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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 400
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
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.
详细描述
Detailed Description This study is a target trial emulation (TTE) designed to compare the causal effects of neoadjuvant immunochemotherapy (nICT) versus neoadjuvant chemoradiotherapy (nCRT) in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). The TTE framework, as proposed by Hernán and Robins, is used to emulate a hypothetical randomized controlled trial using observational data.
Data Source: Electronic health records (EHR) from Henan Cancer Hospital, including medical records, pathology reports, imaging reports, prescription systems, radiotherapy records, and follow-up systems, covering the period from January 2013 to December 2025.
Target Trial Specification:
- Eligibility: Age ≥18 years; histologically confirmed ESCC; clinical stage cT3-4a N0-2 M0 or cT2N+ M0 (AJCC 8th edition); ECOG PS 0-1; no prior antitumor therapy for esophageal cancer; curative surgical intent at Time Zero.
- Treatment Strategies: Strategy A (nCRT): platinum-based chemotherapy with concurrent radiotherapy (41.4-50.4 Gy). Strategy B (nICT): PD-1 inhibitor combined with platinum-based chemotherapy (2-4 cycles).
- Assignment: In the target trial, patients are randomized 1:1. In the emulation, patients are assigned based on actual treatment received, with propensity score overlap weighting to simulate randomization.
- Follow-up: Time Zero is defined as the day before the first neoadjuvant treatment order. Follow-up continues until death, loss to follow-up, or administrative end of study (December 31, 2026). A grace period of up to 180 days is allowed for treatment initiation (i.e., the order date must be within 180 days from Time Zero). Patients who initiate treatment beyond this window are excluded from the primary analysis or evaluated separately in sensitivity analyses.
- Outcomes: Primary: Overall Survival (OS). Secondary: Event-Free Survival (EFS), pathological complete response (pCR) rate, tumor regression grade (TRG), R0 resection rate, and safety (≥grade 3 adverse events per CTCAE v5.0, postoperative complications per Clavien-Dindo classification).
Statistical Analysis:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Radiotherapy (Radiation)
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.
干预措施: Platinum-based Chemotherapy (Drug)
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.
干预措施: Platinum-based Chemotherapy (Drug)
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.
干预措施: PD-1 Inhibitor (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From Time Zero up to 10 years
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.
次要结局
- 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)
- Incidence of Postoperative Complications(From surgery through 90 days postoperatively)
研究者
YanZheng,MD
Director
Henan Cancer Hospital