Dose escalation based on 18 F-FDG PET/CT response in definitive chemoradiotherapy of locally advanced esophageal squamous cell carcinoma: a phase III, open-label, randomized, controlled trial (ESO-Shanghai 12).

INTRODUCTION: Definitive chemoradiotherapy has established the standard non-surgical treatment for locally advanced esophageal cancer. The standard dose of 50-50.4 Gy has been established decades ago and been confirmed in modern trials. The theorical advantage of better local control and technical advances for less toxicity have encouraged clinicians for dose escalation investigation. 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) have the potential to tailor therapy for esophageal patients not showing response to CRT and pioneers the PET-based dose escalation.

METHODS AND ANALYSIS: The ESO-Shanghai 12 trial is a prospective multicenter randomized phase 3 study in which patients are randomized to either 61.2 Gy or 50.4 Gy of radiation dose by PET response. Both groups undergo concurrent chemoradiotherapy with paclitaxel/cisplatin regimen for 2 cycles followed by consolidation chemotherapy for 2 cycles. Patients with histologically confirmed ESCC [T1N1-3M0, T2-4NxM0, TxNxM1 (Supraclavicular lymph node metastasis only), (AJCC Cancer Staging Manual, 8th Edition)] and without any prior treatment of chemotherapy, radiotherapy or surgery against esophageal cancer will be eligible. The primary endpoints included overall survival in PET/CT non-responders (SUVmax  > 4.0) and overall survival in total population. Patients will be stratified by standardized uptake volume, gross tumor volume and tumor location. The enrollment could be ended, when the number of PET/CT non-responder reached 132 and the total population reached 646 for randomization.

ETHICS AND DISSEMINATION: This trial has been approved by the Fudan University Shanghai Cancer Center Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations. Trial registration The trial was initiated in 2018 and is currently recruiting patients. Trial registration number NCT03790553.