Abstract Treatment of brain metastases (BMs) in non-small cell lung cancer (NSCLC) has been transformed by CNS-penetrant tyrosine kinase inhibitors (CNS-TKIs) directed at targetable genomic alterations (TGAs). Limited real-world data exist regarding upfront and salvage radiation in these patients. We conducted an IRB-approved retrospective study of consecutive patients with NSCLC BMs treated with SRS between 2017 and 2021. Patients were classified into two cohorts: 1) those with TGAs treated with CNS-TKIs and 2) those without TGAs. Clinical data were extracted from the medical record. Regression analyses were used to assess the relationship between CNS-TKI, use of SRS and WBRT, and presence of leptomeningeal disease (LMD). We identified 158 patients with 353 BMs, with 58 patients in Group 1(G1), and 100 patients in Group 2 (G2). G1 patients had these TGAs: EGFR (n=32), ALK (n=16), ROS1 (n=8), RET (n=2.) Median follow-up was 18 months for G1 and 8 months for G2 (p=0.03). G1 patients received SRS at a median of 224±74 days from BM diagnosis versus 34±17 days in G2 (p=1.9x10-7). Lesions treated in G1 patients were more likely to have been present at BM diagnosis (G1:65%, G2:50%, p=0.029). There was no difference in salvage WBRT use between groups (G1: 13.8% G2: 11%, p=0.60). There was a trend toward more LMD among G1 patients (10/58 (17%) vs. 6/100 (6%), p=0.054). This study represents one of the largest evaluating patterns of brain RT in patients with NSCLC BMs on CNS-TKIs. While these agents delay time to SRS, 65% of lesions needing SRS were present at initial BM diagnosis, suggesting that local progression remains a concern. There was no difference in the use of salvage WBRT, despite higher rates of LMD in G1 patients. Identification of factors predictive of CNS progression may enable optimization of local therapy in conjunction with CNS-TKIs.
Zhu et al. (Fri,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: