RADT-41. THE ROLE OF RADIOTHERAPY IN RESECTED NON-SMALL CELL LUNG CANCER BRAIN METASTASES TREATED WITH CNS-ACTIVE TYROSINE KINASE INHIBITORS

Abstract For patients with non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs), the development of CNS-active tyrosine kinase inhibitors (CNS-TKIs) has transformed the treatment of brain metastases (BMs). For patients with resected BMs with AGAs, the benefits of adjuvant radiotherapy (RT) with TKI vs. TKI alone are unclear. Here we compare outcomes of patients with NSCLC with AGAs and resected BMs treated with CNS-TKIs, with and without adjuvant RT. We performed a retrospective analysis of consecutive patients with NSCLC with AGAs who underwent craniotomy for BMs at two institutions from March 2015 to June 2024. CNS-TKIs were defined as TKIs with >50% intracranial objective response rate in published studies. We identified 61 patients, 41 of whom received RT with a median collective follow-up of 29.3 months. AGAs included alterations in EGFR (n=42), ALK (9), ROS1 (4), MET (4), and RET (2), 77% of patients had gross total resection with no difference between groups (p=0.27). Patients receiving RT were more likely to have a single brain metastasis (p=0.046). Of patients undergoing RT, 20 received stereotactic radiotherapy (≤5 fractions), 18 had fractionated RT to the cavity (range 10-14 fractions), and 2 had hippocampal-avoidant whole brain RT (HA-WBRT). The 2-year rate of local recurrence (LR) with TKI alone was 18.3% vs, 3.2% with RT+TKI (p=0.011). There was no difference in 2-year intracranial recurrence (52.6% vs, 35.2%, p=0.31) or median overall survival (43.1 vs 43.5 months, p=0.50). Of 5 pts with LR, 3 required repeat craniotomy and postoperative RT; 1 received HA-WBRT. In this multi-institutional retrospective study, forgoing adjuvant RT for CNS-TKI alone was not associated with worse survival or intracranial recurrence but was associated with increased LR. More data are needed to understand the risks of LR and salvage treatments when treating patients with NSCLC resected BMs with AGAs.