Clinical evaluation of low-dose radiation therapy for immunotherapy resistance in advanced non-small cell lung cancer.

BACKGROUND: Standard second-line chemotherapy yields unsatisfactory response rates for such heavily pretreated populations, creating an urgent unmet clinical need for novel salvage regimens. This study assessed the clinical efficacy of low-dose radiation therapy (LDRT) combined with immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) who exhibited resistance to chemotherapy combined with immunotherapy. METHODS: A prospective, single-arm exploratory study was conducted in patients with advanced NSCLC who were resistant to chemotherapy combined with immune checkpoint inhibitors (ICIs). The treatment regimen consisted of LDRT (<10 Gy) administered in combination with the original ICI. Platinum-based chemotherapy was discontinued, while single-agent chemotherapy was maintained at the original dose or at a reduced dose, as clinically appropriate. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS), as well as changes in peripheral blood leukocyte and lymphocyte counts and in CD3+, CD4+, and CD8+ T-cell levels prior to and following treatment. RESULTS: A total of 19 patients were enrolled between February 2023 and February 2026. Among the 19 evaluable patients, the median PFS was 3.0 months, and the median OS was 21.5 months. The ORR was 36.84%, and the DCR was 73.68%. Subgroup analyses indicated that sex, pathological type, and programmed-death ligand 1 expression had no statistically significant association with survival outcomes. Peripheral blood lymphocyte counts decreased significantly after treatment compared with baseline (P=0.02), whereas other immune indicators indicated no statistically significant differences. CONCLUSIONS: LDRT combined with ICIs was associated with clinical responses in a subset of patients with advanced NSCLC who demonstrated resistance to prior immunotherapy-based treatment. These findings suggest that LDRT may represent a potential therapeutic approach for patients with immunotherapy resistance and limited tolerance for chemotherapy.