Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in patients ≥ 65 years old: a multi-institutional retrospective study.

BACKGROUND: Surgery is the preferred treatment for large vestibular schwannomas (VS). Good tumor control and cranial nerve outcomes were described in selected Koos IV VS after single-session stereotactic radiosurgery (SRS), but outcomes in elderly patients have never been specifically studied. The aim of this study is to report clinical and radiological outcomes after single-session SRS for Koos IV VS in patients ≥ 65 years old. METHOD: This multicenter, retrospective study included patients ≥ 65 years old, treated with primary, single-session SRS for a Koos IV VS, and at least 12 months of follow-up. Patients with life-threatening or incapacitating symptoms were excluded. Tumor control rate, hearing, trigeminal, and facial nerve function were studied at last follow-up. RESULTS: One-hundred and fifty patients (median age of 71.0 (IQR 9.0) years old with a median tumor volume of 8.3 cc (IQR 4.4)) were included. The median prescription dose was 12.0 Gy (IQR 1.4). The local tumor control rate was 96.0% and 86.2% at 5 and 10 years, respectively. Early tumor expansion occurred in 6.7% and was symptomatic in 40% of cases. A serviceable hearing was present in 16.1% prior to SRS and in 7.4% at a last follow-up of 46.5 months (IQR 55.8). The actuarial serviceable hearing preservation rate was 69.3% and 50.9% at 5 and 10 years, respectively. Facial nerve function preservation or improvement rates at 5 and 10 years were 98.7% and 91.0%, respectively. At last follow-up, the trigeminal nerve function was improved in 14.0%, stable in 80.7%, and worsened in 5.3% of the patients. ARE were noted in 12.7%. New hydrocephalus was seen in 8.0% of patients. CONCLUSION: SRS can be a safe alternative to surgery for selected Koos IV VS in patients ≥ 65 years old. Further follow-up is warranted.

Stereotactic radiosurgery versus active surveillance for asymptomatic, skull-based meningiomas: an international, multicenter matched cohort study.

OBJECTIVE: The optimal management of asymptomatic, skull-based meningiomas is not well defined. The aim of this study is to compare the imaging and clinical outcomes of patients with asymptomatic, skull-based meningiomas managed either with upfront stereotactic radiosurgery (SRS) or active surveillance. METHODS: This retrospective, multicenter study involved patients with asymptomatic, skull-based meningiomas. The study end-points included local tumor control and the development of new neurological deficits attributable to the tumor. Factors associated with tumor progression and neurological morbidity were also analyzed. RESULTS: The combined unmatched cohort included 417 patients. Following propensity score matching for age, tumor volume, and follow-up 110 patients remained in each cohort. Tumor control was achieved in 98.2% and 61.8% of the SRS and active surveillance cohorts, respectively. SRS was associated with superior local tumor control (p < 0.001, HR = 0.01, 95% CI = 0.002-0.13) compared to active surveillance. Three patients (2.7%) in the SRS cohort and six (5.5%) in the active surveillance cohort exhibited neurological deterioration. One (0.9%) patient in the SRS-treated and 11 (10%) patients in the active surveillance cohort required surgical management of their meningioma during follow-up. CONCLUSIONS: SRS is associated with superior local control of asymptomatic, skull-based meningiomas as compared to active surveillance and does so with low morbidity rates. SRS should be offered as an alternative to active surveillance as the initial management of asymptomatic skull base meningiomas. Active surveillance policies do not currently specify the optimal time to intervention when meningioma growth is noted. Our results indicate that if active surveillance is the initial management of choice, SRS should be recommended when radiologic tumor progression is noted and prior to clinical progression.

Stereotactic radiosurgery versus active surveillance for incidental, convexity meningiomas: a matched cohort analysis from the IMPASSE study.

BACKGROUND: The optimal treatment strategy of asymptomatic, convexity meningiomas, remains unclear. OBJECTIVE: The purpose of this study was to define the safety and efficacy of stereotactic radiosurgery (SRS) in the management of patients with asymptomatic convexity meningiomas. METHODS: Data of SRS-treated patients from 14 participating centers and patients managed conservatively for an asymptomatic, convexity-located meningioma were compared. Local tumor control rate and development of new neurologic deficits were evaluated in the active surveillance and in the SRS-treated cohorts. RESULTS: In the unmatched cohorts, there were 99 SRS-treated patients and 140 patients managed conservatively for an asymptomatic, convexity meningioma. Following propensity score matching for age, there were 98 patients in each cohort. In the matched cohorts, tumor control was achieved in 99% of SRS-treated, and in 69.4% of conservatively managed patients (p < 0.001). New neurological deficits occurred in 2.0% of patients in each of the matched cohorts (p = 1.00). Increasing age was predictive of tumor growth [(OR 1.1; 95% CI (1.04 - 1.2), (p < 0.001)]. CONCLUSION: This is one of the first reports to suggest that SRS is a low risk and effective treatment strategy for asymptomatic incidentally discovered convexity meningiomas. In this study, tumor control was achieved in significantly more patients after radiosurgery compared to those managed with active surveillance. SRS may be offered at diagnosis of an asymptomatic convexity meningioma and should be recommended when meningioma growth is noted on follow-up.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in young patients: a multi-institutional study.

PURPOSE: Surgery is the treatment of choice for large vestibular schwannomas (VS). Stereotactic radiosurgery (SRS) has been suggested as an alternative to resection in selected patients. However, the safety and efficacy of SRS in Koos grade IV patients ≤ 45 years old has not been evaluated. The aim of this study is to describe the clinical and radiological outcomes of Koos grade IV in young patient managed with a single-session SRS. METHODS: This retrospective, multicenter analysis included SRS-treated patients, ≤ 45 years old presenting with non-life threatening or incapacitating symptoms due to a Koos Grade IV VS and with follow-up ≥ 12 months. Tumor control and neurological outcomes were evaluated. RESULTS: 176 patients [median age of 36.0 (IQR 9) and median tumor volume of 9.3 cm3 (IQR 4.7)] were included. The median prescription dose was 12 Gy (IQR 0.5). Median follow-up period was 37.5 (IQR 53.5) months. The 5- and 10-year progression-free survival was 90.9% and 86.7%. Early tumor enlargement occurred in 10.9% of cases and was associated with tumor progression at the last follow-up. The probability of serviceable hearing preservation at 5- and 10-years was 56.8% and 45.2%, respectively. The probability of improvement or preservation of facial nerve function was 95.7% at 5 and 10-years. Adverse radiation effects were noted in 19.9%. New-onset hydrocephalus occurred in 4.0%. CONCLUSION: Single-session SRS is a safe and effective alternative to surgical resection in selected patients ≤ 45 years old particularly those with medical co-morbidities and those who decline resection. Longer term follow up is warranted.

Stereotactic radiosurgery for asymptomatic petroclival region meningiomas: a focused analysis from the IMPASSE study.

BACKGROUND: The optimal management of asymptomatic, petroclival meningiomas remains incompletely defined. The purpose of this study was to evaluate the safety and efficacy of upfront stereotactic radiosurgery (SRS) for patients with asymptomatic, petroclival region meningiomas. METHODS: This retrospective, international, multicenter study involved patients treated with SRS for an asymptomatic, petroclival region meningioma. Study endpoints included local tumor control rate, procedural complications, and the emergence of new neurological deficits. RESULTS: There were 72 patients (22 males, mean age 59.53 years (SD ± 11.9)) with an asymptomatic meningioma located in the petroclival region who were treated with upfront SRS. Mean margin dose and maximum dose were 13.26 (SD ± 2.72) Gy and 26.14 (SD ± 6.75) Gy respectively. Median radiological and clinical follow-up periods post-SRS were 52.5 (IQR 61.75) and 47.5 months (IQR 69.75) respectively. At last follow-up, tumor control was achieved in all patients. SRS-related complications occurred in 6 (8.33%) patients, with 3 of them (4.17%) exhibiting new neurological deficits. CONCLUSIONS: Upfront SRS for asymptomatic, petroclival region meningiomas affords excellent local tumor control and does so with a relatively low risk of SRS-related complications. SRS can be considered at diagnosis of an asymptomatic petroclival region meningioma. If active surveillance is initially chosen, SRS should be recommended when growth is noted during radiological follow-up.

Radiosurgery for Arteriovenous Malformations and the Impact on Headaches.

BACKGROUND: Arteriovenous malformations (AVMs) can underlie many diverse neurological signs and symptoms. Headaches are a common presentation that can have a significant impact on quality of life. OBJECTIVE: The authors investigated Gamma Knife® stereotactic radiosurgery (SRS) outcomes in patients with AVMs and associated headaches. METHODS: This retrospective study analyzed 102 patients with AVMs who underwent SRS between 1995 and 2013. The patient's headache symptoms led to their AVM diagnosis or developed post hemorrhage of their AVM. Information regarding headache characteristics was obtained from the patient's medical records and at follow-up using a scripted clinical interview. The median imaging follow-up was 61.7 months and clinical follow-up was 89.7 months. The median treatment volume at SRS was 4.1 cm3 and the median marginal dose was 20 Gy. RESULTS: The actuarial AVM obliteration rate was 60% at 5 years and 78% at 10 years. Patients reported that their overall headache severity decreased by -43.6% and their headache frequency was reduced by -53.4%. Headache reduction was reported in 49.1% of patients at 1 year and 69.5% at 5 years. The median time until improvement was 6.5 months. After SRS, headache medication usage decreased in 29% of patients. Permanent adverse radiation effects after SRS occurred in 3% of patients. Until obliteration was complete, the annual risk of a hemorrhage after SRS was 0.4% per year. CONCLUSION: Although recall bias related to a retrospective analysis can impact outcomes, headache symptoms associated with AVMs may potentially be decreased or eliminated in a subset of patients treated with Gamma Knife radiosurgery.

Gamma knife radiosurgery for management of cerebral metastases from esophageal carcinoma.

Esophageal carcinoma rarely results in intracranial metastases but when it does, the patient prognosis is grim. Because of its rarity outcomes after stereotactic radiosurgery (SRS) are not known. We sought to evaluate the outcomes of SRS in the management of esophageal cancer that has spread to the brain. This single institution retrospective analysis reviewed our experience with esophageal metastasis from 1987 to 2013. Thirty patients (36 SRS procedures) with a median age of 59 (37-86 years) underwent Gamma knife(®) SRS. The esophageal origin was adenocarcinoma in 26 patients (87%), squamous cell carcinoma in 3 patients (10%), and mixed neuroendocrine carcinoma in 1 patient (3%). Fifteen patients were treated for a single metastasis and 15 patients were treated for multiple metastases for a total of 87 tumors. The median tumor volume was 5.7 cm(3) (0.5-44 cm(3)) with a median marginal dose of 17 Gy (12-20 Gy). The median survival time from the diagnosis of brain metastasis was 8 months and the median survival from SRS was 4.2 months. This corresponded to a 6-month survival of 45% and a 12-month survival of 19% after SRS. A higher KPS at the time of procedure was associated with an increase in survival (p = 0.023). The local tumor control rate in this group was 92%. Four patients had repeat SRS for new metastatic deposits. One patient developed a new neurological deficit after SRS. SRS proved an effective means of providing local control for esophageal metastases to the brain. Concomitant systemic disease progression at the time of brain metastasis resulted in poor long-term survival.

Integration of magnetoencephalography-generated functional brain maps into dose planning during arteriovenous malformation radiosurgery.

BACKGROUND: Magnetoencephalography (MEG) can delineate critical regions of the cortex and facilitate conformal stereotactic radiosurgery (SRS) dose planning. Despite the substantial role of Gamma Knife® SRS in arteriovenous malformation (AVM) management, MEG-generated maps of critical regions have never been utilized to improve dose planning. PURPOSE: To assess the value of integrating functional brain mapping using MEG with dose planning during treatment of brain AVMs with SRS. METHODS: This case series encompassed 5 patients with motor region AVMs. Noninvasive eloquent cortex mapping was achieved using a whole-head 306-channel Neuromag® Vectorview MEG System 5-10 days before SRS. On the day of SRS, the functional brain maps were integrated onto the intraoperative dose planning magnetic resonance imaging for Leksell GammaPlan® version 10. The median AVM volume treated was 12.7 cm(3), and 18 Gy was the median margin dose. RESULTS: Functional image integration of MEG improved the recognition of critical brain structures adjacent to the AVM. This facilitated anatomical planning designed to reduce the dose to adjacent critical structures while maintaining a therapeutic dose to the AVM target. The 5 patients had no adverse radiation effects during the follow-up. CONCLUSION: Coregistration of MEG data improves the accuracy and dose sparing needed for optimal planning during Gamma Knife SRS.

Intratumoral Hemorrhage in Vestibular Schwannomas After Stereotactic Radiosurgery: Multi-Institutional Study.

BACKGROUND AND OBJECTIVES: Intratumoral hemorrhage (ITH) in vestibular schwannoma (VS) after stereotactic radiosurgery (SRS) is exceedingly rare. The aim of this study was to define its incidence and describe its management and outcomes in this subset of patients. METHODS: A retrospective multi-institutional study was conducted, screening 9565 patients with VS managed with SRS at 10 centers affiliated with the International Radiosurgery Research Foundation. RESULTS: A total of 25 patients developed ITH (cumulative incidence of 0.26%) after SRS management, with a median ITH size of 1.2 cm 3 . Most of the patients had Koos grade II-IV VS, and the median age was 62 years. After ITH development, 21 patients were observed, 2 had urgent surgical intervention, and 2 were initially observed and had late resection because of delayed hemorrhagic expansion and/or clinical deterioration. The histopathology of the resected tumors showed typical, benign VS histology without sclerosis, along with chronic inflammatory cells and multiple fragments of hemorrhage. At the last follow-up, 17 patients improved and 8 remained clinically stable. CONCLUSION: ITH after SRS for VS is extremely rare but has various clinical manifestations and severity. The management paradigm should be individualized based on patient-specific factors, rapidity of clinical and/or radiographic progression, ITH expansion, and overall patient condition.

Risk of new tumor, carotid stenosis, and stroke after Stereotactic Radiosurgery for Pituitary Tumor: A multicenter study of 2254 patients with imaging follow-up.

BACKGROUND: Higher risk of secondary brain tumor, carotid stenosis and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion and stroke after SRS. METHODS: In this multicentric retrospective study, 2,254 patients with PitNET were studied, 1,377 in the exposed group and 877 in the control group. RESULTS: There were 9,840.1 patient-years at risk for the SRS and 5,266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95%CI:0.5%, 4.1%) for SRS and 3.7% (95%CI:0%, 8.7%) for the control group (p=0.6), with an incidence rate of 1.32 per 1,000 and 0.95 per 1,000, respectively. SRS was not associated with increased risk of tumorigenesis when stratified by age (HR: 1.59 [95%CI: 0.57, 4.47], p=0.38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95%CI: 0.2, 1.6) in the SRS and 2% (95%CI: 0, 4.4) in the control group (p=0.8). The 15-year probability of stroke was 2.6% (95%CI: 0.6%, 4.6%) in the SRS and 11.1% (95%CI: 6%, 15.9%) in the control group (p<0.001). In cox multivariate analysis stratified by age, SRS (HR 1.85[95%CI:0.64, 5.35], p=0.26) was not associated with risk of new stroke. CONCLUSION: No increased risk of long-term secondary brain tumor, new stenosis or occlusion and stroke was demonstrated in SRS group compared to control in this study with imaging surveillance.

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.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a multi-institutional study.

OBJECTIVE: Though stereotactic radiosurgery (SRS) is an established safe treatment for small- and medium-sized vestibular schwannomas (VSs), its role in the management of Koos grade IV VS is still unclear. In this retrospective multicenter study, the authors evaluated tumor control and the patient outcomes of primary, single-session SRS treatment for Koos grade IV VS. METHODS: This study included patients treated with primary, single-session SRS for Koos grade IV VS at 10 participating centers. Only those patients presenting with non-life-threatening or incapacitating symptoms and at least 12 months of clinical and neuroimaging follow-up were eligible for inclusion. Relevant data were collected, and the Kaplan-Meier method was used to perform time-dependent analysis for post-SRS tumor control, hearing preservation, and facial nerve function preservation. Univariate and multivariate analyses were performed for outcome measures using Cox regression analysis. RESULTS: Six hundred twenty-seven patients (344 females, median patient age 54 [IQR 22] years) treated with primary SRS were included in this study. The median tumor volume was 8.7 (IQR 5) cm3. Before SRS, serviceable hearing, facial nerve weakness (House-Brackmann grade > I), and trigeminal neuropathy were present in 205 (33%), 48 (7.7%), and 203 (32.4%) patients, respectively. The median prescription dose was 12 (IQR 1) Gy. At a median radiological follow-up of 38 (IQR 54) months, tumor control was achieved in 94.1% of patients. Early tumor expansion occurred in 67 (10.7%) patients and was associated with a loss of tumor control at the last follow-up (p = 0.001). Serviceable hearing preservation rates at the 5- and 10-year follow-ups were 65% and 44.6%, respectively. Gardner-Robertson class > 1 (p = 0.003) and cochlear dose ≥ 4 Gy (p = 0.02) were risk factors for hearing loss. Facial nerve function deterioration occurred in 19 (3.0%) patients at the last follow-up and was associated with margin doses ≥ 13 Gy (p = 0.03) and early tumor expansion (p = 0.04). Post-SRS, 33 patients developed hydrocephalus requiring shunting. Adverse radiation effects occurred in 92 patients and were managed medically or surgically in 34 and 18 cases, respectively. CONCLUSIONS: SRS is a safe and effective method of obtaining tumor control in patients with Koos grade IV VS presenting with non-life-threatening or debilitating symptoms, especially those with surgical comorbidities that contraindicate resection. To decrease the incidence of post-SRS facial palsy, a prescription dose < 13 Gy is recommended.

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.

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.

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.

Comparison of Active Surveillance to Stereotactic Radiosurgery for the Management of Patients with an Incidental Frontobasal Meningioma-A Sub-Analysis of the IMPASSE Study.

Meningioma is a common incidental finding, and clinical course varies based on anatomical location. The aim of this sub-analysis of the IMPASSE study was to compare the outcomes of patients with an incidental frontobasal meningioma who underwent active surveillance to those who underwent upfront stereotactic radiosurgery (SRS). Data were retrospectively collected from 14 centres. The active surveillance (n = 28) and SRS (n = 84) cohorts were compared unmatched and matched for age, sex, and duration of follow-up (n = 25 each). The study endpoints included tumor progression, new symptom development, and need for further intervention. Tumor progression occurred in 52.0% and 0% of the matched active surveillance and SRS cohorts, respectively (p < 0.001). Five patients (6.0%) treated with SRS developed treatment related symptoms compared to none in the active monitoring cohort (p = 0.329). No patients in the matched cohorts developed symptoms attributable to treatment. Three patients managed with active surveillance (10.7%, unmatched; 12.0%, matched) underwent an intervention for tumor growth with no persistent side effects after treatment. No patients subject to SRS underwent further treatment. Active monitoring and SRS confer a similarly low risk of symptom development. Upfront treatment with SRS improves imaging-defined tumor control. Active surveillance and SRS are acceptable treatment options for incidental frontobasal meningioma.

Stereotactic Radiosurgery Compared With Active Surveillance for Asymptomatic, Parafalcine, and Parasagittal Meningiomas: A Matched Cohort Analysis From the IMPASSE Study.

BACKGROUND: The optimal management of asymptomatic, presumed WHO grade I meningiomas remains controversial. OBJECTIVE: To define the safety and efficacy of stereotactic radiosurgery (SRS) compared with active surveillance for the management of patients with asymptomatic parafalcine/parasagittal (PFPS) meningiomas. METHODS: Data from SRS-treated patients from 14 centers and patients managed conservatively for an asymptomatic, PFPS meningioma were compared. Local tumor control rate and new neurological deficits development were evaluated in the active surveillance and the SRS-treated cohorts. RESULTS: There were 173 SRS-treated patients and 98 patients managed conservatively in the unmatched cohorts. After matching for patient age and tumor volume, there were 98 patients in each cohort. The median radiological follow-up period was 43 months for the SRS cohort and 36 months for the active surveillance cohort (P = .04). The median clinical follow-up for the SRS and active surveillance cohorts were 44 and 36 months, respectively. Meningioma control was noted in all SRS-treated patients and in 61.2% of patients managed with active surveillance (P < .001). SRS-related neurological deficits occurred in 3.1% of the patients (n = 3), which were all transient. In the active surveillance cohort, 2% of patients (n = 2) developed neurological symptoms because of tumor progression (P = 1.0), resulting in death of 1 patient (1%). CONCLUSION: Up-front SRS affords superior radiological PFPS meningioma control as compared with active surveillance and may lower the risk of meningioma-related permanent neurological deficit and/or death.

An international multicenter matched cohort analysis of incidental meningioma progression during active surveillance or after stereotactic radiosurgery: the IMPASSE study.

BACKGROUND: The optimal management of patients with incidental meningiomas remains unclear. The aim of this study was to characterize the radiologic and neurological outcomes of expectant and stereotactic radiosurgery (SRS) management of asymptomatic meningioma patients. METHODS: Using data from 14 centers across 10 countries, the study compares SRS outcomes to active surveillance of asymptomatic meningiomas. Local tumor control of asymptomatic meningiomas and development of new neurological deficits attributable to the tumor were evaluated in the SRS and conservatively managed groups. RESULTS: In the unmatched cohorts, 727 meningioma patients underwent SRS and were followed for a mean of 57.2 months. In the conservatively managed cohort, 388 patients were followed for a mean of 43.5 months. Tumor control was 99.0% of SRS and 64.2% of conservatively managed patients (P < .001; OR 56.860 [95% CI 26.253-123.150]). New neurological deficits were 2.5% in the SRS and 2.8% of conservatively managed patients (P = .764; OR 0.890 [95% CI 0.416-1.904]). After 1:1 propensity matching for patient age, tumor volume, location, and imaging follow-up, tumor control in the SRS and conservatively managed cohorts was 99.4% and 62.1%, respectively (P < .001; OR 94.461 [95% CI 23.082-386.568]). In matched cohorts, new neurological deficits were noted in 2.3% of SRS-treated and 3.2% of conservatively managed patients (P = .475; OR 0.700 [95% CI 0.263-1.863]). CONCLUSIONS: SRS affords superior radiologic tumor control compared to active surveillance without increasing the risk of neurological deficits in asymptomatic meningioma patients. While SRS and active surveillance are reasonable options, SRS appears to alter the natural history of asymptomatic meningiomas including tumor progression in the majority of patients treated.

Gamma Knife Radiosurgery for the Management of More Than 15 Cerebral Metastases.

BACKGROUND: The number of metastases that can be treated safely and effectively with Gamma Knife stereotactic radiosurgery (SRS) remains controversial despite continuing evidence to support its expanded utilization. We endeavored to elucidate the survival outcomes for patients who presented with ≥15 brain metastases at the time of initial SRS. METHODS: This retrospective analysis reviewed patients treated for ≥15 brain metastases originating from breast cancer, lung cancer, or melanoma. Ninety-three patients met the inclusion criteria. In this study, 3016 tumors were treated. The median number of tumors at the first SRS procedure was 23 (range, 15-67) for breast cancer, 21 (range, 15-48) for lung cancer, and 21 (range, 15-67) for melanoma. The mean aggregate metastases volume was 8.75 cm3 for breast, 6.89 cm3 for lung, and 9.98 cm3 for melanoma. RESULTS: Patients with breast cancer, lung cancer, and melanoma had a median survival after diagnosis of brain metastases of 18.0, 9.4, and 6.3 months, respectively. The survival after SRS was 16 months for breast cancer, 4.6 months for lung cancer, and 3.1 months for melanoma. Patients with breast cancer had significantly longer survival than patients with lung cancer and melanoma after SRS (P = 0.001). A higher Karnofsky Performance Status score was associated with an increase in survival across all tumor types. Repeat SRS for local or distant progression was performed in 56% of patients with breast cancer, 35% of patients with lung cancer, and 24% of patients with melanoma. CONCLUSIONS: SRS is an effective means of managing extensive brain metastases, particularly in patients with breast cancer. The primary tumor type, systemic disease, and performance status heavily influence survival outcomes.