.1% and 99.8% ± 0.5%, respectively.

Conclusions:

According to the results described in this study, PRIMO using the 6X FFF Varian phase-space files can be used as secondary dose calculation software to check HA plans of Eclipse.


Juan-Francisco CALVO-ORTEGA (GRANADA, Spain), Moragues-Femenía SANDRA, Coral LAOSA-BELLO, Miguel POZO-MASSÓ
00:00 - 00:00 #29315 - P160 Frame application for gamma knife: Evaluation of procedure safety.
P160 Frame application for gamma knife: Evaluation of procedure safety.

Introduction: Application of stereotaxy frame for gamma knife under local anesthesia creates anxiety and phobia in many patients. Syncopal attacks and events of bradycardia have been witnessed at our centre. We tried to analyse the various factors affecting these events and set standards and safety recommendations for the procedure.

Materials and methods

This prospective study was carried out in Gamma Knife Centre , AIIMS, New Delhi over a 6 month period. All patients coming to Gamma knife for various etiologies were asked to fill a anxiety questionnaire before frame application. Baseline pulse rate was evaluated and with every pin application pulse rate was recorded. A VAS ( visual analogue scale) for pain was also administered after the procedure. Twenty percent fall in pulse rate were considered as significant bradycardia. Intraprocedural syncopal events were also recorded. 

Results:

A total of 141 patients were studied of which 6% patients had Intraprocedural syncopal attacks requiring medical treatment while 32% patients had bradycardia.  Having previous surgery, having breakfast before the procedure, duration of pin application, quantity of local anaesthetia, primary diagnosis, sex of patients were not found to alter the syncope or bradycardia events. Patients who were found anxious (score > 18 on the anxiety questionnaire ) had a significantly higher risk of having a procedural event. Previous history of syncope was also associated with 1.7 times more chances of developing Intraprocedural bradycardia. 

Conclusions

Frame application for gamma knives is a relatively safe procedure however procedure rooms should be equipped with emergency drugs.  A Simple anxiety questionnaire can predict  ‘at risk’ patients’ for procedural events


Bhavya PAHWA (New Delhi, India), Deepak AGRAWAL
00:00 - 00:00 #29316 - P161 Dosimetric analysis of single brain metastasis stereotactic radiosurgery treatment.
P161 Dosimetric analysis of single brain metastasis stereotactic radiosurgery treatment.

Purpose: Stereotactic radiosurgery (SRS) is a single-fraction radiation therapy technique for generally treating intracranial lesions and is ensure delivered treatment safely, efficiently, and effectively. This study investigates the change in dosimetric parameters such as target conformity index, target coverage, homogeneity index, dose gradient for CyberKnife (CK) brain SRS plans.

Material and Method: Retrospective SRS treatment plans were made for 20 treated patients with single brain metastasis. The first delivered CK plans (CK-1) and the second re-planned CK plans (CK-2) were evaluated dosimetrically. All plans were normalized to receive the prescribed dose at least 95% of the planning target volume (PTV). Depending on the size of the PTV, one or two fixed cone collimators were used. A median dose of 18 Gy (range, 16-20) was prescribed. The CK-1 and CK-2 plans were normalized to 79-84% and 67-73% isodoses, respectively. For target, Radiation Therapy Oncology Group (RTOG) conformity index (RTOG-CI), Paddick conformity index (P-CI), RTOG homogeneity index (HI); for peripheral dose fall-off, gradient index (GI), 50% isodose distribution R50%, and gradient radius (GR) were calculated.

Results: The median PTV volume was 6.76 cm3 (range, 1.63-40.61). Table 1 summarizes the parameters of PTV and GTV. D2%, D50%, D98%, and Dmean values of CK-2 plans for GTV were higher than those of CK-1. Fig. 1 illustrates the isodose curves of the CK-1 and CK-2 plans for comparison, visually. When CK-1 and CK-2 are compared, the dosimetric indexes are (mean ± standard error of the mean, SEM): RTOG-CI (1.19±0.02 vs. 1.09±0.01, p<0.01); P-CI (0.82±0.01 vs. 0.87±0.01, p<0.01); HI (1.24±0.01 vs. 1.39±0.01, p<0.01); GI (4.20±0.13 vs. 3.60±0.08, p<0.01); R50% (5.00±0.14 vs. 3.93±0.10, p<0.01); GR (0.81±0.05 vs. 0.69±0.04, p<0.01), respectively. Both conformity indexes (RTOG-CI and P-CI) were significantly better in CK-2 plans than in CK-1 plans. There were a statistically significant increase in gross target volume (GTV) dose parameters (D98%, D50%, D2%, and Dmean). A sharp peripheral dose fall-off was determined in CK-2 plans with GI, R50%, and GR analyses. A total MU increase in CK-2 plans was observed. The MUs of the CK-2 plans were larger than those of the CK-1 plans.

Conclusion: In this study, SRS plans of single brain metastasis patients were dosimetrically compared retrospectively. With the new method, better quality plans can be made in terms of dosimetric indexes.


Serdar ŞAHIN (Ankara, Turkey), Ferihan ERTAN, Can AZAK, Fatih GÖKSEL
00:00 - 00:00 #29325 - P162 Comparison of single-isocenter multiple-target HyperArc plans with and without jaw tracking technique.
P162 Comparison of single-isocenter multiple-target HyperArc plans with and without jaw tracking technique.

To evaluate the potential dosimetric gain of using the jaw tracking (JT) technique during inverse optimization of single-isocenter multiple-target (SIMT) SRS HyperArc plans.

Materials and methods:

Ten patients with multiple brain metastases (volumes: 0.11 to 2.12 cm3) were included in this study. The numbers of lesions per patient ranged from 2 to 10 (median: 3). For each one, two SIMT SRS HyperArc plans were planned with and without using the JT technique. Dose calculations were performed with the Eclipse Acuros XB algorithm, using 6X FFF photon beams from a TrueBeam linac equipped with a Millennium 120 MLC. Each plan was projected onto the PTW Octavius 4D phantom to be verified using the PTW 1600 SRS matrix. Measured 3D dose distribution was compared to the planned one by using the 3D gamma index analysis of the PTW Verisoft software. The 2% (local), 2 mm and cutoff values of 10%, 20%, 50%, 80% and 95% referred to the maximum measured dose, were applied.

For each patient, the following metrics were compared between JT and non JT plans: a) D0.1 (minimum dose to 0.1 cm3) to brainstem, optic pathway and lens; b) V12 (volume receiving ≥ 12 Gy) and mean dose of normal brain; c) Paddick conformity (CI) and gradient (GI) indexes for each target; and d) monitor units (MU) and treatment delivery time (TTD).

Results:

1)      The mean ± SD of the 3D gamma pass-rates with 10%, 20%, 50%, 80%, and 95% cutoff dose values, were respectively (JT vs. no JT): (96.7±3.1)% vs. (93.5±4.6)%, (99.2±1.3)% vs. (98.6±2.3)%, (98.6±3.5)% vs. (98.3±4.5)%, (98.6±2.2)% vs. (98.8±2.0)%, and (95.9±7.3)% vs. (97.4±5.4)%. See Table 1.

2)      The differences (JT vs. no JT) found on the dosimetric metrics of the clinical plans were (mean ± SD): a) (-0.1±0.4) Gy, (-0.2±0.2) Gy, (-0.2±0.2) Gy for D0.1 to brainstem, optic pathway and lens, respectively; b) (-0.1±0.1) cm3 and (-0.2±0.1) Gy for the V12 and mean dose of the normal brain, respectively; c) 0.00±0.01 and -0.15±0.30 for CI and GI, respectively; d) (299±189) MU and (23±7) sec for MU and TTD, respectively.

 

Conclusions:

1)      Dosimetric verifications revealed similar results between JT and no JT SIMT HyperArc plans.

2)      Negligible differences were found on the dosimetric metrics evaluated for the clinical SIMT HyperArc plans.

3)       JT technique did not provide a remarkable reduction of the V12 value, which is the parameter related with the probability of radiation induced brain necrosis.


Juan-Francisco CALVO-ORTEGA (GRANADA, Spain), Moragues-Femenía SANDRA, Coral LAOSA-BELLO, Miguel POZO-MASSÓ, Antonia ZAMORA-PÉREZ
00:00 - 00:00 #29354 - P163 Evaluation of a commercial 2D array for patient-specific QA of SRS plans.
P163 Evaluation of a commercial 2D array for patient-specific QA of SRS plans.

Aim:

To investigate the accuracy of a 2D array for patient-specific QA (PSQA) of SRS plans.

Methods and materials:

Twenty patients with multiple brain metastases were included in this study (volumes: 0.1 to 10.3 cm3, equivalent diameter: 9 to 27 mm). The number of lesions per patient ranged from 1 to 10 (median: 2). For each one, a single-isocenter SRS plan was planned with the Varian HyperArc technique. HyperArc consist of 4 no coplanar VMAT arcs of 6X FFF photon beams from a Varian TrueBeam linac, equipped with a Millennium 120 MLC. Plans were calculated using the Varian Eclipse Acuros XB algorithm.

PSQA of each plan was performed using two setups:

1)      The PTW 1600 SRS matrix sandwiched between two 3 cm polystyrene slabs.

2)     Radiochromic film inserted in a special PTW slab, and also sandwiched between two 3 cm polystyrene slabs. This PTW slab replaces the PTW 1600 SRS matrix by keeping the same geometry, i.e., detector layer of the PTW 1600 SRS matrix is at the same depth as the film. Film dosimetry was done using the radiochromic.com web-based application.

For each setup, two projections of the clinical SRS plan onto the respective phantom were done, such that the centroids of the smallest and largest targets coincide with the detector center. In this way, 2D measurements were performed for the smallest and largest targets of each SRS plan (total: 35 targets).

For each target, the 2D dose distribution measured with each setup was compared to the respective Eclipse-based distribution using the gamma index analysis. The following criteria were used: 3% (global dose difference), distance-to-agreement of 1 mm and 10% dose cutoff. Gamma passing rates (GPRs) obtained with the PTW 1600 SRS matrix and film were compared. The Bland-Altman (B&A) statistical method was used to compare the performance of the PTW 1600 SRS detector against the film (gold standard).

Results:

On average, the PTW 1600 SRS device produced very similar GPRs to the film dosimetry (99.7% ± 0.6% vs. 99.3% ± 1.0%). The B&A analysis showed a small bias of 0.4% (SD: ± 1.2%), and 95% limits of agreements within 3% between both measurement methods.

Conclusions:

The B&A analysis revealed that the PTW 1600 SRS detector can replace the film-based method for PSQA, for the target size range included in this study. Faster and online measurements can be performed with the array as an advantage over the film method.


Juan-Francisco CALVO-ORTEGA (GRANADA, Spain), Moragues-Femenía SANDRA, Coral LAOSA-BELLO, Miguel POZO-MASSÓ, Antonia ZAMORA-PÉREZ
00:00 - 00:00 #29387 - P164 Dosimetric accuracy of CyberKnife Stereotactic Radiosurgery for Perioptic lesions.
P164 Dosimetric accuracy of CyberKnife Stereotactic Radiosurgery for Perioptic lesions.

Purpose: This study aimed to evaluate the dosimetric accuracy of Cyberknife (CK) for benign perioptic tumor using patient specific head phantom.

Methods: Patient specific head phantoms was fabricated using a 3D-printer to be dosimetrically equivalent to actual target regions of benign perioptic tumor case treated via Cyberknife radiosurgery. Head phantom QA plan was produced using the original CK contour set (target and optic nerve). The head phantom containing the Gafchromic EBT3 film was irradiated using Cyberknife 6D skull tracking method. The dose distributions calculated by MultiPlan Treatment Planning System (version 5.6) was compared with those measured by film dose using gamma analysis method. After moved rotating (1 degree) and translating (1-5mm) the couch table prior to beam delivery, we checked the 6D skull tracking accuracy according to the beam irradiation.

Results: Gamma passing rates for the 2%/1 mm and 2%/2 mm criteria was found to be 84.11 ± 2.12% and 93.61±1.39% greater than the acceptance criteria 80% and 90%. 

Conclusions: Dosimetric verification with patient-specific head phantoms could be successfully implemented as the evaluation method for CK perioptic tumor radiosurgery delivery with 6D skull tracking system.


Kyoungjun YOON (Korea, Korea), Byungchul CHO, Jungwon KWAK, Chiyoung JEONG, Minjae PARK, Youngmoon GOH, Seongwoo KIM, Si Yeol SONG, Sang-Wook LEE, Young Hyun CHO
00:00 - 00:00 #29446 - P165 A dose calculation algorithm for Gamma Knife treatment room shielding optimization.
P165 A dose calculation algorithm for Gamma Knife treatment room shielding optimization.

Background: Today’s methods for designing treatment rooms for radiotherapy systems often involve assumptions that lead to overestimations of the wall thicknesses required to meet dose-rate constraints outside the room. The Leksell Gamma Knife (LGK) radiosurgery system has built-in shielding that results in primarily scattered photons leaking into the room. The field of leakage radiation therefore has a wide spectrum of energies, up to the primary energies of cobalt-60, and is highly anisotropic. These properties of the field make standard site planning methods difficult to adapt to the LGK.

Methods: A fast dose calculation algorithm has been developed that can be run iteratively in an optimization setting aiming to find optimal treatment room shielding. The dose algorithm uses phase spaces describing the radiation field around the LGK. These include data on energy, position, and direction of individual leakage photons, obtained from Monte Carlo simulations involving a full geometrical model of the LGK. To determine the dose outside the room resulting from a photon from the phase space, the dose algorithm uses a look-up table of averaged water depth-dose profiles, obtained from Monte Carlo simulations. Each depth-dose profile corresponds to a certain photon energy, angle of incidence to a wall, and wall thickness. The dose in a water layer along the outside of the treatment room walls is obtained by raytracing photons from the phase space and summing their dose contributions at the location where they would hit the walls. A dose calculation can be executed in about one second on a personal computer.

The dose algorithm has been incorporated into two different optimization schemes where variables such as the dose rate limit outside the room, level of occupancy outside, and expected LGK usage are considered when finding optimal wall thicknesses.

Results: The dose algorithm’s accuracy has been validated against full Monte Carlo simulations of an equivalent room, with dose rate distributions from both methods showing good agreement. Both optimization algorithms require a few minutes to run and give similar optimal site plans.  Preliminary results indicate that the optimal site plans found by this method result in thinner walls than conventional methods. The results using the dose algorithm are promising when applied to the LGK and could in principle be expanded to other systems provided the necessary data is available. Future studies will include extending the method for optimizing wall material and LGK positioning within an existing room.


Nelly NYGREN (Stockholm, Sweden), Joakim DA SILVA, Håkan NORDSTRÖM
00:00 - 00:00 #29483 - P166 Braintool a new anthropomorphic phantom to test the accuracy of srs procedures.
P166 Braintool a new anthropomorphic phantom to test the accuracy of srs procedures.

Purpose

To present BrainTool, a new anthropomorphic phantom made to assess the accuracy of brain radiosurgery treatments.  

Materials and Method:

A synthetic human brain T1/MRI study was segmented, simplified, and 3D printed. The printed objects were glued to two PMMA disks thus creating four compartments. Each compartment was filled with different substances to create realistic MRI and CT brain contrasts. A water-equivalent silicon rubber casing covers the phantom giving it a realistic head look. Eight markers were attached inside the BrainTool to test the accuracy of image registration procedures. A holder hosting an ionization chamber can be inserted into the BrainTool to assess the targeting accuracy. BrainTool can be placed on any CT, MRI or linac couch or fixed to a Lexell stereotactic frame. To exemplify a possible use of BrainTool, we measured the registration accuracy and the targeting accuracy of a GammaKnife system. 

Registration accuracy- CT and T1 MRI images of the BrainTool phantom were sent to GammaPlan (Elekta) system and registered with the provided tool. The distances between correspondent markers' positions in CT and MRI registered studies were evaluated and mean and range values were calculated. Registrations were carried out in the entire image or in a smaller user-defined region of interest (ROI) inside the phantom.

Targeting accuracy- It was assessed by comparing planned and measured target positions. The measured target position was obtained using an iterative cross scan approach aimed to localize the camera measuring point. Planned and measured target positions uncertainty were both assessed. 

Results:

In Fig. 1, a picture of the BrainTool phantom, a CT slice with measured HU and axial coronal and sagittal slice of a  T1 weighted MR images, are shown. Two NiCl2 solutions (1.2 mmol/l and 0.8 mmol/l) were used to fill the phantom and simulate grey and white matter T1 relaxation times (650 ms and 1200 ms). Several T1 or T2 MRI relaxation times, can be simulated by choosing different solutions or concentrations.

Registration accuracy – The mean distances between correspondent markers in CT and MRI registered studies were  1.2± 0.5mm; range [1.0mm -1.4mm] and 0.3 ± 0.2mm; range [0.0mm -0.6mm] for the entire image and the selected ROI, respectively.

Targeting accuracy - Targeting mismatches along x, y and z and cumulative (r) were x=-0.7±0.5 mm, y=0.3±0.4 mm z= -0.9± 0.4 mm and r=1.2±0.8 mm, respectively.

Conclusions: We have developed a phantom and exemplified its use in brain radiosurgery treatments. 


Stefania PALLOTTA, Silvia CALUSI, Chiara ARILLI, Elisa MUSSI, Pecchioli GUIDO, Marta CASATI, Livia MARRAZZO, Cinzia TALAMONTI, Mauro LOI (Firenze, Italy), Margherita ZANI
00:00 - 00:00 #29725 - P167 A practical strategy for incorporating the convolution algorithm in the Leksell GammaPlan software for daily treatment planning.
P167 A practical strategy for incorporating the convolution algorithm in the Leksell GammaPlan software for daily treatment planning.

An advanced dose calculation algorithm for tissue heterogeneity in the dose calculations became available about 10 years with the Leksell GammaPlan version 10. Despite an apparent benefit of accurate inclusion of the heterogeneity effects in the treatment plan, the adoption of the technical feature has not progressed as it should be. One drawback for its routine applications is its rather slow computation. The aim of this study, therefore, is to establish criteria for the need for the convolution algorithm and a procedure to include the heterogeneity effects in the treatment without lengthy calculation. We analyzed 79 Gamma Knife radiosurgery cases, consisting of 154 tumors. There were various disease types, tumor locations, tumor sizes, the number of fractions, and prescription doses. All treatments were based on treatment plans using the TMR10 algorithm (TMR10). We did CT scans in addition to routine MRI scans for the treatments. By applying an appropriate CT number-to-density table data, we repeated the dose calculations with the convolution algorithm (Conv). We compared the volumetric dose data obtained by using these dose calculations algorithms. Specifically, we calculated the ratios between the TMR10 and Conv for the following parameters: treatment volume (TxtVol), the volume covered by half of the prescription dose (TxtVol2), the minimum, maximum, and mean doses in the target (minDose, maxDose, and meanDose), the volume of tumor covered by the prescription isodose (covVol), and the average of each of the preceding six ratios (avgRatio). We categorized those parameters for locations of tumors, specifically, using the shortest distance of the skull surface from the tumor center (distC) and the edge of the tumor (distE) as well as the overlap of the tumor with bony structures. The results showed that avgRatio increased, reaching a saturated value of 0.92, as distE increased. There was a statistically significant difference in avgRatio between tumors of distE < 1cm and 1 < distE < 2cm. On the other hand, maxDose was about 0.93, being almost independent of distE. Our data showed that there was about a 7% overestimation of delivered dose with TMR10, and implied that the heterogeneity effects must be considered for the volume dose calculations by applying the convolution algorithm when the distance of the skull surface from the closest point of the tumor was less than 1 cm.


Yoichi WATANABE (Minneapolis, USA), Damien MATHEW, N GOPISHANKAR
00:00 - 00:00 #29872 - P168 Quantifying the targeting accuracy of the Vantage stereotactic frame.
P168 Quantifying the targeting accuracy of the Vantage stereotactic frame.

Introduction

The Vantage frame, unlike its predecessor, the Leksell G frame, has no indexing marks displaying stereotactic coordinates. Its curved surfaces do not lend themselves to the easy construction and insertion of a Known Target Phantom, which is the gold standard for measuring imaging/targeting accuracy. However, measurement of targeting accuracy is a prerequisite in SRS.

 

Methods and Materials

Two procedures were used to measure the targeting accuracy associated with the use of the Vantage frame.

 

1.     Comparison of landmarks between MR and CBCT.

A Vantage frame was fixed to an RTsafe Prime phantom with an MR geometric insert. The apparatus was imaged using three different MR scanners and CT. Landmarks in the phantom were compared between MRI and CT and the differences noted in each dimension.

 

2.     Polymer gel

A VIPAR polymer gel insert was placed inside the Prime phantom and a Vantage frame attached, imaged with MRI and a treatment plan simulating a multiple target treatment was delivered. This allowed potential targeting errors due to MR distortion to be measured at multiple locations within the phantom. The gel was allowed to rest for 24 hours before being rescanned using a set of dual echo MR sequences. Dose distributions were compared between those recorded by the gel and those exported from the TPS using DICOMRT.

 

Results

1.     Discrepancies between MRI and CT are summarised in the table below:

2.     Polymer gel

3D gel revealed centre of gravity geometric offsets of <1.0mm.

 

Summary

We have verified that the targeting accuracy of the Vantage frame is better than 1mm. Given our knowledge of targeting errors using the Leksell G Frame, the Vantage frame appears to match or exceed this performance, particularly in combination with 3T scanners.

 

The Vantage frame can be commissioned with a series of simple tests to verify accuracy.


Ian PADDICK (London, United Kingdom), Diana GRISHCHUK, Anna KARANATSIOU
00:00 - 00:00 #29937 - P169 Long-term Performance of Gamma Knife Perfexion/Icon Sector Positioning Using Statistical Process Control.
P169 Long-term Performance of Gamma Knife Perfexion/Icon Sector Positioning Using Statistical Process Control.

Background: The large fractional doses, steep dose gradients, and small targets found in intracranial radiosurgery require extremely low procedural uncertainty. Gamma Knife radiosurgery achieves this in part by minimizing beam delivery uncertainty. The radiation body of Perfexion/Icon GKRS units contain a static tungsten collimator. Outside of this collimator are 192 60Co sources that are housed within 8 sectors of 24 sources each. Each sector can move linearly over the collimator driven by a set of 8 corresponding sector drives. The GKRS control system ensures this motion is within tolerance (±100 µm) and records extensive internal data in treatment logs. These data can be analyzed through statistical process control (SPC) methods which are designed to detect changes in process behavior. The purpose of this study was to characterize the long-term (8+ year) performance of a Perfexion/Icon unit and use SPC methods to determine if performance changes could be detected at levels lower than existing QA and internal manufacturer performance tolerances.

Methods: In-house software was developed to parse Perfexion/Icon log-files and store relevant information on shot delivery in a relational database. A last-in, first-out (LIFO) queuing algorithm was created to heuristically match messages associated with a given delivered shot. Filtering criteria were developed to filter QA and uncompleted shots. For each resulting matched shot, the achieved versus planned sector position was determined for each sector drive. Exponentially weighted moving average (EWMA) control charts were plotted to characterize system performance and statistical control limits were determined.

Results: 53879 shots were delivered over the 8+ year span in the study. The mean difference across the 8 sectors ranged from 1.59 to 7.22 µm, with 97.5% of all shots within 21 µm. The EWMA centerline ranged from 1.19 to 7.88 µm, with an upper control limit (UCL) of -2.69 to -12.12 µm and lower control limit (LCL) from 13.80 to 2.75 µm. Sector position was consistent and accurate with no systematic deviations in sector positioning observed over time.

Conclusion: Over many years of clinical use the sector positions of the Gamma Knife Perfexion/Icon demonstrate extremely low positioning uncertainties. The EWMA control chart method can be utilized to track performance over time and can potentially detect changes in performance at levels much smaller than the control-system enforced tolerance of ±100 µm.


Tatiana BEJARANO (Charlottesville, USA), David SCHLESINGER, Jason SHEEHAN
00:00 - 00:00 #29995 - P170 Feasibility of isodose-shaped scintillation detectors for the measurement of gamma knife output factors.
P170 Feasibility of isodose-shaped scintillation detectors for the measurement of gamma knife output factors.

Purpose: Scintillation detectors were 3D printed based on a gamma knife (GK) dose distribution to calculate the volume averaging effect. The collimator output factors were measured using isodose-shaped scintillators (ISSs) and compared with those of a micro-diamond detector and previous reports.

Methods: An absorbed dose distribution in a spherical dosimetry phantom with a radius of 8 cm was obtained from GK treatment planning software (Leksell GammaPlan (LGP), Elekta AB, Stockholm, Sweden). Two types of ISSs were fabricated to fit the 97.2% (ISS-1) and 95.6% (ISS-2) isodose surfaces. The volume averaging correction factors were obtained by dividing the absorbed dose to water in the central voxel (CV) by that in the ISS. The correction effect due to the difference between the ISS and water was calculated by Monte Carlo simulations. Ten ISS detectors, five of each type, were used to measure the output factors of the 4 and 8 mm collimators of a GK IconTM to assess system consistency. The output factors of seven GKs were measured using two ISS detectors, one of each type, and a PTW T60019 (PTW, Freiburg, Germany) micro-diamond detector.

Results: The detector output ratios (DORs) measured using the five ISSs of each type were consistent, with standard uncertainties less than 0.2%. In the 4 mm field, the volume averaging correction factor ratios were 1.018 and 1.026, and the output factors after all corrections were 0.827 (0.006) and 0.825 (0.006) for ISS-1 and ISS-2, respectively. In the 8 mm field, the volume averaging correction factor ratios were 1.000 for both ISS types, and the output factors were 0.898 (0.003) and 0.900 (0.003) for ISS-1 and ISS-2, respectively. The ISS detectors could measure the output factors of a GK with uncertainties comparable to that of the PTW 60019 detector. The output factors of all detectors decreased with the dose rate.

Conclusion: The volume averaging effect of an ISS developed in-house could be calculated using known dose distributions. The collimator output factors of the GK Perfexion/Icon™ models measured using ISS detectors were consistent with those of a commercial synthetic micro-diamond detector and recent studies.


Tae-Hoon KIM, Hye Jeong YANG, Thomas SCHAARSCHMIDT, Young Kyun KIM, Hyun-Tai CHUNG (Seoul, Korea)
00:00 - 00:00 #30019 - P171 Utilization of cone beam computed tomography for comparing stereotactic coordinate systems in frame-based radiosurgery.
P171 Utilization of cone beam computed tomography for comparing stereotactic coordinate systems in frame-based radiosurgery.

The new model of the Leksell Gamma Knife Icon is equipped with additional technical functionalities for fractionated treatment, namely a cone beam computed tomography (CBCT). Performing CBCT before treatment enables to define the stereotactic space, and to correct the radiation plan in case the patient's position changes. 

The purpose of this work was to assess differences between frame-based and CBCT defined stereotactic space, to identify predictors of the observed findings and to assess their effects on the clinical outcome. 

The study included 122 patients treated on the LGK Icon unit from July 2018 to December 2019. Both the information about the differences (rotational and translational shifts) between frame-based and CBCT-defined centers of the stereotactic and maximum shot displacement (MSD) were reported by the registration module of treatment planning system. We also collected the potential predictors of the differences. To identify the cause of the observed discrepancies between traditional and CBCT localizations, 19 parameters were investigated. Multiple linear regressions were performed to evaluate associations between parameters.

Discrepancies between the coordinate systems were revealed depending on the localization method. 2.4% out of 122 cases exceeded 1 mm and 1 degree in translational and rotational shifts, respectively. Tumor coverage decreased more than 5% in 4.9 percent of cases.

As a result of linear regression analysis, we found that the fiducial errors, weight of the patient, diagnosis, KPS were predictors of the increased rotational and translational shifts, as well as the MSD.

Fifty-one patients diagnosed with multiple brain metastases were analyzed to determine the effect of stereotactic coordinate shifts on clinical outcome. The follow-up brain MRI scan showed an increase of 10 (5.3%) and 3 (5.8%) irradiated targets after 3 and 6 months, respectively. The increases in the remaining (7 of 188) targets were differentiated as post-radiation changes.

However, the resulting sample of patients is insufficient to assess the effect of target coverage differences on clinical outcome. Using the methods of mathematical statistics based on the data on the onset of local recurrence in patients with metastases, it was found that the minimum required sample size should be at least 425 patients for a complete analysis of the effect of coordinate systems shifts on the clinical outcome. As the next step of the study, it is planned to increase the patient sample under consideration to assess the effect of the existing difference between the two methods of localization on the clinical outcome of treatment.


Irina BANNIKOVA, Aleksandra DALECHINA, Andrey GOLANOV (Moscow, Russia), Valery KOSTJUCHENKO
00:00 - 00:00 #30057 - P172 Isocenter placement for treatment planning using machine learning.
P172 Isocenter placement for treatment planning using machine learning.

Isocenter placement is important in creating Gamma Knife treatment plans. The recently released inverse planner – Leksell Gamma Knife® (LGK) Lightning (Elekta AB, Sweden) has an isocenter placement algorithm that automatically generates a set of isocenters based on the target’s geometric description. The algorithm has generally shown very good performance. However, to limit complexity, the number of isocenters is limited, resulting in suboptimal plans for some large targets. Exploring the entire space of possible isocenters would likely allow for better plans but would require solving an enormously expensive optimization problem, making it undesirable in clinical workflow. We propose a data-driven approach that generates a set of isocenter locations without exploring the entire search space at inference.

Instead of running a larger optimization problem, we use a machine learning (ML) model to predict the best possible isocenters based on training data. We first increase the search space by relaxing the constraints on the number of isocenter candidates (degrees of freedom) in the optimization problem. The corresponding (time-consuming) LGK Lightning optimization is then run offline for many cases, identifying and storing isocenter positions surviving the optimization for each case. An ML model is then trained to map the surviving isocenter sets from target feature descriptors. We use a convolutional neural network that resembles U-Net. We generated isocenters from a dataset of 2921 cases with a large variation in size and shape, and split them into a training set (2337 cases) and a validation set (584 cases).  We evaluated LGK Lightning-optimized plans from both the relaxed isocenter placement (max-out) and the ML algorithm against those from the current isocenter placement algorithm. We compared their results on Paddick conformity index (PCI) and beam-on-time (BOT) with different low-dose and BOT weights; and the number of proposed isocenters for the optimization problem.

Our results show that the max-out algorithm results in better dose conformity but longer BOT than the current fill algorithm in LGK Lightning. For tumors larger than 3cm3, the PCI is 2.13% (+-1.74%) better with 5.23% (+-14.35%) longer BOT but 904% (+-474%) more isocenters. The ML model shows similar behavior: the PCI is 0.64% (+-2.18%) better with 6.51% (+-13.4%) longer BOT and has 184% (+-125%) more isocenters than the current fill algorithm.


Kenneth LAU (Stockholm, Sweden), Håkan NORDSTRÖM, Joakim DA SILVA, Marcus HENNIX, Joakim WANG ERLANDSSON, Clara KÖRTING, John DAHLBERG, Björn SOMELL
00:00 - 00:00 #30059 - P173 Plan assessment metrics for dose painting in stereotactic radiosurgery.
P173 Plan assessment metrics for dose painting in stereotactic radiosurgery.

OBJECTIVES: Dose painting radiotherapy treatments, which deliver non-uniform radiation doses to targets, are becoming increasingly feasible with advancements in imaging and treatment precision. While the high precision of stereotactic radiosurgery (SRS) makes dose painting treatments a good match, there are currently no suitable metrics specifically for assessing dose painting SRS treatment plans. 

In existing dose painting assessment metrics, target overdose and underdose are equally weighted, thus emphasising uniformity. SRS plans, however, avoid underdose more than overdose and do not prioritise uniformity. SRS metrics also prioritise selectivity and dose fall-off to reduce healthy tissue dose, and these metrics are calculated based on the prescription dose. We propose a set of metrics that would meet the needs of SRS clinicians and allow calculations with non-uniform dose painting prescriptions.

METHODS: Sample dose painting SRS prescriptions are created from anonymised Gamma Knife SRS cases, apparent diffusion coefficient MRI images, and a range of intensity-to-prescription functions. These prescription functions include polynomial and sigmoid functions of various parameters, to allow for subsequent applications of different images and thus indications of radiosensitivity. Treatment plans are found by semi-infinite linear programming optimisation, based on clinically determined isocentres. 

Current dose painting metrics include quality factor (QF) and indices of achievement, dose-hotness, and dose-coldness, and are applied to the resultant plans without changes. Modified QF formulas that separate underdose and overdose are considered. Modified versions of current SRS metrics, including coverage, selectivity, conformity, efficiency, and gradient indices, are proposed. For coverage index, individual voxel prescriptions are considered in calculations instead of typical single prescriptions. For the other indices, where voxels outside the target are considered, both the minimum and mean target prescriptions are used in calculations. 

RESULTS: The merits of various existing metrics and modified metrics are demonstrated and discussed. Combined use of two modified conformity indices using both minimum and mean prescription dose can replace the use of a typical conformity index, and modified efficiency index using minimum dose is a suitable replacement for gradient index as it is less sensitive to maximum dose boost. The increased complexity of dose painting SRS plans means more metrics may have to be used in tandem in assessing plan quality, but the modified SRS metrics have the advantage of giving equal values as the original metrics when applied to single prescription dose plans. 


Benjamin THAM (Toronto, Canada), Catherine COOLENS, Håkan NORDSTRÖM, Nelly NYGREN, Dionne ALEMAN
00:00 - 00:00 #30103 - P174 Parallel optimisation of multiple Gamma Knife treatment plans.
P174 Parallel optimisation of multiple Gamma Knife treatment plans.

Leksell Gamma Knife (LGK) (Elekta AB, Sweden) treatment plans have traditionally been created by manually placing shots at different positions inside the target. Since recently, the treatment planning system also includes the Lightning optimisation tool, eliminating the time-consuming manual shot placement by calculating the mathematically optimal plan according to given clinical constraints and preferences. The planner controls trade-offs by selecting importance weights for the different metrics. Although this generally reduces planning time, it is an iterative process; metrics produced for a set of weights differ for each patient case (due to anatomical differences), and the planner likely tweaks the weights and reruns the optimisation several times to achieve a plan with desired trade-offs.

To speed up planning and ensure plan quality is not compromised by the planner overlooking a ‘better’ set of weights due to time constraints, it is desirable to create plans corresponding to many sets of weights simultaneously. The planner would then ‘navigate’ the corresponding set of plans in real time and choose the most desirable one. With the current optimisation, this would be time-consuming for larger cases.

The alternating direction method of multipliers (ADMM) offers a way of leveraging parallel computer architectures (e.g. GPUs) to simultaneously solve the same optimisation problem for many sets of weights. To increase the span of clinical trade-offs, however, Lightning employs a two-pass optimisation where the second-pass problem depends on the result of the first, making parallel optimisation with ADMM infeasible. We have devised a scheme where the second pass is expressed in a unified way for many sets of weights, while still being equivalent to that of Lightning, making it suitable for ADMM. The scheme has been implemented in a prototype plan optimisation tool including ADMM and a Lightning-like solver.

Preliminary results for four cases optimised on modern laptops are given in Table 1. Considerable speed-ups were seen comparing ADMM and Lightning-like optimisation of 27 plans on the CPU: the largest target required 73 instead of 648 seconds. Differences in clinical metrics between plans produced by the two methods were negligible. Further benefit was seen running ADMM on the GPU: even the largest target required less than 10 seconds to generate all 27 plans. Based on these initial findings, we conclude that employing the new scheme and optimising using ADMM could allow several tens of treatment plans, corresponding to different trade-offs, to be simultaneously generated without interrupting the clinical workflow.


Joakim DA SILVA (Stockholm, Sweden), Marcus HENNIX, Håkan NORDSTRÖM
00:00 - 00:00 #30113 - P175 Effectiveness of a cranial distortion correction software using a novel measurement method.
P175 Effectiveness of a cranial distortion correction software using a novel measurement method.

Purpose

The accuracy of a stereotactic treatment is primarily limited by the least accurate process in the whole chain of events. QA is often performed on the dose delivery and planning rather than the localization. MRI datasets are subjected to distortions, due to the nonlinearity of gradient fields, and may cause incorrect target definition.

This study aimed to analyze the impact of a patient-specific algorithm, Cranial Distortion Correction Elements (CDCE) (Brainlab), to correct spatial distortion in cranial MR images by using a novel software-only evaluation paradigm with defined increment values of the distortion and noise present in clinical images.

 

Materials and Methods

A non-bias simulated T1 MRI normal brain dataset (Brainweb) is used to create synthetic CT.

By introducing controlled distortion in simulated datasets, we can evaluate the influence of the Noise (Gaussian noise percent multiplied by the brightest tissue intensity) and Intensity non-uniformity ("RF").

For this study, we have used 17 MRI datasets ranging from 0 to 9% noise and from 0 to 40% RF. These MRIs were corrected using the synthetic CT as a base modality for the distortion correction. To evaluate the impact of the distortion correction, each image set, non-corrected and corrected, was compared to the original simulated MRI with 0% noise and 0% RF using Root mean square error (RMSE) as a comparison metric. The RMSE was calculated for each MRI slice and the average RMSE for the entire datasets was used for comparison.

 

Results

On average, the CDCE software allows for an improvement based on the RMSE correlation between the baseline MRI and the distorted MRI. For the corrected datasets, the RMSE ranges between 9.83 (SD 4.20) and 55.58 (SD 16.99) and average at 33.36 (SD 14.06). 

For the non-corrected datasets, the RMSE ranges between 7.70 (SD 0.44) and 83.14 (SD 13.48) and average at 44.18 (SD 25.93). As a control, we measured the RSME between the original MRI and the corrected dataset averaging for all slices to 14.01 (SD 6.27) to evaluate the error baseline linked to the correlation between image modalities.

 

Conclusion

The results of the CDCE software show an improvement increasing in correlation with the noise and intensity non-uniformity levels. This provides to the stereotactic treatments an added robustness and reliability related to the accuracy of the MR images and independent from any distortion level and, per extension, to the target definition and patient positioning.


Tristan BELLOEIL-MARRANE, Adrián GUTIÉRREZ (Brussels, Belgium), Jelle SMEULDERS, Thierry GEVAERT, Mark DE RIDDER
00:00 - 00:00 #30135 - P176 Investigating the application of anti-scatter grid to Leksell Gamma Knife Icon.
P176 Investigating the application of anti-scatter grid to Leksell Gamma Knife Icon.

Leksell Gamma Knife (LGK) Icon is a system dedicated to noninvasive intracranial treatments that demand high precision and accuracy. It enables mask-based fractionated stereotactic radiotherapy and radiosurgery thanks to the implementation of the Cone Beam Computed Tomography (CBCT) imaging system and a motion tracking system. The stereotactic reference is deduced by co-registering stereotactic CBCT images taken on the day of treatment to planning non-stereotactic images. This sets demands on the accuracy of a co-registration algorithm whose performance is connected to the CBCT image quality.

One of the major causes for degradation of the CBCT image quality is scattered radiation. The amount of scattered radiation usually can be reduced by increasing the distance between the object and the detector. Due to geometrical constraints, in the case of the LGK Icon, the detector is placed close to the patient’s head, leading to a large scatter component. Nevertheless, the current image quality allows for the separation of bone, soft tissue and air which is sufficient for patient positioning.

However, considering that the scattered radiation is a few times higher than the primary, further improvements in the image quality might lead to even better patient positioning. Therefore, we investigated scatter rejection by employing anti-scatter grids composed of lead or tungsten lamellae and interspacing material. We performed simulation studies in which we considered various grid characteristics and compared the performance of one-dimensional and two-dimensional anti-scatter grids. In this contribution, the simulation studies together with the obtained results, such as the effect on scatter to primary ratio and contrast to noise ratio, will be presented.

 


Brankica ANDELIC (Stockholm, Sweden), Håkan NORDSTRÖM, Joakim DA SILVA
00:00 - 00:00 #30149 - P177 Source Target Guide (STG) Geometry Framework.
P177 Source Target Guide (STG) Geometry Framework.

STG Geometry Framework is to describe, define, measure, model, and correct the geometric errors in SRS/SBRT. It has currently five principles:

 

1.                  Geometry error is the vector difference of the tumor volume (Target) from the radiation field (Source);

2.                  Geometry errors are of two types - systematic and random:

a.      The systematic error is due to an SRS machines’ mechanical imperfection.  Systematic error can be measured and modeled before the treatment starts;

b.      The Random error is due to patient motion.  Random error occurs during the process of patient setup and radiation delivery.  It can be monitored (tracked) and corrected in real time;

3.                  An SRS machine is divided into three subsystems by the roles each plays: Source, Target, and Guide:

a.      The Source Subsystem (SS) focus radiation beams to a focal point from multiple directions;

b.      The Target Subsystem (TS) fixes a patient's head to a table using frame or mask, and moves the target to the source;

c.       The modern Guide Subsystem (GS), working with a Treatment Planning System (TPS), guides the movement of the table during the treatment setup using an absolute measuring “ruler” such as CBCT or stereo X-ray, and tracks the motion of the target during the treatment delivery using a relative measuring “ruler” such as non-radiation, optical or infrared based IGRT.  The classic GS uses BRW stereotactic system, laser, and cross hair for SRS setup;

4.                  The focal point in SS is unique by nature and is chosen as the reference point (origin) for a 4D Cartesian space. This point is named Source Subsystem Isocenter (SSI) or Source Isocenter (SI). This point is commonly called Radiation Isocenter (RI);  

5.                  The same point is also the reference point of a 4D Cartesian system in TPS, with name in Treatment Planning Isocenter (TPI).  The source-target relationship defined in TPS is materialized in machine via co-registration between the CT of TPS and the CBCT of machine. The TPS shall exactly model a mechanical-imperfect SRS machine so that What you see is what you get (WYSIWYG) is achieved.

From the principles in the STG Framework, the geometry of any SRS machine, and radiotherapy machine in general, can be established.  Some confusion concepts and terminology such as various isocenters can be clarified. Some clarifications are discussed for Gamma Knife and LINAC in the abstracts by the same author. 


Tanxia QU (New York, USA)
00:00 - 00:00 #30155 - P178 Geometry error in Gamma Knife ICON SRS per Source Target Guide (STG) Geometry Framework.
P178 Geometry error in Gamma Knife ICON SRS per Source Target Guide (STG) Geometry Framework.

STG Geometry Framework is a system to describe, define, measure, model, and correct geometric error in SRS/SBRT.  Its five principles are introduced in the first of this abstract series, “Source Target Guide (STG) Geometry Framework.”

GK ICON’s Source Subsystem (SS) materializes the SRS feature of non-coplanar radiation beams to the focal point, Source Subsystem Isocenter (SSI), by having 192 x 3 (max 192 can be used simultaneously) stationary collimators milled with better than 0.1 mm precision.

GK ICON’s Target Subsystem (TS) fixes patient’s head in either frame or frameless (mask) to a table which moves with precision of 0.1 mm in translation only (there is no need for rotation). The Target Subsystem Isocenter (TSI) is where the target shall be. With frame fixation, the random error is not monitored and assumed zero.    

GK ICON’s Guide Subsystems (GS) is of two kinds: classic and modern.  The classic GS uses the MR indicator on a G-frame to identify the location of tumor. Its precision depends on the image modality with MR’s average error around 0.5mm.  The modern GS has CBCT for setup and HDMM (High-Definition Motion Management) for real time motion tracking.  CBCT has precision better than 0.1 mm and HDMM 0.02 mm, respectively.  The precision of co-registration between MR and CBCT contributes to the setup error.

Per STG Framework, the two tests described in the Appendix B2 (“CONFIRMING UCP AND RFP COINCIDENCE”) and Appendix B3 (“CONFIRMING ACCURATE ALIGNMENT OF TREATMENT SITE WITH RFP”) in AAPM TG 178 are the same test, film-pin-prick phantom to verify the coincident between the source and the target, at different locations with different coordinates in the 4D Cartesian space, both LGK machine and LGP planning system.

According the function and purpose, the terms “radiation focal point” (RFP), treatment site (represented by the pin-prick on the film), and “unit center point” (UCP) are the SSI, TSI, and Treatment Planning Isocenter (TPI) in STG Framework, respectively. This naming convention is in-line with the terms used in Linac SRS.  The film-pin-prick test is like the Winston-Lutz test in Linac SRS.

In mask fixation of GK ICON, patient may move during CBCT which cause the HDMM not starting at zero position.  Future studies will focus on the random error which could be in several minimeters.


Tanxia QU (New York, USA)
00:00 - 00:00 #30165 - P180 Quality Assurance of Congruence of Isocenters for High Precise SRS System.
P180 Quality Assurance of Congruence of Isocenters for High Precise SRS System.

Introduction: The localization procedure of the LINAC SRS is the last step before dose delivery.  And there could be some discrepancies between imaging system and radiation beam isocenters. And the congruence between these isocenters is an important factor to accomplish the plan dose distribution in the patient treatment. Therefore, in this quality assurance procedure, the isocenters between these systems was evaluated in 3-Dimension with combination CBCT, KV and MV beam Winston Lutz test.  

 

Methods and Materials: A plan was done in Eclipse treatment planning system based on a simulation CT image set of a standard imaging Winston Lutz cube phantom. The phantom was then placed on the 4D table of a Varian 21iX LINAC. First, CBCT imaging process was applied to the phantom, after the CBCT image set was matched to that of simulation CT images, the discrepancy was done by applying the couch shift. Then another CBCT imaging was taken to verify the new phantom position matching the planning CT. Then a Winston-Lutz test was accomplished with MV radiation beam.  After that, a KV-pair was taken and a 2-dimensional match was analyzed, and the discrepancy could be resolved by applying the couch shift. Then any other KV-pair image set was taken, and registration was executed to verify the KV image and Digital reconstructed radiography (DRR) pair alignment. At this setup, another set of Winston-Lutz test was taken. Finally, the two Winston-Lutz Test image sets were analyzed by Dose Lab Pro, and the results were used to determine the isocenter congruence of the system.

 

Results: In this study, for the CBCT registration setup, the Winston-Lutz result in x, y, z were -0.72mm, 1.87mm, and -1.67mm; for KV-pair registration, the Winston-Lutz result in x, y, z were 0.69mm, 0.81mm, -1.70mm. And The difference between KV-pair setup and CBCT setup isocenter is 1.41mm, -1.06mm and -0.01mm at the assumption of CBCT and KV registration to simulation CT at ideal condition.

 

Conclusion and Discussion: The isocenter congruence could be estimated by combination of Imaging registration method and Winston-Lutz test during SRS. And variables involve couch accuracy, shaking during the shift applying, registration selection and its accuracy, image set distortion and so on. In addition, decomposition approach could be further used to find the priority parameters affect the system accuracy. Finally, theoretical model could be developed for automatic extreme precise system.


Kaile LI (Hagerstown, MD, USA)
00:00 - 00:00 #30167 - P181 Geometric Error in LINAC SRS per Source Target Guide (STG) Geometry Framework.
P181 Geometric Error in LINAC SRS per Source Target Guide (STG) Geometry Framework.

The principles in STG Geometry Framework for the systematic error only are:

1.      An SRS machine can be divided to three subsystems:  Source, Target, and Guide;

2.      The focal point of the Source Subsystem, named the Source Subsystem Isocenter (SSI), is unique and is chosen as the reference point for a 4D Cartesian system in both real world and virtual world (TPS);

In LINAC, SSI is a point that has the shortest distances to two or more skew lines defined by the Collimator Axes of Rotation (CAoR) at chosen gantry angles.

Elekta and Varian define the SSI using four and eight evenly distributed gantry angles, using the Flexmap and the IsoLock, respectively. Some observations and discussions:

1.      Source Subsystem Isocenter depends on MV energy, beam steering, filter or filter free, dose, dose rate, collimator AoR choices, Bearing Ball (BB) phantom material, image processing algorithms, etc.  A Bare Bearing Ball (BBB) is preferred over BB;

2.      The Source Subsystem Error (SSE) map is the vector distance of CAoR from SSI as a function of gantry angle. Please note that is vector error includes the collimator walkout, gantry sag and wobble but excludes the MLC error which needed to be considered separately;

3.      The Target Subsystem (TS) plays no roles in determining SSI;

4.      The center of the BB in the Flexmap and IsoLock, representing the Target Subsystem Isocenter (TSI), is at SSI when the table angle is zero. The Target Subsystem Error (TSE) map is the vector distance of TSI from SSI as a function of table angle. Please note that the direction of table rotation may affect the error;

5.      The concept of “isocenter size” is replaced by the max of sum of the TSE and SSE;

6.      Guide Subsystem (GS)’s CBCT is not used to determine the SSI, but to “remember” where it is by the procedures of Elekta’s Flexmap and Varian’s IsoCal, respectively. The calibrated CBCT becomes an absolute GS ruler and is used to guide the table movement in target setup;

7.      The room laser shall be aligned to SSI. The lasers are also SSI surrogate which could be used to setup phantoms for IGRT calibration;

8.      In TG 142, the QA test of “Coincidence of radiation and mechanical isocenter” means the coincident between the Source Subsystem Isocenter and the Target Subsystem Isocenter.


Tanxia QU (New York, USA)
00:00 - 00:00 #30171 - P182 Clinical implementation of Lightning for the Gamma Knife Icon.
P182 Clinical implementation of Lightning for the Gamma Knife Icon.

Introduction

Lightning is a new Inverse Planning module available for Leksell Gamma Plan version 11.3.1. Prior inverse planning was limited for GK because it couldn’t outperform experienced manual planners. This module allows automatic planning using coverage, OAR tolerance dose(s), low dose/beam on time priorities and also allows final manual adjustments after dose calculation such as add/move/delete shot(s) and/or re-normalising the plan. Clinical implementation of this module is a practice-changing event and needs thorough investigation.

 

Methods and Materials

The following tasks were chosen to assess the clinical implementation of the new module:

1.     To investigate whether optimal parameters exist for Lightning plans, a series of benchmarking targets were planned with Low dose and Beam on Time weightings between 0.1 and 1.0 in 0.1 increments yielding a total of 100 plans per targetThe optimisation algorithm has 100% reproducibility ie. It produces exactly the same plan for the same optimisation parameters. Beam on time, conformity and gradient were assessed for each plan with the aim of finding whether optimal weighting values exist.

2.     Treatment planning methods used since the implementation of Lightning were captured for every patient. Each plan was allocated one of the following categories: Manual planning, “Single click” Lightning with default 50:50 weighting, Lightning with weighting adjustment and Lightning with manual shot modifications.

Results

1.   Low Dose/Beam on Time weighting matrices revealed that there is no ‘sweet spot’ so parameters need to be varied by the user to achieve their idea of an optimal plan. 

2.   After the first two months of use around 50% of plans were created with Lightning. This proportion has not significantly changed after 10 months though the number of plans with manual adjustments has increased. The planning method used appears to depend on the target size and complexity. For single targets > 1cc Lightning becomes the preferable method of planning and this rises to >80% for targets >5cc.

 

Summary

Lightning is a well design and intuitive module which achieves a clinically acceptable planning results in a short time. It is particularly useful for planning large single targets and for multiple targets. The available tools allow the user to optimise the plan in terms of OAR tolerance doses, target coverage, gradient index and treatment time, but a “final touch” by an experienced planner may be still useful in order to further improve the selectivity and conformity of the plan. 


Diana GRISHCHUK (London, United Kingdom), Anna KARANATSIOU, Ian PADDICK
00:00 - 00:00 #30220 - P183 Effect of Standard Wiston Lutz (WL) versus Wiston Lutz (WL) Off-Isocenter test for Multiple Brain Metastases.
P183 Effect of Standard Wiston Lutz (WL) versus Wiston Lutz (WL) Off-Isocenter test for Multiple Brain Metastases.

To suggest a method to perform an additional check to the standard Wiston Lutz (WL)  test in order to evaluate the concordance between the mechanical and the radiation field when using treatment of multiple brain metastases with a single isocenter. Using the ET Verification Head Phantom (VHP), BrainLAB, Feldkirchen, Germany, which contains three 5mm diameter tungsten carbide spheres (BB) placed in 3D non-coplanar locations; an immobilization mask was created and a CT scanner was taken and exported to Eclipse (Varian Medical System, CA, USA). Different plans were created as follows: Plan1, choosing one BB as the isocenter, the traditional WL was emulated test with that sphere as a target. Plan 2, keeping the same BB as the target, the isocenter was moved 3cm away from the sphere. Plan 3 was similar to plan 2 but with the sphere at 6cm from the isocenter. In all plans, a 2x2cm2 square MLC aperture was centered on the BB. The phantom was positioned on the linac using ExacTrac 6D Patient Positioning system. The plans were delivered using a Truebeam Novalis system with portal imaging acquisition; each time the couch was moved a portal image acquisition was taken and then verify with the Exactrac the phantom position and if necessary reposition it and take another portal image. The location of the sphere with respect to the MLC aperture was visualized and analyzed using the DoseLab (Varian Medical System, CA, USA) software with the same protocol that the traditional WL test. The WL test using the VHP was performed with and without Exactrac correction for the plans with the tungsten ball at 3cm and 6cm from the isocenter. Results showed that Exactrac repositioning reduces the inherent machine deviation for off-isocenter targets. However, differences between radiation and mechanical field increase as the distance increase from the Isocenter. The test showed some differences that are out of tolerance can be corrected with Exactrac; however, at some distances from the Iso although Exactrac correction is performed, values cannot reach values within tolerances. This work recommend that when using treatment of multiple brain metastases with a single isocenter, this test must be performed in order to evaluate the concordance between the mechanical and the radiation field and decide if a greater PTV is necessary or that lesions that are at certain distances may need an extra isocenter


Juan Carlos PAZ LOZADA (Cali, Colombia), Vacca Campos NESTOR DANIEL, Juan David ARIAS SALGADO, Velasco Carbonero FELIPE ANDRES

"Tuesday 21 June"

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08. Eposters - Radiobiology

00:00 - 00:00 #29398 - P184 Institutional experience with multiple radiation fractionation regimens for the treatment of portal vein tumor associated thrombosis.
P184 Institutional experience with multiple radiation fractionation regimens for the treatment of portal vein tumor associated thrombosis.

Objectives: The optimal radiation dose and fractionation for treatment of portal vein tumor thrombosis (PVTT) remains an area of active investigation. Here, we report on our institutional experience with multiple fractionation regimens for the treatment of PVTT.

Methods: We retrospectively assessed 36 patients with malignant PVTT treated from 2004 to 2021 at our institution, reviewing baseline characteristics, toxicity, and outcomes. The Kaplan-Meier (KM) method was utilized to estimate progression-free survival (PFS), local control (LC) and overall survival (OS). Chi-Square test  and ordinal regression analyses were used to compare baseline patient and tumor characteristics, radiation details, and treatment outcomes. Toxicity was graded using CTCAE v5.0 criteria.

Results: The median biologically effective dose (BED) was 62 Gray (Gy) (Range 33.60-105.60) and fractionation schemes ranged from 3 to 25 fractions ,including conventional fractionation,  hypofractionation (< 10 fractions), and stereotactic body radiation treatments (SBRT) (≤ 5 fractions), with median treatment volumes of 174 cc (Range 16.5-1685). Treatment was well tolerated with no grade 2+ acute or late toxicities. Hypofractionation was associated with lower acute toxicity (p<0.05).   Hypofractionation was also associated with smaller treatment volumes (median 133 cc) compared to conventional fractionation (median 798  cc, p<0.001).  The 1-year LC, PFS and OS was 50%, 32%, and 44%, respectively, and did not differ among treatment regimens, PVTT etiology, or location of the PVTT within the portal system. While baseline bilirubin levels did not correlate with response, lower post-treatment  bilirubin levels assessed at a median of 4 weeks after radiation were associated with a favorable PVTT response (p<0.05).    Larger radiation treatment volumes were associated with an increase in neutrophil to lymphocyte ratio (NLR) values post-treatment (p<0.05).   Patients with high baseline neutrophil to lymphocyte ratio (NLR), a negative prognostic sign in multiple cancers, trended toward worse survival (p=0.051) with a cutoff value of 4.0.

Conclusion: Taken together, our data suggests hypofractionated smaller treatment volumes had lower acute toxicity and improvement  in the immune biomarker neutrophil-to-lymphocyte ratio, with similar outcomes to more protracted regimens. The convenience of a short treatment course coupled with a 4 week post-treatment bilirubin assessment may be predictive of response and warrants validation in larger prospective studies.


Ebenezer ASARE (Charlottesville, USA), Hanna BATCHELOR, Einsley JANOWSKI
00:00 - 00:00 #29439 - P185 - WITHDRAWN - Hypofractionated gamma knife radiosurgery for intracranial pathologies: single center prospective analysis of feasibility, safety, efficacy, and complication profile.
P185 - WITHDRAWN - Hypofractionated gamma knife radiosurgery for intracranial pathologies: single center prospective analysis of feasibility, safety, efficacy, and complication profile.

Background: Conventionally GKRS is a single fraction therapy. Hypofractionated GKRS needs evaluation on long term for its radiobiology and practical application. 

 

Objective: The study aims at evaluating the feasibility, safety, efficacy, and complication profile of hypofractionated radiosurgery for various intracranial pathologies. 

 

Methodology: All patients with intracranial pathologies not suitable for single session GKRS are included in this prospective analysis for the study duration of 2010-2018. These patients either had a larger tumor volume (>14cc) or it was not possible to spare the neighboring organs at risk (OARs)from unacceptable radiation exposure in a single setting. Patients received the hfGKRS with Leksell G frame in situ. Radiation was delivered in 2-3 fractions with interfraction interval of 24 hours. Target dose in each fractionation was calculated by LQ model and consideration of BED for individual pathology. Similarly, permissible radiation exposure to OARs was calculated for individual fraction. Patients were followed up on 6 months, 1,2, and 3 year on regular clinical and radiologic parameters. Any complication was notified on CTCAE 3.0 criteria. Patients were more than three years of clinicoradiologic follow up were included in the analysis. 

 

Results:202 patients received hfGKRS. 169 (89 male) could be included in the final analysis as per inclusion criteria. 41% received three fractions while 59% received two fraction GKRS. 77 patients needed hfGKRS because of their large volume(Figure 1) while rest needed due to close vicinity to OARs(Figure 2). Two benign confined cavernous sinus hemangiomas were successfully treated with 5 Gy in five fractions.76% complex AVM had complete nidus obliteration while non-AVM pathologies had98% progression free survival at 3-years follow up.hfGKRS for complex AVM has slightly lower rate of obliteration but also lesser rate of interval bleed and complications than volume fractionation schemes. 8 patients rebled in 1284 patient years. No patient suffered CTCAE grade III or more injury.2% patients suffered radiation induced brain edema while radiation necrosis developed in 8.1% patients. 

 

Conclusion: hfGKRS is a suitable alternative to single session GKRS and IMRT in view of its acceptable safety, efficacy, and complication profile. 


Manjul TRIPATHI (Chandigarh, India)
00:00 - 00:00 #29645 - P186 Irradiation of a pregnant on Leksell Gamma Knife Perfexion/Icon.
P186 Irradiation of a pregnant on Leksell Gamma Knife Perfexion/Icon.

Purpose: General approach for a pregnant in order to minimize dose to fetus is to avoid any radiation. Medical application of radiation can be approved in special urgent cases when risk of not treating patient is larger than risk of fetus irradiation. The most sensitive period for embryo is 4-8 weeks after conception and minimal dose that can potentially cause in some percentage effects to a fetus is being estimated to 100 mGy. The purpose of this study was to make an assessment of risk for fetus when treating pregnant on Leksell Gamma Knife (LGK) Icon/Perfexion. Three clinical cases of pregnant were also treated in our center and direct dose measurements on these patients performed.             

Materials and Method: As a part of a separate study, in-vivo TLD measurement was performed on 80 standard patients treated on LGK Perfexion. Measurements included following organs/sites: eyes, thyroid, chest, abdomen, pelvis, knee and ankle. It also provided a very good estimation for expected dose to fetus in the case of a pregnant woman treatment. Altogether three pregnant patients (26th, 20th and 26th week pregnancy) were treated on LGK Perfexion and Icon. Patients included following diagnoses: multiple brain metastases from breast and melanoma and uveal melanoma. For direct dose measurement two RAD-60S electronic dosimeters were positioned on a patient to fetus location and kept during the whole treatment process.

Results: Dose measured to pelvis area for 80 patients showed average 0.73 mGy (median 0.49 mGy). Mean dose as measured by two electronic dosimeters in location of fetus for three irradiated women was 1.28 mGy, 0.49 mGy and 0.55 mGy. Thus mean dose obtained to fetus estimated by these measurements was approximately eighty, two-hundred and one-hundred-eighty times lower than dose of 100 mGy which is consider to be a minimal dose that can potentially cause some effects.       

Conclusions: Dose to fetus that is received during LGK Perfexion/Icon treatment is generally very low, typically below 1 mGy. This dose is one-hundred times lower than dose that is considered to be a minimal dose that can potentially cause some effects to fetus. Direct measurement on three pregnant patients proved this estimation.   

Keywords: Leksell gamma knife, treatment of pregnant, extracranial doses, dose to fetus   

 

This study was supported by the Ministry of Health, Czech Republic - conceptual development of research organization (Na Homolce Hospital - NNH, project No. IG174701).


Josef NOVOTNY (Prague, Czech Republic), Gabriela SIMONOVA, Roman LISCAK
00:00 - 00:00 #29812 - P187 A study to compare dynamic conformal arc therapy with volumetric modulated arc therapy for Stereotactic Radiosurgery.
P187 A study to compare dynamic conformal arc therapy with volumetric modulated arc therapy for Stereotactic Radiosurgery.

Purpose: Stereotactic Radiosurgery (SRS) is a highly precise technique to treat Intracranial lesions with very high dose radiation therapy. Objective of this study is to compare different techniques of dynamic conformal arc therapy (DCAT) with volumetric modulated arc therapy (VMAT) for SRS patients.

Material/Methods: A retrospective study of five SRS patients treated with 15Gy in single fraction was chosen for this study. All the plans were generated using 6MV photon DCAT with non-coplanar beams (NC) for Elekta Synergy™ linear accelerator. The another set of plans were generated using same optimization method by changing VMAT technique with flattening filter (FF) and flattening filter free (FFF) for Versa HD™ linear accelerator. The reference NC-DCAT plans were compared with VMAT-FF and VMAT-FFF. All the plans were analysed using dose volume histogram(DVH). For dosimetric comparison, conformity index(CI), Monitor Units(MUs), Integral dose (ID), D98%, D2%, D50%, max dose and mean dose coverage to planning target volume (PTV) were analysed. In addition, dose volume received by critical organs such as brain, brain stem and optic chiasma were compared.

Results: A total 15 plans were generated for dosimetric comparison. The results of D98%, D2%, D50%, max dose and mean dose PTV did not show any significant difference between DCAT, VMAT-FF and VMAT-FFF plans. A slight increase of CI was observed in DCAT plan as compared to VMAT-FF and VMAT-FFF. No significant dose difference was observed in brain stem, optic nerve, optic chiasma among three plans. Dose volume received by normal brain V12Gy, V10Gy and V5Gy were significantly less in VMAT-FF and VMAT-FFF as compared to DCAT plan. On the contrary, significant reduction of total MU were found in DCAT plan when compared with VMAT-FF and VMAT-FFF plan.

Conclusion: The quality of SRS plan using DCAT was almost similar to VMAT FF & FFF plans. However, both VMAT plans achieved better dose reduction in normal brain with increase of MU as compared to DCAT plan.

 


Manishi BANSAL (Mohali, India), Mohandass P, D PALANIVELU, M HARI PRASATH, Narendra Kumar BHALLA, Ankush JINDAL
00:00 - 00:00 #29946 - P188 Assessment of the alpha/beta ratios of pituitary adenomas and craniopharyngiomas.
P188 Assessment of the alpha/beta ratios of pituitary adenomas and craniopharyngiomas.

PURPOSE

Hypofractionated radiosurgery (HFSRS) has been recently considered as an alternative to single fraction stereotactic radiosurgery (SFSRS) for perioptic lesions. To estimate and quantify a possible benefit from HFSRS versus SFSRS, the value of the alpha/beta ratio must be known, for both lesions and organs at risk. Recently the a/ß ratio for the anterior visual pathway (AVP) has been found to be relatively small (1.03Gy). While a/ß ratios for Meningiomas and Chordomas have been investigated, a/ß ratios for Pituitary Adenomas (PA) or Craniopharyngiomas (CFG) have never been published to the best of our knowledge.

 

METHOD AND MATERIALS

The a/ß ratios were estimated from meta-analyses of studies on treatments performed including SFSRS, HFSRS, and radiotherapy (RT), using the Fraction Equivalent (FE) method. Physical doses were corrected for repair effects during treatment, based on the biphasic repair process of sublethal damage, with repair halftimes of 0.19h and 2.16h. While treatment times during a RT fraction are generally sufficiently shorter than one halftime of fast repair of sublethal damage, repair effects need to be considered for HFSRS and particularly for SFSRS. 35 studies fulfilling the equivalency criteria with fraction numbers 1-30 were included to assess the a/ß ratio of PA, while 19 studies with fraction numbers 1-31 were included to assess the a/ß ratio of CFG. Clinical data provided from our center were added, including HFSRS for 41 PA and 10 CFG, and SRS for 84 PA and 8 CFG, with a mean follow-up period of 23m (HFSRS) and 27m (SRS).

 

RESULTS

The FE plot method revealed an a/ß ratio for non-functional PA of 2.47Gy, confidence interval [2.29-2.64Gy], while for functional PA an a/ß ratio of 4.91Gy was found, confidence interval [4.45-5.34Gy]. For CFG we found a low a/ß ratio of 0.83Gy, confidence interval [0.67-1.03Gy].

 

CONCLUSION

Pondering the concept of the biphasic repair process of sublethal damage, a/ß ratios can be much smaller than calculated with the traditional uncorrected FE method. As expected, a/ß ratios for both functional and nonfunctional PA are much larger compared to the a/ß ratio of the AVP. Theoretically, an increased Single Fraction Equivalent Dose (SFED) to the lesion of more than 14% for functional PA and of almost 6% for nonfunctional PA can be achieved with optimized HFSRS schedules, while maintaining constant the risk of visual deterioration from RION, by widening the therapeutic ratio. No therapeutic gain can be expected from hypofractionation for CFG.


Herwin SPECKTER (Santo Domingo, Dominican Republic), Giancarlo HERNANDEZ, Jose BIDO, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Jairo SANTANA, Wenceslao HERNANDEZ, Luis MORENO, Ismael PERALTA, Jeffrey PAULINO, Peter STOETER
00:00 - 00:00 #29967 - P189 Modeling and comparison of responses to irradiation in cell cultures of relapsed and primary glioblastomas.
P189 Modeling and comparison of responses to irradiation in cell cultures of relapsed and primary glioblastomas.

 

Optimal schemes of irradiation for recuurensed glioblatomas not determined yet.  An important task is to assess the radiosensitivity of human glioblastoma cells when exposed to various total and single doses and understanding whether radiosensitivity changes with repeated irradiation of cells.

Cell cultures that were selected for the study were obtained from 6 patients during removing glioblastoma (GB), three of whom underwent radiation therapy before the second surgery, and three more patients had not previously been irradiated.  Irradiation was carried out on by TrueBeam STx linac (Varian, USA). A bremsstrahlung photon beams energy of 6 MeV were chosen for the experiment in a wide range of doses and three different fractionation regimens: 1, 3 and 5 fractions. To assess the response of cells to irradiation, the changes in their proliferative activity were assessed by the MTT test.   The dose ranges for irradiation for 3 and 5 fractions had to be equivalent to a single exposure, so they were calculated using the biologically effective dose (BED) and LQ models. The shape of the dose-effect curves obtained by us in this experimental study is not uniformly decreasing, as according to the accepted LQ model. The dynamics for cells from a previously irradiated tumor and tumors undergoing irradiation for the first time were markedly different. The number of fractions of irradiation influences to the shape of the dose-response curve. For cells previously exposed to irradiation, the drop in proliferative activity at low doses was not so significant, which indicates that the subpopulation of radiosensitive cells was smaller.  The sensitivity of GB culture's cells during repeated irradiation is lower at all dose intervals, which indicated the resistance of such cells to irradiation.

Quantitative estimates of dose-response curves could be used to predict the response of glioblastomas to irradiation in clinical practice, to select the most effective and safe irradiation regimens, to assess the risks and prospects for the use of repeated irradiation in case of relapses. It is necessary to build a mathematical model that most accurately describes the dynamics of changes in the metabolic activity of cells depending on the dose of ionizing radiation.

The research was supported financially by RFBR (Project No. 18-29-01061).


Natalia ANTIPINA (Moscow, Russia), Andrey GOLANOV, Anna NIKOLAEVA, Galina PAVLOVA, Anna OVECHKINA
00:00 - 00:00 #30131 - P190 Fractionated radiotherapy for brain tumors using mask system of Leksell Gamma Knife Icon.
P190 Fractionated radiotherapy for brain tumors using mask system of Leksell Gamma Knife Icon.

[Objectives] Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment.

[Methods] We retrospectively analyzed 973 patients (1145 times) with brain tumors who underwent fractionated radiotherapy using mask system of Leksell Gamma Knife Icon for the first four years at Rakusai Shimizu Hospital. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule. The most common disease was metastasis (639 patients), followed by meningioma (159), vestibular schwannoma (66), pituitary adenoma (28), glioma (20), and others (61).

[Results] The reasons for the select of fractionated schedule (including duplication) were large volume (618 times), near the eloquent area (505), and recurrence (296). For large malignant tumors, we selected fractionated schedules as follows; 7.0 Gy x 5Fr (5-10 ml), 4.2Gy x 10Fr (10-20ml), 3.7Gy x 10Fr (20-30ml), 3.2Gy x 10Fr (30ml-). Survival rates were 82/73/64% at 6/12/24 months post-treatment, with only 3/4/5% of neurological deaths at 6/12/24 months after treatment. Poor local control rates were 9/18/27% at 6/12/24 months post-treatment. Preservation rates of neurological function were 93/89/86% at 6/12/24 months post-treatment. Serious complications occurred in only 1/1/3% of patients at 6/12/24 months post-treatment.

[Conclusions] Although these results are limited to short periods, survival rates, local control rates and qualitative survival rated in patients unsuitable for stereotactic radiosurgery, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges.

 

 


Takuya KAWABE (Kyoto, Japan), Manabu SATO
00:00 - 00:00 #30137 - P191 Gamma Knife® plan optimization with fixed beam on times.
P191 Gamma Knife® plan optimization with fixed beam on times.

Objectives

There are studies indicating that the overall treatment time affects the Biological Equivalent Dose (BED), and hence the potential outcome, of a LGK treatment even when the prescription dose is fixed.

 

To investigate this, multiple treatment plans for the same target with varying treatment times and calibration dose-rates in the range 1.5-3.5Gy/min have been created using LGP Lightning. Standard metrics for the plans as and BED were calculated for each plan.  Based on the results, decisions can be taken upon the treatment time to be used to achieve a specific BED while still maintaining a good overall plan quality.

 

Materials and methods

Optimized plans for five acoustic schwannomas, with various tumour sizes 0.891cc to 7cc with a prescription dose of 12Gy were created. The cochlea was as a risk-organ outlined with a small margin and a maximum dose constraint of 4Gy. For each case the Paddick (PCI) and gradient indices (GI) were calculated. BED was calculated using the formula by Millar and Hopewell.  

 

Results

For fixed 45-minute treatments, varying the dose-rate between 1.5 Gy/min to 3.5Gy/min for all the tumour sizes, the average PCI increased from 0.83 to 0.90 and the average GI decreased from 2.96 to 2.57. Increasing the beam on time from 45 to 60 minutes for a fixed dose-rate 2Gy/min increased the average PCI from 0.83 to 0.89 and decreased the average GI from 2.96 to 2.62. Increasing either dose-rate or treatment time will improve the quality of the plan, but this is an exponential effect with diminishing returns.

With Lightning generated plans, the prescription dose is also, to a good approximation, an iso-BED surface for a given treatment time. The BED calculated on the prescription isodose surface varies mainly with the total treatment time (10-80 minutes) between approximately 65Gy2.47 down to 51Gy2.47 and not on other details such as reference dose rate and number of shots. Furthermore, the variation of BED on the prescription iso-dose surface is less than 5% for almost all combinations of treatment time and dose-rate.

 

Conclusion

The results indicate that quality plans can be created for a wide range of treatment times even for low reference dose-rates. BED depends mainly on the overall treatment time and prescription dose and not on the number of shots or the reference dose rate. 


Jonas JOHANSSON (Stockholm, Sweden), Håkan NORDSTRÖM, Ian PADDICK
00:00 - 00:00 #30195 - P192 Adjuvant immunotherapy versus fractionation in stereotactic radiosurgery – a modelling study.
P192 Adjuvant immunotherapy versus fractionation in stereotactic radiosurgery – a modelling study.

Purpose: While the principle of radiation therapy is based on the direct cell-killing resulting from radiation-induced lethal DNA damages, the importance of the immune system and its response to the treatment has been increasingly recognised in recent years. In addition to the immune response induced by the radiation, the clinical interest in combining high-dose radiotherapy with immunotherapy has seen a dramatic increase in the recent years. However, many question marks remain, none the least with respect to the fractionation and timing of the immunotherapy in relation to the radiotherapy. For hypoxic tumours, determining the optimal treatment schedule could be particularly challenging with respect to the dynamic nature of the tumour oxygenation. It was the purpose of this modelling study to investigate the impact of fractionation on the outcome of radioimmunotherapy with particular focus on the tumour reoxygenation.

Materials and Methods: Hypoxic tumours were simulated using a three-dimensional model of heterogeneous and dynamic tumour oxygenation. The outcome of stereotactic radiotherapy in combination with immune therapy was simulated using a Poisson-based model for tumour control probability taking into account the surviving fraction on voxel level. The voxelised survival was calculated using the linear-quadratic model modified to include the effect of immunotherapy by considering the evolution of the number of tumour infiltrating immune effector cells and the number of antigen molecules during the treatment. The modification of the radiosensitivity on voxel level resulting from the heterogeneous tumour oxygenation was also accounted for in the survival calculation, and considering both static and dynamic oxygenation pattern between radiotherapy fractions.   

Results: For a well-oxygenated tumour with a hypoxic fraction of <1%, the tumour control probability for a single fraction of 20 Gy with or without adjuvant immunotherapy was 100% and 98% respectively. For a tumour with 10% hypoxia, the TCP after a dose of 20 Gy was raised from 1% for radiotherapy only, to 99% with adjuvant immunotherapy. Interestingly, fractionating the radiotherapy treatment into four fractions of 33 Gy total dose (isoeffective with respect to 20 Gy x 1) and including reoxygenation between fractions, the TCP was 97% even without immunotherapy.

Conclusions: Adjuvant immunotherapy could significantly increase the tumour control probability in stereotactic radiosurgery for hypoxic tumours. The effect from allowing for fast reoxygenation by fractionating the treatment into only four fractions could achieve a similar effect, demonstrating the potential benefit from fractionation for hypoxic tumours in particular.


Emely KJELLSSON LINDBLOM (Stockholm, Sweden), Alexandru DASU
00:00 - 00:00 #30197 - P193 Evaluation of Lung SBRT Dosimetric Parameters Correlated to Decrease in Absolute Lymphocyte Count.
P193 Evaluation of Lung SBRT Dosimetric Parameters Correlated to Decrease in Absolute Lymphocyte Count.

Purpose: Lymphocytes are remarkably sensitive to radiation therapy, and treatment related lymphopenia (TRL) is a well-known side-effect of radiation therapy. Moderate to severe TRL decreases immunological function and may suppress immunoresponse to tumors. This analysis seeks to identify dosimetric parameters of lung SBRT associated with a decrease of absolute lymphocyte count.

Methods and Materials: We have conducted a statistical analysis of data collected for 86 lung cancer patients treated via SBRT adhering to RTOG 0915/0813 objectives. The data includes dose-volume parameters and CBC with differential for lymphocyte measurements at before and after the start of SBRT to lung was collected retrospectively. The difference in absolute lymphocyte count (ALC) for all participants from day 0, start of SBRT to the post treatment level was analyzed with a single sample t-test. Chi square and bivariate analyses were used to evaluate for correlation of between ALC change with PTV size, age, tumor location and recorded dosimetric values.

Results: Data was analyzed for 86 patients ranging from 50 to 92 years of age with median age of 71.  Of 86 patients, 33 patients had centrally located tumors. Dosimetric values were recorded at the time of planning and included in this analysis include max/mean/integral dose, V5Gy, V10Gy, V15Gy, and V20Gy for the heart, aorta, vena cava, pulmonary artery, lungs, and thoracic spine contoured per protocol. By day 25, the mean decrease in ALC is 0.432 k/µL (p<0.001, 95% CI 0.304-0.561). The integral dose for combined vasculature and heart structure was found to correlate with ALC change (p = 0.03). Additionally, Lung V20Gy and V15Gy were found to correlate with ALC change (p = 0.03 and p = 0.045). PTV size, age, tumor location, and other dosimetric parameters showed no statistically significant association with change in ALC though a trend towards significance was noted for PTV size (p=0.09).

Conclusions: Patients undergoing lung SBRT showed a significant decrease in ALC following initiation of treatment. Increasing integral dose to the combined vasculature and heart structure as well as lung V20Gy and V15Gy were associated with decreased ALC, and increasing PTV size trended toward significance. Additional dosimetric analysis of lymph node volumes may yield further insight.


David COUSINS (Charlottesville, USA), Cam NGUYEN, Donald MULLER, Timothy MCMULLEN, James LARNER, Krishni WIJESOORIYA

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09. Eposters - Imaging

00:00 - 00:00 #29406 - P195 Comparison of contrast clearance analysis and MRI to differentiate between tumor recurrence and pseudoprogression in a Gamma Knife Center.
P195 Comparison of contrast clearance analysis and MRI to differentiate between tumor recurrence and pseudoprogression in a Gamma Knife Center.

Purpose

Radionecrosis/pseudoprogression is a well-characterized toxicity associated with radiation for intracranial lesions which can be difficult to differentiate from tumor progression on follow-up imaging, making treatment decisions challenging in this patient population. This study has the goal to show the clinical application of the contrast clearance for proper diagnose and treatment.

Methods

All patients who had undergone contrast clearance analysis (CCA) to distinguish treatment response from tumor progression as part of their follow-up for prior stereotactic radiosurgery were included. Demographical data as well as clinical, complementary treatment, radiographical, and CCA evaluation of patients and their tumor pathology were assessed. A comparison of a clinician’s evaluation of follow-up MRI imaging versus CCA imaging was performed.

Results

Seventy patients were evaluated in this study. The most common primary disease of included patients was metastasis, especially non-small cell lung cancer, followed by glioblastomas and atypical meningioma. The majority (96.47%) of treated patients had multiple brain metastases, accounting for a total of 425 lesions, being 104 suspicious of pseudoprogression or recurrence. Multiple imaging follow-up led to 146 tumor analyses. From the 38 lesions diagnosed as recurrence based on MRI, only 12 (32%) were considered positive on CCA, which would lead to 17.8% overtreatment. Other 21 lesions (14.38%) evaluated as tumor by CCA were classified as pseudoprogression or equivocal by MRI. Inter-rater reliability using Cohen’s kappa coefficient showed poor strength of agreement at 0.09 between the two modalities.

Conclusion

CCA imaging is a promising tool to distinguish tumor progression from radiation necrosis in the setting of radiosurgical treatment, lowering the chances of not treating recurrent lesions or overtreating pseudoprogression, therefor, increasing patient’s safety. Further studies are needed to clearly show its sensitivity and positive predictive value and comparison with other diagnostic methods.


Amade BREGY, Victor GOULENKO, Lindsey LIPINSKI, Robert PLUNKETT, Dheerendra PRASAD (Buffalo, NY, USA)
00:00 - 00:00 #29428 - P196 What are the optimal follow-up scan intervals for SRS targets?
P196 What are the optimal follow-up scan intervals for SRS targets?

Objective: A retrospective study to assess the timing of repeat imaging and tumour size after Gamma Knife radiosurgery (SRS) in metastasis, primary brain tumors and vascular malformations. 

 

Methods: A total of 66 patients were assessed over a 1 year period. 29 patients received radiosurgery with initial follow-up scans at 3 months and 37patients had initial follow-up scans at 6 months.  In both groups subsequent follow-up scan was at 12 months after initial imaging.  All patients in the metastatic group had follow-up MRI scan at 3 and 6 months after SRS.  In the AVM group only MRI/MRA imaging was performed on follow-up. 

 

Results:

There were 21 patients with meningiomas, 11 patients with vestibular schwannomas, 7 patients with non-secreting pituitary adenoma, 2 patients with jugular schwannomas and 11 patients with metastases. There were 5 patients with AVM’s and 4 patients with cavernomas. The rest were single cases of ependymoma, central neurocytoma, heamangioblastoma, trigeminal schwannoma and glioma .     

In patients with meningioma half the patients had no change or slight increase in size at both 3 months and 6 months imaging.  Subsequent imaging showed reduction in size. All patients with vestibular schwannoma there was either no change or an increase in tumour size at 3 months and 6 months.  With the exception of 1 case there was a reduction in tumour size on subsequent imaging.  In the metastatic group, size changes and additional lesions were seen in 3 months.  All patients with AVM showed size reduction at 6 months.  There was no rebleed or size change in the cavernoma group.      

 

Conclusion:The timing for benign tumours, it is.recommended to repeat imaging between 6 months to 1 year following radiosurgery and imaging for AVM is within 6 months and 3 months for metastasis. 


Ramesh KUMAR (Kuala Lumpur, Malaysia), Yu May LEE, Bee Hong SOON, Jegan THANABALAN, Charng Jeng TOH, Farizal FADZIL, Fuad ISMAIL, Marfuah EEZAMUDDEEN, Shaizone AZURA MOHAMED MUKARI, Rozman ZAKARIA, Siti KHADIJAH HAMSAN
00:00 - 00:00 #29676 - P197 MGMT promotor methylation status and implications for weekly adaptive radiotherapy for glioblastoma.
P197 MGMT promotor methylation status and implications for weekly adaptive radiotherapy for glioblastoma.

Purpose: Integrated MRI-linear accelerator (MR-Linac) technology allows for daily soft tissue visualization, on-line adaptive replanning and potential for safe margin reduction. We report preliminary findings of weekly tumor reduction in a consecutive series of MGMT-methylated glioblastoma (GBM) patients treated on the MR-Linac (MRL).

Methods and materials: UNITED (NCT04726397) is a phase II trial investigating the safety and feasibility of margin reduced MR-guided adaptive radiotherapy in GBM using the MRL. Patients treated with 60 Gy in 30 fractions or 40 Gy in 15 fractions with concomitant temolozomide (TMZ) are eligible. A 5 mm clinical target volume (CTV) expansion is applied to the gross tumor volume (GTV), which is extended to include abnormal T2-FLAIR. Patients undergo weekly on-line adaptive replanning based on a contrast-enhanced T1 and T2-FLAIR MRL-MRI taken in the treatment position.

Results: The first five consecutive MGMT-methylated patients are reported. All patients had IDH wild-type GBM and the mean age was 60 years (range: 44-76 years). Compared to the Day 1 MRL plan, weekly average GTV changes at fraction 6, 11, 16, 21, and 26 were -7.8% (range, +1.1% to -14.0%), -17.6% (range, -3.7% to -24.3%), -15.5% (range, -5.8% to -25.0%), -20.4% (range, -7.4% to -38.1%) and -22.0% (range, -3.6% to -35.7%), respectively. Average CTV reductions were 4.3%, 11.6%, 7.6%, 14.0% and 14.0% at the same respective time points. In comparison, the first five treated unmethylated patients exhibited consistent weekly growth patterns in the GTV during RT.

Conclusions: Our preliminary findings support a treatment adaptation protocol for GBM, in particular for patients with methylated GBM, given the volume reductions observed. Clinical outcomes from the UNITED clinical trial will inform endpoints including failure patterns, quality of life, and treatment tolerance.


K. Liang ZENG (Toronto, Canada), Arjun SAGHAL, Sten MYREHAUG, Hany SOLIMAN, Chia-Lin TSENG, Mark RUSCHIN, James PERRY, Mary Jane LIM-FAT, Sunit DAS, Jay DETSKY
00:00 - 00:00 #29800 - P198 Machine learning-supported MRI Radiomics to predict the volumetric response in meningiomas after Gamma Knife radiosurgery.
P198 Machine learning-supported MRI Radiomics to predict the volumetric response in meningiomas after Gamma Knife radiosurgery.

Background

In previous studies, we analyzed the potential of both Diffusion Tensor Imaging and of Texture Analysis of Magnetic Resonance Imaging to predict the volumetric response of benign meningiomas to Gamma Knife radiosurgery (GKRS). In this study, we analyzed the value of meningioma morphology in the prediction of volumetric changes induced by GKRS.

 

Methods

The retrospective prediction model of meningioma responsiveness to GKRS included T1-weighted, non-contrast enhanced MRI scans obtained from 93 patients before GKRS. Imaging data was processed and analyzed through the QMENTA cloud platform and meningioma morphology was quantified by calculation of 337 shape, first-order and second order radiomic features. This analysis was performed on original 3D unfiltered MR images and images modified by Laplacian of Gaussian (LoG), logarithm and exponential filters.

 

Results

Sixty calculated features significantly correlated with the outcome defined as meningioma volume change per month. The predictive model was created based on all radiomic and twelve non-radiomic features using the LASSO regression machine learning method. Thereby, LoG-sigma-1-0-mm-3D_firstorder_InterquartileRange (coefficient weight = -9.916) and logarithm_ngtdm_Busyness (coefficient = 0.002) were selected as the most predictively robust and non-redundant features. The radiomic score based on these two radiomic features produced an AUC = 0.81. Its values ranged between -2.89 and 2.48, whereby score values up to -1.31 defined a subgroup of 50 patients with consistent absence (0%) of tumor progression.

 

Conclusions

This is the first report of a strong association between the MRI radiomic features and the volumetric meningioma response to radiosurgery. The clinical importance of the early and reliable prediction of meningioma responsiveness to GKRS is based on its potential to guide individualized treatment strategies.


Herwin SPECKTER (Santo Domingo, Dominican Republic), Marko RADULOVIC, Kire TRIVODALIEV, Velicko VRANES, Johanna JOAQUIN, Wenceslao HERNANDEZ, Jose BIDO, Giancarlo HERNANDEZ, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Peter STOETER
00:00 - 00:00 #29930 - P199 Radiomics-based machine learning methods for the prediction of acoustic neuroma response to cyberknife treatment: a multicenter study.
P199 Radiomics-based machine learning methods for the prediction of acoustic neuroma response to cyberknife treatment: a multicenter study.

Aim: To predict acoustic neuroma response to radiosurgery, using machine learning (ML) methods based on radiomic features extracted from pre-treatment MR images.

Materials: Patients with acoustic neuroma and treated with radiosurgery (12Gy/1 fraction or 18Gy/3 fractions) in our two institutes from 2004 to 2016 were retrospectively evaluated. Inclusion criteria were having contrast-enhanced T1-weighted MR images available before and at 24 and 36 months after treatment. Clinical, audiometric and treatment data were collected at the same time points. Lesions were classified as stable, reduced or increased according to the volume variation assessed on the pre- and post-radiosurgery MR images. Tumours were semi-automatically segmented on the pre-treatment MR images using the level tracing effect of the 3DSlicer software. Pre-treatment images were pre-processed in three steps: i) uniformity correction; ii) deskulling to isolate brain voxels; iii) Z-score transformation to standardize voxel intensities within the brain. For each patient 851 radiomic features were extracted on the 3D segmented regions from the processed images and after wavelet transformation, using PyRadiomics. We trained and tested ML methods to predict the lesion increase at 24 and, separately, 36 months after radiosurgery, using a nested cross-validation (CV) scheme (outer loop: 5 folds; inner loop: 3 folds). On the training set of each outer loop feature selection was performed using Least Absolute Shrinkage Selector Operator (LASSO) and the selected features were used as input to separately build four ML classification methods. Parameters of LASSO and ML methods were tuned in the inner loops. To overcome class imbalance during training Synthetic Minority Oversampling Technique (SMOTE) was used. Finally trained models were tested on the corresponding held-out patients in each outer loop to evaluate balanced accuracy, sensitivity and specificity. 

Results: We included 95 patients (age 62±12 years, 42 males [44%]) treated with Cyberknife® at our institutes. All results are summarized in Table 1. The Neural Network was the best algorithm for predicting the response at 24 months (average test set accuracy 71%, sensitivity 60%, specificity 82%) and 36 months (accuracy 66%, sensitivity 50%, specificity 83%). Features selected for each experiment are reported in Table 2. 

Conclusions: These preliminary results indicate that the proposed methods have great potential in distinguishing, before radiosurgery, patients with tumour volume increase from patients with stable or reduced lesions. Subsequent studies are ongoing to assess the robustness and reproducibility of these results. Radiomics-based ML methods may be useful for improving the management of patients with acoustic neuroma.


Isa BOSSI ZANETTI (Milano, Italy), Riccardo PASCUZZO, Natascha Claudia D'AMICO, Domenico AQUINO, Paolo SODA, Sara MORLINO, Valentina PINZI, Marcello MARCHETTI, Elena DE MARTIN, Giancarlo BELTRAMO, Laura FARISELLI
00:00 - 00:00 #29986 - P200 Development of methodology and instruments of using diffusion data of magnetic resonance tomography in diagnostics and stereotactic radiotherapy of intracranial pathology.
P200 Development of methodology and instruments of using diffusion data of magnetic resonance tomography in diagnostics and stereotactic radiotherapy of intracranial pathology.

In clinical practice, and especially in stereotactic radiotherapy planning, the significance of diffusion-weighted imaging (DWI) is growing. This makes the existence of software capable of quickly processing and reliably visualizing diffusion data, as well as equipped with tools for their analysis in terms of different tasks.

We are developing the «MRDiffusionImaging» software on C++. The subject part has been moved to separate class libraries and can be used on various platforms. The «MRDiffusionImaging» software is equipped with a unique set of tools for working with diffusion images. An algorithm for "masking" diffusion MRI series based on T2-weighted images was developed using a deformable surface model to exclude tissues that are not related to the area of interest from the analysis. A tool for calculating the coefficient of average diffusion and fractional anisotropy (FA) has been created, on the basis of which it is possible to build quantitative maps for solving various clinical tasks. Clustering and segmenting images functionality based on the k-means method has been created to individualize the clinical target volume and further assessment of response to the treatment. White matter tractography was realized using two algorithms: deterministic (fiber assignment by continuous tracking) and global approach provided by Hough transform. The second algorithms tests candidate curves in the voxel, assigning to each one a score computed from the diffusion data, and then select the curves with the highest scores as the potential anatomical connections. The limitations of the algorithm of fiber assignment by continuous tracking include the following: 1) overestimation of the FA threshold leads to the difficulty of visualizing tracts in the area of cerebral edema and subcortical regions of the brain; 2) a decrease of the step size leads to a decrease in the number of tracts; 3) lack of information about the error in the fiber tracking procedure; 4) the impossibility of resolving crossing and “kissing” tracts. We present experimental results on diffusion tensor mages (DTI) and high-angular resolution diffusion images (HARDI) volumes of 1,5T and 3T human brain datasets.

The «MRDiffusionImaging» will improve the efficiency and accuracy of diagnostics and stereotactic radiotherapy of intracranial pathology. As part of further work, it is planned to improve the developed tools using advanced methods, test the tools on a group of patients with glioblastomas and functional pathologies, and develop a draft methodology for using diffusion in practical radiation therapy for consideration and adoption in professional the radiotherapy community.


Kseniia Aleksandrovna URAZOVA, Gennadiy Efimovich GORLACHEV, Aleksandr Petrovich CHERNYAEV, Andrev Vladimirovich GOLANOV (Moscow, Russia)
00:00 - 00:00 #30044 - P201 CT-guided fiducial placement for robotic stereotactic body radiotherapy: efficacy and safety.
P201 CT-guided fiducial placement for robotic stereotactic body radiotherapy: efficacy and safety.

Introduction 
Robotic Stereotactic Body Radiotherapy (SBRT) employs radiopaque fiducial markers implanted near the tumor for real-time tracking. Fiducials are usually placed before simulation under CT or ultrasound guidance. This represents a limitation to treatment availability and may result in potential treatment delay. 
In our Institution, an in-house percutaneous CT-guided fiducial placement procedure was implemented for pelvic SBRT. The aim of our study is to evaluate the performance and side effects of in-house fiducial placement.

Methods
Patients underwent percutaneous fiducial insertion with a 18 G needle under CT guidance, using a radiopaque skin marker to calculate the depth of target location from body surface (Figure 1). One week after placement, simulation CT and orthogonal X-ray imaging were acquired to verify fiducial usability for SBRT tracking. Data from a consecutive cohort of patients treated with fiducial-guided, robotic-arm pelvic SBRT were collected from January 2018 to September 2021. 
Success rate was defined as the implanted/tracked fiducials ratio. Kruskal Wallis-test was used to compare median success rate over time.

Results
In the observed time frame, 282 patients underwent CT-guided fiducial placement, accounting for 883 implanted fiducials (median 3, range 1-4). Implantation sites were the prostate bed, extra-spinal bones and pelvic lymph nodes in 158 (56%), 37 (13%) and 87 (31%) patients, respectively. Side effects consisted of minor bleeding at the insertion site and transient pain requiring medication after 24 hours in 5 patients (2%). 
No grade >2 toxicity was observed.

Overall success rate was 86% (719/833); median success rate per procedure was 100% (range 50-100%). Among the 114 fiducials rejected for tracking, failure was due to migration in 63 cases (55%) and misplacement in 51 cases (45%).  Overall success rate increased across the observed time window from 2018 (53/73, 74%) to 2019 (245/293, 84%) to 2020 (246/272, 90%) to 2021 (175/195, 90%) (Figure 2). A consistent, statistically significant improvement in median success rate was observed over time from 2018 (75%, Interquartile Range, IQR 67-100%) to 2019 (100%, IQR 75-100%) to 2020 (100%, IQR 75-100%)  to 2021 (100%, IQR 100-100%) : p= 0.0008.

Conclusions
Our in-house percutaneous CT-guided fiducial placement is a safe procedure requiring minimal standard equipment, resulting in success rates comparable with published experiences performed in a dedicated interventional radiology setting. A consistent improvement in median success rate was observed over 4 years, suggesting the need for appropriate interventions to shorten the learning curve.


Mauro LOI (Firenze, Italy), Maria Grazia CARNEVALE, Vanessa DI CATALDO, Giulio FRANCOLINI, Carolina ORSATTI, Luisa CAPRARA, Luca BURCHINI, Lucia ANGELINI, Raffaella DORO, Laura MASI, Pierluigi BONOMO, Lorenzo LIVI
00:00 - 00:00 #30119 - P202 THE EFFECT OF MRI DISTORTION ON LOCAL CONTROL IN STEREOTACTIC RADIOTHERAPY OF BRAIN METASTASES.
P202 THE EFFECT OF MRI DISTORTION ON LOCAL CONTROL IN STEREOTACTIC RADIOTHERAPY OF BRAIN METASTASES.

ABSTRACT

Purpose/Objectives: In brain stereotactic radiotherapy, gross tumor volume is delineated with the guidance of MRI. However, especially in peripheral lesions, the lesion may not be clearly identified due to MRI distortion. Our aim in this study is to compare local control rates in peripheral lesions compared to central lesions.

Methods and Materials: Adult patients who underwent SRT for brain metastases and whose file data were complete were included in the study. Brain was contoured in all patients, and then the area was drawn inward one centimeter from the brain contour and the 'brain-1 cm' area was defined as 'Localization-1'. Then, another 1 cm from 'Localization 1' was drawn towards the central area and 'Localization 2' area was created. The 'localization 2' area is the distance between 1 to 2 cm from the lateral border of the whole brain in 3D. Lesions remaining more medially were defined as central (Figure 1). The follow-up and local successes were noted and analyzed. SPSS Ver. 22 software package was used for statistical analysis and the statistical significance limit was accepted as p<0.05 and below.

Results Between 21.02.2019 and 12.01.2021, 18 patients and 56 lesions that underwent cranial SRS and SRT for brain metastasis in Ankara City Hospital were analyzed. The lesion and treatment details are summarized in Table 1. The median follow-up period of the patients was 6 (range 1-34) months. The most common lesion localization was right occipitale (n=9; 16.1%) and left parietale (n=9; 16.1%). The primary of 9 (50.0%) patients were lung cancer; 4 (22.2%) were breast and 5 (27.8%) were other cancers. The 25 (44.6%) of the lesions were in localisation 1; 19 (33.9%) were at localisation 2 and 12 (21.4%) were central. Local progression was observed only in one centrally located lesion (at 4.47 month after SRT). The median PFS of the lesions was 5.4 (range 1-34) months. There was no significant difference between the three arms in terms of time from RT to progression (p=0.240) (Figure 2).

Conclusion: According to the results of our study, no significant difference was observed between peripheral lesions and central lesions in terms of local control and PFS. The number of patients in this study is relatively small and the follow-up period is short. The validity of the hypothesis will be tested over a longer follow-up period and a higher number of patients.

Keywords: Stereotactic radiosurgery, Stereotactic Radiotherapy, MRI Distortion, Brain Metastasis 


Hüseyin Furkan ÖZTÜRK (Ankara, Turkey), Gonca ALTINIŞIK İNAN, Yılmaz TEZCAN
00:00 - 00:00 #30120 - P203 Deep learning-based skull data extraction from real MRI to improve dose planning accuracy in Gamma Knife radiosurgery: a proof of concept study.
P203 Deep learning-based skull data extraction from real MRI to improve dose planning accuracy in Gamma Knife radiosurgery: a proof of concept study.

Purpose: Dose planning for Gamma Knife radiosurgery (GKRS) uses the magnetic resonance (MR)-based tissue maximum ratio (TMR) algorithm, which calculates radiation dose without considering heterogeneous radiation attenuation in the tissue. In order to plan the dose considering the radiation attenuation, the Convolution algorithm should be used, and additional radiation exposure for computed tomography (CT) and registration errors between MR and CT are entailed. This study investigated the clinical feasibility of synthetic CT (sCT) from GKRS planning MR using deep learning.

Methods: The model was trained using frame-based contrast-enhanced T1-weighted MR images and corresponding CT slices from 54 training subjects acquired for GKRS planning. The model was applied prospectively to 60 lesions in 43 patients including benign tumor such as meningioma and pituitary adenoma, metastatic brain tumors, and vascular disease of various location for evaluating the model and its application. We evaluated the sCT and compared between treatment plans made with MR only (TMR 10 plan), MR and real CT (rCT; Convolution with rCT [Conv-rCT] plan), and MR and synthetic CT (Convolution with sCT [Conv-sCT] plan).

Results: The mean absolute error (MAE) of 43 sCT was 107.35±16.47 Hounsfield units. The TMR 10 treatment plan differed significantly from plans made by Conv-sCT and Conv-rCT. However, the Conv-sCT and Conv-rCT plans were similar.

Conclusion: This study showed the practical applicability of deep learning based on sCT in GKRS. Our results support the possibility of formulating GKRS treatment plans while considering radiation attenuation in the tissue using GKRS planning MR and no radiation exposure.


So Hee PARK (Daegu, Korea), Dong Min CHOI, Hyun Ho JUNG, Jin Woo CHANG, Hwiyoung KIM, Won Seok CHANG
00:00 - 00:00 #30181 - P204 A machine learning predictive model for post-treatment edema after meningioma Gamma Knife radiosurgery.
P204 A machine learning predictive model for post-treatment edema after meningioma Gamma Knife radiosurgery.

Meningiomas are benign lesions that can spread all over the skull.  Tumors adjacent to a sinus or draining vein can result in venous congestion and in formation of peritumoral edema. Sterotactic radiosurgery can worsen an existing edema or make a new edema appear in a delayed fashion (5-10% of cases). In the present work we built a predictive machine learning model for new edema formation following meningioma gamma knife radiosurgery.  Our dataset consists of single-institution patients treated for meningioma with Gamma Knife radiosurgery, either in single fraction or in 3-5 fractions, with at least six months imaging follow-up.  The predictive model is built on radiomic features from planning MRI, patients clinical  characteristics and plan dosimetric data. Machine learning methods are used to tackle data imbalance and multiple meningiomas treatment in single patient. Game theoretical explanations and counterfactual examples are utilized to provide insights  at individual prediction level.


Matteo CHIEREGATO (Brescia, Italy), Giorgio SPATOLA, Mauro MORASSI, Karol MIGLIORATI, Milena COBELLI, Chiara BASSETTI, Matteo BAGNALASTA, Claudio BNÀ, Marco GALELLI, Alberto FRANZIN
00:00 - 00:00 #30183 - P205 Meningioma radiosurgery using [68Ga]-DOTATATE PET/MRI for target definition and follow-up.
P205 Meningioma radiosurgery using [68Ga]-DOTATATE PET/MRI for target definition and follow-up.

Background: The optimal post-surgical management of meningiomas is a subject of debate. In patients with a gross total resection (Simpson Grade 1-3), the highest risk for progression is likely from occult residual disease. Postoperative [68Ga]-DOTATATE PET/MRI can differentiate postoperative changes from residual meningioma in such patients and aid in accurately defining stereotactic radiosurgical targets. We wanted to further explore DOTATATE imaging’s utility through assessing responses of meningiomas to radiosurgery.

Methods: Patients underwent postoperative imaging using DOTATATE PET/MRI as part of our IRB-approved prospective trial. The co-registered DOTATATE PET and gadolinium-enhanced T1 weighted MR imaging were employed for radiosurgery planning. MR imaging for surveillance purposes was routinely performed in all patients and post-radiosurgical DOTATATE PET/MRI imaging was performed in a subset of patients after an interval of approximately 6-12 months; some patients declined repeat PET imaging. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVR) of the meningioma / superior sagittal sinus SUV were obtained. RANO criteria were applied to determine MRI-determined size change significance. Paired t-tests were used for statistical analyses.

Results: Twenty-nine meningiomas (in 13 patients) underwent DOTATATE PET/MRI evaluation for radiosurgical planning. 46% (6/13) of subjects received SBRT and 54% (7/13) received SRS. Post-RT DOTATATE PET/MRI demonstrated a 46.4% SUV decrease (p-value = 0.0001) and a 60.8% SUVR decrease (p-value < 0.0001). Of 21 measurable lesions, the size product decreased by 21%. This decrease was statistically significant (p-value = 0.0008) albeit below the 25% decrease defined as clinically significant by RANO guidelines. To date, all patients remain stable radiographically without evidence of recurrence (mean follow-up post RT: 14 months; range: 6-24 months).

Conclusions: DOTATATE PET SUV and SUVR demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant but not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising approach to aid in response assessment for meningiomas treated with radiosurgery. Longer-term follow-up is needed to determine correlations between the degree of post-RT SUV and/or SUVR decrease and progression-free-survival.

 


Jonathan P.s. KNISELY (New York, USA), Sean H. KIM, Michelle ROYTMAN, Se Jung CHANG, Rohan RAMAKRISHNA, Susan C. PANNULLO, Theodore E. SCHWARTZ, Joseph R. OSBORNE, Rajiv MAGGE, Eaton LIN, Jana IVANIDZE
00:00 - 00:00 #30193 - P206 Prognostic value of tumor sphericity in the volumetric response of brain metastases treated with stereotactic radiosurgery.
P206 Prognostic value of tumor sphericity in the volumetric response of brain metastases treated with stereotactic radiosurgery.

Objective:

To determine the prognostic value of tumor sphericity in the volumetric response of brain metastases treated with stereotactic radiosurgery from different primary tumors and regardless of the number of lesions

Material and methods:

Retrospective analysis of patients with brain metastases treated with stereotactic radiosurgery in the National Institute of Neurology and Neurosurgery “Manuel Velasco Suarez” located in Mexico City, without previous whole brain radiotherapy, irrespective of the primary tumor and the number of lesions.  The diagnostic contrast-enhanced T1-weighted magnetic resonance and the image at the end of the follow up were used to delineate the metastases and then it was processed using the LIFEx software to determine the volume and sphericity. The metastases were divided using a sphericity cutoff value of 0.8. The RANO-BM volumetric adaptation was used to classify the response. A statistical analysis was performed to determine the prognostic value.

Results:

 The analysis was performed in 35 patients with a total number of 177 brain metastases, median age of 54 years (Range 65), all the patients had a Karnofsky performance status ranging from 80-100%, the median follow up was 18.4 months (Range 55.2 months), the most common primary tumors were: lung (24.9%), kidney (24.9%), breast (19.2%) and thyroid (17.5%). The median tumor sphericity was 0.777 (Range 0.347). There was a statistically significant difference (p=0.001) between the primary tumors and the sphericity value with a greater percentage of lung cancer metastases in the group of sphericity 0.8, and kidney, breast, and thyroid metastases in the group of sphericity < 0.8. Also, there was a statistically significant difference (p=0.015) in the brain metastases that presented an increase of volume greater than 72% at the end of follow up in the group of sphericity < 0.8. There was no difference in the groups that presented complete response and partial response between the sphericity classification.

Conclusions:

The tumor sphericity represents an important radiomic parameter that has diagnostic and prognostic value, this study found differences that may help to distinguish metastases of different primary tumors and it was found that less spheric metastases tend to present tumor progression at the end of the follow up. This study has the limitations of its retrospective nature but helps to stablish the relevance of radiomics in the diagnostic and prognostic value of brain metastases for future studies.


Juan Carlos HEREDIA GUTIÉRREZ (Ciudad de Mexico, Mexico), Gabriel Alejandro CONTRERAS PALAFOX, Sergio MORENO JIMENEZ, Alejandro RODRIGUEZ - CAMACHO, Guillermo Axayacalt GUTIÉRREZ ACEVES

"Tuesday 21 June"

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EPOSTERS10
00:00 - 00:00

10. Eposters - Others / Alternatives

00:00 - 00:00 #29311 - P207 Training in Radiosurgery, 5 of experience of the International Master in Radiosurgery of the Central Nervous System, Complutense University of Madrid.
P207 Training in Radiosurgery, 5 of experience of the International Master in Radiosurgery of the Central Nervous System, Complutense University of Madrid.

Radiosurgery emerged as a technique for the treatment of functional lesions in the 60s, thanks to technological advance it has extended its indications today to the whole body, becoming an avant-garde technique not only in the treatment of cancer, but also of pathology. vascular benign tumors and functional pathology and pain.

With the launch of the Master's Degree in Cranio-Spinal Radiosurgery, was filled the specific training  in CNS Radiosurgery and it was proposed to offer a comprehensive course for specialists from Spain and Latin America to familiarize them with the most frequent indications for the use of this technique. , that the participant acquires the basic principles of physics, modulation and radiobiology that allow them to be competent in this discipline and in the near future, the main drivers of radiosurgery projects in their place of origin.

Provide the necessary training so that at the end of the course the participants have the knowledge to integrate human teams and provide radiosurgery treatments in an appropriate way and in accordance with the international standards of norms and practices of the discipline.

The master is composed of a theoretical part and practical modules.

There is no similar training in the world that includes all the available technology, GammaKnife, Cyberknife, LINAC, Protons and lately ZAP-X.

A university degree demonstrates and certifies their training and serves as a legal document, the students obtain between 90 and 130 ECTS credits.

40 students and 19 prestigious teachers have participated in it and every year there is an avalanche of requests to participate in it, both from neurosurgeons and radiation oncologists

We like to demostrate our experience how to prepare and to trasmit knowledge to the neurosurgeons and radiation oncologist that whant to work and to use the radiosurgery in  their clinical practics. The ISRS giva us the las years two grands 2500 $ each to help the students. 

I thnik that is extremly important to extend these idea of training in radiosurgery, but not in one specific technology. What we trasmit to our students is the idea that : Radiosurgery is a concept of treating the patient not one technology


Kita SALLABANDA DAIZ, Kita SALLABANDA DAIZ (Madrid, Spain)
00:00 - 00:00 #29411 - P208 Comparison between Lightning and Leksell GammaPlan.
P208 Comparison between Lightning and Leksell GammaPlan.

Objective

The new plan-optimization tool, Lightning, was added to the Leksell GammaPlan (LGP) software for the Gamma Knife Radiosurgery usage.  We compare four planning modalities, two using standard LGP and two using the new Lightning planning software.

 

Methods:

 

Thirty-eight cases were compared under four different planning techniques. First, using the LGP, a manual planning added by the standard optimization tool. Second, we analyzed the inverse planning technique. Third, the Lightning without consideration for risk structures, and fourth, the Lightning with consideration of organs at risk. Both LGP optimization and Lightning were kept in their default mode, without changing their parameters and all plans had the same dose prescription. At the end of the planning, it was analyzed and compared the total time for planning, number of shots, coverage, selectivity, gradient index, bean-on time, and maximum dose received by risk structures.

 

Results

The Lightning software was able to provide plans with better coverage and gradient index (8% and 15% improvement respectively) but had 12% decrease in selectivity. Delivery time had 5% reduction with 226% increase in the number of shots and 57% reduction on time needed to plan. Only Compared to the other modalities, only Lightning with protection of risk structures were able to create an adequate tolerance dose to organs at risk. Histogram comparison showed similar plan qualities, for exception when maximum protection dose was considered.

Conclusion

The new Lightning software showed to be efficient to deliver a quick and good plan allowing the planner to test different options of settings to achieve the most desirable plan. It took less time to calculate shot placement, protection of structures and the ideal isodose line than the standard planning with the LGP. This can be useful to plan multiple and complex targets at a faster time, orient beginners to develop their planning skills, maintain an adequate coverage while preserving risk structures, and increase the patient's tolerance and acceptance to the treatment. 


Victor GOULENKO, Matthew PODGORSAK, Dheerendra PRASAD (Buffalo, NY, USA)
00:00 - 00:00 #29801 - P209 Paroxysmal atrial fibrillation in elderly: worldwide preliminary data of LINAC-based STereotactic Arrhythmia Radioablation prospective phase II trial.
P209 Paroxysmal atrial fibrillation in elderly: worldwide preliminary data of LINAC-based STereotactic Arrhythmia Radioablation prospective phase II trial.

Aim: In elderly, paroxysmal Atrial Fibrillation (AF) is difficult to treat with drugs, or by Catheter ablation, so a non-invasive approach should be favourite. No data are published about the use or radiosurgery for AF, thus in the present analysis the preliminary data of Linac-based STereotectic Arrythmias Radioablation (STAR) for elderly affected by paroxysmal AF were reported.

Methods: Inclusion criteria were: age >70 years; symptomatic paroxysmal AF; intolerance or non-response to anti-arhythmic therapy (AAT).  All patients performed 1-week ECG-Holter monitoring, a complete transthoracic echocardiogram before and after STAR. Patients were immobilized using a vac-lock bag and Computed Tomography (CT, 1mm slice-thickness), in the supine position were performed: CT with/without contrast; 4-Dimension CT. STAR was performed in free-breathing with a PTV prescription total dose (Dp) of 25Gy/1 fraction. Flattening Filter Free (FFF), Volumetric Modulated Arc Therapy (VMAT) plan was generated, normalizing 100% Dp to 95% of the volume, while large intra-target dose heterogeneity D2% (PTV)<150%Dp was accepted. The treatment was optimized and delivered by TrueBeamTM (Varian Medical System). Image-guided radiotherapy with Cone Beam CT and Surface-Guided RadioTherapy with Align-RT were used to reduce set-up error and to monitor patients during fraction. The primary endpoint is the 1-month post-STAR safety, as complete STAR delivery and no acute treatment-related adverse events more than G3, assessed according to the Common Terminology Criteria for Adverse Events (version 5.0).

Results: From May 2021 to January 2022, 5 patients were treated and followed. AAT was stopped after enrollment. For primary endpoint, no acute treatment-related adverse events were registered (>G1). Only 1 patient experienced G1 esophagitis (7 days from STAR), improved by 5 days of medical therapy. The treatment plan was delivered with 3 no coplanar arcs, in all cases. The mean Overall Treatment Time (OTT) was 3minutes.

For all treated patients with a mean follow-up of 4 months (patients 1-4), no late side effects were reported, and at 3 months, a rare atrial ectopy was documented without AF recurrences. No patients started AAT after radiotherapy

Conclusion: The present collected data are promising, showing the safety of LINAC-based STAR for AF for the first 5 patients worldwide. This new ablation approach could represent a valid non-invasive alternative for elderly who were excluded from catheter ablation.


Fabiana GREGUCCI (Acquaviva delle Fonti, Italy), Antonio DI MONACO, Ilaria BONAPARTE, Alessia SURGO, Federica TROISI, Elena LUDOVICO, Nicola VITULANO, Federico QUADRINI, Roberta CARBONARA, Maria Paola CILIBERTI, Massimo GRIMALDI, Alba FIORENTINO
00:00 - 00:00 #29893 - P210 Experimental radiosurgery of cardiac targets.
P210 Experimental radiosurgery of cardiac targets.

Background: Stereotactic irradiation  may be considered as a promising alternative to catheter ablation in patients with different types of tachyarrhythmia.

Purpose of this experimental study was to develop a technique by stereotactic radiosurgery for ablation  in order to create a stable functional and morphological damage in heart tissue with subsequent analysis of precision, efficiency and safety.

Materials and methods: The research was carried out on four pigs. The animals were 10-12 weeks old, the average weight was 30 ± 2.7 kg. Under intravenous sedation, contrast-based CT scans of the heart  to assess the anatomy of the chambers of the heart and adjacent organs as well as  the degree of displacement of the heart chambers in one respiratory and cardiac cycle  were performed. Planning system Eclipse was used for calculation of   dose distribution. Animals were divided into groups according to the zones of planned radiation exposure: 1st animal atrioventricular (AV) node (mean dose 35 Gy), 2nd animal - AV node and the apex of the left ventricle (LV) (mean doses 40/35 Gy, respectively), 3rd animal - pulmonary veins muscle sleeves and left atrium (dose 30 Gy), 4th - AV node and free wall of the LV (mean doses 45/40 Gy, respectively).

Mean GTV= 4 cc (1,9-7,9)  Mean PTV= 12,4 cc (7,5-20,9)

Margin PTV-GTV= 3 mm

QA procedures were performed including  absolute dosimetry and plan verification (gamma index: 3%/1mm- 98%). TrueBeam STx linac (Varian) as a source of 6 MeV FFF photon beams during the experimental irradiation was used. Positioning and  verification was performed by CBCT.

For electrophysiological control, loop recorders were implanted in each animal. The long-term follow-up period was six months, followed by morphological examination of autopsy material.

Results: The electrophysiological effect of the ablation was considered to be achieved in cases of complete AV-block development. This effect was developed in two out of three animals, whose AV- node was exposed: 2nd animal - 40 Gy on 108th day of observation and 4th animal - 45 Gy on 21st day of observation. No cardiac arrhythmias were recorded in all cases.

The results of macro- and microscopic examination showed significant changes (massive fields of fibrous tissue of various degrees of maturity  with focal hemorrhages of various ages and granulations which were surrounded by cardiomyocytes with coagulated and vacuolated cytoplasm) exactly in the target zones.

Conclusion:  Precision, safety and efficiency of radiosurgery  for cardiac lesions were shown in our experiments.  

 


Natalia ANTIPINA (Moscow, Russia), Andrey GOLANOV, Anna NIKOLAEVA, Irina TAIMASOVA, Valerii VASKOVSKII, Alexander SHMIGELSKII
00:00 - 00:00 #29940 - P211 Telemedicine utility in the routine management of Gamma Knife Radiosurgery patients.
P211 Telemedicine utility in the routine management of Gamma Knife Radiosurgery patients.

Background:  While telemedicine provided necessary measures to maintain continuity in care for cancer patients during the early phases of the COVID-19 pandemic, the utility of remote encounters in post-pandemic medicine, especially as it relates to radiosurgery, remains unknown. 

Methods:  Retrospective data was gathered from telemedicine encounters in the routine management of radiosurgery patients from 2020 to 2021.  The diagnoses, demographics, and distances to primary clinics were used develop a predictive model of patient utilization of telehealth modalities over traditional in-person encounters via Cox proportional regression analysis.

Results:  208 patients completed 331 telemedicine encounters over 12 months.  Metastases and meningiomas comprised 60% of diagnoses.  Median age was 62 years with median household income and residential population of $44,752 USD and 7634 people.  The one-way mean and median travel distances were 74.6 and 66.3 miles.  The total potential road mileage for all patients was 44,596 miles.  118 (57%) patients completed video visits during the first encounter while 90 (43%) opted for telephone encounters.  At 12 months, 138 patients (66%) utilized video-visits and 70 (34%) used telephone-visits.  Predictors of video-visit use were video-enabled visit during the first encounter (HR 2.806, p<0.001), total potential distance traveled (HR 1.681, p<0.05), and the need for more than one visit per year (HR 2.903, p<0.001).  

Conclusions:  Telemedicine use can be effective in a specialty radiosurgery practice with positive predictors of use being pre-existing patient comfort levels with video-conferencing, total annual travel distance, and number of visits per year.    


Christopher CIFARELLI (Morgantown, USA), Joshua WEIR, Daniel CIFARELLI
00:00 - 00:00 #30203 - P212 Interobserver varibility between a medical expert, doctors at the beginning and doctors at the end of one year of radiosurgery fellowship.
P212 Interobserver varibility between a medical expert, doctors at the beginning and doctors at the end of one year of radiosurgery fellowship.

Introduction: The results of radiosurgery depend largely on a proper and precise contouring of the target volume. The impact of protocol deviations in which the imprecision of tumor volumetric delimitation is one of the components has been associated with discouraging clinical outcomes. In this paper we present a cross-sectional, analytical institutional study with the following objective: Quantify the degree of interobserver variability in the delimitation of target intracranial volumes, between a medical expert, doctors at the beginning and doctors at the end of one year of radiosurgery fellowship.

Methods: 7 cases of pituitary adenomas, 25 of brain metastases, 9 of vestibular schwannomas, 13 of meningiomas and 17 of arteriovenous malformations were selected. 5 observers were included: 2 at the beginning of training, 2 at the end of training and one expert. To evaluate the degree of agreement between observers, the following metrics were used: DICE similarity coefficient, coefficient of variation and hausdorff distance. 

Results: The degree of agreement obtained in the delimitation of volumes, of most of the pathologies, was greater between observers at the end of training and the expert, compared to that obtained between observers without training and the expert (meningioma 86% vs 84%, pituitary adenoma 80% vs 79% and vestibular schwannoma 82% vs 76%), with a statistical significance in metastases (90% vs 83%, p= 0.05). In arteriovenous malformations, the degree of agreement of the observers without training with the expert was greater (61% vs 57%) without achieving a statistically significant difference (p = 0.21).  

Conclusions: The fellowship in radiosurgery improves the variability for delineation of volumes between observers. A dosimetric study is required to evaluate its impact on therapeutic index.


Alejandro RODRIGUEZ - CAMACHO (Ciudad de México, Mexico), Gabriel Alejandro CONTRERAS PALAFOX, Juan Carlos HEREDIA GUTIÉRREZ, Sergio MORENO JIMENEZ
08:00

"Tuesday 21 June"

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A20
08:00 - 09:00

BREAKFAST SEMINAR
Physics - Accuracy

Moderators: Elena DE MARTIN (Medical physicist) (Milan, Italy), Ian PADDICK (Consultant Physicist) (London, United Kingdom)
Coordinator: Ian PADDICK (Coordinator, London, United Kingdom)
08:00 - 08:20 Margins in the radiosurgery era: dosimetric, biological, physical limits. Timothy SOLBERG (Senior Advisor for Emerging Technology) (Keynote Speaker, Sonoma Valley, USA)
08:20 - 08:40 State of the art in motion management for SBRT treatments. Carlo CAVEDON (Keynote Speaker, Verona, Italy)
08:00 - 09:00 Understanding « Robust » treatment planning in RT/SRS. Thierry GEVAERT (Head of Medical physics) (Keynote Speaker, Brussels, Belgium)
SILVER ROOM

"Tuesday 21 June"

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B20
08:00 - 09:00

BREAKFAST SEMINAR
Re-irradiation for Body Tumors

Moderators: Alba FIORENTINO (BARI, Italy), Ciro FRANZESE (MD) (Milano, Italy)
Coordinator: Alba FIORENTINO (Coordinator, BARI, Italy)
08:00 - 08:20 Reirradiation for recurrent prostate cancer: state of art and future direction. Berardino DE BARI (Keynote Speaker, Switzerland)
08:20 - 08:40 Dose constraints and tumor dose in the reirradiation setting. Nicolaus ANDRATSCHKE (Consoultant) (Keynote Speaker, Zürich, Switzerland)
08:40 - 09:00 Reirradiation in head and neck tumors. Pierluigi BONOMO (Keynote Speaker, Florence, Italy)
RED 2 ROOM

"Tuesday 21 June"

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C20
08:00 - 09:00

BREAKFAST SEMINAR
NF2 and Rare Brain Tumors

Moderators: Fabio BARONE (Consultant Neurosurgeon) (Catania, Italy), Bente Sandvei SKEIE (MD, PhD) (Bergen, Norway)
Coordinator: Alfredo CONTI (Coordinator, Bologna, Italy)
08:00 - 08:20 Vestibular schwannomas in NF2: which approach? Michele LONGHI (Neurosurgeon) (Keynote Speaker, Verona, Italy)
08:20 - 08:40 Pilocytic astrocytomas. Andrey GOLANOV (Chief of the Department) (Keynote Speaker, Moscow, Russia)
08:40 - 09:00 Brainstem tumors. Zeno PERINI (Neurosurgeon) (Keynote Speaker, Vicenza, Italy)
BLUE 2 ROOM
09:15

"Tuesday 21 June"

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A21
09:15 - 10:15

PLENARY SESSION
Special Topics: SRS, HIFU, LITT, RF ablation : alternatives or complementary tools? / Integration of immunotherapy and interventional oncology

Moderators: Francesco DI MECO (Head Department of Neurosurgery) (Milan, Italy), Dheerendra PRASAD (Professor and Medical Director) (Buffalo, NY, USA), David SCHLESINGER (Medical Physics) (Charlottesville, VA, USA, USA)
Coordinator: Jason SHEEHAN (Coordinator, Charlottesville, USA)
09:15 - 09:30 Focused ultrasound for brain diseases. Francesco PRADA (Keynote Speaker, Milan, Italy)
09:30 - 09:45 SRS versus HIFU for tremor. Jean REGIS (PROFESSEUR) (Keynote Speaker, MARSEILLE, France)
for “SRS”
09:45 - 10:00 SRS versus HIFU for tremor. Andres LOZANO (Alan & Susan Hudson Cornerstone Chair in Neurosurgery, University Health Network) (Keynote Speaker, Toronto, Canada)
for “HIFU”
10:00 - 10:15 Integration of immunotherapy and interventional oncology. Gianpaolo CARRAFIELLO (Keynote Speaker, Italy)
SILVER ROOM
10:15 COFFEE BREAK AND EXHIBITION
10:45

"Tuesday 21 June"

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A23
10:45 - 11:30

PLENARY SESSION
Special Topic: The Combination of Immunotherapy with SRS/SBRT

Moderators: Filippo DE BRAUD (CHEF OF DEPARTMENT) (MILANO, Italy), Paul SPERDUTO (Radiation Oncology) (Durham, USA)
Coordinator: Paul SPERDUTO (Coordinator, Durham, USA)
10:45 - 11:00 Introduction. Paul SPERDUTO (Radiation Oncology) (Keynote Speaker, Durham, USA)
11:00 - 11:30 The philosophy of immunotherapy. Filippo DE BRAUD (CHEF OF DEPARTMENT) (Keynote Speaker, MILANO, Italy)
SILVER ROOM
11:30

"Tuesday 21 June"

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A23.1
11:30 - 12:00

PLENARY SESSION
The Lars Leksell Lecture

ISRS President: Laura FARISELLI (director) (ISRS President, milan, Italy)
ISRS Past President: Ian PADDICK (Consultant Physicist) (ISRS Past President, London, United Kingdom)
ISRS Vice President: Marc LEVIVIER (Chef de Service) (ISRS Vice President, Lausanne, Switzerland)
11:30 - 12:00 The Lars Leksell Lecture. Dade LUNSFORD (Keynote Speaker, Pittsburgh, USA)
SILVER ROOM
12:00

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A24
12:00 - 13:00

PARALLEL SESSION
Advanced Integrated Imaging (e.g. MR-Linac)

Moderators: Filippo ALONGI (Verona, Italy), Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA), Robert SMEE (Senior Staff Specialist) (Randwick, Australia)
Coordinator: Caroline CHUNG (Coordinator, Houston, USA)
12:00 - 13:00 Pelvic lymph node metastases with MR-Linac. Petra KROON (Medical Physicist) (Keynote Speaker, Utrecht, The Netherlands)
12:00 - 13:00 MRI-guided RT for heart sarcoma. Luca BOLDRINI (Medical doctor) (Keynote Speaker, Rome, Italy)
12:00 - 13:00 PET-based SRS planning and response assessment in neuro-oncology. Jonathan KNISELY (Faculty) (Keynote Speaker, New York, USA)
SILVER ROOM

"Tuesday 21 June"

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B25
12:00 - 13:00

PARALLEL SESSION
Functional SRS

Moderators: Alessandra GORGULHO (Director) (SÃO PAULO, Brazil), Jean REGIS (PROFESSEUR) (MARSEILLE, France), Giorgio SPATOLA (Neurosurgeon) (Brescia, Italy)
Coordinator: Jean REGIS (Coordinator, MARSEILLE, France)
12:00 - 13:00 Network mapping in SRS for psychiatric disorders. Sameer SHETH (Associate Professor of Neurosurgery) (Keynote Speaker, Houston, USA)
12:00 - 13:00 Role of SRS in anorexia nervosa. Roberto MARTINEZ-ALVAREZ (Neurosurgeon) (Keynote Speaker, Madrid, Spain)
12:00 - 13:00 Role of BED in Functional SRS. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Keynote Speaker, Lausanne, Switzerland)
RED 2 ROOM
13:00 SPONSORED LUNCH SYMPOSIUM

"Tuesday 21 June"

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A25b
13:00 - 14:00

SPONSORED LUNCH SYMPOSIUM

BLUE 2 ROOM
14:00

"Tuesday 21 June"

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A26.1
14:00 - 18:30

VISIT OF POSTERS AND EXHIBITION

SILVER ROOM

"Tuesday 21 June"

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B26
14:00 - 18:30

Meeting of the Leksell Gamma Knife Society

Kindly note that this is a dedicated LGK Society meeting for LGK practitioners and LGKS members participating in the 15th Congress of the International Stereotactic Radiosurgery Society (ISRS).

> Please fill in the registration form here (use right clic for opening)
RED 2 ROOM

"Tuesday 21 June"

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C26
14:00 - 18:30

Affiliated Societies & Patients Associations

BLUE 2 ROOM