Radiation biology considerations of proton therapy for gastrointestinal cancers

Clinical enthusiasm for proton therapy (PT) is high, with an exponential increase in the number of centers offering treatment. Attraction for this charged particle therapy modality stems from the favorable proton dose distribution, with low radiation dose absorption on entry and maximum radiation deposition at the Bragg peak. The current clinical convention is to use a fixed relative biological effectiveness (RBE) value of 1.1 in order to correct the physical dose relative to photon therapy (i.e., proton radiation is 10% more biologically effective then photon radiation). In recent years, concerns about the potential side effects of PT have emerged. Various studies and review articles have sought to better quantify the RBE of PT and shine some light on the complexity of this problem. Reduction in biologic hot spots of non-target tissue is paramount in proton radiation therapy (RI) planning as the primary benefit of proton RT is a reduction in organ at risk (OAR) irradiation. New and emerging clinical data is in support of variable proton biological effectiveness and demonstrate late toxicity, presumably associated with high biological dose, to OAR. Overall, PT has promise to treat many cancer sites with similar efficacy as conventional RT but with fewer acute and late toxicities. However, further knowledge of biologic effective dose and its impact on both cancer and adjacent OAR is paramount for effective and safe treatment of patients with PT.