Efficacy and Safety of Large-field Postoperative Radiotherapy Using Three-dimensional Radiation Technique for Local Advanced Thoracic Esophageal Squamous Cell Carcinoma: A Phase II Clinical Trial

Abstract

This trial aimed to explore the feasibility and safety of large-field postoperative radiotherapy for locally advanced (T3-4 or N+, M0) esophageal cancer using three-dimensional radiation technique. This trial is a single-center single-arm, phase II clinical trial initiated in 2014. Patients who underwent a radical transthoracic resection with negative margins within 3 months and histologically confirmed as esophageal squamous cell carcinoma (pT3-4 or N+, M0 according to AJCC 7th) were eligible for this study. Radiotherapy was delivered with total dose of 40Gy in 20 fractions using three-dimensional conformal radiation technique including conformal and intensity modulated radiotherapy. TV included tumor bed, anastomosis site, bilateral supraclavicular region, all mediastinal lymph node site, left gastric and celiac trunk lymph node site. The primary endpoint was 2-year local control rate. The secondary endpoint was overall survival (OS) and adverse events. 70 patients were enrolled in this phase II study from 2014 to 2016. The majority of patients were Ilia (40%), IIIA (27.1%) and IIIB (27.1%). 17 patients died. The 2 year-local control rate is 67.29%. Median OS was 57months. The 1, 2, 3 and 4-year OS rate were 92.75%, 69.57%, 60.87%, 53.47%. Locoregional recurrence was found in 28 patients (40%), most of which in mediastinal lymph node region (16 patients) and supraclavicular lymph node region (10 patients), followed by anastomosis (5 patients), celiac lymph node region (3 patients). 18 patients (25.7%) was found hematogenous recurrence. Nearly all patients complete the whole course postoperative radiotherapy with the completion rate of 97.1%, except for two patients. Although the tumor volume is relatively high with the median PTV volume of 1273.22cm3, despite the average dose of the heart is slightly higher, the dose volume histogram parameters of the other normal tissue and organ dose-volume are relatively ideal. Incidences of acute grade 3 hematological toxicity including 4(5.7%) leukopenia and 1(1.4%) neutropenia. In term of acute grade 3 nonhematological toxicity, nausea and vomiting (7.1%) were the most frequent AE followed by fatigue (2.8%) and radiation induced pneumonitis (1.4%). Nobody suffered grade 4 hematological or nonhematological AE. A No late AE occurred. This study is the first phase II study of postoperative radiotherapy in three-dimensional era, which proves that the dose distribution of large-field radiation is feasible and the toxicity is acceptable. It provides a basis for further exploration of higher dose large-field radiation and combined chemotherapy.