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A randomized phase III trial commenced in Japan in February 2018. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced unresectable esophageal carcinoma. The purpose of this study is to confirm the superiority of induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) followed by conversion surgery or definitive CRT over definitive CRT alone for overall survival (OS) in patients with locally advanced unresectable squamous-cell carcinoma of thoracic esophagus. A total of 230 patients will be accrued from 47 Japanese institutions over 4.5 years. The primary endpoint is OS, and the secondary endpoints are progression-free survival, complete response rate of CRT, response rate of DCF, adverse events of DCF and CRT, late adverse events and surgical complications. This trial has been registered at the Japan Registry of Clinical Trials as jRCTs031180181., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

About 80% of cases of locally advanced unresectable thoracic oesophageal squamous cell carcinoma recur within the irradiation fields after chemoradiotherapy. Radiation dose escalation using advanced radiotherapy techniques is expected to improve clinical outcomes by reducing local and regional recurrence. The current study aimed to determine the recommended escalated radiation dose for these patients. Patients with locally advanced unresectable thoracic oesophageal squamous cell carcinoma with good performance status underwent chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) with elective nodal irradiation. SIB-IMRT was delivered in five fractions per week. The radiation dose to the unresectable gross tumour was escalated from 66 Gy to a planned maximum dose of 72 Gy in 3 Gy increments in a standard 3 + 3 design. The doses to the resectable component, superficial tumours and elective nodal regions were fixed as 60, 51 and 48 Gy, respectively. Cisplatin and 5-fluorouracil were concurrently administered. Dose-limiting toxicity (DLT) was defined as acute grade 3 oesophagitis, grade 2 pneumonitis, grade 2 cardiac toxicity and a failure to complete planned radiotherapy within 60 days. Locoregional control and overall survival were estimated using the Kaplan–Meier method. Nine patients were enrolled. DLTs occurred in one of six and two of three patients at doses of 66 and 69 Gy, respectively. All DLTs were grade 3 oesophagitis. The recommended dose was determined as 66 Gy delivered in 30 fractions based on the predefined criteria. With a median follow-up period of 23 months, the 1-year locoregional control and overall survival rates were 67 (95% confidence interval = 19–90) and 78% (95% confidence interval = 36–94), respectively. The recommended radiation dose in chemoradiotherapy using SIB-IMRT with elective nodal irradiation was 66 Gy delivered in 30 fractions. • Recommended radiation dose in CRT using SIB-IMRT with ENI was 66 Gy in 30 fractions. • Oesophagitis is a major dose-limiting toxicity. • The results are consistent with reported dose-volume metrics of the oesophagus. • Omitting ENI is probably needed for a further dose escalation. [ABSTRACT FROM AUTHOR]