A Comparative Analysis of Photon versus Proton Beam Therapy in Neoadjuvant Concurrent Chemoradiotherapy for Intrathoracic Squamous Cell Carcinoma of the Esophagus at a Single Institute

SIMPLE SUMMARY: Radiotherapy for an esophageal malignancy results in undesired radiation exposure to nearby critical organs such as the heart, lungs, and spinal cord, leading to unfavorable clinical outcomes. Although only utilized at a few centers, proton beam radiotherapy spares adjacent organs from radiation exposure more effectively than conventional photon radiotherapy. We confirmed that, in terms of sparing adjacent organs from radiation, proton beam radiotherapy, as a modality of neoadjuvant chemoradiotherapy, was significantly superior to conventional photon radiotherapy for locally advanced esophageal squamous cell carcinoma with an even distribution of intrathoracic locations, and may lead to improved clinical outcomes. ABSTRACT: Background: Proton beam therapy (PBT), as a neoadjuvant chemoradiotherapy (nCRT) modality, is expected to result in better outcomes than photon-based radiotherapy (RT) for esophageal cancer, particularly adenocarcinoma. This study reports the results of nCRT for locally advanced esophageal squamous cell carcinoma (ESCC) using both modalities. Methods: We retrospectively reviewed the records of patients who underwent nCRT for ESCC between 2001 and 2020. A median of 41.4 Gy or cobalt gray equivalents of radiation was delivered using either photons or protons, with concurrent chemotherapy. Dosimetric and clinical parameters were compared between the two groups. Results: Of the 31 patients, the lungs and heart of the proton group (n = 15) were exposed to significantly less radiation compared to the photon group (n = 16). No significant differences in short-term postoperative outcomes or lymphocyte count were observed between the groups, and there were no significant differences between the photon and proton groups in 2-year overall survival (67.8% vs. 68.6%, p = 0.867) or 2-year disease-free survival (33.3% vs. 34.5%, p = 0.749), with a median follow-up of 17 months. Conclusions: PBT provided a significant dosimetric benefit over photon-based RT during nCRT for ESCC; however, it did not improve clinical outcomes.