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

Abstract

Thirteen patients with early glottic cancer were enrolled for a phase 1 dose escalation trial of stereotactic ablative radiation therapy. Doselimiting toxicities, specifically grade 3 late toxicities, occurred in 2 of 6 patients who received 55 Gy in 11 fractions. Hypofractionated radiation therapy at doses of 59.5 Gy in 17 fractions was well tolerated with acceptable voice outcomes, quality of life, and local control. 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

Is Single Cord Irradiation Going to Be a New Standard for T1a Glottic Carcinoma?

“…Considering dose volume relationship on normal tissue complications, it is reasonable to increase the total dose if irradiated volume is decreased. The present study and a series by Al Mamgani et al (17). The abovementioned studies usually calculated dose EQD2 choosing an a/b ratio of 10 without time factor.…”

“…Results of previous and present studies are summarized in Table 4. Overall local control rates seem excellent for patients with T1 glottic cancer treated with single cord irradiation (17). Optimal dose and fractionation, however, will be determined in further studies.…”

“…At a median follow up of 25.7 months, no recurrences were observed in dose level 2 (34). Kang et al conducted a phase 1 clinical trial for SBRT in early glottic cancer with a different concept (17). They described two CTVs: one entire larynx and the second one with only gross tumor volume.…”

“…Two of six patients developed GIII late laryngeal toxicity in 55 Gy in 11 fraction dose level. Trial was closed early because of high toxicity rate for early glottic cancer (17). High laryngeal edema rate is probably due to inclusion of the entire larynx as a part of target volume.…”

“…Therefore, this resulted in diminished early complication rate and better voice quality may be achieved without compromising local control (11)(12)(13)(14)(15). After their publications, a new approach, "SBRT to the involved vocal cord, " for early glottic tumors has gained attention and has been investigated by other institutions (14,16,17). Mitigation of side effects from radiation exposure is very important for the group of patients who are prone to have tobacco-related vascular disease (15) and also likely to improve voice quality.…”