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MO_2_2498 - Outcomes in BRAFV600e-mutant melanoma brain metastases managed with radiosurgery: a multi-institutional assessment of craniotomy mitigation

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Outcomes in BRAFV600e-mutant melanoma brain metastases managed with radiosurgery: a multi-institutional assessment of craniotomy mitigation
S. Dajani1, C. D. Abraham Jr2, J. Huang2, P. W. Sperduto3, J. A. Sosman4, S. Chandra4, C. G. Robinson2, S. Acharya5, I. B. Helenowski6, O. Bloch7, and T. J. Kruser8; 1Rosalind Franklin University of Medicine and Science, North Chicago, IL, 2Washington University School of Medicine, Department of Radiation Oncology, St. Louis, MO, 3Gamma Knife Center, University of Minnesota Medical Center, Minneapolis, MN, 4Northwestern University Lurie Cancer Center, Chicago, IL, 5Washington University in St. Louis, Department of Radiation Oncology, Saint Louis, MO, St. Louis, MO, 6Department of Preventive Medicine, Division of Biostatistics, Northwestern University, Chicago, IL, 7Department of Neurological Surgery, Northwestern University Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 8Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL

Purpose/Objective(s): Recent clinical trials have demonstrated clinical activity of primary medical therapy in BRAFV600e-mutant melanoma brain metastases. However, complications of local progression such as craniotomy rates have been underreported in these studies. We hypothesized that early utilization of radiosurgery may be associated with improved outcomes in this patient population.

Materials/Methods: An IRB-approved retrospective review of BRAFV600e-mutant melanoma brain metastases treated with stereotactic radiosurgery (SRS) was conducted at two tertiary academic centers. Survival analyses were performed using Kaplan–Meier methods. Cox regression analyses were used to identify prognostic factors related to overall survival. All time to events were calculated from the date of radiosurgery.

Results: A total of 49 patients with BRAFV600e-mutant melanoma brain metastases were treated between February 2010 and October 2017. Forty patients (81.6%) received a BRAF inhibitor, 23 (47%) received anti-CTLA4 therapy, and 17 (35%) were treated with anti-PD-1 therapy; only 5 (10%) received combined checkpoint inhibition. Twenty-five patients received SRS prior to receiving systemic therapy; 12 of these SRS cases were post-operative after upfront craniotomy for first presentation of metastatic disease. The actuarial one-year overall survival from SRS for the cohort was 55.4%. Age, KPS, craniotomy, local failure, number of targets, and radiation necrosis were not associated with overall survival. One-year distant brain failure rate was 58% and was negatively associated with overall survival (p=0.01). Median time from brain metastases diagnosis to radiosurgery was 29 days, and patients with an interval to radiosurgery longer than the median had an inferior one-year survival (39.8%) compared to patients with early radiosurgery (73.8%; p=0.02). Twenty-six patients (53%) of patients underwent a craniotomy at some point in their clinical course. Twelve patients (46%) were on systemic therapy at the time of their craniotomies, including five patients on BRAF-directed therapy. Three patients managed with systemic therapy for known brain metastases in lieu of SRS progressed to require craniotomy before SRS was utilized at a median of 155 (range 62-409) days. Eight patients required craniotomy after SRS; the 6- and 12- month rates of craniotomy after SRS were 11% and 16% respectively. Five patients required a 2nd craniotomy procedure, all after preceding SRS.

Conclusion: Craniotomy is a common procedure in patients with brain metastases from BRAFV600e-mutant melanoma. Early utilization of SRS may be associated with improved oncologic outcomes while the craniotomy rate after SRS appears modest. Approaches that attempt to defer SRS in melanoma patients should be tested in randomized studies, with close attention to resultant craniotomy rates.

Author Disclosure: S. Dajani: None. C.D. Abraham: Employee; Phillips Medical Systems. J. Huang: Speaker's Bureau; Viewray Inc. Travel Expenses; Viewray Inc. P.W. Sperduto: Independent Contractor; Univ. of Minnesota. Partnership; Minneapolis Radiation Oncology, PA. Co-Director; University of Minnesota Gamma Knife Center. J.A. Sosman: None. S. Chandra: Research Grant; Bristol Myers Squibb. Consultant; EMD Serono, Bristol Myers Squibb, Regeneron. C.G. Robinson: Research Grant; Varian Medical Systems, Elekta. Speaker's Bureau; Varian Medical Systems, DFINE. Advisory Board; Radialogica. Stock Options; Radialogica. S. Acharya: None. I.B. Helenowski: None. O. Bloch: Consultant; BrainLab. T.J. Kruser: Employee; Northwestern Memorial Hospital. Consultant; Varian Medical Systems. Advisory Board; Abbvie Inc.

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