Predicted probabilities of brain injury after carbon ion radiotherapy for head and neck and skull base tumors in long-term survivors

•Carbon ion radiotherapy (CIRT) is useful to treat head and neck tumors.•Radiation-induced brain injury (RIBI) is an adverse effect of irradiation.•The tolerance dose of the brain in CIRT is unclear.•Risk factors for RIBI in long-term survivors following CIRT were determined.•CIRT variables were used to generate a probability profile for RIBI treatment. We aimed to determine the risk factors for radiation-induced brain injury (RIBI11Abbreviations: RIBI, radiation-induced brain injury; CIRT, carbon ion radiotherapy; HNC/SBT, head and neck cancers and skull base tumors; AE, adverse event; DVH, dose volume histogram; LQ, linear–quadratic; MRI, magnetic resonance imaging; CT, computed tomography; GTV, gross tumor volume; CTV, clinical target volume; OAR, organs at risk; RBE, relative biological effectiveness; CTCAE, Common Terminology Criteria for Adverse Events; EUD, equivalent uniform dose; AIC, Akaike Information Criterion; SOBP, Spread-Out Bragg Peak; IMRT, intensity-modulated radiotherapy) after carbon ion radiotherapy (CIRT) to predict their probabilities in long-term survivors. We evaluated 104 patients with head, neck, and skull base tumors who underwent CIRT in a regimen of 32 fractions and were followed up for at least 24 months. RIBI was assessed using the Common Terminology Criteria for Adverse Events. The median follow-up period was 45.5 months; 19 (18.3 %) patients developed grade ≥2 RIBI. The maximal absolute dose covering 5 mL of the brain (D5ml) was the only significant risk factor for grade ≥2 RIBI in the multivariate logistic regression analysis (p = 0.001). The tolerance doses of D5ml for the 5% and 50% probabilities of developing grade ≥2 RIBI were estimated to be 55.4 Gy (relative biological effectiveness [RBE]) and 68.4 Gy (RBE) by a logistic model, respectively. D5ml was most significantly associated with grade ≥2 RIBI and may enable the prediction of its probability.