Synergistic efficacy of radiotherapy and immunotherapy enhances clinical outcomes in patients with advanced non-small cell lung cancer

BACKGROUND: Immunotherapy has become a primary treatment for advanced non-small cell lung cancer (NSCLC), although drug resistance is inevitable. Radiotherapy enhances immunotherapy efficacy, particularly in early to mid-stage NSCLC. However, the synergistic effects of radiotherapy and immunotherapy in advanced NSCLC remain controversial. METHODS: We retrospectively analyzed data from 141 stage IV NSCLC patients treated with first-line immunotherapy or chemoimmunotherapy at Hangzhou Cancer Hospital. Patients were divided into groups receiving radiotherapy combined with immunotherapy versus immunotherapy alone. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Cox regression method. Subgroup Cox regression analyses were performed to optimize the combination regimens. RESULTS: The combined therapy group showed longer PFS (16.9 vs. 8.49 months, HR 0.57, p = 0.006) and OS (69.93 vs. 24.62 months, HR 0.60, p = 0.04). Subgroup analysis indicated that non-squamous NSCLC patients without immunotherapy rechallenge benefited most. Radiotherapy added to immunotherapy in lung or brain metastases showed a trend toward improved PFS (lung: 19.34 vs. 6.03 months, HR 0.62, p = 0.30; brain: 22.72 vs. 7.80 months, HR 0.59, p = 0.29). Concurrent (HR 0.41, p = 0.02) or consolidation radiotherapy (HR 0.32, p = 0.003) during immunotherapy offered greater PFS benefits than symptom-relief radiotherapy. Both stereotactic body radiotherapy and conventional radiotherapy yielded similar survival outcomes. Incidence of grade 3 or higher pneumonia post-lung-radiotherapy was 3.45%. CONCLUSIONS: Our study highlights the synergistic efficacy of combining radiotherapy with immunotherapy in advanced NSCLC. Optimizing patient selection, targeting specific sites, effective timing, and tailored radiotherapy regimens significantly improved PFS and OS, providing crucial insights for enhancing clinical outcomes in advanced NSCLC.