A Trial Estimating The Optimal Radiation Volume Of Postsurgical Radiation For Patients With Esophageal Cancer

Study Overview
=================
Brief Summary
-----------------
A randomized phase II trial to estimate the optimal radiation volume of postsurgical radiation for patients with locoregionally advanced thoracic esophageal squamous cell carcinoma (T3-4, any N, M0).

Detailed Description
-----------------
Patient Population: Thoracic esophageal squamous cell carcinoma after esophagectomy with at least 15 lymph nodes removed for adequate nodal staging. T3-4, any N, M0. Scheme: After esophagectomy, patients are firstly stratified by 2 factors: (1)number of lymph node metastasis (<3 or >=3) and (2)tumor resection status (R1 resection or R2 resection). Note: Pathological R0 resection status is required for this study. So here R1 and R2 resection are not actually pathological status of resection, only clinical judgement by physician based on the chest-CT before esophagectomy. Then patients are randomized to 2 arms: Arm A: Large field radiation (tumor bed + ENI (elective nodal irradiation)) + Sequential chemotherapy (4 cycles). Arm B: Small field radiation (tumor bed only) + Sequential chemotherapy (4 cycles).

Official Title
-----------------
A Randomized Phase II Trial Estimating The Optimal Radiation Volume Of Postsurgical Radiation For Patients With Locoregionally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Conditions
-----------------
Esophageal Squamous Cell Carcinoma

Intervention / Treatment
-----------------
* Radiation: enlarge irradiation volume
* Radiation: Small volume radiation
* Drug: cisplatin
* Drug: fluorouracil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 and ≤70 Performance status 0-1 Weight is not less than 90% of it before operation Registration within 8 weeks after esophagectomy Histologically proven primary thoracic esophageal squamous cell carcinoma R0 resection and number of lymph nodes dissected ≥15 after esophagectomy Pathological stage of T3-4N0-3M0 Chest and abdominal contrast enhanced CT within 6 weeks prior to registration(PET/CT scan is selective) Without supraclavicular nodes and abdominal regions nodes existed after surgery Without neo-adjuvant chemotherapy and radiotherapy WBC≥ 4.0X109/L ,Absolute neutrophil count (ANC) ≥ 2.0X109/L Platelets ≥ 100X109/L Hemoglobin ≥ 90g/L(without blood transfusion) AST (SGOT)/ALT (SGPT) ≤ 2.5 x upper limit of normal, Bilirubin ≤ 1.5 x upper limit of normal Creatinine ≤ 1.5 x upper limit of normal Sign study-specific informed consent prior to study entry Exclusion Criteria: Multiple primary esophageal tumors Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible). Severe, active comorbidity, defined as follows: 3.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months 3.2 Transmural myocardial infarction within the last 6 months 3.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration 3.4 Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration 3.5 Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception. Prior systemic chemotherapy, prior radiation therapy or prior target drug therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>After esophagectomy, patients in Arm A will receive Large field radiation (tumor bed + ENI (elective nodal irradiation)) + Sequential chemotherapy | Radiation: enlarge irradiation volume<br>* In Arm A, postsurgical radiation target volume includes tumor bed and elective nodes area<br>Drug: cisplatin<br> <br> Drug: fluorouracil<br> <br> |
| Active Comparator: B<br>After esophagectomy, patients in Arm B will receive small field radiation (tumor bed only) + Sequential chemotherapy | Radiation: Small volume radiation<br>* In Arm B, postsurgical radiation target volume includes tumor bed only<br>Drug: cisplatin<br> <br> Drug: fluorouracil<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | To evaluate if the survival outcome of postsurgical radiation with a small target volume involved tumor bed only is not worse than a large volume (tumor bed and elective nodes) for patients with locoregionally advanced thoracic esophageal squamous cell carcinoma. |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | To evaluate the incidence rate of adverse events-especially radiation-induced lung toxicity |  | 
| Failure pattern | To evaluate the rationality of radiation target volumes by analyzing the therapeutic failure patterns especially by comparing the in-field and out-of-field recurrences. |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thoracic esophageal squamous cell carcinoma, esophagectomy, radiation, tumor bed, elective nodal irradiation