Neoadjuvant Chemoradiotherapy Versus Neoadjuvant Immunochemotherapy for Resectable Esophageal Cancer: A Target Trial Emulation Study
TTE-ESCC
A Virtual Randomized Controlled Trial Comparing Neoadjuvant Chemoradiotherapy Versus Neoadjuvant Immunochemotherapy for Resectable Esophageal Cancer Based on Real-World Data: A Target Trial Emulation Study Protocol
1 other identifier
observational
400
0 countries
N/A
Brief Summary
Esophageal squamous cell carcinoma (ESCC) is highly prevalent in China, with most patients presenting with locally advanced disease. Neoadjuvant chemoradiotherapy (nCRT) is the current standard of care, while neoadjuvant immunochemotherapy (nICT) has emerged as a promising alternative. However, no large-scale randomized controlled trial has directly compared nICT versus nCRT for long-term overall survival (OS) in this population. This study aims to compare the causal effects of nICT versus nCRT on OS and other key outcomes in patients with resectable locally advanced ESCC using target trial emulation (TTE) methodology. This is a single-center, retrospective, observational cohort study using TTE. Data are derived from electronic health records (EHR) of esophageal cancer patients hospitalized at Henan Cancer Hospital between January 2013 and December 2025. Patients meeting eligibility criteria (age ≥18 years; histologically confirmed ESCC; clinical stage cT3-4a N0-2 M0 or cT2N+ M0; ECOG PS 0-1; no prior antitumor therapy) are assigned to nICT or nCRT groups based on actual treatment initiation. Propensity score overlap weighting is used to balance baseline covariates. The primary outcome is overall survival (OS). Secondary outcomes include event-free survival (EFS), pathological complete response (pCR) rate, tumor regression grade (TRG), R0 resection rate, and safety. This study will provide real-world causal evidence on the comparative effectiveness of nICT versus nCRT in the Chinese ESCC population.
Trial Health
Trial Health Score
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participants targeted
Target at P75+ for all trials
Started Aug 2026
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 17, 2026
CompletedStudy Start
First participant enrolled
August 20, 2026
CompletedFirst Posted
Study publicly available on registry
August 21, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 20, 2028
August 21, 2026
August 1, 2026
1.4 years
August 17, 2026
August 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
Overall Survival (OS) is defined as the time from Time Zero (the day before the first neoadjuvant treatment order) to death from any cause. Patients alive at the time of analysis are censored at the date of last known contact.
From Time Zero up to 10 years
Secondary Outcomes (6)
Event-Free Survival (EFS)
From Time Zero up to 10 years
Pathological Complete Response (pCR) Rate
At the time of surgery
Tumor Regression Grade (TRG)
At the time of surgery
R0 Resection Rate
At the time of surgery
Incidence of Treatment-Related Adverse Events
From treatment initiation through 90 days after treatment completion
- +1 more secondary outcomes
Study Arms (2)
Neoadjuvant Immunochemotherapy (nICT) Group
Patients who initiated neoadjuvant immunochemotherapy (PD-1 inhibitor combined with platinum-based chemotherapy) within 180 days after Time Zero. Treatment includes PD-1 inhibitors (e.g., camrelizumab, sintilimab, toripalimab, tislelizumab) combined with paclitaxel/nab-paclitaxel and cisplatin/carboplatin, planned for 2-4 cycles, followed by surgery when feasible.
Neoadjuvant Chemoradiotherapy (nCRT) Group
Patients who initiated neoadjuvant chemoradiotherapy (platinum-based chemotherapy with concurrent radiotherapy) within 180 days after Time Zero. Radiotherapy is typically administered at 41.4-50.4 Gy in fractionated doses, with concurrent platinum-based chemotherapy, followed by surgery when feasible.
Interventions
Concurrent radiotherapy administered as part of neoadjuvant chemoradiotherapy, typically 41.4-50.4 Gy in fractionated doses, combined with platinum-based chemotherapy.
Platinum-based chemotherapy administered as part of neoadjuvant treatment, combined with either concurrent radiotherapy (nCRT) or PD-1 inhibitors (nICT).
PD-1 inhibitors administered as part of neoadjuvant immunochemotherapy, combined with platinum-based chemotherapy for 2-4 cycles.
Eligibility Criteria
The study population consists of patients with locally advanced esophageal squamous cell carcinoma (ESCC) diagnosed at Henan Cancer Hospital between January 2013 and December 2025. Eligible patients are those who meet the inclusion criteria and initiated either neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant immunochemotherapy (nICT) within 180 days after Time Zero. Patients are identified from electronic health records (EHR) including medical records, pathology reports, imaging reports, and prescription systems.
You may qualify if:
- Age ≥ 18 years at the time of diagnosis.
- Histologically confirmed esophageal squamous cell carcinoma (ESCC).
- Clinical stage cT3-4a N0-2 M0 or cT2N+ M0 (AJCC 8th edition), with no distant metastasis (M1), based on clinical staging records available at Time Zero.
- ECOG performance status 0-1 (or proxy: total hospitalization days ≤14 days in the past year if ECOG PS is missing).
- No prior antitumor therapy for esophageal cancer (surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy).
- Curative surgical intent documented at Time Zero.
You may not qualify if:
- Distant metastasis (M1) or clinically determined unresectable disease.
- Active concurrent malignancy within 5 years prior to diagnosis (excluding basal cell carcinoma of the skin or carcinoma in situ).
- Severe comorbidities significantly limiting life expectancy or precluding neoadjuvant therapy (proxy: total hospitalization days \>30 days in the past year).
- Pregnancy or lactation.
- Known contraindications or hypersensitivity to the study drugs.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- RETROSPECTIVE
- Sponsor Type
- OTHER GOV
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director
Study Record Dates
First Submitted
August 17, 2026
First Posted
August 21, 2026
Study Start
August 20, 2026
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
August 20, 2028
Last Updated
August 21, 2026
Record last verified: 2026-08
Data Sharing
- IPD Sharing
- Will not share