Late cardiac toxicity of neo-adjuvant chemoradiation in esophageal cancer survivors: A prospective cross-sectional pilot study

• Published in: Radiotherapy and oncology Vol. 167; pp. 72 - 77
• Main Authors: Beukema, Jannet C., de Groot, Crystal, Plukker, John T.M., Vliegenthart, Rozemarijn, Langendijk, Johannes A., van Luijk, Peter, van Melle, Joost P., Prakken, Niek H.J., Muijs, Christina T.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.02.2022
• Subjects: Cardiac toxicity; Esophageal cancer; Radiation toxicity; Radiation toxicity; Esophageal cancer; Cardiac toxicity
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2021.11.029

•Dose dependent myocardial fibrosis plays a central role in late cardiac toxicity.•An increased rate of atrial fibrillation was found in the irradiated patient group.•Atrial fibrillation has hemodynamic consequences and an effect on global health.•Patients showed lower scores on role functioning after neoadjuvant CRT. Although cure rates in esophageal cancer (EC) have improved since the introduction of neoadjuvant chemoradiation (nCRT), evidence for treatment-related cardiac toxicity is growing, of which the exact mechanisms remain unknown. The primary objective of this study was to identify (subclinical) cardiac dysfunction in EC patients after nCRT followed by surgical resection as compared to surgery alone. EC survivors followed for 5–15 years after curative resection with (n = 20) or without (n = 20) nCRT were enrolled in this prospective cross-sectional pilot study. All patients underwent several clinical and diagnostic tests in order to objectify (sub)clinical cardiac toxicity including cardiac CT and MRI, echocardiography, ECG, 6-minutes walking test, physical examination and EORTC questionnaires. We found an increased rate of myocardial fibrosis (Linear late gadolinium enhancement (LGE) 4 vs. 1; p = 0.13; mean extracellular volume (ECV) 28.4 vs. 24.0; p < 0.01), atrial fibrillation (AF) (6 vs. 2; p = 0.07) and conduction changes in ECG among patients treated with nCRT as compared to those treated with surgery alone. The results suggested an impact on quality of life in terms of worse role functioning for this patient group (95.0 vs. 88.8; p = 0.03). Based on our analyses we hypothesize that in EC patients, radiation-induced myocardial fibrosis plays a central role in cardiac toxicity leading to AF, conduction changes and ultimately to decreased role functioning. The results emphasize the need to verify these findings in larger cohorts of patients.