A higher dose of radiation did not improve outcomes in patients undergoing concurrent chemoradiotherapy (CCRT) for inoperable esophageal squamous cell carcinoma (ESCC), according to results of a phase 3 trial published in Clinical Cancer Research.
The trial did not meet its primary endpoint of locoregional progression-free survival (LRPFS), as there was no significant difference with a radiation dose of 60 Gy or 50 Gy.
In addition, patients who received the 60 Gy dose had a higher incidence of severe radiation-related pneumonitis.
The phase 3 trial (ClinicalTrials.gov Identifier: NCT01937208) enrolled 319 patients with stage IIA-IVA ESCC. They were randomly assigned 1:1 to receive a 60 Gy or 50 Gy radiation dose to the tumor and regional lymph nodes. Patients also received concurrent weekly chemotherapy (docetaxel 25 mg/m2 and cisplatin 25 mg/m2) and 2 cycles of consolidation chemotherapy (docetaxel 70 mg/m2 and cisplatin 25 mg/m2 on day 1-3).
The radiotherapy completion rate was 88.2% in the 60 Gy cohort and 96.6% in the 50 Gy cohort (P <.01). The entire 5 courses of weekly CCRT was completed by 58.1% of patients in the 60 Gy cohort and 63.5% in the 50 Gy cohort.
The objective response rate at 4 weeks after treatment completion was 90.6% in the 60 Gy cohort and 93.4% in the 50 Gy cohort.
At a median follow-up of 34.0 months for the overall study population (319 patients), and 55.2 months for survivors (153 patients), there was no significant difference between the arms with regard to LRPFS, progression-free survival (PFS), or overall survival (OS).
The median LRPFS was 36.0 months in the 60 Gy cohort and 34.5 months in the 50 Gy cohort (hazard ratio [HR], 1.00; 95% CI, 0.75-1.35; P =.98). The 3-year LRPFS rates were 49.5% and 48.4%, respectively.
The median PFS was 27.7 months in the 60 Gy cohort and 25.5 months in the 50 Gy cohort (HR, 0.97; 95% CI, 0.73-1.30; P =.86). The 3-year PFS rates were 46.4% and 46.1%, respectively.
The median OS was 45.3 months in the 60 Gy cohort and 41.2 months in the 50 Gy cohort (HR, 0.99; 95% CI, 0.73-1.35; P =.96). The 3-year OS rates were 53.1% and 52.7%, respectively.
Grade 3 or higher adverse events (AEs) were observed in 54.7% of patients in the 60 Gy cohort and 50.9% in the 50 Gy cohort (P =.50). A higher proportion of patients experienced grade 3 or higher radiation-related pneumonitis in the 60 Gy cohort than in the 50 Gy cohort (7.5% vs 3.1%; P =.03).
In the 60 Gy cohort, there were 7 fatal AEs possibly related to treatment — 4 cases of esophageal fistula, 1 case of esophageal bleeding, and 2 pulmonary-related deaths. In the 50 Gy cohort, there were 8 fatal AEs possibly related to treatment — 4 cases of esophageal fistula, 2 cases of esophageal bleeding, and 2 pulmonary-related deaths.
Based on these outcomes, the researchers concluded that “50 Gy should be the recommended radiation dose of CCRT in the treatment of ESCC.”
Xu Y, Dong B, Zhu W, et al. A phase III multicenter randomized clinical trial of 60 Gy vs 50 Gy radiation dose in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma. Clin Cancer Res. February 18, 2022. doi:10.1158/1078-0432.CCR-21-3843