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

2026年8月17日 更新者：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.

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

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.

研究の種類

観察的

入学 (推定)

400

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

サンプリング方法

非確率サンプル

調査対象母集団

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.

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

コホートと介入

グループ/コホート
介入・治療
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.
放射線：Radiotherapy
Concurrent radiotherapy administered as part of neoadjuvant chemoradiotherapy, typically 41.4-50.4 Gy in fractionated doses, combined with platinum-based chemotherapy.
薬：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.
薬：Platinum-based Chemotherapy
Platinum-based chemotherapy administered as part of neoadjuvant treatment, combined with either concurrent radiotherapy (nCRT) or PD-1 inhibitors (nICT).
薬：PD-1 Inhibitor
PD-1 inhibitors administered as part of neoadjuvant immunochemotherapy, combined with platinum-based chemotherapy for 2-4 cycles.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Overall Survival (OS)
時間枠：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

二次結果の測定

結果測定
メジャーの説明
時間枠
Event-Free Survival (EFS)
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Henan Cancer Hospital

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年8月20日

一次修了 (推定)

2027年12月31日

研究の完了 (推定)

2028年8月20日

試験登録日

最初に提出

2026年8月17日

QC基準を満たした最初の提出物

2026年8月17日

最初の投稿 (実際)

2026年8月21日

学習記録の更新

投稿された最後の更新 (実際)

2026年8月21日

QC基準を満たした最後の更新が送信されました

2026年8月17日

最終確認日

2026年8月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • 2026-366

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

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米国FDA規制医薬品の研究

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米国FDA規制機器製品の研究

いいえ

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