Radiation-Induced Myocardial Fibrosis in Long-Term Esophageal Cancer Survivors

• Published in: International journal of radiation oncology, biology, physics Vol. 110; no. 4; pp. 1013 - 1021
• Main Authors: de Groot, Crystal, Beukema, Jannet C., Langendijk, Johannes A., van der Laan, Hans Paul, van Luijk, Peter, van Melle, Joost P., Muijs, Christina T., Prakken, Niek H.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2021
• Subjects: Aged; Cancer Survivors; Dose-Response Relationship, Radiation; Esophageal Neoplasms - pathology; Esophageal Neoplasms - radiotherapy; Esophageal Neoplasms - therapy; Esophagectomy; ESOPHAGUS; Female; FIBROSIS; Fibrosis - etiology; Heart - diagnostic imaging; Heart - radiation effects; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium - pathology; Neoadjuvant Therapy - adverse effects; NEOPLASMS; PATIENTS; RADIATION DOSES; Radiation Injuries - pathology; RADIOLOGY AND NUCLEAR MEDICINE; Radiotherapy Dosage; TOXICITY; WHO
• ISSN: 0360-3016; 1879-355X; 1879-355X
• DOI: 10.1016/j.ijrobp.2021.02.007

Radiation-induced cardiac toxicity is a potential lethal complication. The aim of this study was to assess whether there is a dose-dependent relationship between radiation dose and myocardial fibrosis in patients who received neoadjuvant chemoradiation (nCRT) for esophageal cancer (EC). Forty patients with EC treated with a transthoracic esophagectomy with (n = 20) or without (n = 20) nCRT (CROSS study regimen) were included. Cardiovascular magnetic resonance imaging (1.5 Tesla) for left ventricular (LV) function, late gadolinium enhancement, and T1 mapping were performed. Extracellular volume (ECV), as a surrogate for collagen burden, was measured for all LV segments separately. The dose-response relationship between ECV and mean radiation dose per LV myocardial segment was evaluated using a mixed-model analysis. Seventeen nCRT and 16 control patients were suitable for analysis. The mean time after treatment was 67.6 ± 8.1 (nCRT) and 122 ± 35 (controls) months (P = .02). In nCRT patients, we found a significantly higher mean global ECV of 28.2% compared with 24.0% in the controls (P < .001). After nCRT, LV myocardial segments with elevated ECV had received significantly higher radiation doses. In addition, a linear dose–effect relation was found with a 0.136% point increase of ECV for each Gy (P < .001). There were no differences in LV function measures and late gadolinium enhancement between both groups. Myocardial ECV was significantly higher in long-term EC survivors after nCRT compared with surgery only. Moreover, this ECV increase was linear with the radiation dose per LV segment, indicating radiation-induced myocardial fibrosis.