Normal tissue complications from low-dose proton therapy.

Proton therapy is an attractive method to attenuate toxicities of radiotherapy because of the decrease of integral radiation dose to normal tissues, which should lead to fewer late side effects. This potential benefit is of particular interest in the pediatric population, since children are more vulnerable to the risks of radiation. In addition, overall survival rates for pediatric malignancies continue to improve, which will lead to more long-term survivors who will be at risk from the late effects of radiation therapy that was used for treatment. In this review, the potential benefits afforded by proton therapy in the low-dose area for radiosensitive organs will be evaluated. Because robust clinical information is not available for low-dose proton therapy, information from the experience of photon therapy in radiosensitive structures will be reviewed. In general, because the low-dose bath is reduced or on occasion eliminated with the use of proton therapy, a reduction of early and late toxicities related to low-dose radiotherapy such as vomiting, mucositis, cardiovascular complications, pulmonary injury, and developmental effects in children is expected. Other authors review the current evidence and potential benefits supporting the use of proton therapy for the reduction in neuro-cognitive sequelae and secondary malignancies. Currently, a relative biological effectiveness of 1.1 is used in clinical situations to calculate the equivalent biologic dose for proton therapy relative to photon therapy. The unit of dose is commonly referred to as gray equivalent (GyEq). The interaction of a proton at a cellular level is postulated to lead to a higher frequency of double-strand breaks, so in theory there is a higher probability of cell kill and a lower probability of mutagenesis. At this time, however, once the physical properties of the interaction of proton with matter are accounted for, there is no definite data that 1 GyEq has any different biologic outcome than 1 Gy delivered with photon therapy. In the Bragg peak, there is greater uncertainty of dose deposition and associated biologic effect. In clinical practice, therefore, one avoids placing the Bragg peak on critical structures such as the brainstem, spinal cord, or optic chiasm. In summary, it appears that normal tissue tolerance of proton radiotherapy is likely to be similar to photon radiation for equivalent biologic doses. Overall, it is anticipated that there will be a lower risk of normal tissue toxicity associated with proton therapy because of a lower delivered dose outside of the target tissue.