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

Overview

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.

Interventions

• 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) t

Primary outcome measures

• Progression-free survival (PFS) [Time frame: one year]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Screening

Study locations

China · 2 centers

• Jinhua Municipal Central Hospital — Jinhua
• The central Hospital of Lishui City — Lishui

Identifiers

NCT: NCT06792786 · ZJLSRT002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗