Proton Radiation Therapy: A Systematic Review of Treatment-Related Side Effects and Toxicities

Cancer is the second leading cause of death worldwide. Around half of all cancer patients undergo some type of radiation therapy throughout the course of their treatment. Photon radiation remains (RT) the most widely utilized modality of radiotherapy despite recent advancements in proton radiation therapy (PBT). PBT makes use of the particle's biological property known as the Bragg peak to better spare healthy tissue from radiation damage, with data to support that this treatment modality is less toxic than photon RT. Hence, proton radiation dosimetry looks better compared to photon dosimetry; however, due to proton-specific uncertainties, unexpected acute, subacute, and long-term toxicities can be encountered. Reported neurotoxicity resulting from proton radiation treatments include radiation necrosis, moyamoya syndrome, neurosensory toxicities, brain edema, neuromuscular toxicities, and neurocognitive toxicities. Pulmonary toxicities include pneumonitis and fibrosis, pleural effusions, and bronchial toxicities. Pericarditis, pericardial effusions, and atrial fibrillations are among the cardiac toxicities related to proton therapy. Gastrointestinal and hematological toxicities are also found in the literature. Genitourinary toxicities include urinary and reproductive-related toxicities. Osteological, oral, endocrine, and skin toxicities have also been reported. The side effects will be comparable to the ones following photon RT, nonetheless at an expected lower incidence. The toxicities collected mainly from case reports and clinical trials are described based on the organs affected and functions altered.