The Role of Hypofractionation in Proton Therapy

SIMPLE SUMMARY: Hypofractionation is a radiation oncology concept in which larger doses per fraction are administered and therefore less fractions are prescribed in a given treatment course. This concept has been increasingly utilized in recent years in external beam radiotherapy (EBRT). Hypofractionation has the potential benefits of reducing the length of treatment and also treatment costs. In the case of proton beam therapy (PBT), which is a limited resource with only 99 facilities currently in operation worldwide in 2021, hypofractionation also has the benefit of potentially increasing the number of patients able to access PBT. This review article will discuss the reported clinical data and radiobiology of hypofractionated PBT. The aim is to report on the current knowledge of hypofractionation in PBT and the issues which still require investigation. Over 50 published manuscripts reporting clinical results involving hypofractionation and PBT were included in this review, where the most common treatment regions were prostate, lung and liver. Future clinical trials are still needed to determine the optimal fractionation regime. ABSTRACT: Hypofractionated radiotherapy is an attractive approach for minimizing patient burden and treatment cost. Technological advancements in external beam radiotherapy (EBRT) delivery and image guidance have resulted in improved targeting and conformality of the absorbed dose to the disease and a reduction in dose to healthy tissue. These advances in EBRT have led to an increasing adoption and interest in hypofractionation. Furthermore, for many treatment sites, proton beam therapy (PBT) provides an improved absorbed dose distribution compared to X-ray (photon) EBRT. In the past 10 years there has been a notable increase in reported clinical data involving hypofractionation with PBT, reflecting the interest in this treatment approach. This review will discuss the reported clinical data and radiobiology of hypofractionated PBT. Over 50 published manuscripts reporting clinical results involving hypofractionation and PBT were included in this review, ~90% of which were published since 2010. The most common treatment regions reported were prostate, lung and liver, making over 70% of the reported results. Many of the reported clinical data indicate that hypofractionated PBT can be well tolerated, however future clinical trials are still needed to determine the optimal fractionation regime.