###### Abstract  
The epicardial adipose tissue (EAT), mainly composed of brown adipose tissue, is a metabolically active tissue releasing various bioactive factors with a critical role in metabolic diseases. The EAT is often irradiated during radiotherapy in patients with esophageal cancer due to its proximity to the target region. We aimed to evaluate the effect of radiation to the EAT on survival outcomes in patients with esophageal cancer receiving neoadjuvant chemotherapy followed by esophagectomy. We analyzed data on 36 patients with esophageal cancer treated with trimodal therapy between 2012 and 2017. The median follow-up period was 22.0 months. The 3-year overall survival and progression-free survival rates were 39.7% and 32.5%, respectively. Multivariate analysis revealed that higher EAT-REI was independently associated with worse overall survival (hazard ratio: 1.002, \(p\) = 0.028) and progression-free survival (hazard ratio: 1.002, \(p\) = 0.03). The cutoff value with the highest accuracy for avoiding mortality was EAT-REI = 68.8 cGy/mL (area under the curve, 0.78, \(p\) = 0.006). The 3-year overall survival rate in patients with EAT-REI \(\geq\)68.8 and \(<\)68.8 was 21.7% and 71.9%, respectively (\(p\) = 0.003). The EAT should be considered an organ at risk during radiotherapy in patients with esophageal cancer. EAT-REI might serve as a biomarker of survival outcomes in these patients.  
esophageal cancer; neoadjuvant chemoradiation; squamous cell carcinoma; epicardial adipose tissue +
Footnote †: journal: Medical Oncology  
Previous studies have reported that the radiation dose-volume to the lung is associated with worse survival outcomes in these patients; hence, minimizing the lung radiation dose-volume was one of the treatment goals during the radiotherapy planning process. In order to optimize the lung radiation dose-volume, the heart, trachea/bronchus, great vessels, spinal cord, muscles, adipose tissue, and other soft tissues may receive a higher radiation dose. A higher RT dose delivered to the lung and heart has been reported to impair the survival of lung and breast cancer patients [6; 7; 8]. However, the impact of adipose tissues in the thorax, such as the left main coronary artery fat tissue, peri-thoracic adipose tissue (TAT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT), still needs to be determined.  
Epicardial adipose tissue (EAT) is a unique thoracic adipose tissue located between the myocardium and the visceral layer of the pericardium. EAT is a metabolically active tissue releasing various bioactive factors that can affect the prognosis of patients with metabolic diseases [9; 10]. It is characterized by a highly active fatty acid metabolism and high expression of thermogenic genes. EAT is considered to function in a manner similar to brown adipose tissue with the expression of uncoupling protein-1 (UCP-1), brown adipocyte differentiation transcription factor PR-domain-missing 16 (PRDM16), and peroxisome-proliferator-activated receptor \(\gamma\) co-activator-1\(\alpha\) (PGC-1\(\alpha\)) [11]. Hence, the radiation dose on EAT may have an impact on the survival outcomes of patients with esophageal cancer undergoing NACRT. As EAT is commonly irradiated during esophageal cancer radiotherapy, the associations between radiation on EAT and survival need to be determined.  
We hypothesized that the EAT dose-volume could impact the survival outcomes of patients with esophageal squamous cell carcinoma (ESCC) undergoing NACRT. This study aimed to evaluate the EAT dose-volume and their associations with survival outcomes in patients with ESCC undergoing NACRT.