Impact of Relative Biologic Effectiveness for Proton Therapy for Head and Neck and Skull-Base Tumors: A Technical and Clinical Review

Abstract

Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy's potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice.

Keywords: head and neck and skull-base cancers; proton therapy; relative biological effectiveness.

Figure 1

Biological dose estimations from various phenomenological RBE models from Rørvik et al. [61], Phys Med Biol 63 (18), 185,013 (2018). © Institute A physics and engineering in medicine, reproduced with the permission of IOP Publishing Ltd. BEL, CAR, CHE, FRE, JON, MAI, MCN, PLR, RØRU, RØRW, TIL2, UNK, WED, and WIL represent various phenomenological models included in the study. Please refer to Table 1 in [61] for details on each model. LETd, the dose-averaged linear energy transfer, is represented on the right axis. RBE indicates relative biological effectiveness.