Randomized Study on Different Radiation Doses in Neoadjuvant Chemoradiation Therapy for Resectable Thoracic...

Radiation dose selection for neoadjuvant chemoradiation therapy (nCRT) in esophageal squamous cell carcinoma (ESCC) varies widely in clinical practice, and prospective randomized data addressing this question are lacking. This trial compared 2 commonly used radiation dose regimens in nCRT for resectable thoracic ESCC.

This single-center, phase 2 prospective, randomized controlled trial enrolled patients with locally advanced thoracic ESCC from February 22, 2018, to February 22, 2021. Patients were randomized 1:1 to receive nCRT with either 50.4 Gy/28F or 41.4 Gy/23F, concurrent with weekly paclitaxel and carboplatin. The primary endpoint was 2-year progression-free survival (PFS).

A total of 147 patients were randomized (50.4 Gy, n = 72; 41.4 Gy, n = 75), of whom 101 underwent surgical resection. Pathologic complete response occurred in 23 of 46 patients (50.0%) in the 50.4-Gy group and 18 of 55 patients (32.7%) in the 41.4-Gy group (P = .078). Using major pathologic response (MPR) as an alternative endpoint, the 50.4 Gy/28F regimen significantly increased the MPR rate to 73.9%, compared with 52.7% in the low-dose group (P = .029). In the intention-to-treat population analysis, the 2-year PFS rates were 56.7% for the high-dose group and 49.3% for the low-dose group, with a hazard ratio (HR) of 0.72 (95% CI, 0.46-1.11; P = .14). Two-year overall survival (OS) rates were similar between groups. Grade ≥2 radiation esophagitis occurred more frequently in the 50.4-Gy group, whereas postoperative complication rates were comparable.

Dose escalation from 41.4 to 50.4 Gy in nCRT for resectable ESCC did not improve PFS or OS but was associated with a higher MPR rate and increased esophagitis. These findings support current evidence that routine dose escalation does not confer a survival advantage, while providing randomized ESCC-specific data to inform individualized treatment decisions.