A randomized controlled phase III multicenter study on dose escalation in definitive chemoradiation for patients with locally advanced esophageal cancer: ARTDECO study.

Abstract

281 Background: To analyze the effect of radiation dose escalation to the primary tumor on local control, locoregional control, survival and toxicity in definitive chemoradiation for esophageal cancer. Methods: Patients with clinical stage T2-4, N0-3, M0 carcinoma of the esophagus were randomized between a standard dose of 50.4 Gy/1.8 Gy/5,5 weeks to the tumor and regional lymph nodes (SD) versus the same dose combined with an integrated boost of 0,4 Gy per fraction (total 61,6 Gy) to the primary tumor (HD). Chemotherapy consisted of 6 weekly concurrent carboplatin (AUC 2) and paclitaxel (50 mg/m2) in both arms. The primary endpoint was local progression free survival (LPFS) and 260 patients were needed to detect a difference of 15% (power: 80%). Secondary endpoints were locoregional progression free survival (LRPFS), overall survival (OS) and toxicity. Patients were stratified for histological subtype. Results: Between September 2012 and June 2018, 260 patients were included. Reasons for inoperability were proximal localization and patient preference (44%), comorbidity (30%), unresectable lymph nodes (11%), T4 (5%), local recurrence 2% and combinations (7%). 61% of the patients had a squamous cell carcinoma (SCC) and 39% had an adenocarcinoma (AC). 94% completed radiation treatment and 85% had at least 5 courses chemotherapy. Median follow up time was 45 months. 3-year LPFS was 70% in the SD arm versus 76% in the HD arm (ns). LPFS for SCC and AC was 74% versus 81% and 62% versus 65% for SD and HD, resp. (ns). 3-year LRPFS was 53% and 63% for the SD and HD arm resp. (p = 0.08). 1 year any progression free survival was 60% for SCC and 50% for AC, without a significant difference between SD and HD (p = 0,5). 3-year OS was 41% versus 40% for SD and HD resp. Overall grade 4 and 5 CTC toxicity was 12% and 4% in the SD arm versus 14% and 10% in the HD arm, resp. Conclusions: In definitive chemoradiation for esophageal cancer, radiation dose escalation up to 61,6 Gy to the primary tumor did not result in a significant increase in local control over 50,4 Gy. Numerical improvement of locoregional control after HD was observed with an increase in toxicity and without improving OS. Clinical trial information: NL38343.018.11.

Radiation dose escalation can improve local disease control and survival among esophageal cancer patients with large primary tumor volume receiving definitive chemoradiotherapy

“…However, escalated radiation dose resulted in numerical increase in toxicity but did not improve the overall survival. [ 16 ] In line with the ARTDECO trial, the present study did not observe the benefit in local disease control or survival from increasing radiation dose in our whole cohort. Interestingly, we found that increasing radiation dose to more than 60 gray in patients with large primary tumor volume (≥ 55.3 cm 3 ) can improve local disease control and overall survival ( Fig 4 ).…”

High vs. Low Radiation Dose of Concurrent Chemoradiotherapy for Esophageal Carcinoma With Modern Radiotherapy Techniques: A Meta-Analysis

“…Our meta-analysis showed that although esophagus-related toxicity and pulmonary injury were the main severe late toxicities, high radiation dose did not increase the toxicities, which finally convert to the survival benefit. Two nearly closed RCTs reported the initial results by conference abstracts, which could not be included in this study (37,38). Xu et al (37) showed no difference toward 1 and 2 y-OS or treatment toxicity between the HD-RT (60 Gy) and LD-RT (50 Gy) groups.…”

“…Two nearly closed RCTs reported the initial results by conference abstracts, which could not be included in this study ( 37 , 38 ). Xu et al ( 37 ) showed no difference toward 1 and 2 y-OS or treatment toxicity between the HD-RT (60 Gy) and LD-RT (50 Gy) groups.…”

“…Moreover, the result renewed at the 2018 Chinese Society for Radiation Oncology (CSTRO) annual meeting showed a marked but nonstatistically significant improvement of 3 y-OS (63.1 vs. 55.7%, P = 0.199), which may be due to the limited sample size. The ARTDECO study ( 38 ) reported that the HD-RT (61.6 Gy) group did not result in a better OS or local–regional control than LD-RT (50.4 Gy) group. However, the radiation dose escalation was only delivered to the primary tumor with a numerical improvement of the local–regional control.…”

A national study to assess outcomes of definitive chemoradiation regimens in proximal esophageal cancer

“…In the era of modern RT techniques, dose escalation in CRT for EC has been investigated in 260 patients with EC by the randomized ARTDECO study, including 72 patients (28%) with proximal EC. Radiation dose escalation up to 61.6 Gy versus 50.4 Gy to the primary tumor in CP-based CRT did not improve local control and OS [32].…”