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Neoadjuvant Chemoradiotherapy Versus Neoadjuvant Immunochemotherapy for Resectable Esophageal Cancer: A Target Trial Emulation Study (TTE-ESCC)

17 août 2026 mis à jour par: YanZheng,MD, Henan Cancer Hospital

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

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.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

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:

  • Primary Analysis: Overlap weighting using propensity scores to balance baseline covariates; weighted Cox proportional hazards models to estimate hazard ratios (HR) with 95% confidence intervals for OS and EFS.
  • Secondary Analysis: pCR, TRG, and R0 rates compared between groups in the surgical subgroup.
  • Sensitivity Analyses: Per-protocol analysis, clone-censor-weight method, E-value for unmeasured confounding, different Time Zero definitions, different grace periods (4 weeks, 12 weeks), complete-case analysis vs multiple imputation.
  • Sensitivity Analyses: Per-protocol analysis, clone-censor-weight method, E-value for unmeasured confounding, different Time Zero definitions, different grace periods (4 weeks, 12 weeks), complete-case analysis vs multiple imputation.
  • Subgroup Analyses: By age, sex, tumor location, clinical stage, ECOG PS, and diagnosis period (2013-2019 vs 2020-2025).

Sample Size: Based on historical data, the target sample size is approximately 150-200 patients per group, with a total enrollment of approximately 400 patients (final sample size determined after data extraction and pilot feasibility assessment).

Ethics: Approved by the Medical Ethics Committee of Henan Cancer Hospital (Approval No. 2026-366-001). A waiver of informed consent was granted for this retrospective study.

Type d'étude

Observationnel

Inscription (Estimé)

400

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

Méthode d'échantillonnage

Échantillon non probabiliste

Population étudiée

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.

La description

Inclusion Criteria:

  1. Age ≥ 18 years at the time of diagnosis.
  2. Histologically confirmed esophageal squamous cell carcinoma (ESCC).
  3. 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.
  4. ECOG performance status 0-1 (or proxy: total hospitalization days ≤14 days in the past year if ECOG PS is missing).
  5. No prior antitumor therapy for esophageal cancer (surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy).
  6. Curative surgical intent documented at Time Zero.

Exclusion Criteria:

  1. Distant metastasis (M1) or clinically determined unresectable disease.
  2. Active concurrent malignancy within 5 years prior to diagnosis (excluding basal cell carcinoma of the skin or carcinoma in situ).
  3. Severe comorbidities significantly limiting life expectancy or precluding neoadjuvant therapy (proxy: total hospitalization days >30 days in the past year).
  4. Pregnancy or lactation.
  5. Known contraindications or hypersensitivity to the study drugs.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

Cohortes et interventions

Groupe / Cohorte
Intervention / Traitement
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.
Radiation: Radiotherapy
Concurrent radiotherapy administered as part of neoadjuvant chemoradiotherapy, typically 41.4-50.4 Gy in fractionated doses, combined with platinum-based chemotherapy.
Médicament: Platinum-based Chemotherapy
Platinum-based chemotherapy administered as part of neoadjuvant treatment, combined with either concurrent radiotherapy (nCRT) or PD-1 inhibitors (nICT).
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.
Médicament: Platinum-based Chemotherapy
Platinum-based chemotherapy administered as part of neoadjuvant treatment, combined with either concurrent radiotherapy (nCRT) or PD-1 inhibitors (nICT).
Médicament: PD-1 Inhibitor
PD-1 inhibitors administered as part of neoadjuvant immunochemotherapy, combined with platinum-based chemotherapy for 2-4 cycles.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Overall Survival (OS)
Délai: 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.
From Time Zero up to 10 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Event-Free Survival (EFS)
Délai: From Time Zero up to 10 years
Event-Free Survival (EFS) is defined as the time from Time Zero to the first occurrence of death, disease progression, local recurrence, distant metastasis, or inoperability, whichever occurs first.
From Time Zero up to 10 years
Pathological Complete Response (pCR) Rate
Délai: At the time of surgery
Pathological complete response (pCR) is defined as the absence of viable tumor cells in the primary tumor and all resected lymph nodes (ypT0 ypN0) on postoperative pathological examination.
At the time of surgery
Tumor Regression Grade (TRG)
Délai: At the time of surgery
Tumor regression grade assessed according to Mandard criteria or Chinese standard (TRG 0-3) on postoperative pathological examination.
At the time of surgery
R0 Resection Rate
Délai: At the time of surgery
R0 resection rate is defined as the proportion of patients achieving microscopically margin-negative resection on postoperative pathological examination.
At the time of surgery
Incidence of Treatment-Related Adverse Events
Délai: From treatment initiation through 90 days after treatment completion
Incidence and severity of treatment-related adverse events (≥grade 3), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
From treatment initiation through 90 days after treatment completion
Incidence of Postoperative Complications
Délai: From surgery through 90 days postoperatively
Incidence and severity of postoperative complications graded according to the Clavien-Dindo classification (≥grade III) and Esophagectomy Complications Consensus Group (ECCG) criteria.
From surgery through 90 days postoperatively

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Henan Cancer Hospital

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

20 août 2026

Achèvement primaire (Estimé)

31 décembre 2027

Achèvement de l'étude (Estimé)

20 août 2028

Dates d'inscription aux études

Première soumission

17 août 2026

Première soumission répondant aux critères de contrôle qualité

17 août 2026

Première publication (Réel)

21 août 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

21 août 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

17 août 2026

Dernière vérification

1 août 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 2026-366

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

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