The global landscape of particle beam radiotherapy trials over the past 15 years

Particle beam radiotherapy (PBRT), with its advantageous physical and biological properties, holds promise for improving therapeutic outcomes. To elucidate future clinical trial designs and policy decisions, we conducted this cross-sectional analysis of PBRT trials.

We identified and analyzed the PBRT trials registered on ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform from September 27, 2007 to June 3, 2023, examining key characteristics and comparing completed trials with those terminated prematurely.

A total of 416 PBRT trials were identified, comprising 285 proton therapy trials and 131 carbon ion therapy trials. The number of PBRT trials increased steadily from 101 (2007-2012) to 172 (2017-2023) but declined sharply after 2021. Despite decades of development, more than 70% of PBRT trials remained in phase I/II, and more than 50% had sample sizes of fewer than 50 participants (carbon ion: 67.9%; proton: 49.5%). Compared with proton therapy trials, carbon ion trials tended to exclude elderly individuals more strictly (P < 0.001). Carbon ion trials were conducted predominantly in Asia (77.1%) and were more likely to receive government funding (22.1% vs. 7.7%, P < 0.001). Digestive system cancers and prostate cancer have been the primary indications for PBRT trials, although the proportion of head and neck tumors has been increasing annually. Moreover, Early termination trials were more common among preregistered (P = 0.002), small sample-size (P < 0.001), elderly inclusive (P = 0.020), and nongovernment-funded (P = 0.003) clinical trials. Compared with PBRT, photon radiotherapy features standardized trial designs and provides greater flexibility in terms of age limitations.

Despite decades of development, clinical application of PBRT remains in the preliminary exploration stage. Our study provides a comprehensive overview of PBRT trials over the past fifteen years, offering crucial guidance for future trial designs and policy formulation.