Biological considerations when comparing proton therapy with photon therapy

Owing to the limited availability of data on the outcome of proton therapy, treatments are generally optimized based on broadly available data on photon-based treatments. However, the microscopic pattern of energy deposition of protons differs from that of photons, leading to a different biological effect. Consequently, proton therapy needs a correction factor (relative biological effectiveness) to relate proton doses to photon doses, and currently, a generic value is used. Moreover, the macroscopic distribution of dose in proton therapy differs compared with photon treatments. Although this may offer new opportunities to reduce dose to normal tissues, it raises the question whether data obtained from photon-based treatments offer sufficient information on dose-volume effects to optimally use unique features of protons. In addition, there are potential differences in late effects due to low doses of secondary radiation outside the volume irradiated by the primary beam. This article discusses the controversies associated with these 3 issues when comparing proton and photon therapy.