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.

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.

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.

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. 

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 BED_{98% ­}and brain V_84Gy2, which was equivalent to V_12Gy 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 BE_­D_98% but comparable brain V_84Gy2 (p=0.677) between the Staged-SRS and SF-SRS plans. No dosimetric advantages of Staged-SRS over HF-SRS were observed. Tumor BED_98% 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 V_84Gy2 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.

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.

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.

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.

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.

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.

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. 

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.

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 (V_12Gy < 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 V_12Gy 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.

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.

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.

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.

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.

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.

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.

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/D_99% (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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. 

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.

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.

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.

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.

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. 

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.

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 (V12GyHT_acc) 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 V12HTGy_acc 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.

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.

[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.

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.

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

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.

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.

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.

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 treatment.  A total of 195 metastatic lesions were treated, including 71 lesions with PTV volume bellow 0.5 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. 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.

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.

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

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.

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. 

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.

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.

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

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: