Radiation Therapy and Cardiac Death in Long-Term Survivors of Esophageal Cancer: An Analysis of the Surveillance, Epidemiology, and End Result Database.

Laila Gharzai,Vivek Verma,Abhijeet R Bhirud,Chi Lin,Kyle A Denniston,Nathan R Bennion,Helge Bruns

doi:10.1371/journal.pone.0158916

Laila Gharzai, Vivek Verma + Show 5 more

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https://doi.org/10.1371/journal.pone.0158916

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Journal: PloS one	Publication Date: Jul 18, 2016
Citations: 45	License type: CC BY 4.0

Affiliation: University of Nebraska Medical Center

Abstract

ObjectiveRadiation 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.Methods5,630 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.ResultsPatients 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.ConclusionsRecognizing 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.

Highlights

Esophageal cancer is the eighth most commonly diagnosed malignancy worldwide and the sixth leading cause of cancer death [1]
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 Radiation therapy (RT)
The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group

Summary

Introduction

Esophageal cancer is the eighth most commonly diagnosed malignancy worldwide and the sixth leading cause of cancer death [1]. The overall incidence of esophageal cancer has increased slowly over time; the adenocarcinoma subtype has seen a four hundred percent rise in incidence since the 1970s [2]. Despite multi-modality treatment, overall five-year survival is poor, with only 18% of patients surviving five years from diagnosis [4]. Radiation therapy (RT) can produce acute toxicities, which largely self-remit, but can lead to more chronic toxicities. These late effects of RT are not well studied in diseases with poorer prognoses owing to poor survival. Anatomic proximity of the esophagus to the heart, lungs, and other regions of the esophagus, can cause chronic toxicities in these organs that can compromise quality of life (and potentially survival) in esophageal cancer survivors

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