Hypofractionated radiotherapy in head and neck cancer: current evidence and future directions, with a focus on laryngeal cancer

Radiotherapy (RT) remains a cornerstone in the management of head and neck squamous cell carcinoma (HNSCC) across both definitive and multimodality treatment settings. While hypofractionated radiotherapy (HFRT) has become an established standard of care for several solid tumors, including prostate, breast, lung, and rectal cancers, its adoption in HNSCC has been more cautious owing to the complex anatomy of the head and neck region, the proximity of numerous critical organs at risk, and concerns regarding severe late toxicity. However, major advances in intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), image guidance, adaptive radiotherapy, and radiobiological understanding have renewed interest in HFRT as a strategy to maintain oncological efficacy while reducing overall treatment time. Additional drivers include the need to optimize healthcare resource utilization, improve access to radiotherapy in low- and middle-income countries, and minimize hospital visits, as highlighted during the COVID-19 pandemic. Recent prospective evidence has further strengthened the rationale for carefully selected hypofractionated approaches in HNSCC. In elderly and frail patients, the phase III ELAN-RT trial has also provided prospective evidence regarding a tailored hypofractionated approach for patients unable to undergo standard treatment. Among head and neck subsites, laryngeal cancer—particularly early-stage glottic carcinoma—represents the most mature clinical model for HFRT and therefore constitutes the principal focus of this review, while evidence from other HNSCC subsites is examined to assess the broader applicability of hypofractionated treatment strategies. This review critically summarizes the radiobiological rationale, current clinical evidence, technological advances, and ongoing challenges surrounding radical HFRT in HNSCC, with particular emphasis on laryngeal cancer, and discusses future directions for its broader implementation in clinical practice.