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

Int J Radiat Oncol Biol Phys. 2019 Sep 1;105(1):104-109. doi: 10.1016/j.ijrobp.2019.03.011. Epub 2019 Mar 14.


Purpose: The 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.

Methods and materials: Thirteen 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 Gy to the gross tumor volume and 47.6 Gy to the remaining larynx, delivered in 17 fractions. The second arm dose was 55 Gy and 40.7 Gy 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.

Results: The median follow-up was 37 months (range, 6-41.4) for the first arm and 14.5 months (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.

Conclusions: The 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Early Termination of Clinical Trials*
  • Edema / etiology
  • Follow-Up Studies
  • Glottis
  • Humans
  • Laryngeal Diseases / etiology
  • Laryngeal Neoplasms / pathology
  • Laryngeal Neoplasms / radiotherapy*
  • Larynx / radiation effects
  • Middle Aged
  • Radiation Dose Hypofractionation
  • Radiation Injuries / complications
  • Radiation Injuries / pathology
  • Radiosurgery / adverse effects
  • Radiosurgery / methods*
  • Stomatitis / etiology
  • Ulcer / etiology

Associated data

  • CRiS/KCT0001805