Novel use of proton beam therapy for neoadjuvant treatment of radiation-associated squamous cell carcinoma of the esophagus

Secondary esophageal cancers from prior thoracic radiation therapy are rare but challenging cases to deliver standard combined modality therapy as part of a curative approach. In patients with prior exposure to cardiopulmonary-toxic chemotherapy or radiotherapy, management requires meticulous multidisciplinary evaluation given the morbidity associated with surgery in the previously irradiated thorax and re-irradiation of the spinal cord, heart, and lungs. Oftentimes, suboptimal treatment regimens, either with compromised radiation coverage, attenuated chemotherapy doses, or exclusion of surgery, are required to avoid significant toxicity. The physical properties inherent to protons allow for optimal coverage of tumor while achieving remarkably low dose to surrounding normal tissue compared to standard photon treatment. Proton therapy has been studied across various disease sites and may facilitate treatment intensification for radiation-associated esophageal tumors. While no comparative studies have evaluated the efficacy and safety of protons versus photons for esophageal cancer, three cases of radiation-associated esophageal cancer presented in this series are exemplary to highlight the benefit of protons in this unique clinical circumstance. The technical considerations in planning, including passively scattered versus pencil-beam scanning technique, as well as the clinical course and tolerance to treatment, are discussed, which may guide consideration of this advanced treatment modality in this disease site.