Abstract PO-073: Mutational status and clinical outcomes following systemic therapy and focal radiation for melanoma brain metastases
Authors: Vasudevan Harish N. , Susko Matthew S. , Ma Lijun , Nakamura Jean L. , Raleigh David R. , Boreta Lauren , Fogh Shannon , Theodosopoulos Philip V. , McDermott Michael W. , Tsai Katy K. , Sneed Penny K. , Braunstein Steve E. 
Published: April 2021

Abstract
Brain metastases are the most common intracranial neoplasm yet clinical outcomes remain poor. The purpose of this study was to evaluate the efficacy of multimodal therapy comprising surgery followed by focal radiation, and/or systemic therapy and elucidate clinically significant biomarkers for resected melanoma brain metastases. Forty consecutive patients with newly diagnosed melanoma brain metastases who underwent surgical resection and targeted mutational analysis at UCSF between 2011 and 2020 were identified. Demographic, clinical, and outcome data were extracted from the medical record and institutional cancer registry. Surgical cavity local recurrence free survival (LRFS), intracranial progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The median age of patients in this cohort was 58 years (range: 27-75 years) with median MRI follow up of 13.15 months. Twenty patients (50%) were treated with concurrent stereotactic radiation (1-5 fractions) and systemic therapy while 16 patients (40%) were treated with systemic therapy only. Mutational testing demonstrated the most common pathogenic variant was BRAF V600E, found in 16 patients (40%), while the remaining 24 patients (60%) did not harbor this mutation. Microsatellite instability (MSI) estimation was available for 8 patients (20%), all of which were found to be MSI low (&lt;2%). Median LRFS was significantly improved with combined focal radiation and systemic therapy compared to systemic therapy alone (NR versus 15 months, p=0.01; log-rank test). Patients harboring BRAF V600E mutations had worse intracranial PFS compared to those without V600E mutation (4 months versus 12 months, p=0.048; log-rank test), as well as a trend toward worse OS (NR vs 13 months, p=0.09; log-rank test). Systemic agent choice was heterogeneous, with 24 patients (60%) treated with immunotherapy alone, 12 patients (30%) treated with dual BRAF/MEK inhibitor therapy alone, and the remainder treated with mixed regimens (10%) with no differences in efficacy or toxicity between these subgroups. Our results suggest combined focal radiation and systemic therapy is effective for melanoma brain metastases. Moreover, specific molecular alterations such as BRAF V600E mutation are associated with poorer outcomes, and all brain metastases in our cohort were MSI low. Limitations of our study include its retrospective nature, limited sample size, and heterogeneity of systemic regimens, and future prospective validation and multiplatform genomic analysis are needed to build on our findings.
Citation Format: Harish N. Vasudevan, Matthew S. Susko, Lijun Ma, Jean L. Nakamura, David R. Raleigh, Lauren Boreta, Shannon Fogh, Philip V. Theodosopoulos, Michael W. McDermott, Katy K. Tsai, Penny K. Sneed, Steve E. Braunstein. Mutational status and clinical outcomes following systemic therapy and focal radiation for melanoma brain metastases [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-073.