Study Protocol: Prospective Study of Concurrent Chemoradiotherapy with S-1 and Hypofractionated Radiotherapy for Outpatients with Early Glottic Squamous Cell Carcinomas.

Background: The recommended treatment strategies for early glottic carcinoma with intent of larynx preservation are primarily radiotherapy. However, the outcomes of radiotherapy for bulky T1 or T2 glottic carcinoma are unsatisfactory. We designed a protocol consisting of concurrent chemoradiotherapy using S-1 as the radiosensitizer. We have performed this protocol in patients with favorable T2 lesions and demonstrated its efficacy and safety. In contrast, we have treated non-bulky T1 glottic carcinomas with 2.25 Gy per fraction, for a total of 25-28 fractions, starting in 2011 to improve efficacy and shorten the treatment period. Since this treatment strategy was implemented for T1 disease, no local failure has occurred to date, and it appears to be almost as safe as radiotherapy using 2.0 Gy per fraction. With the aim of improving the local control rate and shortening the treatment period primarily for favorable T2 disease, we changed the dose of radiation in our protocol from 2.0 Gy to 2.25 Gy per fraction, for a total of 25 fractions (from 30 fractions). The present study aims to evaluate the efficacy and safety of this new protocol. Methods: This study will be conducted as a clinical, prospective, single-armed, non-randomized trial. Patients are to receive S-1 (55.3 mg /m2 /day, once daily) and radiotherapy (2.25 Gy per fraction, for a total of 25 fractions). S-1 and radiotherapy are started on the same day that radiotherapy is performed, 3-6 hours after oral administration of S-1. The primary study aim is the 3-year local control rate. The secondary study aims are overall survival, voice-preservation survival, disease-free survival, complete response rate, completion rate, and toxicity. Result and conclusion: This is the first single-center, non-randomized, prospective study of concurrent chemoradiotherapy with S-1 and hypofractionated radiotherapy to be conducted. The trial will evaluate the efficacy and safety of our protocol.