A Phase III Multicenter Randomized Clinical Trial of 60 Gy versus 50 Gy Radiation Dose in Concurrent Chemoradiotherapy for Inoperable Esophageal Squamous Cell Carcinoma

Abstract

Purpose: In this multicenter phase 3 trial, the efficacy and safety of 60 Gy and 50 Gy doses delivered with modern radiotherapy technology for definitive concurrent chemoradiotherapy (CCRT) in patients with inoperable esophageal squamous cell carcinoma (ESCC) were evaluated. Patients and Methods: Patients with pathologically confirmed stage IIA‒IVA ESCC were randomized 1:1 to receive conventional fractionated 60 Gy or 50 Gy to the tumor and regional lymph nodes. Concurrent weekly chemotherapy (docetaxel 25 mg/m2; cisplatin 25 mg/m2) and two cycles of consolidation chemotherapy (docetaxel 70 mg/m2; cisplatin 25 mg/m2 days 1‒3) were administered. Results: A total of 319 patients were analyzed for survival, and the median follow-up was 34.0 months. The 1- and 3-year locoregional progression-free survival (PFS) rates for the 60 Gy group were 75.6% and 49.5% versus 72.1% and 48.4%, respectively, for the 50 Gy group [HR, 1.00; 95% confidence interval (CI), 0.75‒1.35; P = 0.98]. The overall survival rates were 83.7% and 53.1% versus 84.8% and 52.7%, respectively (HR, 0.99; 95% CI, 0.73‒1.35; P = 0.96), whereas the PFS rates were 71.2% and 46.4% versus 65.2% and 46.1%, respectively (HR, 0.97; 95% CI, 0.73‒1.30; P = 0.86). The incidence of grade 3+ radiotherapy pneumonitis was higher in the 60 Gy group (nominal P = 0.03) than in the 50 Gy group. Conclusions: The 60 Gy arm had similar survival endpoints but a higher severe pneumonitis rate compared with the 50 Gy arm. Fifty Gy should be considered as the recommended dose in CCRT for ESCC.

Paclitaxel and cisplatin combined with concurrent involved-field irradiation in definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma: a phase II clinical trial

“…Many differences in patient and tumor factors could have produced those conflicting results. Recent multicenter, phase III randomized studies reported that 50 Gy is as effective as 60 Gy in ESCC, both in Europe (ARTDECO study) and China (Xu et al) [19,20]. In Xu et al 's study, the incidence of radiation-related pneumonia of grade 3 or above in the 60 Gy group was higher than that in the 50 Gy group (7.5% vs 3.1%, P = 0.03).…”

The impact of radiation dose on the efficacy of definitive chemoradiotherapy in patients with locally advanced esophageal carcinoma: a systematic review and meta-analysis

“…Undoubtedly, the findings of three recent randomized controlled trials must be discussed. This study included the ARTDECO study 14 and the study conducted by Xu et al, 15 whereas the CONCORDE study 30 only reported the results of conference abstracts, which could not be included in this study. According to the ARTDECO study, there was no significant difference in PFS, OS, and Locoregional progression-free survival (LRPFS) between the HD-RT (61.6 Gy) group and LD-RT (50.4 Gy) group.…”

“… 7 , 8 Simultaneously, dose escalation has been shown in numerous clinical trials and meta-analyses to improve local control (LC) and OS with no increase in serious side effects, raising the possibility that this factor may be advantageous in CCRT. 9–13 Nevertheless, the ARTDECO study 14 and the study undertaken by Xu et al 15 came to oppose, indicating that dose escalation has no benefit on OS. Hence, the recommended radiation dose remains controversial.…”

Radiation Dose-Effect Relation in Patients with Esophageal Squamous Cell Carcinoma: A National Cancer Center Data and Literature-Based Analysis

“…Analogously, subgroup analysis of the current study revealed that patients with KPS ≥ 80, indicating superior treatment tolerance, and patients with T3-4 lesion or lymph node metastasis, indicating a higher tumor burden, tended to show survival benefit in radiation dose escalation. The negative findings of recently published prospective clinical trials [ 9 , 10 ] may be partially attributed to the heterogeneous nature of the study population. That study population included a large proportion of patients without lymph node metastasis (accounting for 30.4% and 26.1% of the cases).…”

“…Several phase 1/2 clinical trials have revealed the safety and superior survival outcomes in patients received definitive radiotherapy of radiation dose boost over 60 Gy [6][7][8]. But two recently published phase 3 clinical trials demonstrated survival benefit was not attained with a radiation dose over 60 Gy [9,10]. e optimal radiation dose for definitive treatment of ESCC remains debatable in the era of conformal RT and intensity-modulated RT (IMRT).…”