Risk factors for radiation-induced rib fractures following proton beam therapy for stage I non-small cell lung cancer: a retrospective study

Abstract

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.

Keywords

• Proton therapy
• Rib fracture
• Toxicities of thoracic radiation
• Lung cancer