Simultaneous Integrated Boost for Mediastinal Lymph Node Recurrence After Radical Surgery of Esophageal Cancer

Study Overview
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Brief Summary
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Esophageal cancer (EC) ranks the seventh most diagnosed malignant tumor (572,000 new cases) and the sixth cancer-related mortality (509,000 deaths) worldwide in 2018. The incidence of EC is strikingly varying among the regions and sexes. Approximately 70% of EC cases occur in men, and there is a 2-fold to 3-fold difference in incidence and mortality rates between regions worldwide. According to the latest reported in 2017, esophageal cancer ranks the sixth most common cancer and the fourth leading cause of cancer-mortality in China. Currently, esophagectomy is considered as the standard treatment for resectable EC patients. However, the prognosis of stage IIA-III esophageal cancer after esophagectomy remains poor, and local regional lymph node recurrence is the major patterns of recurrence, and mediastinal lymph node recurrence is one of the most common sites. Previous retrospective study has found that salvage chemoradiotherapy is a effective treatment option for these patients. However, the optimal dose remains unknown. In addition, no prospective trials have been conducted to investigate the efficacy and toxicities of salvage chemo-radiotherapy by using simultaneous integrated boost for the treatment of mediastinal lymph node recurrence after radical surgery of esophageal Cancer

Official Title
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Phase I/II Dose Escalation by Simultaneous Integrated Boost for Mediastinal Lymph Node Recurrence After Radical Surgery of Esophageal Cancer

Conditions
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Salvage Radiotherapy, Dose-escalation, Esophageal Cancer, Mediastinal Lymph Node Recurrence

Intervention / Treatment
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* Radiation: treatment group(phase I)
* Radiation: treatment group (phase II)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histo-pathologically proven diagnosis of esophageal squamous cell carcinoma. Age ≥18 and ≤80 ECOG performance status 0-1. Clinical diagnosis of ≤5 mediastinal lymph nodes recurrence after esophagectomy. Patients without distant metastasis and life expectancy ≥ 3 months. adequate liver and renal function and adequate bone marrow reservation. Written, signed informed consent. Exclusion Criteria: Prior radiotherapy to recurrence site of esophageal cancer. Other co-existing malignancies or malignancies diagnosed within the last 5 years. Pregnant women. Women who are breastfeeding a baby. Patients with uncontrolled serious medical or mental illnesses.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br> | Radiation: treatment group(phase I)<br>* Dose-escalation plan (phase I) Radiotherapy: LEVEL 1: dose given at PTV-G will be 58.8Gy/28 fractions； 2.1Gy/per fraction; LEVEL 2: dose given at PTV-G will be 64.4Gy/28 fractions； 2.3Gy/per fraction; LEVEL 3: dose given at PTV-G will be 70Gy/28 fractions； 2.5Gy/per fraction Concurrent chemotherapy: 5-Fu/capecitabine/S-1+DDP or S-1 or Capecitabine<br>Radiation: treatment group (phase II)<br>* Radiotherapy dose was prescribed according to phase I trial results; Concurrent chemotherapy: 5-Fu/capecitabine/S-1+DDP or S-1 or Capecitabine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity(DLT) of Simulatianeous Integrated Boost (SIB) | DLT was defined as grade 4 or higher hematological toxicities and/or grade 3 or higher nonhematological toxicities. | up to 3 months | 
| Overall survival (phase II) | Survival time was measured from the date of study enrollment to the date of death or last follow-up; | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (phase I) | Survival time was measured from the date of study enrollment to the date of death or last follow-up; | up to 1 year | 
| Late toxicity (phase I) | late toxicity were grade according to RTOG and CTCAE criteria | up to 2 year | 
| Overall survival (phase II) | Survival time was measured from the date of study enrollment to the date of death or last follow-up; | up to 2 year | 
| acute Toxicity (phase II) | acute toxicity were grade according to CTCAE criteria | up to 3 months | 
| late Toxicity (phase II) | late toxicity were grade according to RTOG and CTCAE criteria | up to 2 year | 
| 1-year local progression-free survival | From treatment initiation to first documented local progression or death or censor | up to 1 year |