Arterial effects of anthracycline: structural & inflammatory assessments in non-human primates and lymphoma patients.

in Clinical science (London, England : 1979) by Stephen Rankin, Caitlin Fountain, Alastair J Gemmell, Daire Quinn, Alasdair Henderson, John McClure, Sandy Small, Balaji Venugopal, Pamela McKay, Piotr J Slomka, David Colville, Mark Petrie, Giselle C Mendelez, Ninian N Lang

TLDR

  • This study found that anthracycline exposure in non-human primates was associated with aortic fibrosis and vacuolization, but not in patients with lymphoma.

Abstract

Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma. &#160;Methods1) African Green monkeys (AGM) received doxorubicin (30-60 mg/m2/biweekly intravenously, cumulative dose: 240 mg/m2). Blinded histopathologic analyses of the ascending aorta were performed 15 weeks after the last doxorubicin dose and compared to 5 age- and gender-matched healthy, untreated AGMs. 2) Analysis of the thoracic aorta of patients with diffuse large B-cell lymphoma (DLBCL), at baseline and after doxorubicin exposure, was performed using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in this observational study by maximal tissue-to-background ratio (TBRmax).</p> &#160; Results: In AGMs, doxorubicin exposure was associated with greater aortic fibrosis (collagen deposition: doxorubicin 6.23±0.88% vs. controls 4.67±0.54%; p=0.01) and intracellular vacuolization (doxorubicin 66.3±10.1 vs controls 11.5±4.2 vacuoles/field, p<0.0001) than untreated controls. In 101 patients with DLBCL, there was no change in aortic TBRmax after anthracycline exposure (TBRmax 1.46 ± 0.16 vs 1.44 ± 0.14 respectively, p=0.14). Univariate analyses yielded similar results.</p> &#160;Conclusions: In a large animal model, anthracycline exposure was associated with aortic fibrosis. In patients with lymphoma, anthracycline exposure was not associated with aortic inflammation. Further research is required to elucidate the mechanisms of anthracycline-related vascular harm.

Overview

  • This study aimed to investigate the effects of anthracyclines, such as doxorubicin, on the aorta in non-human primates and patients with lymphoma.
  • The main focus of the study was to evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines and to assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma.
  • The study used a combination of histopathological analyses in non-human primates and positron emission tomography/computed tomography (PET/CT) in patients with lymphoma to investigate the effects of anthracyclines on the aorta.

Comparative Analysis & Findings

  • In non-human primates, doxorubicin exposure was associated with greater aortic fibrosis and intracellular vacuolization compared to untreated controls.
  • However, in patients with lymphoma, anthracycline exposure was not associated with changes in aortic inflammation or increased fibrosis.
  • The study found no significant difference in aortic inflammation or fibrosis between patients with lymphoma who received anthracyclines and those who did not.

Implications and Future Directions

  • The findings of this study suggest that anthracycline exposure may not be directly associated with increased aortic inflammation or fibrosis in patients with lymphoma.
  • However, further research is needed to elucidate the mechanisms of anthracycline-related vascular harm and to determine the long-term effects of anthracycline exposure on the aorta.
  • Furthermore, the study highlights the importance of developing novel approaches to minimize the risk of anthracycline-related cardiovascular toxicity in patients with lymphoma.
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