Lymphocyte-sparing Thoracic Radiotherapy for Esophageal Squamous Cell Carcinoma

Lymphocyte-sparing Thoracic Radiotherapy vs Conventional Radiotherapy for Esophageal Squamous Cell Carcinoma Treated With Neoadjuvant Therapy: an Open Label, Randomized Controlled Trial

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors. Although neoadjuvant chemoradiotherapy combined with surgery has significantly improved the survival rate of patients with locally advanced esophageal cancer, approximately half of the patients will experience local regional recurrence or distant metastasis. Lymphocytes are crucial immune cells in the human body, playing a key role in combating infections and tumor development. In recent years, an increasing body of research has indicated that lymphocyte depletion is a significant factor associated with poor prognosis in various solid tumors, including esophageal cancer. The lymphocyte depletion caused by radiotherapy has garnered considerable attention from oncologists. However, there is still a lack of prospective clinical research data on lymphocyte protection in thoracic tumors. Therefore, this study aims to provide high-level evidence from evidence-based medicine regarding the correlation between lymphocyte depletion and prognosis in esophageal cancer patients, offering more effective strategies and methods to improve the outcomes of neoadjuvant chemoradiotherapy for esophageal cancer.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Cancer
• Intervention / Treatment: Radiation: lymphocyte-sparing radiotherapy; Radiation: conventional radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 212
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wei-Xiang Qi, Dr.; Phone Number: +8602164370045; Email: qwx12055@rjh.com.cn

Study Locations

• China
  • Shanghai, China, 200025
    • Recruiting
    • Ruijin Hospital, Shanghai JiaoTong University School of Medicine
    • Contact: Wei-Xiang Qi, Dr.; Phone Number: 02164370045; Email: qwx12055@rjh.com.cn
    • Principal Investigator: shengguang zhao, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients are able to understand and are willing to participate in the trial, and a signed consent form can be obtained;
2. Pathologically confirmed esophageal squamous cell carcinoma;
3. locally advanced ESCC (cT3-4 or N+);
4. the age of patients should be more than 18 years, and less than 80 years;
5. aged between 18 and 80 years;
6. KPS score of patients should be more than 80

Exclusion Criteria:

1. diagnosis of metastatic esophageal cancer;
2. Patient refuses to receive systemic drug treatment;
3. clinical diagnosis of pleural metastasis or malignant pleural effusion;
4. Pregnant or breastfeeding women;
5. Severe non-cancerous medical comorbidities that affect the implementation of radiotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lymphocyte-sparing radiotherapy; Firstly, ensure coverage of the PTV (Planning Target Volume). Secondly, limit the doses to the heart, bilateral lungs, and spinal cord to meet the required dose constraints. While maintaining target coverage and traditional OAR (Organs At Risk) dose constraints, also address dose limits for the TVB1-12 thoracic vertebral bodies, ribs, spleen, and major thoracic blood vessels to protect the lymphocyte	Radiation: lymphocyte-sparing radiotherapy; the radiotherapy regimen is 41.4Gy/23Fx. Ensure 95% coverage of the PTV (Planning Target Volume) and limit the doses to the heart, bilateral lungs, and spinal cord to meet the required dose constraints. While maintaining target coverage and traditional OAR (Organs At Risk) dose constraints, also address dose for lymphocyte-relate organs including the TVB1-12 thoracic vertebral bodies, ribs, spleen, and major thoracic blood vessels.
Active Comparator: conventional radiotherapy; ensure coverage of the PTV (Planning Target Volume) and limit the doses to the heart, bilateral lungs, and spinal cord to meet the required dose constraints. do not limits the dose for lymphocyte-related organs	Radiation: conventional radiotherapy; the radiotherapy regimen is 41.4Gy/23Fx. Ensure 95% coverage of the PTV (Planning Target Volume) and limit the doses to the heart, bilateral lungs, and spinal cord to meet the required dose constraints. do not limit dose for lymphocyte-relate organs including the TVB1-12 thoracic vertebral bodies, ribs, spleen, and major thoracic blood vessels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
acute grade 3/4 lymphopenia	from treatment to 1 months after completion of neoadjuvant chemoradiotherapy	1 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	from treatment to death	3 years
recurrence-free survival	from completion of surgery to any recurrence	2 year
Lymphocyte-sparing radiotherapy plan pass rate in lymphocyte-sparing group	the pass rate of the esophageal cancer lymphocyte-sparing plan is evaluated without compromising target volume coverage and conventional normal tissue constraints (heart, lungs, and spinal cord)	within 1 week after completion of neoadjuvat radiotherapy plan;
Incidence of grade 3 or higher hematologic toxicity	The incidence of grade 3 or higher hematologic toxicity during nCRT and within 1 month after treatment between lymphocyte-sparing RT group and conventional RT group.	from neoadjuvant chemoradiotherapy to 1 monther after completion of neoadjuvant chemoradiotherapy
Pathological complete response rate (pCR)	The pCR rate in ESCC patients who underwent nCRT and radical surgery between lymphocyte-sparing RT group and conventional RT group.	1 months after surgery
R0 resection rate	the R0 resection rate in ESCC patients who underwent nCRT and radical surgery between lymphocyte-sparing RT group and conventional RT group.	1 month after surgery
Postoperative complications	which was defined as 30-day postoperative complications graded according to the Clavien-Dindo classification;	1 month after surgery

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: September 11, 2024
• First Submitted That Met QC Criteria: September 11, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: prognosis; neoadjuvant treatment; esophageal cancer; lymphocyte-sparing radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma, Squamous Cell; Neoplasms, Squamous Cell
• Other Study ID Numbers: 2024-210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No