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Updated: Apr 21, 2026
Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
Published on: May 24, 2024
Phase II randomized trial of 41.4 Gy vs. 50.4 Gy in neoadjuvant chemoradiotherapy for resectable esophageal cancer
Ebrahim Esmati1,2, Reza Nazari1, Ali Aqamolaei1
1Department of Radiation Oncology, Cancer Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Background:
The optimal total dose of radiotherapy for non-metastatic resectable esophageal cancer remains unclear. We compared standard (41.4 Gy) versus intensified (50.4 Gy) chemoradiotherapy (CRT) regimen.
Methods:
In a prospective, phase II, randomized controlled trial (Iran Cancer Institute, March 2021-March 2023), non-metastatic resectable esophageal cancer patients were randomly assigned 1:1 to 41.4 Gy or 50.4 Gy plus weekly carboplatin-paclitaxel followed by surgery, unless a clinical complete response (cCR) was confirmed or the patient refused. The primary outcome of the study was the composite major response rate, defined as pathological complete response (pCR)/pathological near complete response (pnCR) for surgical patients and cCR for non-surgical patients. Survival outcomes and toxicity were secondary outcomes.
Results:
Seventy-eight patients were randomized; 70 cases received the allocated CRT in the standard group (34) and intensified group (36). Subsequently, 23 and 21 patients underwent surgery, respectively. The composite major response rate was 54.8% versus 65.6% in the standard and intensified arms, respectively (p = 0.382). The cCR rates were 35.48% vs 45.16%, respectively (p = 0.437). Among resected patients, pCR rates were 45.45% vs 52.38% (p = 0.650), and R0 resection rates were 95.2% vs 100%, respectively. No significant differences were observed between treatment groups in overall and disease-free survival. Grade 2 or higher pneumonitis was significantly more frequent with 50.4 Gy (25% vs 5.9%, p = 0.028). Additionally, cCR predicted pCR with high specificity (90.5%) but modest sensitivity (60%).
Conclusions:
Escalating the total dose of neoadjuvant radiotherapy from 41.4 Gy to 50.4 Gy did not improve response rates or survival but significantly increased pneumonitis. Radiotherapy with a 41.4 Gy dose and concurrent carboplatin-paclitaxel, also known as the CROSS regimen, remains an optimal standard. Our findings also highlight a key clinical dilemma: while a cCR can identify candidates for organ preservation, but does not reliably exclude residual disease.Trial registration: IRCT20250118064427N1 (Registration date: 2025-07-28).
