Hypofractionated radiotherapy for head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma management involves surgery, radiotherapy, and systemic therapies. While normofractionated radiotherapy with concurrent chemotherapy remains standard, alternative fractionation schedules, such as hypofractionation, hold the potential to shorten treatment duration and therefore limit tumour repopulation, as well as improve patient adherence. Studies have explored hypofractionated radiotherapy in both exclusive and postoperative settings for head and neck squamous cell carcinoma. Recent studies like HYPNO randomized phase III trial (delivering 55 Gy in 20 fractions) and HYPORT phase I study (delivering 46.5 Gy in 15 fractions) have shown the feasibility and non-inferiority of hypofractionated radiotherapy compared to standard schedules but these results are insufficient to consider hypofractionated radiotherapy in exclusive and postoperative settings. Hypofractionated radiotherapy has been tested in several clinical situations: for early glottic cancer, in elderly patients, for metastatic disease/in palliative context. For early glottic cancers (T1–T2), moderate hypofractionation is a well-established strategy that showed its non-inferiority in terms of disease control and acceptable toxicity, notably in the JCOG0701 trial (delivery of 60 to 64.8 Gy in 25 to 27 fractions). Stereotactic body radiotherapy for glottic carcinoma has shown encouraging preliminary results in phase I-II studies, particularly when patient selection criteria are applied but caution remains necessary. In elderly patients, split-course hypofractionated radiotherapy reduced fraction number with favourable tolerance profile. The results of the ELAN-RT randomized phase III study support the possibility to prescribe a hypofractionated radiotherapy in elderly people. In palliative settings, hypofractionated radiotherapy regimens such as Christie and Hypo regimens have demonstrated effective symptom control. Overall, hypofractionated radiotherapy represents a promising strategy in selected clinical contexts for head and neck squamous cell carcinoma, but further prospective randomized studies are needed to define optimal indications and confirm long-term outcomes and safety.