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

<b>Background/Objectives</b>: Brain metastases (BrMs) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While the treatment of BrMs requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, the advances in molecular sequencing have improved outcomes in patients with targetable mutations. With a push towards the molecular characterization of cancers, we evaluated the outcomes by treatment modality at our institution with respect to prioritizing RT and targeted therapies. <b>Methods</b>: We identified the patients with NSCLC BrMs treated with surgical resection. The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). The secondary endpoint included index lesion recurrence. The tumor molecular profiles were reviewed. The outcomes were evaluated by treatment modality: surgery followed by adjuvant RT and/or adjuvant systemic therapy. <b>Results</b>: In total, 155/272 (57%) patients who received adjuvant therapy with adequate follow-up were included in this analysis. The patients treated with combination therapy vs. monotherapy had a median FFP time of 10.72 months vs. 5.38 months, respectively (<i>p</i> = 0.072). The patients of Hispanic/Latino vs. non-Hispanic/Latino descent had a statistically significant worse OS of 12.75 months vs. 53.15 months, respectively (<i>p</i> = 0.015). The patients who received multimodality therapy had a trend towards a reduction in index lesion recurrences (χ² test, <i>p</i> = 0.063) with a statistically significant improvement in the patients receiving immunotherapy (χ² test, <i>p</i> = 0.0018). <b>Conclusions</b>: We found that systemic therapy combined with RT may have an increasing role in delaying the time to progression; however, there was no statistically significant relationship between OS and treatment modality.