Postoperative Radiotherapy in Thoracic Esophageal Squamous Cell Carcinoma With Neoadjuvant Chemoradiotherapy

Study Overview
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Brief Summary
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The primary objective is to compare surgery with postoperative radiotherapy (PORT) versus surgery, in terms of the overall survival time (OS) in Stage II or III squamous cell esophageal carcinoma with neoadjuvant chemoradiotherapy(nCRT).

Detailed Description
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Esophageal squamous cell carcinoma (ESCC) is a common type of esophageal carcinoma in China, which is characterized by rapid development and fatal prognosis in most patients. Neoadjuvant chemoradiotherapy (nCRT) has been explored for many years in western countries and Japan, and proved to get survival benefit, especially for locally advanced esophageal cancer. However, the recurrence is the major cause of treatment failure in patients with ESCC. Our hypothesis is that inadequate radiation dose leads to recurrence of ESCC with nCRT and PORT lower recurrence rate and improved OS. As is known, there are no any studies concentrating on PORT in ESCC with nCRT. Patients are randomly assigned to PORT (Group A) or without PORT (Group B) with a 1:1 allocation ratio. The primary outcome is OS assessed with a minimum follow-up of 60 months. Secondary outcomes are progression-free survival (PFS), recurrence-free survival (RFS).

Official Title
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Prospective Randomized Controlled Trial of Postoperative Radiotherapy in Thoracic Esophageal Squamous Cell Carcinoma With Neoadjuvant Chemoradiotherapy

Conditions
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Radiation Oncology

Intervention / Treatment
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* Radiation: Neoadjuvant Radiotherapy Program:
* Drug: Neoadjuvant chemotherapy Program
* Procedure: Esophagectomy program:
* Radiation: Postoperative radiotherapy program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must not have received any prior anticancer therapy Histologically-confirmed squamous cell carcinoma of the esophagus; Tumors of the esophagus are located in the thoracic cavity; Pre-treatment stageⅡ-Ⅲ (AJCC/UICC 8th Edition) Male or non pregnant female Age is between 18 years and 65 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1 or Karnofsky performance status (KPS) of 70 or more; Adequate bone marrow function (White Blood Cells ≥4x109 /L; Neutrophil ≥1.5×109 /L; Hemoglobin≥ 90 g/L; platelets≥100x109 /L); Adequate liver function (Total bilirubin, Aspartate transaminase(AST) and Alanine transaminase (ALT) ≤2x Upper Level of Normal (ULN)); Adequate renal function (serum creatinine (SCr) ≤1.5 x ULN); The patient has provided written informed consent and is able to understand and comply with the study. Exclusion Criteria: Patients with non-squamous cell carcinoma histology; Patients with advanced inoperable or metastatic esophageal cancer; Patients with another previous or current malignant disease； Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease; Age >65 years; Pregnant or lactating female or people during the birth-period who refused to take contraceptives; Uncontrolled seizures or psychiatric diseases, loss of control over their own behavior; Patients who refuse surgery after neoadjuvant chemotherapy; Unsuitable to be enrolled in the trial in the opinion of the investigators

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Neoadjuvant Radiotherapy Program+Neoadjuvant chemotherapy Program+ Esophagectomy program+Postoperative radiotherapy program | Radiation: Neoadjuvant Radiotherapy Program:<br>* Gross tumor volume (GTV) should include the primary tumor and involved regional lymph nodes as identified on pre-treatment diagnostic studies. Clinical target volume (CTV) is defined as the primary tumor plus 3cm expansion superiorly and inferiorly along the length of the esophagus and a 1cm radial expansion.The nodal CTV should be defined by a 0.5cm expansion from the nodal GTV.CTV should also include coverage the nodal region(s) in which the involved lymph node(s). A total dose of 45 Gy in 25 fractions is delivered 5 days per week on workdays with intensity modulated radiotherapy (IMRT).<br>Drug: Neoadjuvant chemotherapy Program<br>* Chemotherapy is delivered concomitantly and composed of two cycles of Docetaxel 60mg per square meter of body-surface area and cisplatin 75mg per square meter of body-surface area every 21 days at the intervals of neoadjuvant radiotherapy.<br>Procedure: Esophagectomy program:<br>* Patients receive esophagectomy in 4-6 weeks after neoadjuvant neoadjuvant chemotherapy<br>Radiation: Postoperative radiotherapy program<br>* A total dose of 18 Gy in10 fractions is delivered 5 days per week on workdays with IMRT.<br>|
| Other: Group B<br>Neoadjuvant Radiotherapy Program+Neoadjuvant chemotherapy Program+ Esophagectomy program | Radiation: Neoadjuvant Radiotherapy Program:<br>* Gross tumor volume (GTV) should include the primary tumor and involved regional lymph nodes as identified on pre-treatment diagnostic studies. Clinical target volume (CTV) is defined as the primary tumor plus 3cm expansion superiorly and inferiorly along the length of the esophagus and a 1cm radial expansion.The nodal CTV should be defined by a 0.5cm expansion from the nodal GTV.CTV should also include coverage the nodal region(s) in which the involved lymph node(s). A total dose of 45 Gy in 25 fractions is delivered 5 days per week on workdays with intensity modulated radiotherapy (IMRT).<br>Drug: Neoadjuvant chemotherapy Program<br>* Chemotherapy is delivered concomitantly and composed of two cycles of Docetaxel 60mg per square meter of body-surface area and cisplatin 75mg per square meter of body-surface area every 21 days at the intervals of neoadjuvant radiotherapy.<br>Procedure: Esophagectomy program:<br>* Patients receive esophagectomy in 4-6 weeks after neoadjuvant neoadjuvant chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | The length of time from enrollment until the time of death | From enrollment to 5 years after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival | The length of time from enrollment until the time of progression of disease | From enrollment to 5 years after the end of treatment | 
| local recurrence rate | The percent of the patient with local recurrence | From enrollment to 5 years after the end of treatment | 
| Side effects | adverse events according to NCI CTCAE 4.0 criteria | From enrollment to 12 weeks after end of the treatment |