Impact of Systemic Therapy Type and Timing on Intracranial Tumor Control in Patients with Brain Metastasis from Non-Small-Cell Lung Cancer Treated With Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) can effectively control brain metastasis (BRM) from non-small-cell lung cancer (NSCLC), although intracranial recurrence from untreated micrometastatic tumor deposits is common without whole-brain radiotherapy. Our goal was to determine if immunotherapy improves distant intracranial progression-free survival (DI-PFS) compared with other systemic therapies in patients treated with SRS.All patients from 2011 to 2019 treated with SRS without previous whole-brain radiotherapy for NSCLC BRM were reviewed. DI-PFS for the entire cohort, and subgroups of patients, was estimated and compared using the Kaplan-Meier/log-rank method.One hundred and thirty-six SRS sessions used to treat 99 patients were reviewed; 98 (72%) for previously untreated BRM and 38 (28%) for recurrent BRM. 35% received immunotherapy (77% concurrent with SRS), 46% received chemotherapy (75% concurrent), and 18% received epidermal growth factor receptor/anaplastic lymphoma kinase (ALK) targeted therapy (85% concurrent). At median follow-up of 13.7 months, 49% developed distant intracranial recurrence. One-year DI-PFS was improved with any use of immunotherapy (58% vs. 39%; P = 0.03) and concurrent immunotherapy versus chemotherapy or targeted therapy (67% vs. 37% vs. 39%, respectively; P = 0.01). In the immunotherapy cohort, 1-year DI-PFS was improved for programmed death-ligand 1 expression ≥50% versus 1%-49% versus 0% (80% vs. 49% vs. 19%, respectively; P0.01), and Lung Immune Prognostic Index 0-1 versus 2 (63% vs. 34%; P = 0.03).Immunotherapy concurrent with SRS, particularly in patients with high programmed death-ligand 1 expression or low Lung Immune Prognostic Index, is associated with improved DI-PFS and no increased risk of radiation necrosis compared with other systemic therapies for NSCLC.