title: Radiation Therapy and Cardiac Death in Long-Term Survivors of Esophageal Cancer: An Analysis of the Surveillance, Epidemiology, and End Result Database.
abstract: OBJECTIVE
  Radiation therapy (RT) for esophageal cancer often results in unintended radiation doses delivered to the heart owing to anatomic proximity. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined late cardiac death in survivors of esophageal cancer that had or had not received RT.
  
  
  METHODS
  5,630 patients were identified that were diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (AC) from 1973-2012, who were followed for at least 5 years after therapy. Examined risk factors for cardiac death included age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/AC), esophageal location (<18cm/18-24cm/25-32cm/33-40cm from incisors), diagnosis year (1973-1992/1993-2002/2003-2012), and receipt of surgery and/or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A Cox model was used to evaluate risk factors for cardiac death in propensity score matched data.
  
  
  RESULTS
  Patients who received RT were younger, diagnosed more recently, had more advanced disease, SCC histology, and no surgery. The RT group had higher risk of cardiac death than the no-RT group (log-rank p<0.0001). The median time to cardiac death in the RT group was 289 months (95% CI, 255-367) and was not reached in the no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.23, 95% CI 1.03-1.47, HR 1.961, 95% CI 1.466-2.624). Lower esophageal subsite (33-40 cm) was also associated with a higher risk of cardiac death. Other variables were not associated with cardiac death.
  
  
  CONCLUSIONS
  Recognizing the limitations of a SEER analysis including lack of comorbidity accountability, these data should prompt more definitive study as to whether a possible associative effect of RT on cardiac death could potentially be a causative effect.
authors.affiliation: College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States of America.
authors.forename: Laila
authors.initials: L
authors.lastname: Gharzai
authors.affiliation: Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, United States of America.
authors.forename: Vivek
authors.initials: V
authors.lastname: Verma
authors.affiliation: Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, United States of America.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Denniston
authors.affiliation: Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, United States of America.
authors.forename: Abhijeet R
authors.initials: AR
authors.lastname: Bhirud
authors.affiliation: Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, United States of America.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Bennion
authors.affiliation: Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, United States of America.
authors.forename: Chi
authors.initials: C
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000453:epidemiology* / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000453:epidemiology* / Q000473:pathology / Q000532:radiotherapy*; D003643:Death; D004938:Esophageal Neoplasms / Q000150:complications / Q000453:epidemiology* / Q000473:pathology / Q000532:radiotherapy*; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000473:pathology* / Q000528:radiation effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016019:Survival Analysis; D017741:Survivors