A Multicenter Prospective Study Evaluating Concurrent Chemoradiotherapy Following Induction Immunochemotherapy for Esophageal Cancer Based on Dynamic ctDNA Monitoring

Esophageal squamous cell carcinoma (ESCC) continues to exhibit high incidence and mortality rates in China, with the majority of patients diagnosed at middle to advanced stages. Concurrent chemoradiotherapy (CCRT) is the standard treatment for unresectable locally advanced ESCC. The 5-year survival rate for advanced esophageal cancer remains below 20%. Immunotherapy has demonstrated definitive efficacy and a favorable toxicity profile in advanced ESCC, and preliminary results of its combination with radiotherapy have been reported. Induction immunochemotherapy followed by concurrent chemoradiotherapy represents a feasible combined treatment strategy. However, optimal biomarkers to identify patients who would benefit from this approach are still lacking. Circulating tumor DNA (ctDNA) status can accurately guide treatment implementation and predict tumor progression. Studies have shown that ctDNA changes precede imaging evidence of recurrence or metastasis, and ctDNA detection can sensitively predict tumor progression and prognosis. Therefore, it is necessary to dynamically monitor ctDNA changes throughout the course of induction immunochemotherapy followed by radical concurrent chemoradiotherapy in esophageal cancer and explore its correlation with prognosis.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer; ctDNA
• Intervention / Treatment: Diagnostic test: Induction Immunochemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhifeng Tian, MD; Phone Number: +8613515789419; Email: tzf419@hotmail.com
• Study Contact Backup: Name: Shubo Ding, MD; Phone Number: +8613750983285; Email: jhyyys@163.com

Study Locations

• China
  • Zhejiang
    • Jinhua, Zhejiang, China, 321000
      • Recruiting
      • Jinhua municipal central hospital
    • Lishui, Zhejiang, China, 323000
      • Recruiting
      • The Central Hospital of Lishui City

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All subjects must sign an informed consent form before initiating any study-related procedures;
• All patients must be aged ≥18 years and ≤75 years;
• Histologically or cytologically confirmed esophageal cancer (squamous cell carcinoma);
• Clinical stage II-IVa, assessed by a surgeon as inoperable, or patient refusal of surgery;
• No prior radiotherapy, chemotherapy, immunotherapy, or biotherapy for esophageal cancer;
• ECOG performance status of 0-1;
• Laboratory test values within the following limits before the first dose of the investigational drug:
• Hematology: WBC ≥3.0×10⁹/L; ANC ≥1.5×10⁹/L; PLT ≥70×10⁹/L; HGB ≥9.0 g/dL;
• Liver function: AST ≤2.5×ULN; ALT ≤2.5×ULN;
• Renal function: Cr ≤1.5×ULN or CrCl ≥40 mL/min;
• Coagulation: INR ≤1.5, APTT ≤1.5×ULN;
• Other: Lipase ≤1.5×ULN, unless clinically/radiographically insignificant if lipase >1.5×ULN.

Exclusion Criteria:

• Insufficient tissue/blood sample available before treatment as required for the study;
• Patient refusal to undergo dynamic ctDNA testing;
• The primary esophageal lesion is in close proximity to the tracheobronchial tree or major blood vessels, with an investigator-assessed high risk of perforation or major hemorrhage;
• History of malignancies other than esophageal carcinoma within the past 5 years (except for curatively treated localized tumors such as carcinoma in situ of the cervix, basal cell carcinoma, or localized prostate cancer);
• History of gastrointestinal bleeding within the past 6 months, or coagulopathy at enrollment, or current thrombolytic or anticoagulant therapy indicating a high risk of bleeding;
• Severe cardiovascular or cerebrovascular diseases;
• History of interstitial lung disease or active pneumonia/tuberculosis;
• Severe allergic reactions to paclitaxel/cisplatin or any monoclonal antibody;
• Any other condition deemed inappropriate for participation in this study as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Induction immunochemotherapy followed by radical concurrent chemoradiotherapy; This is a single-arm, non-randomized study Diagnostic Tests: ctDNA Analysis Dynamic monitoring of ctDNA changes in patients with esophageal cancer.

Diagnostic test: Induction Immunochemotherapy; Induction Immunochemotherapy:Toripalimab 240 mg (immunotherapy) combined with paclitaxel (135 mg/m²) and cisplatin (75 mg/m²) chemotherapy, administered every 3 weeks for 2 cycles. Other Names: - Radiotherapy: 95% PTV 50-50.4 Gy/25-28 fractions, 1.8-2 Gy/fraction; 5 days per week. - Chemotherapy: Weekly paclitaxel (50 mg/m²) combined with cisplatin (25 mg/m²) for 5 cycles. ctDNA Analysis:Initial tissue and blood ctDNA testing prior to treatment (T0) is based on next-generation sequencing (NGS) technology, utilizing tumor-informed assays. Blood ctDNA samples will be collected before chemoradiotherapy, after 20 fractions of radiotherapy, and every 3 months following completion of chemoradiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	We aim to evaluate the progression-free survival (PFS) of patients with unresectable esophageal squamous cell carcinoma who accept concurrent chemoradiotherapy and received sequential treatment with Triptolide injection after radiotherapy.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
locoregional progression-free survival (LRPFS)	locoregional progression-free survival (LRPFS) is defined as the time from treatment to the primary tumor or regional lymph node histopathological progressconfirmed on CT. In the absence of pathology, tumor progression is evident under gastroscopy and/or confirmed by imaging such as PET-CT.	2 years
Overall survival (OS)	Overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence	2 years

Collaborators and Investigators

• Sponsor: The Central Hospital of Lishui City
• Collaborators: Jinhua Central Hospital; People's Hospital of Quzhou; Affiliated Hospital of Jiaxing University

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: January 20, 2025
• First Submitted That Met QC Criteria: January 20, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: prognosis; esophageal cancer; ctDNA; chemoradiotherapy; induction immunochemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: ZJLSRT002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The results of the study were inconclusive.

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