Abstract
BACKGROUND: Understanding and managing radiation-induced adverse events is becoming increasingly important in hypofractionated radiotherapy due to the use of higher doses per fraction compared with conventional radiotherapy. Specifically, toxicities of hypofractionated proton and carbon-ion beam therapy are still unclear. We investigated the clinical, anatomical, and dosimetric risk factors for radiation-induced rib fractures (RIRFs) following passive-scattering proton beam therapy (PBT) for stage I non-small cell lung cancer (NSCLC). METHODS: We retrospectively investigated patients with stage I NSCLC who underwent PBT with 66-70 Gy (relative biological effectiveness [RBE]) in 10 fractions, completing a minimum follow-up of 36 months. Rib fractures were detected by follow-up chest computed tomography (CT) examination, independent of symptoms of thoracic pain. Dose-volume histograms of separately contoured ribs on planning CT images were calculated by the treatment planning system in a retrospective manner. Kaplan-Meier and Cox proportional hazards analyses were performed on individual ribs to identify significant risk factors associated with RIRF. RESULTS: Among the 85 patients finally involved in this study, we identified 116 fractured ribs in 55 participants (64.7%). The 2- and 3-year frequencies of experiencing any RIRF were 36.5% and 52.9%, respectively. The median time-to-fracture was 23.5 months (range: 5-65). We used a total of 224 ribs irradiated over 50 Gy (RBE)-including all the detected fractured ribs-for statistical analysis. Univariate and multivariate analyses revealed the maximum-rib dose to a small volume, position of the maximum-dose point, bone mineral density, 1st rib number, and use of systemic corticosteroids to be related to the incidence of RIRFs. CONCLUSIONS: In addition to dosimetric parameters, factors related to skeletal structure and bone strength are crucial predictors of proton RIRFs and should be considered for safer radiation therapy.