Resident Physician University of California San Francisco San Francisco, California, United States
Disclosure(s):
Ramin Morshed, MD: No financial relationships to disclose
Introduction: While genetic alterations associated with brain metastases (BMs) have been previously explored, there are limited data examining their association with surgical treatment outcomes. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgical resection across multiple cancer types.
Methods: A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and distant CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 cancer genes was performed to detect mutations. Cox proportional hazards analyses were performed to identify clinical features and gene mutations associated with CNS recurrence.
Results: Ninety patients undergoing resection of 91 BMs composed the cohort. Primary pathologies 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%). Genes most frequently mutated in the cohort included TP53 (64% of specimens), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types including NSCLC (n=9, 49.9%), melanoma (n=6, 27.3%), breast (n=2, 13.3%), gastrointestinal (n=3, 25%), and renal cell carcinoma (n=1, 25%). In multivariate Cox proportional hazard analyses including patient and treatment factors, CDKN2A/B Co-deletion was associated with increased risk of local (HR 4.07, 95%CI 1.32-12.54, p=0.014) and distant (HR 2.28, 95%CI 1.11-4.69, p=0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status.
Conclusion : CDKN2A/B co-deletion detected in brain metastases is associated with increased CNS recurrence after BM surgical resection. Additional work is needed to determine whether escalation of care in patients with this mutation may improve outcomes.
