A Phase 2 Trial of Efficacy and Safety of Intraoperative Radiation Therapy for Locally Advanced Laryngocarcinoma

Abstract

For locally advanced laryngeal cancer (LAL), the local recurrence rate remains 19-40% after radical surgery with postoperative radiotherapy alone or with concurrent chemoradiotherapy in patients with unfavorable prognostic factors. We evaluate local control and acute toxicity of intraoperative radiation therapy (IORT) as a tumor bed boost for locally advanced laryngeal cancer in this prospective phase 2 trial. This phase II clinical study in which a total of 63 LAL patients (T2N1-3/T3N0-3/T4N0-3) were selected and received IORT (T2: 8-10Gy, T3,4:12-15 Gy) as a tumor bed boost during radical surgery, then received external-beam radiation therapy (EBRT) at a total dose of 54-60Gy within 6 weeks after surgery, 5 times per week, 1.8-2Gy per time, 30 times in total. The median follow-up time was 20 months (7 -39 months). The primary outcome was the local control (LC) and 2 - year survival rate determined using the Kaplan-Meier method. This study is registered with ClinicalTrials.gov, NCT04278638. A total of 63 patients consented to participate in the study; 59 males and 4 females, median age was 61 years (40-81 years), 14 patients had supraglottic LAL, 44 patients had glottic LAL and 5 patients had subglottic LAL. 10 patients showed high differentiation and 44 patients showed moderate differentiation and 9 patients showed low differentiation with laryngeal squamous cell carcinoma. 3 patients were in T2N1-2 stage, 40 patients in T3N0-2 stage, and 20 patients in T4N0-2 stage, 48 patients received total laryngectomy and 15 patients received hemilaryngectomy; 16 patients were lymph node-positive and 1 patient developed vascular tumor thrombus after surgery. After surgery combined with IORT and EBRT, the 1- and 2- year LC rates were 98.2% and 93.1 %, respectively, 2-year overall survival rate was 97.4%. Pharyngeal fistula was observed in 1 patient (1. 6 %) and wound infection in 3 patients (4.8%). Radiation Therapy Oncology Group (RTOG) grade 3 pain and RTOG grade 4 dyspnea were noted in one patient (1.6%) and 2 patients (3.2 %), respectively. In summary, our prospective phase II trial proved that the addition of intraoperative radiotherapy as a tumor bed boost to postoperative radiotherapy provided local therapeutic benefit to patients with locally advanced laryngeal cancer. Our data support the safety of this combined therapy. Additional investigation is warranted to determine the role of intraoperative radiotherapy in the local treatment of locally advanced laryngeal cancer.