Sparing lymphocytes during preoperative adjuvant radiotherapy for oesophageal squamous cell carcinoma (SPARE): protocol for an open-label, randomised controlled trial.

INTRODUCTION

Oesophageal squamous cell carcinoma (ESCC) ranks among the most aggressive malignancies and carries a poor prognosis. Lymphocytes play a key role in combating infections and suppressing tumourigenesis. Many studies have established a close association between lymphocyte depletion and adverse therapeutic outcomes in oesophageal cancer. Nevertheless, high-quality data validating the clinical efficacy and safety of lymphocyte-sparing thoracic radiotherapy regimens for ESCC remain scarce.

MATERIALS AND

METHODS

This prospective, open-label, randomised controlled trial aims to determine whether lympho-nTRT-ESO reduces the incidence of acute grade 3-4 lymphopaenia in patients with ESCC undergoing neoadjuvant chemoradiotherapy (nCRT), compared with conventional thoracic radiotherapy (RT). A total of 212 participants will be enrolled and randomly allocated in a 1:1 ratio to either the lymphocyte-sparing RT (RT) group or the conventional RT group. All patients will receive standardised nCRT, which will deliver a total dose of 41.4 Gy in 23 fractions. For the lymphocyte-sparing RT group, RT planning prioritises the planning target volume (PTV) coverage and conventional organ-at-risk (OAR) constraints while applying dose constraints to lymphocyte-related OARs (LOARs). These LOARs include the T1-T12 vertebral bodies, ribs, spleen and major cardiovascular structures (heart and large blood vessels), with optimisation performed only after PTV coverage and standard OAR constraints are satisfied.

ETHICS AND DISSEMINATION: This trial was approved by the Ethics Committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (RJ 2024-210) on 11 July 2024 and registered on ClinicalTrials.gov (NCT06596954) before participant recruitment. All participants should provide written informed consent to be eligible. We planed to publish the primary and secondary results of this study in scientific peer-reviewed journals and present at radiation oncology conferences.

TRIAL REGISTRATION NUMBER: NCT06596954.