SURG-04. CDK2NA/B, SMAD4, AND PIK3R1 MUTATIONS ARE ASSOCIATED WITH INCREASED RISK OF LOCAL RECURRENCE AFTER SURGICAL RESECTION OF BRAIN METASTASES

Abstract

Abstract BACKGROUND While resection of brain metastases (BMs) offers favorable local disease control, factors and genetic alterations associated with local recurrence are not well defined. This study examined patient, tumor, treatment, and genetic factors associated with local recurrence. METHODS A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical outcome and genetic data available. Local recurrence was the primary outcome of the study. Next-generation sequencing of coding regions in over 500 cancer genes was performed to detect mutations. Cox proportional hazards analysis was performed to identify patient, tumor, treatment, and genetic factors associated with local recurrence. RESULTS We identified 91 patients who underwent surgical resection of a BM with available data, of which 80 (87.1%) underwent preoperative radiotherapy or received some form of adjuvant radiation to the resection cavity. Primary pathologies in the cohort included non-small cell lung cancer (24.2%), melanoma (24.2%), breast cancer (16.5%), gastrointestinal cancers (13.2%), gynecologic cancers (4.4%), renal cell carcinoma (4.4%), and other cancers (13.2%). Eleven patients (12.1%) developed postoperative recurrence at the surgical site with 6- and 12-month PFS of 91.2% and 84.2%. Multivariate Cox proportional hazard analysis identified cancer type (Gyn and RCC vs Others: OR 39.4, p=0.002), CDK2NA/B co-deletion (OR 37.52, p=0.0009), PIK3R1 mutation (OR 56.88, p=0.003), and SMAD4 mutation (OR 134.8, p=0.0007) to be associated with time to local recurrence. Overall survival and length of follow-up were not different based on mutational status of these genes, demonstrating that results were not due to survival bias. CONCLUSIONS Genetic alterations within BMs impact clinical outcomes after surgical resection. Further work is needed to determine if targeted therapies for BMs with these alterations can decrease rates of local recurrence.