Median Margin Dose Research Articles

Stereotactic radiosurgery as the initial management option for small-volume hypothalamic hamartomas with intractable epilepsy: a 35-year institutional experience and systematic review.

Young patients with hypothalamic hamartomas (HHs) often present with intractable epilepsy. Currently there are no established management guidelines for HH. The authors retrospectively reviewed their single-institution experience to delineate the role of stereotactic radiosurgery (SRS). Seven patients with HHs (4 females; median age 13.7 years, range 2.5-25 years) with no prior resection underwent SRS between 1987 and 2022. The clinical history, epilepsy profile, radiographic findings, and neurological outcomes were characterized. HH topographical types were classified according to the Régis classification. Outcome measures included Engel seizure classification, HH response, and the need for additional surgical interventions. All patients had Engel class IV epilepsy. A Leksell Gamma Knife was used to deliver a median margin dose of 18 Gy (range 16-20 Gy) to a median hamartoma volume of 0.37 cm3 (range 0.20-0.89 cm3). Seizure reduction was confirmed in 6 patients, and 2 patients had regression of their hamartoma. Two patients underwent resection and/or laser interstitial thermal therapy after SRS. At follow-up, 1 patient was seizure free, 4 patients achieved Engel class II, 1 patient had Engel class III, and 1 patient had Engel class IV seizure outcomes. SRS as the initial management option for HH was associated with a low risk of adverse effects. In this institutional series reviewing small-volume HHs treated with SRS, no adverse radiation effect was detected, and the majority of patients experienced seizure reduction. SRS should be considered as the first-line treatment for seizure control in patients with small-volume HHs.

Long-term results of upfront, single-session Gamma Knife radiosurgery for large cystic vestibular schwannomas.

Anecdotally, cystic vestibular schwannomas (cVSs) are regarded to have unpredictable biologic activity with poorer clinical results, and most studies showed a less favorable prognosis following surgery. While stereotactic radiosurgery (SRS) is a well-established therapeutic option for small- to medium-sized VSs, cVSs are often larger, thus making upfront SRS more complicated. The purpose of this retrospective study was to assess the efficacy and safety of upfront SRS for large cVSs. The authors reviewed the data of 54 patients who received upfront, single-session Gamma Knife radiosurgery (GKRS) with a diagnosis of large cVS (> 4 cm3). Patients with neurofibromatosis type 2, multiple VSs, or recurrent VSs and < 24months of clinical and neuroimaging follow-up were excluded. Hearing loss (48.1%) was the primary presenting symptom. The majority of cVSs were Koos grade IV (66.7%), and the most prevalent cyst pattern was "mixed pattern of small and big cysts" (46.3%). The median time between diagnosis and GKRS was 12months (range, 1-147months). At GKRS, the median cVS volume was 6.95 cm3 (range, 4.1-22 cm3). The median marginal dose was 12Gy (range, 10-12Gy). The mean radiological and clinical follow-up periods were 62.2 ± 34.04months (range, 24-169months) and 94.9 ± 45.41months (range, 24-175months), respectively. At 2, 6, and 12years, the tumor control rates were 100%, 95.7%, and 85.0%, respectively. Tumor shrinkage occurred in 92.6% of patients (n = 50), tumor volume remained stable in 5.6% of patients (n = 3), and tumor growth occurred in 1.9% of patients (n = 1). At a median follow-up of 53.5months, the pre-GKRS tumor volume significantly decreased to 2.35 cm3 (p < 0.001). While Koos grade 3 patients had a greater possibility of attaining higher volume reduction, "multiple small thick-walled cyst pattern" and smaller tumor volumes decreased the likelihood of achieving higher volume reduction. Serviceable hearing (Gardner-Robertson Scale I-II) was present in 16.7% of patients prior to GKRS and it was preserved in all of these patients following GKRS. After GKRS, 1.9% of patients (n = 1) had new-onset trigeminal neuralgia. There was no new-onset facial palsy, hemifacial spasm, or hydrocephalus. Contrary to what was believed, our findings suggest that upfront GKRS seems to be a safe and effective treatment option for large cVSs.

RADT-04. SINGLE SESSION GAMMA KNIFE RADIOSURGERY TO TREAT PATIENTS WITH 20 OR MORE BRAIN METASTASES

Abstract BACKGROUND Stereotactic Radiosurgery (SRS) has become a primary management option for brain metastases (BMs). This present study aims to review outcomes in patients with ≥ 20 BMs treated in a single session SRS and to identify predictors of local tumor control (LTC) and overall survival (OS). METHODS We identified 75 patients including 26 non-small cell lung cancer (NSCLC), 21 small cell lung cancer (SCLC), 14 breast cancer (BC), and 14 melanoma patients who underwent SRS for ≥ 20 BMs between 2014 and 2020. The median number of tumors was 24 (range 20 – 52), and the median cumulative tumor volume was 3.70 cc (0.13 – 62.49 cc). The median margin dose was 16 Gy (14 – 20 Gy). Median skull integral dose was 5492 mJ (range 1372 – 11243 mJ). The median treatment time for each session was 160 min. Outcome variables were assessed using univariate and multivariate analyses with p &amp;lt; 0.05. RESULTS Median OS after SRS was 5.8 months (range 0.1 – 73.2 months). Primary cancer type and concurrent immunotherapy were significant predictive factors for patient OS after SRS (p = 0.01, 0.05, and 0.02, respectively). LTC rate at 6 and 12 months after SRS was 95.7% and 83.7%, respectively. Thirty (40.0%) patients underwent additional SRS and 3 patients (4%) received post-SRS WBRT due to distant tumor recurrence. The median time to distant recurrence was 5 months (range 2-28 months). SRS-induced adverse radiation effects (ARE) events were observed in 3 patients (4.0%; 1 NSCLC, 1 SCLC, and 1 melanoma). CONCLUSIONS Our results suggest that patients with ≥ 20 BMs can be safely treated with SRS with an excellent LTC rate and a low risk of ARE. Newly developed BMs can be treated with repeat SRS. This single-session SRS allows patients to proceed with systemic cancer care without interruption.

Stereotactic radiosurgery and local control of brain metastases from triple-negative breast cancer.

Stereotactic radiosurgery (SRS) is an effective treatment for intracranial metastatic disease, but its role in triple-negative breast cancer requires further study. Herein, the authors report overall survival (OS) and local tumor control in a multiinstitutional cohort with triple-negative breast cancer metastases treated with SRS. Patients treated from 2010 to 2019 at 9 institutions were included in this retrospective study if they had biopsy-proven triple-negative breast cancer with intracranial metastatic lesions treated with SRS. Patients were excluded if they had undergone prior SRS, whole-brain radiation therapy, or resection of the metastatic lesions. A retrospective chart review was conducted to determine OS, local control, and treatment efficacy. Sixty-eight patients with 315 treated lesions were assessed. Patients had a median Karnofsky Performance Status of 80 (IQR 70-90) and age of 57 years (IQR 48-67 years). Most treated patients had 5 or fewer intracranial lesions, with 34% of patients having a single lesion. Treated lesions were small, having a median volume owf 0.11 cm3 (IQR 0.03-0.60 cm3). Patients were treated with a median margin dose of 18 Gy (IQR 18-20 Gy) to the median 71% isodose line (IQR 50%-84%). Overall, patients had a 1-year OS of 43% and 2-year OS of 20%. Most patients (88%) were followed until death, by which time local tumor progression had occurred in only 7% of cases. Furthermore, 76% of the lesions demonstrated regression. Tumor volume was correlated with local tumor progression (p = 0.012). SRS was very well tolerated, and only 3 patients (5%) developed symptomatic radiation necrosis. SRS is a safe and efficacious treatment for well-selected patients with triple-negative breast cancer, especially for those with a favorable performance status and small- to moderate-volume metastatic lesions.

Stereotactic radiosurgery for orbital cavernous hemangiomas.

The goal of this study was to assess the safety and efficacy of single-session Gamma Knife radiosurgery (GKRS) for orbital cavernous hemangiomas (OCHs). Patients who presented with an OCH between September 1999 and May 2022 and were treated with single-session GKRS were included in this single-center cohort study. There were 23 patients (7 males and 16 females) in this study. The median margin dose was 12 Gy (range 11-13 Gy). The median clinical and radiological follow-ups were 45 months (range 5-190 months) and 45 months (range 6-190 months), respectively. Nine (69.2%) of 13 patients with visual acuity impairment had improvement in best corrected visual acuity. Of the 8 patients with visual field defects, 5 patients (62.5%) had complete resolution. Tumor regression was observed in 22 patients (95.7%). The mean relative reduction in tumor volume was 82.6% ± 23.7%. The relative reductions in tumor volume were 33%, 49%, 72%, 84%, and 89% at 6, 12, 24, 36, and 48 months, respectively. Adverse effects of radiation were not observed. GKRS appears to be safe and efficacious for treating OCHs over long-term follow-up. The treatment is associated with a high rate of regression in OCHs and remarkable improvement in both visual acuity and visual field deficits.

The longitudinal volumetric response of vestibular schwannomas after Gamma Knife radiosurgery.

Gamma Knife radiosurgery (GKRS) is an effective treatment for vestibular schwannomas (VSs) and has been used in > 100,000 cases worldwide. In the present study the authors sought to define the serial volumetric tumor response of Koos grade I-IV VS after radiosurgery. A total of 201 consecutive VS patients underwent GKRS at a single institution between 2015 and 2019. All patients had a minimum follow-up of 18 months and at least 2 interval postprocedure MRI scans. The contrast-enhanced tumor volumes were contoured manually and compared between pre- and post-GKRS imaging. The percentages of tumor volume change at 18 months (short-term follow-up) and up to 5 years after GKRS (long-term follow-up) were compared with the baseline tumor volume. An increase of 20% was considered a significant increase of tumor volume. Trends of tumor volume over time were assessed with linear models using time as a continuous variable. A test for linear trend was evaluated according to the initial Koos tumor classification. Koos grade II VS was the most frequently occurring tumor (n = 74, 36.8%), followed by grade III (n = 57, 28.4%), grade I (n = 41, 20.4%), and grade IV (n = 29, 14.4%). The mean tumor volume at the time of GKRS was 2.12 ± 2.82 cm3 (range 0.12-18.77 cm3) and the median margin dose was 12 Gy. Short-term follow-up revealed that tumor volumes transiently increased in 34.2% and 28.4% of patients at 6 and 18 months, respectively, regardless of Koos grade. Linear regression analysis of Koos grade II, III, and IV tumors showed a significant longitudinal volume decrease on long-term follow-up. At last follow-up (median 30 months, range 18-54 months), 19 patients (9.4%) showed a persistent increase of tumor volume. Five patients received additional management after GKRS. Although selected VS patients demonstrate an early and measurable transient volumetric increase after GKRS, > 90% have stable or reduced tumor volumes over an observed period of up to 5 years. Volumetric regression is most pronounced in Koos grade II, III, and IV tumors and may not be fully detectable until 3 years after GKRS.

Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature.

Simple Summary Meningiomas are the most common tumours of the central nervous system (CNS). Despite their benign histology, proximity to critical neurovascular structures may lead to significant morbidity with tumour growth. This is the case for cavernous sinus meningiomas (CSMs), as their growth may surround critical neuro-vascular structures and cause significant morbidity. Radical microsurgical resection carries a high risk of additional neurological deficits, as well as the risk of death. Current management of these tumours, where treatment is indicated, has moved away from radical surgery towards radiotherapy/radiosurgery. This is particularly the case for patients who have residual or recurring tumours after previous surgery. There are many reports that describe the effectiveness of using stereotactic radiosurgery (SRS) for CSMs; however, large cohort analyses are lacking. This multicentre analysis reports the outcome data of over 1000 patients with CSMs who were treated with SRS. SRS shows a high local tumour control rate with few complications. These results agree with previous reports in the literature. SRS is a valuable primary or adjuvant treatment option for CSMs.Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24–233). Median tumour volume was 6.2 cc (+/−7), and the median marginal dose was 14 Gy (+/−3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6–233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

Outcomes after gamma knife radiosurgery for intraventricular meningiomas.

Intraventricular meningiomas (IVMs) are rare tumors with considerable treatment-associated morbidity due to their challenging location. Treatment with stereotactic radiosurgery (SRS) is sparsely reported in the literature. We describe our experience over the last 35years using Gamma knife radiosurgery (GKRS) for IVMs. We retrospectively reviewed the GKRS database identifying 2501 meningiomas treated at the University of Pittsburgh Medical Center over the last 35years. Nineteen patients with (12 males, mean age = 53.2years, range 14-84) 20 IVMs were identified. Headache was the most frequent presenting symptom (N = 12), and the trigone of the lateral ventricle was the most common location (N = 18). The median tumor volume was 4.8cc (range, 0.8-17). The median margin dose was 14Gy (range, 12-25) delivered at 50% isodose line. At a median follow-up of 63.1months (range, 6-322.4) symptom control was achieved in 18 (94.7%) patients. The overall progression-free survival (PFS) was 95% at 5years, and 85% at 10-years. After Log-rank test, patients who underwent GKRS within 12months after diagnosis (vs. ≥ 12months, X2: 4.455, p = 0.035), patients treated with primary GKRS without prior biopsy (vs. prior biopsy, X2: 4.000, p = 0.046), and patients with WHO grade I meningioma (vs. WHO II, X2: 9.000, p = 0.003) had a longer PFS. Imaging showed peritumoral edema in seven cases at a median of 10.5 (range, 6.13-24.3) months after GKRS. Only three of these patients were symptomatic and were successfully managed with oral medications. Cox´s regression revealed that a V12Gy ≥ 10cc [HR: 10.09 (95% CI: 2.11-48.21), p = 0.004], and tumor volume ≥ 8cc [HR: 5.87 (95% CI: 1.28-26.97), p = 0.023] were associated with a higher risk of peritumoral edema. GKRS is an effective and safe management option for intraventricular meningiomas. Early GKRS should be considered as a primary management modality for small and medium sized IVM and adjuvant management for residual IVMs.

Long-term outcomes of staged Gamma Knife radiosurgery for giant cavernous sinus hemangiomas: a single-center retrospective study.

Cavernous sinus hemangiomas (CSHs) are rare benign tumors originating from the cavernous sinus. Gamma Knife radiosurgery (GKRS) has been recommended as a primary treatment for small- to medium-sized CSHs. The optimal treatment for giant CSHs is still controversial. In this study, the authors retrospectively reviewed the effectiveness and safety of staged GKRS treatment for giant CSHs. Twenty-two patients with giant CSH who received staged GKRS treatment in the Gamma Knife Treatment Center of Henan Province during the period from January 1, 2011, to December 31, 2018, were enrolled in this study. Six patients had received microsurgery before GKRS, the other 16 patients were diagnosed according to clinical symptoms and MR images. All of the enrolled patients received 2-stage GKRS, and the mean interval between the two GKRS treatments was 6.5 months (range 6-12 months). For the first GKRS, the median isodose line was 48% (range 45%-50%), the median marginal dose was 13 Gy (range 11.5-14 Gy), and the median coverage of CSHs was 80% (range 70%-88%). For the second GKRS treatment, the median isodose line was 50% (range 45%-55%), the median marginal dose to the CSHs was 10.5 Gy (range 9-12.5 Gy), and the median coverage of the CSHs was 88% (range 80%-94%). All of the patients received an outpatient review of an enhanced MR image of the head and a clinical physical check every 6 months after the first GKRS treatment. The mean follow-up duration was 52 months (range 24-84 months). The tumor control rate was 100% 24 months after staged GKRS, and at the last follow-up the mean tumor shrinkage rate was 96.7% (range 90.6%-100%) and the mean residual CSH volume was 2.1 ml (range 0-8.5 ml). Twenty patients suffered central nervous system (CNS) injury symptoms to varying degrees before staged GKRS treatment. Complete symptom recovery was found in 11 (55%) patients, improved symptoms in 5 (25%) patients, and no change in 4 (20%) patients after treatment. Only 1 patient suffered temporary preexisting headache aggravation and 1 patient suffered temporary preexisting diplopia aggravation 1 week after receiving the first GKRS treatment. Subacute or chronic complications were not detected after staged GKRS. Staged GKRS is an effective treatment for giant CSHs. Because of the impressively low incidence of adverse effects, staged GKRS may be considered as a primary treatment for giant CSHs.

Stereotactic radiosurgery for prostate cancer cerebral metastases: an international multicenter study.

As novel therapies improve survival for men with prostate cancer, intracranial metastatic disease has become more common. The purpose of this multicenter study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of intracranial prostate cancer metastases. Demographic data, primary tumor characteristics, SRS treatment parameters, and clinical and imaging follow-up data of patients from nine institutions treated with SRS from July 2005 to June 2020 for cerebral metastases from prostate carcinoma were collected and analyzed. Forty-six patients were treated in 51 SRS procedures for 120 prostate cancer intracranial metastases. At SRS, the mean patient age was 68.04 ± 9.05 years, the mean time interval from prostate cancer diagnosis to SRS was 4.82 ± 4.89 years, and extracranial dissemination was noted in 34 (73.9%) patients. The median patient Karnofsky Performance Scale (KPS) score at SRS was 80, and neurological symptoms attributed to intracranial involvement were present prior to 39 (76%) SRS procedures. Single-fraction SRS was used in 49 procedures. Stereotactic radiotherapy using 6 Gy in five sessions was utilized in 2 procedures. The median margin dose was 18 (range 6-28) Gy, and the median tumor volume was 2.45 (range 0.04-45) ml. At a median radiological follow-up of 6 (range 0-156) months, local progression was seen with 14 lesions. The median survival following SRS was 15.18 months, and the 1-year overall intracranial progression-free survival was 44%. The KPS score at SRS was noted to be associated with improved overall (p = 0.02) and progression-free survival (p = 0.03). Age ≥ 65 years at SRS was associated with decreased overall survival (p = 0.04). There were no serious grade 3-5 toxicities noted. SRS appears to be a safe, well-tolerated, and effective management option for patients with prostate cancer intracranial metastases.

Endocrine disorders after primary gamma knife radiosurgery for pituitary adenomas: A systematic review and meta-analysis.

Gamma Knife radiosurgery (GKRS) is feasible for pituitary adenomas, but post-surgery GKRS may cause severe hormone deficits. We reviewed the literature on primary GKRS for pituitary adenoma focusing on radiation-induced hormone deficiencies. PubMed, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include studies describing primary GKRS for pituitary adenomas. Pooled-rates of GKRS-induced hormone deficiencies and clinical-radiological responses were analyzed with a random-effect model meta-analysis. We included 24 studies comprising 1381 patients. Prolactinomas were the most common (34.2%), and 289 patients had non-functioning adenomas (20.9%). Median tumor volume was 1.6cm3 (range, 0.01-31.3), with suprasellar extension and cavernous sinus invasion detected in 26% and 31.1% cases. GKRS was delivered with median marginal dose 22.6Gy (range, 6-49), maximum dose 50Gy (range, 25-90), and isodose line 50% (range, 9-100%). Median maximum point doses were 9Gy (range, 0.5-25) to the pituitary stalk, 7Gy (range, 1-38) to the optic apparatus, and 5Gy (range, 0.4-12.3) to the optic chiasm. Pooled 5year rates of endocrine normalization and local tumor control were 48% (95%CI 45-51%) and 97% (95%CI 95-98%). 158 patients (11.4%) experienced endocrinopathies at a median of 45months (range, 4-187.3) after GKRS, with pooled 5-year rates of 8% (95%CI 6-9%). GKRS-induced hormone deficiencies comprised secondary hypothyroidism (42.4%) and hypogonadotropic hypogonadism (33.5%), with panhypopituitarism reported in 31 cases (19.6%). Primary GKRS for pituitary adenoma may correlate with lower rates of radiation-induced hypopituitarism (11.4%) than post-surgery GKRS (18-32%). Minimal doses to normal pituitary structures and long-term endocrine follow-up are of primary importance.

Long-Term Risks of Hemorrhage and Adverse Radiation Effects of Stereotactic Radiosurgery for Brain Arteriovenous Malformations.

The information about long-term risks of hemorrhage and late adverse radiation effects (AREs) after stereotactic radiosurgery for brain arteriovenous malformations (AVMs) is lacking. To evaluate the long-term risks of hemorrhage and late ARE rates in patients with AVM treated with Gamma Knife surgery (GKS). We examined 1249 patients with AVM treated with GKS. The Spetzler-Martin grade was I in 313 patients (25%), II in 394 (32%), III in 458 (37%), and IV/V in 84 (7%). The median treatment volume was 2.5 cm3, and the median marginal dose was 20 Gy. The median follow-up period was 61 months. The 5- and 10-year nidus obliteration rates were 63% and 82%, respectively. The 5- and 10-year cumulative hemorrhage rates were 7% and 10%, respectively. The annual hemorrhage rate was 1.5% for the first 5 years post-GKS, which decreased to 0.5% thereafter. During the follow-up period, 42 symptomatic cyst formations/chronic encapsulated hematomas ([CFs/CEHs], 3%) and 3 radiation-induced tumors (0.2%) were observed. The 10- and 15-year cumulative CF/CEH rates were 3.7% and 9.4%, respectively. GKS is associated with reduced hemorrhage risk and high nidus obliteration rates in patients with AVM. The incidence of late AREs tended to increase over time. The most common ARE was CF/CEH, which can be safely removed; however, careful attention should be paid to the long-term development of fatal radiation-induced tumors.

A volume matched comparison of survival after radiosurgery in non-small cell lung cancer patients with one versus more than twenty brain metastases.

Treatment of patients with a large number of brain metastases using radiosurgery remains controversial. In this study we sought to conduct a volume matched comparison to evaluate the clinical outcome of patients with > 20 brain metastases and compared it with patents with solitary brain tumor form non-small cell lung cancer (NSCLC). Between 2014 and 2020, 26 NSCLC patients (925 tumors) underwent stereotactic radiosurgery (SRS) for > 20 metastases in a single procedure (median margin dose = 16Gy, median cumulative tumor volume = 4.52cc); 56 patients underwent SRS for a single metastasis (median margin dose = 18Gy, median volume = 4.74cc). The overall survival (OS), local tumor control (LC), adverse radiation effect (ARE) risk, and incidence of new tumor development were compared. No difference in OS was found between patients with > 20 brain metastases (median OS = 15months) and patients with solitary metastasis (median OS = 12months; p = 0.3). In the solitary tumor cohort, two of 56 (3.5%) tumors progressed whereas in the > 20 cohort only 3 of 925 (0.3%) tumors showed progression (*p = 0.0013). The rate of new tumor development was significantly higher in patients with > 20 tumors (***p = 0.0001). No significant difference of ARE rate was found (7.5% for > 20 tumors vs. 8.7% for single metastasis). Patients with > 20 tumors showed significantly better LCwithsimilar OS compared to patients with solitary tumors. Current guidelines that restrict the role of SRS to patients with 1-4 tumors should be revised.

145 A Matched Cohort Comparison of Survival After Radiosurgery for Non-Small Cell Lung Cancer Patients with One Versus More than Twenty Brain Metastases

INTRODUCTION: Confusion remains as to whether it is the number or the cumulative volume of brain metastases that affects survival of patients with metastatic non-small cell lung cancer (NSCLC). We retrospectively compared outcomes after stereotactic radiosurgery (SRS) in patients with a solitary metastasis matched by volume to patients with = 20 metastases with the same cumulative tumor volume. METHODS: From 2014 to 2020, 26 NSCLC patients (925 tumors) underwent Gamma knife® SRS for = 20 metastases in a single procedure (median margin dose = 16 Gy, median cumulative tumor volume = 4.52 cc). During the same interval 57 patients underwent SRS for a single metastasis (median margin dose = 18 Gy, median volume = 4.74 cc). The overall survival (OS), local tumor control (TC), adverse radiation effects (ARE), and incidence of new tumor development were compared. RESULTS: When controlled for the same tumor volume, we found no significant difference in median OS between patients with = 20 brain metastases (median survival = 15 months) compared to single metastasis patients (median survival = 12 months, p = 0.3). In the solitary tumor cohort, two of 57 tumors (3.5%) progressed whereas in the = 20 cohort only 3 of 925 treated tumors (0.3%) showed progression (p = 0.0013). The rate of new tumor development was significantly higher in patients with = 20 tumors (***p = 0.0001). Seventeen out of 26 (65%) patients in = 20 cohort developed new metastases that required salvage SRS compared to 8 out of 57 (14%) patients in the solitary tumor group. There was no significant difference in the rate of ARE between these groups (7.5% for = 20 tumors vs. 8.7% for single metastasis). CONCLUSION: Compared to patients with solitary tumors, patients with = 20 tumors showed significantly better LC with similar OS. We support the revision of guidelines that select SRS eligible patients based on the cumulative volume rather than number of their brain metastatic disease.

Metastatic Neoplasm Volume Kinetics Following 2-Stage Stereotactic Radiosurgery

Multisession staged stereotactic radiosurgery (SRS) represents an alternative approach for management of large brain metastases (LBMs), with potential advantages over fractionated SRS. This study investigated clinical efficacy and safety of 2-stage stereotactic radiosurgery (2-SSRS) in patients with LBMs. Patients with LBMs treated with 2-SSRS between 2014 and 2020 were evaluated. Demographic, clinical, and radiologic data were obtained. Volumetric measurements at first SRS session, second SRS session, and follow-up imaging studies were obtained. Characteristics that might predict response to 2-SSRS were evaluated through Fisher exact or Mann-Whitney U test. The study included 24 patients with 26 LBMs. Median (range) marginal doses for first and second SRS sessions were 15 Gy (14-18 Gy) and 15 Gy (12-16 Gy), respectively. Median (range) tumor volumes at first SRS session, second SRS session, and 3-month follow-up were 8.1 cm3 (1.5-28.5 cm3), 3.3 cm3 (0.8-26.1 cm3), and 2.2 cm3 (0.2-10.1 cm3), respectively. Of 26 lesions, 24 (92%) demonstrated early local control following the first SRS session, with 17 lesions (71%) demonstrating a decrease of ≥30% in T1 postcontrast MRI volume before the second SRS session and 3 lesions (12%) remaining stable. Eventually, 4 lesions showed disease progression after 2-SSRS. The median time to local progression was not reached; the median time to intracranial progression was 9.1 months. Our study supports the effectiveness and safety of 2-SSRS as a treatment modality for patients with LBMs, especially in poor surgical candidates. The local failure rate and low occurrence of adverse effects are comparable to other staged radiosurgery studies.

Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.

The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs). This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic. Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE. Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.

Radiation necrosis in renal cell carcinoma brain metastases treated with checkpoint inhibitors and radiosurgery: An international multicenter study

Patients with renal cell carcinoma (RCC) brain metastases are frequently treated with immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS). However, data reporting on the risk of developing radiation necrosis (RN) are limited. RN rates were compared for concurrent therapy (ICI/SRS administration within 4 weeks of one another) and nonconcurrent therapy with the χ2 test. Univariable logistic regression was used to identify factors associated with developing RN. Fifty patients (23 concurrent and 27 nonconcurrent) with 395 brain metastases were analyzed. The median follow-up was 12.1 months; the median age was 65 years. The median margin dose was 20 Gy, and 4% underwent prior whole-brain radiation therapy (WBRT). The median treated tumor volume was 3.32 cm3 (range, 0.06-42.38 cm3 ); the median volume of normal brain tissue receiving a dose of 12 Gy or higher (V12 Gy) was 8.42 cm3 (range, 0.27-111.22 cm3 ). Any-grade RN occurred in 17.4% and 22.2% in the concurrent and nonconcurrent groups, respectively (P = .67). Symptomatic RN occurred in 4.3% and 14.8% in the concurrent and nonconcurrent groups, respectively (P = .23). Increased tumor volume during SRS (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.19; P = .04) was associated with developing RN, although V12 Gy (OR, 1.03; 95% CI, 0.99-1.06; P = .06), concurrent therapy (OR, 0.74; 95% CI, 0.17-2.30; P = .76), prior WBRT, and ICI agents were not statistically significant. Symptomatic RN occurs in a minority of patients with RCC brain metastases treated with ICI/SRS. The majority of events were grade 1 to 3 and were managed medically. Concurrent ICI/SRS does not appear to increase this risk. Attempts to improve dose conformality (reduce V12) may be the most successful mitigation strategy in single-fraction SRS.

Efficacy of Gamma Knife Radiosurgery in Refractory Obsessive-Compulsive Disorder: An Indian Experience

Background Obsessive-compulsive disorder (OCD) is a chronic debilitating psychiatric condition with adverse impact on patient's sociooccupational health. Refractoriness to pharmacotherapy and psychotherapy is not uncommon. Gamma Knife radiosurgery (GKRS) is the comprehensively used and reviewed treatment modality in refractory OCD worldwide. In India, the past two decades of increasing GKRS availability has failed to create the necessary local awareness of its usefulness in refractory OCD. Limited native literature deepens the problem. Objective To analyze our experience with GKRS in refractory OCD, and report the safety and efficacy/long-term outcome in patients using the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS). Materials and Methods A retrospective review of patients receiving GKRS for refractory OCD between 2000 and 2020 was carried out. Case files of the eligible ( n = 9) patients were reviewed for clinical, radiotherapeutic, and outcome data. Additionally, patients were contacted via telephone to enquire about their experiences, and to obtain retroactive consent for GKRS in June 2021. Information obtained was collated, computed, and analyzed. Results Male-to-female sex ratio was 8:1. Mean age at the time of GKRS and mean duration of OCD prior to GKRS was 30.1 ± 9.4 and 10.2 ± 5.8 years, respectively. Mean baseline Y-BOCS score was 29.6 ± 4.7. Our first patient received cingulotomy, while the rest underwent anterior capsulotomy. Median margin dose (50% isodose) was 70 Gy. Also, 23.8 ± 7.7 was the mean Y-BOCS score at the last follow-up (median = 30 months). Overall, 44.4% patients showed full/partial response (≥25% reduction in Y-BOCS score) at the last follow-up. In anterior capsulotomy (eight patients), patients with moderate/severe OCD showed better response (4/5 responders) than those with extreme OCD (0/3 responders). Single case of cingulotomy resulted in no response (<25% reduction in Y-BOCS score). No adverse radiation effects were noted. Also, 55.6% patients gave retroactive consent telephonically. Conclusion GKRS is a safe and effective noninvasive treatment modality for refractory OCD. Ventral anterior capsule is the preferred target. Maximum radiation doses of 120 to 160 Gy are well tolerated. Extremely severe OCD cases fared poorer. Proper awareness about the availability and efficacy of GKRS in refractory OCD is required in India.

Outcomes of Gamma Knife Radiosurgery for Brain Metastases From Anaplastic Lymphoma Kinase Rearrangement-Positive and EGFR Mutation-Positive Non-Small Cell Lung Cancer.

IntroductionThe outcomes after gamma knife radiosurgery (GKRS) were retrospectively analysed in patients with brain metastases from anaplastic lymphoma kinase (ALK) rearrangement-positive and epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) to evaluate the efficacy, safety and difference for overall survival and local tumor control.MethodsThe medical records were retrospectively reviewed of 607 patients (25 ALK-positive, 171 EGFR-positive, and 411 wild type) with 2959 tumors who had undergone GKRS.ResultsThe median overall survival time after initial GKRS was 14 months. Driver gene mutation-positive patients had significantly longer overall survival than wild type patients (p < 0.0001), and ALK-positive patients survived significantly longer than EGFR-positive patients (p = 0.04). Multivariate analysis showed the unfavorable factors significantly affecting overall survival outcomes were older age, lower Karnofsky Performance Status score, multiple intracranial metastases, uncontrolled primary cancer, uncontrolled extracranial metastases, no administration of immune checkpoint inhibitors, and driver gene mutation-negative cases. Seventy-three patients died of uncontrolled brain metastases at a median of 12 months. Driver gene mutations had no influence (p = 0.33), and ALK-positive and EGFR-positive patients showed no significant difference in neurological survival (p = 0.83). A total of 174 patients demonstrated distant brain control failure at a median of 15 months. ALK-positive type was significant compared with EGFR-positive type (p = 0.047), but driver gene mutation-positive and -negative types showed no significant difference in the development of new brain metastases (p = 0.2). The median tumor volume was 1.06 cm3 in the driver gene mutation-positive type and 1.85 cm3 in wild type. The median marginal dose was 20 Gy in both types. The 6-, 12-, and 24-month local tumor control rates were 97.3%, 96.1%, and 95.9%, respectively. Driver gene mutations had a significantly positive impact on local tumor control (p = 0.001), and ALK-positive and EGFR-positive types showed no significant difference (p = 0.95). A total of 193 tumors had radiation injury at a median of 12 months after GKRS. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 8.1%, and 8.7%, respectively. Driver gene mutations significantly induced radiation damage (p = 0.021), and the ALK-positive type was affected more than the EGFR-positive type (p = 0.02).ConclusionsALK rearrangement-positive NSCLC patients tended to have significantly longer survival, but had higher incidence of new intracranial metastases due to long-term survival after GKRS, compared with EGFR mutation-negative and driver gene mutation-negative NSCLC patients. GKRS induced significantly satisfactory local tumor control in driver gene mutation-positive tumors but GKRS-related complication frequency was higher, especially in ALK-positive NSCLC patients. Therefore, more careful imaging follow-up is necessary after GKRS for patients with driver gene mutation-positive NSCLC.

Concurrent vs. Sequential Stereotactic Radiosurgery and Immune Checkpoint Inhibition in Melanoma Brain Metastases: An International Cooperative Group Study

Multiple single institution retrospective studies have suggested that managing melanoma brain metastases (MBM) with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is associated with improved overall survival (OS) when administered concurrently (within 4 weeks) rather than sequentially (ICI and SRS administered more than 4 weeks apart). However, there is a paucity of data quantifying the risk of developing radiation necrosis (RN) in this setting.The International Radiosurgery Research Foundation approved the analysis. The Kaplan Meier method and log-rank test were used to compare OS and local control (LC) at 1- and 2-years post SRS. Factors associated with the development of RN and OS were further analyzed using logistic and Cox proportional hazards regression models. The null hypothesis was rejected for P < 0.05.There were 254 patients with 1,322 MBM treated across 10 international institutions. The median follow-up was 12.9 months, median age was 63 years (interquartile range [IQR]: 51-73 years), BRAF mutation was present in 46.6% of patients, active extracranial disease was present in 70% of patients, and the median Karnofsky Performance Status (KPS) was 90. SRS/ICI was administered concurrently in 46.5% of patients. All patients were treated on the stereotactic radiosurgery platform. The median margin dose was 20 Gy (IQR: 18-21 Gy), median number of fractions was 1 (range: 1-4), mean total brain metastasis volume was 3.4 cc and the mean V12 Gy was 8.7 cc. Radiation necrosis occurred in 14.2% of patients (5.9% Grade 1; 5.1% Grade 2; 2.8% Grade 3; 0.4% Grade 4). Overall survival at 1-year was 77.4% vs. 72.1%, and at 2-years was 63.1% vs. 46.1% (P = 0.048) for concurrent and sequential therapy, respectively. Local control at 1-year was 91.5% vs. 84.6%, and at 2-years was 84.9% vs. 75.6% (P = 0.12) for concurrent and sequential therapy, respectively. On multivariate logistic regression total treated brain metastasis volume (odds radio [OR]: 1.11; 95% confidence interval [CI]: 1.03-1.20; P = 0.008) was associated with a higher risk of development of RN; however, sequential therapy (OR: 0.97; 95% CI: 0.46-2.06; P = 0.94), and V12 (OR: 0.98; 95% CI: 0.95-1.01; P = 0.22) were not statistically significant. On multivariate cox regression, sequential therapy (hazard ratio [HR]: 1.58; 95% CI: 1.05-2.42; P = 0.03) and KPS (HR: 0.96; 95% CI: 0.94-0.98; P < 0.001) were prognostic factors for OS, while the presence of extracranial disease (HR: 1.03; 95% CI: 0.66-1.59; P = 0.90) and age (HR: 1.01; 95% CI: 1.00-1.02; P = 0.25) were not prognostic.In appropriately selected patients with MBM, concurrent administration of SRS/ICI may be associated with improved OS without an increased risk of RN when compared to sequential therapy. The risk of RN appears to increase with irradiated brain volume; therefore, hypofractionated SRS may be considered in patients with high volume disease. Prospective data are needed to further evaluate these findings.E.J. Lehrer: None. J. Gurewitz: None. T.D. Malouff: ASTRO Bylaws Committee. K. Bernstein: None. D. Kondziolka: None. P. Bonney: None. S.I. Patel: Independent Contractor; Alberta Health Services. Research Grant; Alberta Cancer Foundation. Travel Expenses; University Hospital Foundation. Chair; Alberta Health Services. Co-Director; Alberta Health Services. Manage and screen wish applications; Make-A-Wish Foundation (Northern Alberta Chapter). J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.K. Fakhoury: None. C.G. Rusthoven: Employee; SURVIVEiT (nonprofit cancer patient advocacy). Research Grant; Takeda. Advise regarding patient-facing medical content; SURVIVEiT.D. Mathieu: None. C. Deibert: None. P. Picozzi: None. B. Jones: None. C. Lee: None. S. Sharma: None. A. Niranjan: None. J.P. Sheehan: Neuropoint Alliance. M. Ahluwalia: None. D.M. Trifiletti: None.