This study is a multicenter, prospective, randomized phase II trial aimed at exploring the value of adjuvant radiotherapy in patients at high risk of recurrence after neoadjuvant chemoradiotherapy for esophageal cancer. The study primarily includes patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy and surgery and did not achieve complete pathological response (non-pCR) postoperatively and were defined as preoperative clinical stage at T3-4N+M0. Eligible patients will be randomized in a 1:1 ratio into two groups: the observation group and the adjuvant radiotherapy group. The control group consists of patients who receive surgery after neoadjuvant chemotherapy combined with immunotherapy for esophageal cancer, followed by maintenance therapy with PD1/PDL1 inhibitors for up to 1 year or until tumor progression. The adjuvant radiotherapy group receives additional adjuvant radiotherapy on top of the control group's treatment. The specific treatment process involves receiving 2 cycles of neoadjuvant chemotherapy combined with immunotherapy (PD1/PDL1 inhibitors) before potentially curative esophageal cancer surgery. The chemotherapy regimen includes paclitaxel in combination with platinum agents, with a preference for albumin-bound paclitaxel (280mg/m2 on Day 1, or 100mg on Days 1, 8, and 15) in combination with carboplatin (AUC=5). Following surgery, patients start adjuvant radiotherapy 4-6 weeks after the operation, with a radiation dose of 45Gy/25F/5W, completed no later than 8 weeks post-surgery. Two weeks after completing radiotherapy, patients continue with immunotherapy maintenance therapy for up to 1 year or until tumor progression. Subsequently, follow-up visits are scheduled every 3-4 months for the first 3 years, every 6 months for the next 2 years, and annually thereafter. The primary endpoint is 2-year disease-free survival (DFS), and secondary endpoints include overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), recurrence patterns, and safety assessment. Additionally, the study will explore biomarkers predicting treatment efficacy and adverse reactions in subjects, including PD-L1 expression, ctDNA clearance status, infiltrating immune cell types and quantities, cytokine expression, and other tumor biomarkers. This exploration aims to guide stratified precision treatment for patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
146
The start time for radiotherapy is 4-6 weeks after surgery, typically not exceeding 8 weeks. Intensity-modulated radiation therapy (IMRT) will be used, with a total dose of 45Gy administered in 25 fractions, five times per week. The recommended target delineation for radiotherapy is based on the Chinese guidelines for radiation therapy of esophageal cancer, which mainly covers the high-risk lymph node area.
Patients receive surgery after neoadjuvant chemotherapy combined with immunotherapy for esophageal cancer, followed by active survillance and maintenance therapy with PD1/PDL1 inhibitors for up to 1 year or until tumor progression.
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China
RECRUITING2-year DFS
Time between enrollment and recurrence of disease or death
Time frame: 24 months
OS
Overall survival,Time between enrollment and death
Time frame: occurence or end of follow-up(2 years after enrollment), which comes first
LRFS
Time between enrollment and local recurrence
Time frame: 24 months
DMFS
distant metastasis free survival,Time between enrollment and distant metastasis
Time frame: 24 months
HRQoL
The EORTC QLQ-C30 questionnaire will be used. Scale scores will be calculated following the scoring guidelines of the EORTC questionnaires. Scores will be summarized by means of the appropriate descriptive statistics (mean + SD or median + IQR) at each measurement point.
Time frame: 3 months, 1year, 2 years after surgery
Adverse effects recorded during radiotherapy and PD1/PDL1 inhibitors maintaince period
safety
Time frame: occurence or end of follow-up(2 years after enrollment), which comes first
Incidence of Recurrence
including local recurrence and distant metastasis
Time frame: occurence or end of follow-up(2 years after enrollment), which comes first
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