Biological Model for Predicting Toxicity in Head and Neck Cancer Patients Receiving Proton Therapy

To use a linear energy transfer (LET) dependent formula for relative biological effectiveness (RBE) to generate a biological model that can be used to predict toxicity in patients treated with proton therapy for cancer of the head and neck. Patients treated with protons to a dose of 60 to 70 Gy (RBE = 1.1) for head and neck cancer were eligible to participate in this study. Treatment plans were developed using graphics processing unit Monte Carlo calculations. The equation, RBE = (1.1)[0.08(LET )+0.88], was the biological model. The physical model assumes RBE = 1.1. Tumor volumes and organs at risk (OARs) were contoured, and isodose lines were created for 105%-120% of the prescribed dose. Dose to volume of OARs was calculated for both models for comparative purposes. Physician-reported toxicity was graded from 0 to 5 using the Common Terminology Criteria for Adverse Events, version 4.03. Patient-reported outcomes were obtained using the Promis10 and European Organisation for Research and Treatment of Cancer's QLQ-H&N35 instruments. Eleven patients were included in this study. In each case the biological model revealed an increased dose to several OARs compared with the physical model. For selected OARs, the volume receiving >105% of the target dose was 2-fold to 15-fold greater in the biological model than the volume predicted by the physical model. Patients experienced toxicity that was consistent with the dose to OARs predicted by the biological model. Furthermore, 1 patient developed mucosal ulceration and another developed osteoradionecrosis at the location of a biological hot spot. In each case, the biological hot spot was located 2 mm inside the clinical target volume. The results suggest that increases in dose predicted by the biological model are clinically relevant and that LET and RBE corrections and optimization should be a component of the treatment-planning process in proton therapy.