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PURPOSE: Investigating real-world outcomes of moderately hypofractionated radiotherapy (hypoRT) in elderly and multimorbid stage IIB-IIIC non-small-cell lung cancer (NSCLC) patients ineligible for concurrent chemoradiation. METHODS: We retrospectively analysed 70 patients with primary or recurrent stage IIB-IIIC NSCLC (TNM, 8th edition). HypoRT was administered to a total dose of 38-56 Gy in 10-17 fractions (2.5-3.8 Gy/fraction). Patterns of recurrence, survival outcome, and toxicity were assessed. RESULTS: Seventy patients, with a median age of 76.4 years (range: 51.6-88.2 years), who received hypoRT between August 2015 and September 2022, were reviewed. At baseline, the median Charlson Comorbidity Index (CCI) with oncological diagnosis was 8 (range: 3-13). With a median follow-up post-radiotherapy of 63.9 months (95% Confidence Interval [CI]: 34.8-93.1 months), median progression-free survival (PFS) was 7.6 months (95% CI 6.0-11.0 months), and the median overall survival (OS) was 20.7 months (95% CI 16.7-30.7 months). Competing risk analysis revealed 12-month cumulative incidences of locoregional and distant failure in 41% (95% CI 30-53%) and 14% (95% CI 6-23%) of patients, respectively. Following disease progression, 45 patients received subsequent therapy: 25 underwent additional radiotherapy, 22 received systemic treatment (including immunotherapy), and 19 were referred for best supportive care. Treatment was well tolerated; only 3 patients (4%) developed grade 3 pneumonitis. No adverse events of grade > 3 were reported. INTERPRETATION: Moderately hypoRT is a safe, feasible, and effective treatment option for elderly and multimorbid patients with stage IIB-IIIC NSCLC, offering encouraging survival outcomes and low toxicity rates. Future prospective studies are needed to validate these findings and optimise treatment strategies for this high-risk population.
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