Current Advances in Proton FLASH Radiotherapy in Abdominal Cancers

TL;DR

Proton FLASH radiotherapy could improve cancer treatment for abdominal tumors by delivering high doses of radiation safely.

Contribution

This paper reviews recent preclinical and technical advances in proton FLASH for abdominal cancers and highlights challenges for clinical translation.

Findings

Preclinical studies show proton FLASH may reduce toxicity in abdominal cancers.

Treatment planning advances demonstrate feasibility of ultra-high dose rates in complex abdominal geometries.

Clinical translation faces challenges like inconsistent biological responses and lack of standardized dose-rate definitions.

Abstract

Proton FLASH radiotherapy represents one of the most promising frontiers in modern radiation oncology, with the potential to dramatically expand the therapeutic ratio for abdominal cancers. The GI tract has emerged as a critical focus due to its high radiosensitivity and proximity to many abdominal tumors. Preclinical findings on abdominal FLASH effects are encouraging yet inconsistent. The successful clinical translation remains complex, requiring resolution of biological uncertainties, standardization of dose rate metrics, robust treatment planning integration, and validation through well-designed clinical trials. With continued innovation in delivery hardware, planning systems, and mechanistic modeling, FLASH may ultimately enable safer dose escalation or reirradiation in abdominal sites where conventional approaches fall short.

Proton FLASH radiotherapy represents a promising innovation in the treatment of abdominal cancers, offering the potential to expand the therapeutic window by delivering ultra-high dose rates (UHDR) that spare normal tissue while maintaining tumor control. This approach is particularly beneficial for gastrointestinal (GI) tumors, where radiation dose escalation is often limited by the radiosensitivity of nearby organs. This review explores recent preclinical, planning, and technical developments in proton FLASH for abdominal sites and outlines the challenges and future directions for clinical translation. We reviewed the available published literature on proton FLASH radiotherapy, with a focus on abdominal applications. Recent preclinical studies in abdominal models have shown encouraging, though inconsistent, evidence of reduced toxicity with proton FLASH. Parallel advances in treatment planning have also demonstrated technical feasibility in achieving UHDR across complex abdominal geometries. However, key challenges remain, including variability in biological responses, lack of standardized dose-rate definitions, delivery system constraints, and the absence of robust clinical data. Although only limited clinical trials are currently underway, proton FLASH may enable safer hypofractionation, reirradiation, and dose escalation strategies in the future. Its successful clinical translation will require coordinated advances in biology, physics, and technology, supported by rigorous preclinical validation and carefully designed clinical trials.

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