Early Closure of a Phase 1 Clinical Trial for SABR in Early-Stage Glottic Cancer.

Abstract

PURPOSE\nThe early results of a phase 1 study of stereotactic ablative radiation therapy for early-stage glottis cancer were previously reported. However, additional late adverse events occurred in the second arm during the follow-up period. In this study, the dose-limiting toxicities and premature closure of the clinical trial are reported.\n\n\nMETHODS AND MATERIALS\nThirteen patients with cT1-2N0M0 squamous cell carcinoma of the glottis were enrolled between May 2015 and July 2018. Seven patients in the first arm received 59.5\xa0Gy to the gross tumor volume and 47.6\xa0Gy to the remaining larynx, delivered in 17 fractions. The second arm dose was 55\xa0Gy and 40.7\xa0Gy in 11 fractions to the gross tumor volume and the remaining larynx, respectively. Patients were treated according to the simultaneous integrated boost approach with volumetric modulated arc therapy.\n\n\nRESULTS\nThe median follow-up was 37\xa0months (range, 6-41.4) for the first arm and 14.5\xa0months (range, 4.8-21.5) for the second arm. Maximum acute toxicity was grade 2 laryngeal mucositis for each arm. Maximum chronic toxicity was grade 3 laryngeal inflammation, occurring in 2 patients (33.3%) in the second arm. One patient underwent a laryngomicrosurgical biopsy for a vocal cord ulcer, and another patient underwent supraglottic laryngectomy because of arytenoid cartilage necrosis. In the first arm, chronic toxicity was not observed, except for grade 1 laryngeal edema in 1 patient.\n\n\nCONCLUSIONS\nThe phase 1 dose escalation study was terminated early because of the unexpected dose-limiting toxicities occurring in patients in the second arm. It was concluded that stereotactic ablative radiation therapy is not feasible for early-stage glottic cancer owing to treatment-related toxicity.