A randomized controlled phase III trial of comparing local field with additional prophylactic irradiation in chemoradiotherapy for clinical-T1bN0M0 esophageal cancer:JCOG1904/ARMADILLO study.

Abstract

TPS257 Background:Parallel-group controlled trial of esophagectomy versus chemoradiotherapy (JCOG0502) showed chemoradiotherapy (CRT) is considered as a standard treatment option for clinical-T1bN0M0 esophageal squamous cell carcinoma (ESCC) with organ preservation. However, locoregional recurrence after CRT occurs in 20% of patients and requires salvage treatment including salvage surgery, chemo(radio)therapy, and endoscopic resection. Salvage treatments can cause complications and treatment-related death. CRT with elective nodal irradiation (ENI) have been reported to reduce the locoregional recurrence of esophageal cancer. We conduct the clinical trial to evaluate the efficacy of modified CRT with ENI compared with CRT without ENI for the patients with cTbN0M0 ESCC. The primary purpose of this study is to investigate whether modified CRT with ENI reduces the locoregional recurrence that cannot be completely resected by salvage endoscopic resection and preserve esophagus without compromising overall survival. Methods:Eligibility criteria include the followings; thoracic ESCC, adenosquamous, or basaloid cell carcinoma with clinical-T1bN0M0, age 20 or older, performance status 0 or 1, adequate organ function, and patient who do not have a preference to receive a surgical resection as an initial therapy. Patients are randomly assigned to following two arms using the minimization method with a random component to balance institution, tumor length (≤4cm versus > 4cm), and age (≤65 years old versus > 65 years old). Patients in arm A receive CRT consisted of CDDP (70 mg/m2/day, days 1 and 29) and 5-FU (700 mg/m2/day, days 1-4 and 29-32, civ) with concurrent radiotherapy (60 Gy/30 fr without ENI). Patients in arm B receive CRT consisted of CDDP (75 mg/m2/day, days 1 and 29) and 5-FU (1000 mg/m2/day, days 1-4 and 29-32, civ) with concurrent radiotherapy (50.4 Gy/ 28 fr with ENI of 41.4 Gy/23 fr). Primary endpoint is major progression-free survival (MPFS), defined as the time from randomization to the date of death or disease progression except achieving curative resection by salvage endoscopic resection. We assumed 5-year MPFS with arm A to be 70% and expected a 10% improvement for arm B. The planned sample size was calculated as a total of 280 patients (140 patients per arm) with a one-sided alpha of 5%, power of 70%, an accrual period of 4 years, and a follow-up period of 5 years. This trial was activated in July 2020. The study was also registered at the Japan Registry of Clinical Trials (jRCT) as study number jRCTs031200067. Clinical trial information: jRCTs031200067.