Hypofractionated Particle Therapy: A Review of Clinical Data and Implications

Hypofractionated particle therapy (HPT) is an evolving treatment paradigm in radiation oncology, offering enhanced therapeutic ratios through both biological and dosimetric advantages. Proton therapy leverages the Bragg peak phenomenon to reduce the integral dose to normal tissues, a benefit amplified by delivering larger doses per fraction. Carbon ion radiotherapy (CIRT) further augments this approach through high linear energy transfer (LET) and greater relative biological effectiveness (RBE), potentially overcoming radioresistance mechanisms. This review synthesizes updated clinical evidence for HPT, including proton and CIRT across various disease sites. Clinical trial data on efficacy and toxicity are reviewed, including comparisons with photon-based radiotherapy. The clinical outcomes observed thus far highlight the safety and efficacy of biologically intensified HPT regimens, underscoring the need for continued, well-designed phase II/III trials to define optimal indications and fractionation strategies.