Evolution of Particle Radiotherapy: From Physical to Dual Targeting in Precision Medicine

As cancer remains a formidable global health challenge, radiotherapy is evolving toward unprecedented levels of precision. Particle radiotherapy (PRT), utilizing charged particles such as protons and carbon ions, has emerged as a superior alternative to conventional photon-based approaches. While proton therapy (PT) achieves superior physical targeting via the Bragg peak and carbon ion radiotherapy (CIRT) adds biological potency through high linear energy transfer (LET), both modalities are fundamentally constrained by their primary reliance on spatial/macroscopic dose distribution. Against this backdrop, boron neutron capture therapy (BNCT) stands out as an innovative dual-targeting strategy in precision oncology. BNCT combines biochemical selectivity (achieved via tumor-specific boron-10 agents) with cellular-scale physical precision (realized by neutron-irradiation-triggered, locally confined high LET particles). This review delineates the latest progress in particle radiotherapy, specifically highlighting the crucial transition from the established physical targeting of PT and CIRT to the burgeoning dual-targeting innovation of BNCT. We provide an in-depth analysis of mechanistic principles, technological advancements in accelerator-based sources, the pharmacological evolution of boron delivery systems, and the resulting clinical applications. Future directions for the entire particle radiotherapy field center on reducing operational costs, optimizing therapeutic accuracy, conducting robust randomized trials, and exploring synergistic therapies. Critically, BNCT, with its unique dual-targeting mechanism, represents a potentially transformative precision therapy with significant potential for intractable malignancies.