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EPOSTERS1
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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 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 (Martinsburg WV, 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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EPOSTERS2
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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.


Ji SO YOUNG (Gyeonggi-do, Korea), Hwang KIHWAN, Kim CHAE-YONG, Juh RAHYEONG, Han JUNG HO
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 (Hamm, 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

Tuesday 21 June

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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

Tuesday 21 June

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EPOSTERS4
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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)