Different Radiation Dose of Neoadjuvant Chemoradiation for Resectable Thoracic Esophageal Squamous Carcinoma

Study Overview
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Brief Summary
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Esophageal cancer is one of the most common cancers worldwide, while more than half new cases and deaths occurred in China. Surgery is the main curative treatment for this disease, the 5-year survival of EC remains poor, since most diseases are diagnosed at advanced stages. In last decades, several large clinical trials and meta-analyses have demonstrated that neo-adjuvant chemoradiotherapy followed by surgery can significantly increase the overall survival of patients with EC compared with surgery alone, while no effect of nCRT was apparent on postoperative health-related quality of life . However, the optimal radiation dose and surgery timing are still unknown. The investigators hypothesize that patients who receive higher dose (50.4Gy/28F) of neoadjuvant chemoradiation will have better pathologic response and progress-free survival compared to lower dose (41.4Gy/23F) of chemoradiation followed by surgery.

Official Title
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Different Radiation Dose of Neoadjuvant Chemoradiation Followed By Surgery in Treating Patients With Locally Advanced, Resectable Thoracic Esophageal Cancer

Conditions
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Surgery, Esophageal Carcinoma, Neoadjuvant Chemoradiotherapy

Intervention / Treatment
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* Radiation: Higher dose (50.4Gy/28F) of neoadjuvant chemoradiation
* Radiation: Lower dose (41.4Gy/23F) of neoadjuvant chemoradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age:18-70 years Histologically verified squamous carcinoma of the thoracic esophagus. Patients with performance status 0-1 according to the Eastern Cooperative Oncology Group (ECOG) scale at the pre CRT evaluation and judges to be fit for surgery at the pre and post CRT evaluations. Tumors should be resectable or potentially resectable and without distant metastasis, as assessed before neoadjuvant CRT, including clinical stage T2-4N0M0 or T1-4N1M0 according to the 6th AJCC system. Joined the study voluntarily and signed informed consent form No surgical contraindications No serious system dysfunction and immuno-deficiency, Adequate organ function including the following: Hemoglobin ≥10 g/dL, Neutrophils (ANC )≥1.5x109/L, platelet count ≥100x 109/L, TBIL<1.5 x ULN, ALT and AST ≤ 2.5 x ULN, creatinine≤1.5 x ULN Exclusion Criteria: Cervical esophageal cancer (The upper end of the lesion is in the esophagus of the cervical segment). Patients with biopsy (by endoscopic ultrasound, laparoscopy, or laparotomy) proven metastatic supraclavicular or celiac nodes are ineligible. Invasion of the tracheobronchial tree or aorta Tracheoesophageal fistula Concurrent pregnancy or lactation Severe diabetes mellitus with poor blood glucose control History of a second malignancy Patients being unable to undergo esophageal reconstruction with gastric tube, due to prior surgery. Patients undergoing esophageal reconstruction with jejunum. Patients have allergy reaction or contraindications to taxanes.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Active Comparator: Higher dose (50.4Gy/28F) of neoadjuvant chemoradiation<br>Neoadjuvant chemoradiation: RT: 50.4Gy/28F/5.6W; CT: paclitaxel 50mg/m2 d1, qw + CBP AUC2 d1, qw, weekly for 6 wks; Surgery: 4-6 weeks after nCRT | Radiation: Higher dose (50.4Gy/28F) of neoadjuvant chemoradiation<br>* 50.4Gy/28F radiation and concurrent chemotherapy with paclitaxel plus CBP used weekly<br>|
| Active Comparator: Lower dose (41.4Gy/23F) of neoadjuvant chemoradiation<br>Neoadjuvant chemoradiation: RT: 41.4Gy/23F/4.6W; CT: paclitaxel 50mg/m2 d1, qw + CBP AUC2 d1, qw, weekly for 5 wks; Surgery: 4-6 weeks after nCRT | Radiation: Lower dose (41.4Gy/23F) of neoadjuvant chemoradiation<br>* 41.4Gy/23F radiation and concurrent chemotherapy with paclitaxel plus CBP used weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Time from randomization to tumor progression or any deaths | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate in each arm | no cancer cells seen microscopically at the resection margin | analysis is completed 4 weeks after surgery | 
| Complete pathological response rate | using the Chirieac grading system | analysis is completed 4 weeks after surgery | 
| Postoperative complications in each study arm | According to the NCI CTC3.0 | 30 and 90 days after surgery | 
| Treatment failure pattern | including local recurrence or distant metastasis or both | 2 year | 
| Overall survival | by intention to treat and per protocol analyses in each study arm | 5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiation dose