BACKGROUND: Lung cancer remains the leading cause of cancer-related deaths worldwide. Advances in immunotherapy and targeted therapies have improved survival in stage IV non-small cell lung cancer (NSCLC), highlighting the importance of local control of the primary tumor. Hypofractionated radiotherapy (hypo-RT), delivering high biologically effective doses (BEDs) over shorter durations, shows potential in locally advanced NSCLC but is underexplored in metastatic settings. PURPOSE: This retrospective study evaluated 104 patients with stage IV NSCLC who received hypo-RT to the primary tumor at LMU Munich between December 2013 and June 2022. The primary endpoints were overall survival (OS) and progression-free survival (PFS), while the secondary endpoints included local failure-free survival, regional failure-free survival, distant failure-free survival, and the identification of prognostic factors. FINDINGS: Median OS and PFS were 15.4 months (95% confidence interval [CI]: 10.5-24.4) and 3.9 months (95% CI, 3.2-6.2), respectively. Significant predictors of OS included Eastern Cooperative Oncology Group performance status >1 (hazard ratio [HR]: 3.260, P = .0003), male sex (HR: 1.869, P = .038), metastases in >2 organ systems (HR: 2.014, P = .022), and BED < 58.5 Gy (HR: 2.117, P = .017). Predictors of PFS included smoking history <30 pack-years (HR: 1.912, P = .003) and BED < 58.5 Gy (HR: 1.816, P = .025). CONCLUSION: Hypo-RT is effective and feasible in metastatic NSCLC, with higher BEDs improving survival. Findings highlight the importance of personalized treatment strategies integrating clinical, molecular, and therapeutic factors.
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