A. La Rosa1, S. Yarlagadda1, T. Kutuk1, E. Y. Y. Akdemir1, O. Gal1, R. H. Press1, M. D. Hall1,2, Y. Lee1,2, D. J. Wieczorek1,2, R. P. Tolakanahalli1,2, A. Gutierrez1, M. P. Mehta1,2, and R. Kotecha1,3; 1Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 2Department of Radiation Oncology, Florida International University, Herbert Wertheim College of Medicine, Miami, FL, 3Florida International University, Herbert Wertheim College of Medicine, Miami, FL
Purpose/Objective(s): To determine the impact of the selection of systemic therapy on initial radiographic response after stereotactic radiosurgery (SRS), intracranial progression-free survival (iPFS), and overall survival (OS) in a contemporary cohort of Hispanic-majority patients with brain metastases from non-small cell lung cancer adenocarcinomas. Materials/
Methods: Consecutive patients with small brain metastasis (=2 cm in maximum diameter) of lung cancer origin treated with single fraction SRS between 01/17 and 07/22 were included. The cohort was stratified by selection of systemic therapy during or after SRS, categorized by intracranial objective response rate activity from the published literature (low <25%, intermediate 25-50%, and high >50%). Initial response post-SRS, iPFS, and OS were calculated using the Kaplan–Meier method; multivariable analyses were performed to identify factors associated with the outcomes. Results: A total of 524 brain metastases in 101 lung cancer patients (75.2% Hispanic) met inclusion criteria. The median age was 67 years (range [R]: 18-88), median metastases per patient was 9 (R: 1-28), slight female preponderance (56.4%), and 13.9% with oligometastatic disease. Systemic therapy peri-SRS consisted of chemotherapy (ChT) alone (14.8%), immunotherapy (IT) alone (12.9%), ChT+IT (30.7%), targeted therapy (34.7%), or no treatment (6.9%). The numbers of patients (lesions) receiving no, low, intermediate, or high activity systemic therapy were 7(17), 15(67), 46(261), and 33(179), respectively. With a median follow-up (FU) of 18 months (R: 0-75), the estimated intracranial iPFS duration in months (95% CI) for the no, low, intermediate, or high activity systemic therapy was 3.0 (2.1-3.9), 4.0 (2.8-5.2), 8.0 (4.9-11.1), and 16.0 (11.7-20.3), respectively (p < 0.05). OS (months) was similar across the groups regardless of activity level (no: 8.0, low: 24.0, intermediate: 19.0, and high: 20.0, p = 0.18). At first follow-up, complete/partial response rates varied by activity groups: 76.5% (no systemic), 55.2% (low), 59.0% (intermediate), and 50.8% (high) without identifiable differences (p>0.05). Age, gender, KPS, burden of disease status, and the class of agent used were associated with iPFS on MVA analysis (p < 0.05). Additionally, the impact of systemic therapy on iPFS was driven specifically by individual class of agent, with immunotherapy and targeted therapy associated with improved iPFS (HR: 0.52, p<0.05 and HR: 0.58, p<0.05, respectively), compared to chemotherapy alone. Conclusion: Selection of systemic therapy significantly influences iPFS in this diverse and contemporary cohort of lung adenocarcinoma patients with brain metastases treated with stereotactic radiosurgery, however, without an impact on the initial response and without clear signal for OS.
