Vestibular Schwannoma International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS Study.

PURPOSE: The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function. METHODS AND MATERIALS: This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes. RESULTS: In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001). CONCLUSIONS: SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.

The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

The AANS/CNS Section on Tumors: a summary of 40 years of advocacy to advance the care of patients with brain and spine tumors.

The AANS/CNS Section on Tumors was founded 40 years ago in 1984 to assist in the education of neurosurgeons interested in neuro-oncology, and serves as a resource for other national organizations regarding the clinical treatment of nervous system tumors. The Section on Tumors was the first national physicians' professional organization dedicated to the study and treatment of patients with brain and spine tumors. Over the past 40 years, the Section on Tumors has built solid foundations, including establishing the tumor section satellite meetings, founding the Journal of Neuro-Oncology (the first medical journal dedicated to brain and spine surgical oncology), advancing surgical neuro-oncology education and research, promoting neurosurgical involvement in neuro-oncology clinical trials, and advocating for patients with brain and spine tumors. This review provides a synopsis of the Section on Tumors' history, its challenges, and its opportunities, drawing on the section's archives and input from the 17 section chairs who led it during its first 40 years.

Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

Impact of Multiple Sclerosis Subtypes on Pain Management in Patients With Trigeminal Neuralgia After Stereotactic Radiosurgery: An International Multicenter Analysis.

BACKGROUND AND OBJECTIVES: Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS: We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS: Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS ( P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence ( P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION: This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.

Clinical outcomes following stereotactic radiosurgery for cerebral cavernous malformations of the basal ganglia and thalamus.

OBJECTIVE: There are few reports of outcomes following stereotactic radiosurgery (SRS) for the management of cerebral cavernous malformations (CCMs) of the basal ganglia or thalamus. Therefore, the authors aimed to clarify these outcomes. METHODS: Centers participating in the International Radiosurgery Research Foundation were queried for CCM cases managed with SRS from October 2001 to February 2021. The primary outcome of interest was hemorrhage-free survival (HFS) with a secondary outcome of symptomatic adverse radiation events (AREs). Assessment of the association of prognostic factors with HFS was conducted via Kaplan-Meier analysis and log-rank test. Chi-square tests were conducted to assess potential factors associated with the incidence of AREs. RESULTS: Seventy-three patients were identified. The median patient age was 43.5 years (range 4.4-79.5 years). Fifty-nine (80.8%) patients had hemorrhage prior to SRS. The median treatment volume was 0.9 cm3 (range 0.07-10.1 cm3) with a median margin prescription dose (MPD) of 12 Gy (range 10-20 Gy). One-, 3-, 5-, and 10-year HFS were 93.0%, 89.9%, 89.9%, and 83.0%, respectively, with one hemorrhage-related death approximately 1 year after SRS and nearly 60% and 30% of patients having improvement or stability of symptoms, respectively. There was no correlation between lesion size or MPD and HFS. Seven (9.6%) patients experienced AREs (MPDs > 12 Gy in all cases). Lesion size > 1.0 cm3 was correlated with the incidence of an ARE (p = 0.019). Forty-two (93.3%) of 45 patients treated with an MPD ≤ 12 Gy experienced neither hemorrhage nor AREs following SRS versus 17 (60.7%) of 28 patients treated with an MPD > 12 Gy (p = 0.0006). CONCLUSIONS: SRS is a reasonable treatment strategy and confers clinical stability or improvement and hemorrhage avoidance in patients harboring CCMs of the basal ganglia or thalamus. An MPD of approximately 12 Gy is recommended for the management of CCM.

Silent Corticotroph Staining Pituitary Neuroendocrine Tumors: Prognostic Significance in Radiosurgery.

BACKGROUND AND OBJECTIVES: There is conflicting evidence on the significance of adrenocorticotrophic hormone (ACTH) staining in the prognosis of nonfunctioning pituitary neuroendocrine tumors (NFpitNETs). The objective of this study was to define the effect of ACTH immunostaining on clinical and radiographic outcomes of stereotactic radiosurgery (SRS) for NFpitNETs. METHODS: This retrospective, multicenter study included patients managed with SRS for NFpitNET residuals. The patients were divided into 2 cohorts: (1) silent corticotroph (SC) for NFpitNETs with positive ACTH immunostaining and (2) non-SC NFpitNETs. Rates of local tumor control and the incidence of post-treatment pituitary and neurological dysfunction were documented. Factors associated with radiological and clinical outcomes were also analyzed. RESULTS: The cohort included 535 patients from 14 centers with 84 (15.7%) patients harboring silent corticotroph NFpitNETs (SCs). At last follow-up, local tumor progression occurred in 11.9% of patients in the SC compared with 8.1% of patients in the non-SC cohort (P = .27). No statistically significant difference was noted in new-onset hypopituitarism rates (10.7% vs 15.4%, P = .25) or visual deficits (3.6% vs 1.1%, P = .088) between the 2 cohorts at last follow-up. When controlling for residual tumor volume, maximum dose, and patient age and sex, positive ACTH immunostaining did not have a significant correlation with local tumor progression (hazard ratio = 1.69, 95% CI = 0.8-3.61, P = .17). CONCLUSION: In contemporary radiosurgical practice with a single fraction dose of 8-25 Gy (median 15 Gy), ACTH immunostaining in NFpitNETs did not appear to confer a significantly reduced rate of local tumor control after SRS.

Local control and survival after stereotactic radiosurgery for colorectal cancer brain metastases: an international multicenter analysis.

OBJECTIVE: The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM). METHODS: Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22-8.1 cm3), and the median margin dose was 20 Gy (IQR 18-22 Gy). RESULTS: The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4-4.9; p = 0.003 and HR 3.4, 95% CI 1.7-6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19-0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1-2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1-2.4; p = 0.009) were significantly associated with worse OS. CONCLUSIONS: Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.

Stereotactic radiosurgery in the management of non-small cell lung cancer brain metastases: a prospective study using the NeuroPoint Alliance Stereotactic Radiosurgery Registry.

OBJECTIVE: The literature on non-small cell lung cancer (NSCLC) brain metastases (BMs) managed using stereotactic radiosurgery (SRS) relies mainly on single-institution studies or randomized controlled trials (RCTs). There is a literature gap on clinical and radiological outcomes of SRS for NSCLC metastases in real-world practice. The objective of this study was to benchmark mortality and progression outcomes in patients undergoing SRS for NSCLC BMs and identify risk factors for these outcomes using a national quality registry. METHODS: The SRS Registry of the NeuroPoint Alliance was used for this study. This registry included patients from 16 enrolling sites who underwent SRS from 2017 to 2022. Data are prospectively collected without a prespecified research purpose. The main outcomes of this analysis were overall survival (OS), out-of-field recurrence, local progression, and intracranial progression. All time-to-event investigations included Kaplan-Meier analyses and multivariable Cox regressions. RESULTS: Two hundred sixty-four patients were identified, with a mean age of 66.7 years and a female proportion of 48.5%. Most patients (84.5%) had a Karnofsky Performance Status (KPS) score of 80-100, and the mean baseline EQ-5D score was 0.539 quality-adjusted life years. A single lesion was present in 53.4% of the patients, and 29.1% of patients had 3 or more lesions. The median OS was 28.1 months, and independent predictors of mortality included no control of primary tumor (hazard ratio [HR] 2.1), KPS of 80 (HR 2.4) or lower (HR 2.4), coronary artery disease (HR 2.8), and 5 or more lesions present at the time of SRS treatment (HR 2.3). The median out-of-field progression-free survival (PFS) was 24.8 months, and the median local PFS was unreached. Intralesional hemorrhage was an independent risk factor of local progression, with an HR of 6.0. The median intracranial PFS was 14.0 months and was predicted by the number of lesions at the time of SRS (3-4 lesions, HR 2.2; 5-14 lesions, HR 2.5). CONCLUSIONS: In this real-world prospective study, the authors used a national quality registry and found favorable OS in patients with NSCLC BMs undergoing SRS compared with results from previously published RCTs. The intracranial PFS was mainly driven by the emergence of new lesions rather than local progression. A greater number of lesions at baseline was associated with out-of-field progression, while intralesional hemorrhage at baseline was associated with local progression.

Selected-Lesion Stereotactic Radiosurgery (SL-SRS) as a Novel Strategy in the Treatment of Patients With Multiple Brain Metastases.

INTRODUCTION: With the diminishing use of whole-brain radiotherapy (WBRT), there is increasing debate regarding the maximum number of brain metastases that should be treated with stereotactic radiosurgery (SRS). In patients with >10-15 lesions, some groups are proposing a new approach - selected-lesion SRS (SL-SRS) - where only a subset of intracranial lesions are chosen for irradiation. This study is an initial look into this practice. METHODS: This is a cross-sectional exploratory survey study. A survey of 19 questions was created by the International Radiosurgery Research Foundation (IRRF) using open-ended and multiple-choice style questions on SL-SRS practices and indications with the goal of qualitatively understanding how SL-SRS is being implemented worldwide. The survey was distributed to physicians in the United States (US) and internationally who are members of the IRRF and who perform SRS frequently. Ten out of 50 IRRF institutions provided responses reflecting the practices of 16 physicians. RESULTS: SL-SRS is being performed at 8/10 institutions. The most common reasons for using SL-SRS included patients with prior WBRT, patients with progressing systemic disease with central nervous system (CNS)-penetrating or immunotherapies available, specific requests from medical oncology, and cooperative studies using this approach. Lesion size was cited as the most important factor when choosing to irradiate any single lesion. The majority of respondents reported 30 mm and 40 mm as size cutoffs (by largest dimension) for treatment of a lesion in eloquent and non-eloquent locations, respectively. Eloquence of lesion location and attributable symptoms were also considered important. Progression of untreated lesions was the most common reason reported for bringing patients back for additional treatment. CONCLUSION: The responses to this survey show that SL-SRS is being used, allowing for small/asymptomatic brain metastases to be left safely unirradiated. It is currently used in patients who have >10-15 lesions with prior WBRT, those with progression of extracranial disease but with acceptable systemic treatment options, and those with poor functional status. The incorporation of this new approach into clinical trials should be considered for the safe study of the efficacy of new CNS-penetrating systemic therapies.

Stereotactic radiosurgery for haemorrhagic cerebral cavernous malformation: a multi-institutional, retrospective study.

BACKGROUND: Cerebral cavernous malformations (CCMs) frequently manifest with haemorrhages. Stereotactic radiosurgery (SRS) has been employed for CCM not suitable for resection. Its effect on reducing haemorrhage risk is still controversial. The aim of this study was to expand on the safety and efficacy of SRS for haemorrhagic CCM. METHODS: This retrospective multicentric study included CCM with at least one haemorrhage treated with single-session SRS. The annual haemorrhagic rate (AHR) was calculated before and after SRS. Recurrent event analysis and Cox regression were used to evaluate factors associated with haemorrhage. Adverse radiation effects (AREs) and occurrence of new neurological deficits were recorded. RESULTS: The study included 381 patients (median age: 37.5 years (Q1-Q3: 25.8-51.9) with 414 CCMs. The AHR from diagnosis to SRS excluding the first haemorrhage was 11.08 per 100 CCM-years and was reduced to 2.7 per 100 CCM-years after treatment. In recurrent event analysis, SRS, HR 0.27 (95% CI 0.17 to 0.44), p<0.0001 was associated with a decreased risk of haemorrhage, and the presence of developmental venous anomaly (DVA) with an increased risk, HR 1.60 (95% CI 1.07 to 2.40), p=0.022. The cumulative risk of first haemorrhage after SRS was 9.4% (95% CI 6% to 12.6%) at 5 years and 15.6% (95% CI% 9 to 21.8%) at 10 years. Margin doses> 13 Gy, HR 2.27 (95% CI 1.20 to 4.32), p=0.012 and the presence of DVA, HR 2.08 (95% CI 1.00 to 4.31), p=0.049 were factors associated with higher probability of post-SRS haemorrhage. Post-SRS haemorrhage was symptomatic in 22 out of 381 (5.8%) patients, presenting with transient (15/381) or permanent (7/381) neurological deficit. ARE occurred in 11.1% (46/414) CCM and was responsible for transient neurological deficit in 3.9% (15/381) of the patients and permanent deficit in 1.1% (4/381) of the patients. Margin doses >13 Gy and CCM volume >0.7 cc were associated with increased risk of ARE. CONCLUSION: Single-session SRS for haemorrhagic CCM is associated with a decrease in haemorrhage rate. Margin doses ≤13 Gy seem advisable.

Epilepsy associated with cerebral cavernous malformations managed with stereotactic radiosurgery: an international, multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been proposed as an alternative to resection for epilepsy control in patients with cerebral cavernous malformations (CCM) located in critical areas. METHODS: This multicentric, retrospective study evaluated seizure control in patients with a solitary CCM and a history of at least one seizure prior to SRS. RESULTS: 109 patients (median age at diagnosis 28.9 years, interquartile range (IQR) 16.4 years] were included. Prior to SRS, 2 (1.8%) were seizure-free without medication, 35 (32.1%) were seizure-free with antiseizure medications (ASM), 17 (15.6%) experienced an improvement of at least 50% in seizure frequency/intensity with ASM, and 55 (50.5%) experienced an improvement of less than 50% in seizure frequency/intensity with ASM. At a median follow-up of 3.5 years post-SRS (IQR: 4.9), 52 (47.7%) patients were Engel class I, 13 (11.9%) class II, 17 (15.6%) class III, 22 (20.2%) class IVA or IVB and 5 (4.6%) class IVC. For the 72 patients who had seizures despite medication prior to SRS, a delay > 1.5 years between epilepsy presentation and SRS decreased the probability to become seizure-free, HR 0.25 (95% CI 0.09-0.66), p = 0.006. The probability of achieving Engel I at the last follow-up was 23.6 (95% CI 12.7-33.1) and 31.3% (95% CI 19.3-50.8) at 2 and 5 years respectively. 27 patients were considered as having drug-resistant epilepsy. At a median follow-up of 3.1 years (IQR: 4.7), 6 (22.2%) of them were Engel I, 3 (11.1%) Engel II, 7 (25.9%) Engel III, 8 (29.6%) Engel IVA or IVB and 3 (11.1%) Engel IVC. INTERPRETATION: 47.7% of patients managed with SRS for solitary CCM presenting with seizures achieved Engel class I at the last follow-up.

Local Control and Survival Outcomes After Stereotactic Radiosurgery for Brain Metastases From Gastrointestinal Primaries: An International Multicenter Analysis.

BACKGROUND: There are limited data regarding outcomes for patients with gastrointestinal (GI) primaries and brain metastases treated with stereotactic radiosurgery (SRS). OBJECTIVE: To examine clinical outcomes after SRS for patients with brain metastases from GI primaries and evaluate potential prognostic factors. METHODS: The International Radiosurgery Research Foundation centers were queried for patients with brain metastases from GI primaries managed with SRS. Primary outcomes were local control (LC) and overall survival (OS). Kaplan-Meier analysis was used for univariate analysis (UVA) of prognostic factors. Factors significant on UVA were evaluated with a Cox multivariate analysis proportional hazards model. Logistic regressions were used to examine correlations with RN. RESULTS: We identified 263 eligible patients with 543 brain metastases. Common primary sites were rectal (31.2%), colon (31.2%), and esophagus (25.5%) with a median age of 61.6 years (range: 37-91.4 years) and a median Karnofsky performance status (KPS) of 90% (range: 40%-100%). One-year and 2-year LC rates were 83.5% (95% CI: 78.9%-87.1%) and 73.0% (95% CI: 66.4%-78.5%), respectively. On UVA, age >65 years ( P = .001), dose <20 Gy ( P = .006) for single-fraction plans, KPS <90% ( P < .001), and planning target volume ≥2cc ( P = .007) were associated with inferior LC. All factors other than dose were significant on multivariate analysis ( P ≤ .002). One-year and 2-year OS rates were 68.0% (95% CI: 61.5%-73.6%) and 31.2% (95% CI: 24.6%-37.9%), respectively. Age > 65 years ( P = .006), KPS <90% ( P = .005), and extracranial metastases ( P = .05) were associated with inferior OS. CONCLUSION: SRS resulted in comparable LC with common primaries. Age and KPS were associated with both LC and OS with planning target volume and extracranial metastases correlating with LC and OS, respectively. These factors should be considered in GI cancer patient selection for SRS.

Treatment of adverse radiation effects with Boswellia serrata after failure of pentoxifylline and vitamin E: illustrative cases.

BACKGROUND: Adverse radiation effects (AREs) can occur after stereotactic radiosurgery (SRS), and symptomatic cases are often treated with corticosteroids, pentoxifylline, and vitamin E. The supplement 5-Loxin (Boswellia serrata) is an extract of Indian frankincense that inhibits vascular endothelial growth factor expression and has been shown to reduce perilesional edema in brain tumor patients undergoing fractionated radiation. OBSERVATIONS: Three patients underwent SRS for meningioma or metastasis and developed symptomatic AREs at 4 to 8 months. They were initially treated with corticosteroids, pentoxifylline, and vitamin E with transient improvement followed by recurrent neurological symptoms and imaging findings as steroids were tapered off. All patients were rescued by the administration of 5-Loxin with resolution of neurological symptoms and imaging changes, discontinuation of steroids, and no medication side effects. LESSONS: The author's early experience with 5-Loxin has been encouraging, and this supplement has become the author's first-line treatment for acute radiation effects after SRS. The author reserves bevacizumab for significant mass effect or failure of oral therapy. 5-Loxin has many advantages including low cost, ease of use, and patient tolerability. More experience is needed to confirm the role of 5-Loxin in the upfront treatment of AREs.

Stereotactic Radiosurgery for Intraventricular Metastases: A Multicenter Study.

BACKGROUND: Intraventricular metastases (IVMs) are uncommon, and their optimal management remains debatable. OBJECTIVE: To define the safety and efficacy of stereotactic radiosurgery (SRS) in the treatment of IVMs. METHODS: This retrospective, multicenter study included patients managed with SRS for IVMs. SRS-induced adverse events, local tumor or intracranial progression, and the frequency of new-onset hydrocephalus or leptomeningeal spread were documented. Analyses of variables related to patient neuroimaging or clinical outcomes were also performed. RESULTS: The cohort included 160 patients from 11 centers who underwent SRS for treatment of 1045 intracranial metastases, of which 196 were IVMs. The median survival from SRS was 10 months. Of the 154 patients and 190 IVMs with imaging follow-up, 94 patients (61%) experienced distant intracranial disease progression and 16 IVMs (8.4%) progressed locally. The 12- and 24-month local IVM control rates were 91.4% and 86.1%, respectively. Sixteen (10%) and 27 (17.5%) patients developed hydrocephalus and leptomeningeal dissemination post-SRS, respectively. Adverse radiation effects were documented in 24 patients (15%). Eleven patients (6.9%) died because of intracranial disease progression. CONCLUSION: SRS is an effective treatment option for IVMs, with a local IVM control rate comparable with SRS for parenchymal brain metastases. Leptomeningeal spread and hydrocephalus in patients with IVM occur in a minority of patients, but these patients warrant careful follow-up to detect these changes.

Adjuvant versus on-progression Gamma Knife radiosurgery for residual nonfunctioning pituitary adenomas: a matched-cohort analysis.

OBJECTIVE: Radiological progression occurs in 50%-60% of residual nonfunctioning pituitary adenomas (NFPAs). Stereotactic radiosurgery (SRS) is a safe and effective management option for residual NFPAs, but there is no consensus on its optimal timing. This study aims to define the optimal timing of SRS for residual NFPAs. METHODS: This retrospective, multicenter study involved 375 patients with residual NFPAs managed with SRS. The patients were divided into adjuvant (ADJ; treated for stable residual NFPA within 6 months of resection) and progression (PRG) cohorts (treated for residual NFPA progression). Factors associated with tumor progression and clinical deterioration were analyzed. RESULTS: Following propensity-score matching, each cohort consisted of 130 patients. At last follow-up, tumor control was achieved in 93.1% of patients in the ADJ cohort and in 96.2% of patients in the PRG cohort (HR 1.6, 95% CI 0.55-4.9, p = 0.37). Hypopituitarism was associated with a maximum point dose of > 8 Gy to the pituitary stalk (HR 4.5, 95% CI 1.6-12.6, p = 0.004). No statistically significant difference was noted in crude new-onset hypopituitarism rates (risk difference [RD] = -0.8%, p > 0.99) or visual deficits (RD = -2.3%, p = 0.21) between the two cohorts at the last follow-up. The median time from resection to new hypopituitarism was longer in the PRG cohort (58.9 vs 29.7 months, p = 0.01). CONCLUSIONS: SRS at residual NFPA progression does not appear to alter the probability of tumor control or hormonal/visual deficits compared with adjuvant SRS. Deferral of radiosurgical management to the time of radiological progression could significantly prolong the time to radiosurgically induced pituitary dysfunction. A lower maximum point dose (< 8 Gy) to the pituitary stalk portended a more favorable chance of preserving pituitary function after SRS.

Factors associated with progression and mortality among patients undergoing stereotactic radiosurgery for intracranial metastasis: results from a national real-world registry.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been increasingly employed in recent years to treat intracranial metastatic lesions. However, there is still a need for optimization of treatment paradigms to provide better local control and prevent progressive intracranial disease. In the current study, the authors utilized a national collaborative registry to investigate the outcomes of patients with intracranial metastatic disease who underwent SRS and to determine factors associated with lesion treatment response, overall progression, and mortality. METHODS: The NeuroPoint Alliance SRS registry was queried for all patients with intracranial metastatic lesions undergoing single- or multifraction SRS at participating institutions between 2016 and 2020. The main outcomes of interest included lesion response (lesion-level analysis), progression using Response Assessment for Neuro-Oncology criteria, and mortality (patient-level analysis). Kaplan-Meier analysis was used to report time to progression and overall survival, and multivariable Cox proportional hazards analysis was used to investigate factors associated with lesion response, progression, and mortality. RESULTS: A total of 501 patients (1447 intracranial metastatic lesions) who underwent SRS and had available follow-up were included in the current analyses. The most common primary tumor was lung cancer (49.5%, n = 248), followed by breast (15.4%, n = 77) and melanoma (12.2%, n = 61). Most patients had a single lesion (44.9%, n = 225), 29.3% (n = 147) had 2 or 3 lesions, and 25.7% (n = 129) had > 3 lesions. The mean sum of baseline measurements of the lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) was 35.54 mm (SD 25.94). At follow-up, 671 lesions (46.4%) had a complete response, 631 (43.6%) had a partial response (≥ 30% decrease in longest diameter) or were stable (< 30% decrease but < 20% increase), and 145 (10%) showed progression (> 20% increase in longest diameter). On multivariable Cox proportional hazards analysis, melanoma-associated lesions (HR 0.48, 95% CI 0.34-0.67; p < 0.001) and larger lesion size (HR 0.94, 95% CI 0.93-0.96; p < 0.001) showed lower odds of lesion regression, while a higher biologically effective dose was associated with higher odds (HR 1.001, 95% CI 1.0001-1.00023; p < 0.001). A total of 237 patients (47.3%) had overall progression (local failure or intracranial progressive disease), with a median time to progression of 10.03 months after the index SRS. Factors found to be associated with increased hazards of progression included male sex (HR 1.48, 95% CI 1.108-1.99; p = 0.008), while administration of immunotherapy (before or after SRS) was found to be associated with lower hazards of overall progression (HR 0.62, 95% CI 0.460-0.85; p = 0.003). A total of 121 patients (23.95%) died during the follow-up period, with a median survival of 19.4 months from the time of initial SRS. A higher recursive partitioning analysis score (HR 21.3485, 95% CI 1.53202-3.6285; p < 0.001) was found to be associated with higher hazards of mortality, while single-fraction treatment compared with hypofractionated treatment (HR 0.082, 95% CI 0.011-0.61; p = 0.015), administration of immunotherapy (HR 0.385, 95% CI 0.233-0.64; p < 0.001), and presence of single compared with > 3 lesions (HR 0.427, 95% CI 0.187-0.98; p = 0.044) were found to be associated with lower risk of mortality. CONCLUSIONS: The comparability of results between this study and those of previously published clinical trials affirms the value of multicenter databases with real-world data collected without predetermined research purpose.

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS: This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS: The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006). CONCLUSIONS: SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Clinical and radiologic outcomes after stereotactic radiosurgery for meningiomas in direct contact with the optic apparatus: an international multicenter study.

OBJECTIVE: Resection of meningiomas in direct contact with the anterior optic apparatus carries risk of injury to the visual pathway. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative. However, its use is limited owing to the risk of radiation-induced optic neuropathy. Few SRS studies have specifically assessed the risks and benefits of treating meningiomas in direct contact with the optic nerve, chiasm, or optic tract. The authors hypothesized that SRS is safe for select patients with meningiomas in direct contact with the anterior optic apparatus. METHODS: The authors performed an international multicenter retrospective analysis of 328 patients across 11 institutions. All patients had meningiomas in direct contract with the optic apparatus. Patients were followed for a median duration of 56 months after SRS. Neurological examinations, including visual function evaluations, were performed at follow-up visits. Clinical and treatment variables were collected at each site according to protocol. Tumor volumes were assessed with serial MR imaging. Variables predictive of visual deficit were identified using univariable and multivariable logistic regression. RESULTS: SRS was the initial treatment modality for 64.6% of patients, and 93% of patients received SRS as a single fraction. Visual information was available for 302 patients. Of these patients, visual decline occurred in 29 patients (9.6%), of whom 12 (41.4%) had evidence of tumor progression. Visual decline in the remaining 17 patients (5.6%) was not associated with tumor progression. Pre-SRS Karnofsky Performance Status predicted visual decline in adjusted analysis (adjusted OR 0.9, 95% CI 0.9-1.0, p < 0.01). Follow-up imaging data were available for 322 patients. Of these patients, 294 patients (91.3%) had radiographic evidence of stability or tumor regression at last follow up. Symptom duration was associated with tumor progression in adjusted analysis (adjusted OR 1.01, adjusted 95% CI 1.0-1.02, adjusted p = 0.02). CONCLUSIONS: In this international multicenter study, the vast majority of patients exhibited tumor control and preservation of visual function when SRS was used to treat meningioma in direct contact with the anterior optic pathways. SRS is a relatively safe treatment modality for select patients with perioptic meningiomas in direct contact with the optic apparatus.

Stereotactic radiosurgery for glioblastoma considering tumor genetic profiles: an international multicenter study.

OBJECTIVE: Molecular profiles, such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) methylation status, have important prognostic roles for glioblastoma patients. The authors studied the efficacy and safety of stereotactic radiosurgery (SRS) for glioblastoma patients with consideration of molecular tumor profiles. METHODS: For this retrospective observational multiinstitutional study, the authors pooled consecutive patients who were treated using SRS for glioblastoma at eight institutions participating in the International Radiosurgery Research Foundation. They evaluated predictors of overall and progression-free survival with consideration of IDH mutation and MGMT methylation status. RESULTS: Ninety-six patients (median age 56 years) underwent SRS (median dose 15 Gy and median treatment volume 5.53 cm3) at 147 tumor sites (range 1 to 7). The majority of patients underwent prior fractionated radiation therapy (92%) and temozolomide chemotherapy (98%). Most patients were treated at recurrence (85%), and boost SRS was used for 12% of patients. The majority of patients harbored IDH wild-type (82%) and MGMT-methylated (62%) tumors. Molecular data were unavailable for 33 patients. Median survival durations after SRS were similar between patients harboring IDH wild-type tumors and those with IDH mutant tumors (9.0 months vs 11 months, respectively), as well as between those with MGMT-methylated tumors and those with MGMT-unmethylated tumors (9.8 vs. 9.0 months, respectively). Prescription dose > 15 Gy (OR 0.367, 95% CI 0.190-0.709, p = 0.003) and treatment volume > 5 cm3 (OR 1.036, 95% CI 1.007-1.065, p = 0.014) predicted overall survival after controlling for age and IDH status. Treatment volume > 5 cm3 (OR 2.215, 95% CI 1.159-4.234, p = 0.02) and absence of gross-total resection (OR 0.403, 95% CI 0.208-0.781, p = 0.007) were associated with inferior local control of SRS-treated lesions in multivariate models. Nine patients experienced adverse radiation events after SRS, and 7 patients developed radiation necrosis at 59 to 395 days after SRS. CONCLUSIONS: Post-SRS survival was similar as a function of IDH mutation and MGMT promoter methylation status, suggesting that molecular profiles of glioblastoma should be considered when selecting candidates for SRS. SRS prescription dose > 15 Gy and treatment volume ≤ 5 cm3 were associated with longer survival, independent of age and IDH status. Prior gross-total resection and smaller treatment volume were associated with superior local control.