Effects of Preoperative Enteral Immunonutrition for Esophageal Cancer Patients Given Neoadjuvant Chemoradiotherapy

Study Overview
=================
Brief Summary
-----------------
This randomized controlled trial will evaluate the effects of preoperative enteral immunonutrition in esophageal cancer patients undergoing neoadjuvant therapy. The purpose of this study is to determine whether preoperative immune-modulating diet before surgery can improve the rate of complications and other perioperative outcomes.

Detailed Description
-----------------
Esophageal cancer ranks the fourth in mortality and the sixth in incidence among cancers in China according to the latest report of cancer epidemiology. Although the development of neoadjuvant therapy and radical esophagectomy have improved the prognosis of esophageal cancer patients, dysphagia and digestive tract reconstruction can cause malnutrition and infection-related complications. Postoperative enteral and parenteral nutrition have proved to be effective in improving outcomes after esophagectomy. However, whether to provide a preoperative nutritional support for patients with resectable esophageal cancer remains controversial. This prospective randomized controlled trial will evaluate the effects of preoperative enteral immunonutrition in esophageal cancer patients undergoing neoadjuvant therapy. The purpose of this study is to determine whether preoperative immune-modulating diet before surgery can improve the rate of complications and other perioperative outcomes. The sample size is estimated with the hypothesis that preoperative immunonutrition during the neoadjuvant therapy can reduce postoperative nutrition and immune-related complications after esophagectomy. According to the previously published articles, the required sample size of interventional and control arm (ratio=2:1) was calculated as 137 cases and 69 cases to detect the reduction in related complications from 50% to 30% based on a bilateral significance level (α) of 0.05 and a power of test (1-β) of 0.80. Considering an estimated drop rate of 15%, the minimum sample size of this study is 244 patients, 162 cases in the interventional group and 82 in the control group. After signing the informed consent, every eligible participant will be randomized into either group based on a computer-generated random number. Blinding will not be applied to patients and surgeons due to the difficulty in clinical practice but outcomes assessor will be masked.

Official Title
-----------------
Effects of Preoperative Enteral Immunonutrition for Esophageal Cancer Patients Given Neoadjuvant Chemoradiotherapy

Conditions
-----------------
Esophageal Neoplasms

Intervention / Treatment
-----------------
* Dietary Supplement: Preoperative immunonutrition


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed esophageal cancer Staging as cT2N0M0 with high-risk lesions (lymphovascular invasion, ≥3cm, poorly differentiated) / cT1b-2N+M0 / cT3-4aN0-3M0 with the need of neoadjuvant therapy before radical esophagectomy Tolerance with oral intake (at least fluid diet) Eastern Cooperative Oncology Group (ECOG) performance status ≤2 Body Mass Index (BMI) ≥ 18.5 kg/m2 before recruitment Patient's approval and written informed consent Exclusion Criteria: Expected survival time less than 6 months Complete dysphagia Pregnant or breast-feeding women Unable to obey the interventions because of any reasons Serious co-morbidities (cardiac, pulmonary, liver, kidney, brain, hematologic, endocrine and other diseases) in patients who cannot tolerate neoadjuvant therapy and/or surgery History of previous thoracic or abdominal surgery History of other malignant tumor (previous or current)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional group<br>Patients receive omega-3 fatty-acid enriched enteral nutritional emulsion during the neoadjuvant chemoradiotherapy. Patients are meanwhile encouraged to intake 25-30kcal/kg through regular food. | Dietary Supplement: Preoperative immunonutrition<br>* Preoperative immunonutrition includes an omega-3 fatty-acid enriched enteral nutritional emulsion given by oral intake, nasogastric feeding tube or jejunostomy 600ml per day, lasting for the whole period of neoadjuvant chemoradiation. Meanwhile, oral intake is encouraged to reach 25-30kcal/kg through regular food.<br>|
| No Intervention: Control group<br>Patients are encouraged to intake 25-30kcal/kg through regular food without supplemental nutritional support before esophagectomy. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of postoperative nutrition and immune-related complications | Rate of gastrointestinal complications (anastomotic leakage, gastrointestinal dysfunction), metabolic complications (electrolyte disturbances, liver or renal dysfunction) and infectious complications(wound infection, catheter-related infection, pneumonia, sepsis, or other infections requiring antibiotics). | Up to 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion rate of neoadjuvant therapy and esophagectomy |  | 2-3 months before surgery | 
| Adverse events during neoadjuvant chemoradiotherapy |  | 2-3 months before surgery | 
| Pathological complete response rate (pCR) |  | 2-3 months before surgery | 
| Blood loss |  | At operation day | 
| Duration of surgery |  | At operation day | 
| Rate of surgery-related complications | Conversion to open surgery, recurrent nerve injury, cardiac and cerebrovascular accident | At operation day | 
| Length of hospital stay |  | Postoperative in-hospital stay | 
| Hospitalization costs |  | Postoperative in-hospital stay | 
| 30-day and 90-day mortality |  | Up to 90 days after surgery | 
| Weight loss |  | From neoadjuvant chemoradiotherapy to 6 months after surgery | 
| Change in PG-SGA score after surgery |  | From neoadjuvant chemoradiotherapy to 6 months after surgery | 
| Change in biochemical indicators after surgery | WBC, hemoglobin, albumin, CRP, TNF-α, interleukins, IgA, IgG, IgM, fasting blood-glucose | From neoadjuvant chemoradiotherapy to 6 months after surgery | 
| Score of EORTC QLQ-C30 and OES-18 scale | Quality of life | 1-year, 3-year, and 5-year after surgery | 
| Long-term survival | Overall survival (OS) and progression-free survival (PFS) | 1-year, 3-year, and 5-year after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Esophageal Neoplasms, Neoadjuvant Therapy, Enteral Nutrition, Nutrition Therapy