Stereotactic Radiosurgery Dose Reduction for Patients With Brain Metastases From Non–Small Cell Lung Primary on Immunotherapy or Targeted Therapy

BACKGROUND AND OBJECTIVES: Lung cancer is the most common primary neoplasm that metastasizes to the brain. Although stereotactic radiosurgery (SRS) using American Society for Radiation Oncology guideline-suggested doses improves local control, it may increase adverse radiation events (AREs). This study evaluates whether reduced SRS doses can achieve comparable local control while minimizing toxicity in patients with brain metastases from non-small cell lung cancer (NSCLC) primary receiving concurrent systemic therapy. METHODS: We conducted a retrospective study of 264 patients with 1390 metastases from lung primary treated with SRS between December 2015 and January 2025. Of these, 82 patients with 433 metastases had NSCLC and received concurrent systemic therapy, defined as immunotherapy or targeted therapy within 30 days of SRS. Propensity score matching identified 38 patients with 93 metastases in the higher-dose (HD) group (20-24 Gy for <2 cm, 18 Gy for ≥2 to <3 cm) and 42 patients with 93 metastases in the reduced-dose (RD) group (<20 Gy for <2 cm, <18 Gy for ≥2 to <3 cm). RESULTS: Radiographic AREs, including perilesional edema and radiation necrosis, were significantly more common in the HD group than in the RD group (23.7% vs 10.8%, P = .020). Local control was noninferior in the RD group (94.6%) compared with the HD group (90.3%, P = .400). Cumulative progression at 1, 3, and 5 years remained comparable between the RD (13%, 15%, and 15%, respectively) and HD (7.2%, 10%, and 10%, respectively) groups ( P = .500). CONCLUSION: In the contemporary era, RD SRS delivered concurrently with immunotherapy or targeted therapy may lower AREs without compromising local control to treat NSCLC brain metastases.