Proton beam radiotherapy for esophagus cancer: state of the art

The majority of esophageal cancer patients are diagnosed with locoregionally confined disease, which is often amenable to curative intent therapy. Chemoradiotherapy (CRT) improves overall survival (OS) in stage II and III esophagus cancer in the neoadjuvant and definitive settings. Due to the close proximity of organs at risk (OARs), including lungs, heart, stomach, bowel, kidneys, and spinal cord, esophageal CRT can result in profound acute and late toxicities. Acute toxicities can include esophagitis, nausea, vomiting, fatigue, and cytopenias. Late complications may also occur months or years after completion of thoracic radiotherapy, including significant cardiac, pulmonary, liver, kidney, or bowel toxicities, which can be life-threatening or fatal. Photon-based radiotherapy exposes OARs to significant doses of radiation, whereas proton beam therapy (PBT) has unique physical properties, as it lacks an exit dose. This allows PBT to deliver, a more conformal dose to the target and minimize the volume of OARs exposed to radiation. This dosimetric advantage may portend an increased therapeutic ratio of CRT for esophagus cancer. The objective of this review is to discuss the evolution of photon and proton-based radiotherapy techniques, rationale, dosimetric and clinical studies comparing outcomes of photon- and proton-based techniques, ongoing prospective trials, and future directions of PBT as a means of reducing toxicity and improving oncologic outcomes for patients with esophagus cancer.