Current application status of proton beam therapy for gastrointestinal tumors

Abstract Proton beam therapy (PBT) is a novel radiotherapy technique that provides highly conformal delivery of radiation dose to a tumor volume and less dose to neighboring healthy tissues, which depends on the Bragg peak. This dosimetric feature of PBT presents unique advantages for gastrointestinal (GI) malignancies in precise locations near dose-limiting structures in normal tissues, such as the heart and lungs. Because many GI tumors are in anatomically challenging sites, normal tissues may limit dosimetric efforts when treating those GI tumors with conventional photon-based approaches to tumor control. PBT presents a potential unique pathway to giving an increased dose to the tumor volume and minimizing treatment-related toxicity. Overall clinical outcome data give a glimpse into potential benefits of PBT, including minimized cardiopulmonary toxicity for esophageal cancer, improved preservation of liver functional reserve for hepatocellular carcinoma, and decreased gastrointestinal toxicity for pancreatic cancer. These would be especially meaningful aspects with multimodality therapy or in the setting of patients with limited functional reserve. The intent of this review is to summarize the recent clinical experience with PBT in the treatment of major GI malignancies, with a specific focus on clinical outcomes, toxicity, and other important technical considerations. Additionally, this review seeks to provide some insight into barriers to clinical use of PBT: high cost of PBT, limited availability, and the lack of large, randomized clinical trials. Future efforts will benefit from continuing to improve patient selection, elucidating possible synergistic effects with emerging systemic therapies, and producing higher levels of evidence to support broadening clinical application.