Dynamic Changes of CtDNA to Evaluate the Efficacy of Immunoconsolidation Therapy After Radiotherapy and Chemotherapy for Esophageal Cancer

The Central Hospital of Lishui City51 enrolled

Overview

The incidence and mortality of esophageal squamous cell carcinoma are among the highest in China, and most patients are diagnosed in the middle and late stages. Concurrent chemoradiotherapy is the standard treatment for unresectable locally advanced esophageal squamous cell carcinoma. The 5-year formation rate of advanced esophageal cancer is less than 20%. Immunotherapy for advanced esophageal squamous cell carcinoma has definite efficacy and low toxicity, and the results of combined radiotherapy have also been preliminarily reported. Combined immunotherapy after chemoradiotherapy for esophageal cancer is a feasible combination program. But immunotherapy still lacks ideal biomarkers to screen people for advantage. ctDAN status can accurately guide treatment implementation and predict tumor progression. Studies have shown that ctDNA changes are earlier than imaging findings of recurrence or metastasis, and ctNDA detection can sensitively predict tumor progression and prognosis. Therefore, it is necessary to dynamically monitor the changes of ctDNA in immunoconsolidation therapy after radical radiotherapy and chemotherapy for esophageal cancer, and explore its correlation with the curative effect and prognosis of radical radiotherapy and chemotherapy for esophageal cancer.

Study Type

INTERVENTIONAL

Allocation

Purpose

SCREENING

Masking

NONE

Enrollment

Conditions

Esophageal Cancer CtDNA

Interventions

ctDNA detectionDIAGNOSTIC_TEST

dynamically monitor the changes of ctDNA in patients with esophageal cancer Radiation: Radiotherapy 95% PTV50-50.4Gy/25-28fractions, 1.8-2Gy/1 fractions; 5 days a week; 6 weeks. Chemotherapy:weekly paclitaxel (50mg/m²) in combination with carboplatin (AUC=2) chemotherapy, a total of 4-5 cycles. Other Names: Intensity-modulated radiotherapy (IMRT) Drug: Toripalimab Toripalimab (240 mg, intravenously infused) will be administered as the maintenance treatment every 3 weeks within 4 weeks after the completion of radiotherapy for 1 years or until progression, intolerable toxicity, or physician/patient decision Other Names: Immunotherapy ctDNA detection: The first tissue and blood ctDNA test (T0) before treatment is based on next generation sequencing (NGS) technology, and ctDNA test is based on tumor- prior analysis informed assays method. Blood ctDNA testing after chemoradiotherapy was performed every 3 months

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: -1. Age 18-75 years old, male or female; 2.ECOG score 0 \~ 1; 3. Esophageal squamous cell carcinoma was confirmed by pathology. 4. No radiotherapy, chemotherapy or other treatment was given before enrollment; 5. AJCC 8th stage II-IVa, which cannot be treated by surgical evaluation or patients reject operation; 6. Has sufficient organ function, (1) Blood routine: Peripheral blood white blood cell count ≥3.0×10\^9 / L, neutrophil absolute value ≥1.5×10\^9 /L, hemoglobin ≥90 g/L, platelets ≥75×10\^9 / L (No blood transfusion and blood products within 14 days, no use of G-CSF and other blood-stimulating factors to correct), (2) Liver function: total bilirubin ≤1.5× upper limit of normal(ULN), AST and ALT≤2.5× ULN, alkaline phosphatase ≤5× ULN, (3) Renal function: Serum creatinine ≤1.0× ULN or crcl ≥50 ml/min, (4) Adequate haemostasis laboratory data prior to randomization: INR or PT ≤1.5×ULN (If the subject was receiving anticoagulant therapy, as long as the PT was within the intended use range of anticoagulant drugs) (5) Myocardial enzymes were within the normal range. 7\. Sign a consent form. Exclusion Criteria: * 1\. unable to provide a sufficient number of tissue samples/blood samples for the study prior to treatment; 2. The patient refused to accept dynamic ctDNA testing; 3. A history of malignant tumors other than esophageal cancer in the past 5 years (excluding cured local tumors such as cervical carcinoma in situ, basal cell carcinoma, and prostate carcinoma in situ); 4. A history of gastrointestinal bleeding within the past 6 months, or abnormal coagulation at enrollment, or currently receiving thrombolytic or anticoagulant therapy, indicating a higher risk of bleeding; 5. Severe cardiovascular and cerebrovascular diseases; 6. History of interstitial lung disease or active pneumonia/tuberculosis; 7. Severe allergic reaction to paclitaxel/cisplatin chemotherapeutics or any monoclonal antibody; 8. Other conditions deemed unsuitable for participation in this study by the investigator.

Outcomes

Primary Outcomes

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.

Time frame: two years

Secondary Outcomes

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.

Time frame: 2 years

Overall survival (OS)

Overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence