Prioritizing Radiation and Targeted Systemic Therapy in Patients with Resected Brain Metastases from Lung Cancer Primaries with Targetable Mutations: A Report from a Multi-Site Single Institution

Abstract

Brain metastases (BrM) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While treatment of BrM requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, advances in sequencing have improved outcomes with targetable alterations in PDL-1, EGFR, ALK, and KRAS mutations. With a push towards molecular characterization of cancers, we sought out to examine outcomes by treatment modalities at our institution with respect to prioritizing RT and targeted therapies. After IRB approval, we identified patients treated with a surgical resection of BrM from NSCL primaries between 2011 to 2022 at 5 sites at our institution. Tumor molecular profiles were reviewed and patients with PDL-1, EGFR, ALK, and KRAS mutations were evaluated by a treatment modality: surgery alone or in combination with RT (SRS, WBRT) and/or systemic therapy (TKIs -1st-3rd generations, immunotherapy). The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). SAS Studio version 4.4 was used to perform statistical analyses. We identified 272 patients with 162/272 (60%) patients with adequate follow-up included in this analysis. The median follow-up was 27.8 months (range, 0.43 - 134.45 months). There were 59.2% females and 40.7% males, with median ages at diagnosis of 67 years for females and 66 for males, respectively. Of the entire cohort, 102/162 (63%) patients received adjuvant combination RT and systemic therapy, and 60/162 (37%) received adjuvant monotherapy (p <0.0001). The use of systemic therapy was associated with 9.89 months median time to progression vs 4.87 months without it (p = 0.077), respectively. Similarly, patients treated with a combination of RT and systemic therapy had a median FFP time of 9.77 months vs 5.28 months (p = 0.064). No significant difference in OS was found with or without systemic therapy. After resection of BrM from NSCLC with PDL-1, EGFR, ALK, and KRAS mutations, we found that systemic therapy, including TKIs and immunotherapy, may have an increasing role in delaying time to progression. At our institution, as we continue to identify actionable mutations, a statistically significant number of patients continue to be treated with a combination of RT and systemic therapies with a trend toward superior FFP.