Four-Week Hypofractionated Radiotherapy for Early Glottic Cancer: A Prospective Study of Toxicity and Tolerance With Historical Comparison

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INTRODUCTION: Hypofractionated radiotherapy has become an increasingly accepted treatment for early-stage glottic carcinoma, aiming to optimize tumor control while minimizing the impact of accelerated repopulation and treatment prolongation. However, evidence regarding more hypofractionated regimens with fraction sizes above 2.5 Gy remains limited, particularly for T2 disease. METHODS: We conducted a prospective interventional study at the Department of Radiotherapy, American Hellenic Educational Progressive Association (AHEPA) University Hospital, including 23 patients, so far, with histologically confirmed T1-T2N0M0 glottic carcinoma treated with definitive hypofractionated radiotherapy. Treatment consisted of 55 Gy in 20 fractions (2.75 Gy/fraction) delivered with volumetric modulated arc therapy (VMAT) and daily image guidance. The primary endpoint was toxicity; local control was a secondary endpoint, though its evaluation is limited by the relatively short follow-up. Results were also descriptively compared with prior institutional experience using conventional or mildly hypofractionated three-dimensional conformal radiotherapy. RESULTS: At a median follow-up of 16 (range: 1-36) months, 22 of 23 (95.7%) patients achieved a complete response, while one patient (4.3%) had residual disease and underwent successful salvage transoral laser surgery. Two patients experienced local recurrence after initial complete response; both were successfully salvaged surgically and remain disease-free. By Kaplan-Meier analysis, the one-year local control was 91.7% for T1 disease (95% CI: 76.0-100.0%) and 85.7% for T2 disease (95% CI: 59.8-100.0%), corresponding to an overall one-year local control of 91.3% (log-rank p=0.65). All patients were alive at the last follow-up. Acute toxicities were primarily grade 1-2 (larynx, mucosa, skin, esophagus). Grade 3 acute events included hoarseness (n=7) and dysphagia requiring temporary enteral feeding (n=3). Late toxicities were generally mild, with most events grade 1; grade 2 toxicities involved skin, esophagus, or larynx in a few patients. No grade 4 or 5 events occurred. CONCLUSIONS: Hypofractionated VMAT with 55 Gy in 20 fractions is a feasible and safe approach for early glottic carcinoma, providing very good tumor control in T1 disease, acceptable outcomes in T2 disease, and a low incidence of significant toxicity. These findings are consistent with international evidence and compare favorably with prior institutional audit results. Longer follow-up and larger cohorts are required to confirm the durability of local control, particularly in T2 disease.

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