Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients With Multiple Sclerosis: A Multicenter Study.

BACKGROUND: Facial pain response (PR) to various surgical interventions in patients with multiple sclerosis (MS)-related trigeminal neuralgia (TN) is much less optimal. No large patient series regarding stereotactic radiosurgery (SRS) has been published. OBJECTIVE: To evaluate the clinical outcomes of MS-related TN treated with SRS. METHODS: This is a retrospective cohort study. A total of 263 patients contributed by 9 member tertiary referral Gamma Knife centers (2 in Canada and 7 in USA) of the International Gamma Knife Research Consortium (IGKRF) constituted this study. RESULTS: The median latency period of PR after SRS was 1 mo. Reasonable pain control (Barrow Neurological Institute [BNI] Pain Scores I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rates at 1 yr, 2 yr, and 4 yr were 54%, 35%, and 24%, respectively. There was a correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 mo and 12.2 mo in patients achieving BNI-I and BNI > I, respectively (P = .046). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%). CONCLUSION: In this largest series SRS offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control.

The effect of timing of stereotactic radiosurgery treatment of melanoma brain metastases treated with ipilimumab.

OBJECTIVE Melanoma represents the third most common cause of CNS metastases. Immunotherapy has evolved as a treatment option for patients with Stage IV melanoma. Stereotactic radiosurgery (SRS) also elicits an immune response within the brain and may interact with immunotherapy. The authors report on a cohort of patients treated for brain metastases with immunotherapy and evaluate the effect of SRS timing on the intracranial response. METHODS All consecutively treated melanoma patients receiving ipilimumab and SRS for treatment of brain metastases at the University of Virginia between 2009 and 2014 were included in this retrospective analysis; data from 46 patients harboring 232 brain metastases were reviewed. The median duration of clinical follow-up was 7.9 months (range 3-42.6 months). The median age of the patients was 63 years (range 24.3-83.6 years). Thirty-two patients received SRS before or during ipilimumab cycles (Group A), whereas 14 patients received SRS after ipilimumab treatment (Group B). Radiographic and clinical responses were assessed at approximately 3-month intervals after SRS. RESULTS The 2 cohorts were comparable in pertinent baseline characteristics with the exception of SRS timing relative to ipilimumab. Local recurrence-free duration (LRFD) was significantly longer in Group A (median 19.6 months, range 1.1-34.7 months) than in Group B patients (median 3 months, range 0.4-20.4 months) (p = 0.002). Post-SRS perilesional edema was more significant in Group A. CONCLUSIONS The effect of SRS and ipilimumab on LRFD seems greater when SRS is performed before or during ipilimumab treatments. The timing of immunotherapy and SRS may affect LRFD and postradiosurgical edema. The interactions between immunotherapy and SRS warrant further investigation so as to optimize the therapeutic benefits and mitigate the risks associated with multimodality, targeted therapy.

BRAF V600E mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases.

OBJECTIVE Recent advancements in molecular biology have identified the BRAF mutation as a common mutation in melanoma. The wide use of BRAF kinase inhibitor ( BRAFi) in patients with metastatic melanoma has been established. The objective of this study was to examine the impact of BRAF mutation status and use of BRAFi in conjunction with stereotactic radiosurgery (SRS). METHODS This was a single-center retrospective study. Patient's charts and electronic records were reviewed for date of diagnosis of primary malignancy, BRAF mutation status, chemotherapies used, date of the diagnosis of CNS metastases, date of SRS, survival, local tumor control after SRS, and adverse events. Patients were divided into 3 groups: Group A, those with mutant BRAF without BRAFi treatment (13 patients); Group B, those with mutant BRAF with BRAFi treatment (17 patients); and Group C, those with wild-type BRAF (35 patients). Within a cohort of 65 patients with the known BRAF mutation status and treated with SRS between 2010 and 2014, 436 individual brain metastases (BMs) were identified. Kaplan-Meier methodology was then used to compare survival based on each binary parameter. RESULTS Median survival times after the diagnosis of melanoma BM and after SRS were favorable in patients with a BRAF mutation and treated with SRS in conjunction with BRAFi (Group B) compared with the patients with wild-type BRAF (Group C, 23 vs 8 months and 13 vs 5 months, respectively; p < 0.01, log-rank test). SRS provided a local tumor control rate of 89.4% in the entire cohort of patients. Furthermore, the local control rate was improved in the patients treated with SRS in conjunction with BRAFi (Group B) compared with patients with wild-type (Group C) or with BRAF mutation but no BRAFi (Group A) as an adjunct treatment for BMs. CONCLUSIONS BRAF mutation status appears to play an important role as a potent prognostic factor in patients harboring melanoma BM. BRAFi in conjunction with SRS may benefit this group of patients in terms of BM survival and SRS with an acceptable safety profile.

Worse Outcomes After Repeat vs Initial Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations: A Retrospective Matched-Cohort Study.

BACKGROUND: Incompletely obliterated cerebral arteriovenous malformations (AVMs) after initial treatment with stereotactic radiosurgery (SRS) can be treated with a repeat session of SRS. However, the relative efficacy of repeat vs initial SRS is not well specified. OBJECTIVE: To retrospectively compare in matched cohorts the outcomes of repeat vs initial SRS for the treatment of matched cohorts with angioarchitecturally similar AVMs. METHODS: We studied a data set of patients with AVM treated with radiosurgery during the period spanning 1989 to 2013. Patients with AVM who underwent repeat SRS with radiologic follow-up of ≥2 years or nidus obliteration were identified for the study and matched, in a 1:1 fashion that was blinded to outcome, to patients with previously untreated AVMs who underwent initial SRS. Statistical analyses were performed to compare the outcomes after repeat vs initial SRS. RESULTS: The matching approach resulted in 84 patients for the repeat and the initial SRS cohort (mean margin doses, 20.7 and 20.9 Gy, respectively; P = .74). In the repeat SRS cohort, obliteration was achieved in 67%; the radiologic, symptomatic, and permanent radiation-induced change rates were 35%, 10%, and 4%, respectively; and the post-SRS hemorrhage rate was 3.1%/y. Compared with the initial SRS cohort, the repeat SRS cohort had significantly lower obliteration rates (P = .04) and higher post-SRS hemorrhage rates (P = .04). The radiation-induced change rates of the 2 cohorts were not significantly different. CONCLUSION: Repeat SRS yields considerably poorer outcomes than initial SRS for angioarchitecturally comparable AVMs. Further studies in AVM radiobiology and vascular structure are necessary to elucidate this potentially differential response. ABBREVIATIONS: AVM, arteriovenous malformationRIC, radiation-induced changeRBAS, radiosurgery-based arteriovenous malformation scoreSRS, stereotactic radiosurgeryVRAS, virginia radiosurgery AVM scale.

Radiosurgery for Cerebral Arteriovenous Malformations with Associated Arterial Aneurysms.

OBJECTIVE: The radiosurgical outcomes for cerebral arteriovenous malformations (AVM) with AVM-associated arterial aneurysms (AAA) are poorly understood, because many AAAs are embolized before nidal intervention. The aim of this retrospective case-control study is to determine the effect of AAAs on AVM radiosurgery outcomes. METHODS: We evaluated an institutional AVM radiosurgery database from 1989 to 2013. AAAs were classified as intranidal (type I) or prenidal (type II). The case cohort comprised AVMs with patent type I or II AAAs. The control cohort comprised AVMs without AAAs and matched 2:1 to the case cohort. RESULTS: The case cohort comprised 51 AVMs, including 23 with type I and 28 with type II AAAs. The control cohort comprised 102 AVMs without AAAs. The cumulative AVM obliteration, annual postradiosurgery hemorrhage, and radiologically evident radiation-induced changes rates were 67%, 3.3%, and 28%, respectively, for the case cohort, compared with 70%, 2.0%, and 35%, respectively, for the control cohort. The presence of an AAA was not significantly associated with obliteration (P = 0.293), postradiosurgery hemorrhage (P = 0.209), or radiation-induced changes (P = 0.323). The rates of type II AAA occlusion at 3, 5, and 10 years were 46%, 77%, and 95%, respectively. The type II AAA occlusion rate was significantly higher in obliterated AVMs (P = 0.002). CONCLUSIONS: Patent intranidal or prenidal AAAs do not significantly affect AVM radiosurgical outcomes. Occlusion of distal prenidal AAAs commonly occurs after radiosurgery. These findings may support a more conservative stance for embolization before radiosurgery for AVMs with AAAs.

Stereotactic Radiosurgery for Partially Resected Cerebral Arteriovenous Malformations.

OBJECTIVE: Incomplete microsurgical resection of cerebral arteriovenous malformations (AVM) occurs uncommonly. However, such patients harboring postoperative residual nidi remain exposed to the risk of AVM hemorrhage and are therefore reasonable candidates for further intervention. The goals of this retrospective case-control study are to analyze the radiosurgery outcomes for partially resected AVMs and determine the effect of prior resection on AVM radiosurgery outcomes. METHODS: We evaluated a prospective database of AVM patients treated with radiosurgery from 1989-2013. Previously resected AVMs with radiologic follow-up ≥2 years or nidus obliteration were selected for analysis and matched, in a 1:1 fashion and blinded to outcome, to previously unresected AVMs. Statistical analyses were performed to assess relationship between prior resection and AVM radiosurgery outcomes. RESULTS: The matching process yielded 88 patients in each of the previously resected and unresected AVM cohorts. In the resected AVM cohort, the actuarial AVM obliteration rates at 3 and 5 years were 47% and 75%, respectively; the rates of radiologic and symptomatic radiation-induced changes (RICs) were 10% and 3%, respectively; and the annual postradiosurgery hemorrhage risk was 1.1%. The lack of prior AVM resection (P < 0.001) and superficial AVM location (P = 0.009) were independent predictors of radiologic RIC. The actuarial rates of obliteration (P = 0.849) and postradiosurgery hemorrhage (P = 0.548) were not significantly different between the resected and unresected AVM cohorts. CONCLUSIONS: Radiosurgery affords a reasonable risk-to-benefit profile for incompletely resected AVMs. For those with a small-volume residual nidus after resection, radiosurgery should be considered an effective alternative to repeat resection.