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Published in: Insights into Imaging 1/2021

Open Access 01-12-2021 | Computed Tomography | Original Article

Potential role of epicardial adipose tissue as a biomarker of anthracycline cardiotoxicity

Authors: Caterina Beatrice Monti, Simone Schiaffino, Maria Del Mar Galimberti Ortiz, Davide Capra, Moreno Zanardo, Elena De Benedictis, Alberto Gianluigi Luporini, Pietro Spagnolo, Francesco Secchi, Francesco Sardanelli

Published in: Insights into Imaging | Issue 1/2021

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Abstract

Background

We investigated the radiodensity of epicardial (EAT), subcutaneous (SAT), and visceral adipose tissue (VAT) before and after treatment with anthracyclines in a population of breast cancer (BC) patients, and in controls not treated with anthracyclines, to detect a potential role of EAT density as a biomarker of changes related to chemotherapy cardiotoxicity.

Methods

We reviewed BC patients treated with anthracyclines who underwent CT before (CT-t0) and after (CT-t1) chemotherapy, and age- and sex-matched controls who underwent two CT examinations at comparable intervals. On non-contrast scans, EAT was segmented contouring the pericardium and thresholding between -190 and -30 Hounsfield units (HU), and SAT and VAT were segmented with two 15-mm diameter regions of interest thresholded between -195 and -45 HU.

Results

Thirty-two female patients and 32 controls were included. There were no differences in age (p = 0.439) and follow-up duration (p = 0.162) between patients and controls. Between CT-t0 and CT-t1, EAT density decreased in BC patients (-66 HU, interquartile range [IQR] -71 to -63 HU, to -71 HU, IQR -75 to -66 HU, p = 0.003), while it did not vary in controls (p = 0.955). SAT density increased from CT-t0 to CT-t1 in BC patients (-107 HU, IQR -111 to -105 HU, to -105 HU, IQR -110 to -100 HU, p = 0.014), whereas it did not change in controls (p = 0.477). VAT density did not vary in either BC patients (p = 0.911) or controls (p = 0.627).

Conclusions

EAT density appears to be influenced by anthracycline treatment for BC, well known for its cardiotoxicity, shifting towards lower values indicative of a less active metabolism.
Literature
2.
go back to reference Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin 71:7–33CrossRef Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin 71:7–33CrossRef
4.
go back to reference Yeh ETH, Ewer MS, Moslehi J et al (2019) Mechanisms and clinical course of cardiovascular toxicity of cancer treatment I. Oncol Semin Oncol 46:397–402CrossRef Yeh ETH, Ewer MS, Moslehi J et al (2019) Mechanisms and clinical course of cardiovascular toxicity of cancer treatment I. Oncol Semin Oncol 46:397–402CrossRef
5.
go back to reference Narui K, Ishikawa T, Shimizu D et al (2019) Anthracycline could be essential for triple-negative breast cancer: a randomised phase II study by the Kanagawa Breast Oncology Group (KBOG) 1101. Breast 47:1–9CrossRef Narui K, Ishikawa T, Shimizu D et al (2019) Anthracycline could be essential for triple-negative breast cancer: a randomised phase II study by the Kanagawa Breast Oncology Group (KBOG) 1101. Breast 47:1–9CrossRef
6.
go back to reference Cespedes Feliciano EM, Chen WY, Lee V et al (2020) Body composition, adherence to anthracycline and taxane-based chemotherapy, and survival after nonmetastatic breast cancer. JAMA Oncol 6:264CrossRef Cespedes Feliciano EM, Chen WY, Lee V et al (2020) Body composition, adherence to anthracycline and taxane-based chemotherapy, and survival after nonmetastatic breast cancer. JAMA Oncol 6:264CrossRef
7.
go back to reference Raggi P (2014) Epicardial adipose tissue and progression of coronary artery calcium. JACC Cardiovasc Imaging 7:917–919CrossRef Raggi P (2014) Epicardial adipose tissue and progression of coronary artery calcium. JACC Cardiovasc Imaging 7:917–919CrossRef
8.
go back to reference Deng G, Long Y, Yu Y-RR, Li M-RR (2010) Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK–eNOS Pathway. Int J Obes 34:165–171CrossRef Deng G, Long Y, Yu Y-RR, Li M-RR (2010) Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK–eNOS Pathway. Int J Obes 34:165–171CrossRef
9.
go back to reference Yerramasu A, Dey D, Venuraju S et al (2012) Increased volume of epicardial fat is an independent risk factor for accelerated progression of sub-clinical coronary atherosclerosis. Atherosclerosis 220:223–230CrossRef Yerramasu A, Dey D, Venuraju S et al (2012) Increased volume of epicardial fat is an independent risk factor for accelerated progression of sub-clinical coronary atherosclerosis. Atherosclerosis 220:223–230CrossRef
10.
go back to reference Klein C, Brunereau J, Lacroix D et al (2019) Left atrial epicardial adipose tissue radiodensity is associated with electrophysiological properties of atrial myocardium in patients with atrial fibrillation. Eur Radiol 29:3027–3035CrossRef Klein C, Brunereau J, Lacroix D et al (2019) Left atrial epicardial adipose tissue radiodensity is associated with electrophysiological properties of atrial myocardium in patients with atrial fibrillation. Eur Radiol 29:3027–3035CrossRef
11.
go back to reference Goeller M, Achenbach S, Marwan M et al (2018) Epicardial adipose tissue density and volume are related to subclinical atherosclerosis, inflammation and major adverse cardiac events in asymptomatic subjects. J Cardiovasc Comput Tomogr 12:67–73CrossRef Goeller M, Achenbach S, Marwan M et al (2018) Epicardial adipose tissue density and volume are related to subclinical atherosclerosis, inflammation and major adverse cardiac events in asymptomatic subjects. J Cardiovasc Comput Tomogr 12:67–73CrossRef
12.
go back to reference Iacobellis G, Secchi F, Capitanio G et al (2020) Epicardial Fat Inflammation in Severe COVID-19. Obesity 28:2260–2262CrossRef Iacobellis G, Secchi F, Capitanio G et al (2020) Epicardial Fat Inflammation in Severe COVID-19. Obesity 28:2260–2262CrossRef
13.
go back to reference Jacob S, Pathak A, Franck D et al (2016) Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study. Radiat Oncol 11:54CrossRef Jacob S, Pathak A, Franck D et al (2016) Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study. Radiat Oncol 11:54CrossRef
14.
go back to reference Monti CB, Zanardo M, Bosetti T et al (2020) Assessment of myocardial extracellular volume on body computed tomography in breast cancer patients treated with anthracyclines. Quant Imaging Med Surg 10:934–944CrossRef Monti CB, Zanardo M, Bosetti T et al (2020) Assessment of myocardial extracellular volume on body computed tomography in breast cancer patients treated with anthracyclines. Quant Imaging Med Surg 10:934–944CrossRef
15.
go back to reference Yushkevich PA, Piven J, Hazlett HC et al (2006) User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability. Neuroimage 31:1116–1128CrossRef Yushkevich PA, Piven J, Hazlett HC et al (2006) User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability. Neuroimage 31:1116–1128CrossRef
16.
go back to reference Nerlekar N, Thakur U, Lin A et al (2020) The Natural history of Epicardial Adipose Tissue Volume and Attenuation: A long-term prospective cohort follow-up study. Sci Rep 10:7109CrossRef Nerlekar N, Thakur U, Lin A et al (2020) The Natural history of Epicardial Adipose Tissue Volume and Attenuation: A long-term prospective cohort follow-up study. Sci Rep 10:7109CrossRef
17.
go back to reference Therkelsen KE, Pedley A, Rosenquist KJ et al (2016) Adipose tissue attenuation as a marker of adipose tissue quality: Associations with six-year changes in body weight. Obesity 24:499–505CrossRef Therkelsen KE, Pedley A, Rosenquist KJ et al (2016) Adipose tissue attenuation as a marker of adipose tissue quality: Associations with six-year changes in body weight. Obesity 24:499–505CrossRef
18.
go back to reference Evans J (1996) Straightforward statistics for behavioral sciences. Brooks/Cole Publishing, Pacific Grove, California Evans J (1996) Straightforward statistics for behavioral sciences. Brooks/Cole Publishing, Pacific Grove, California
19.
go back to reference Di Leo G, Sardanelli F (2020) Statistical significance: p value, 0.05 threshold, and applications to radiomics—reasons for a conservative approach. Eur Radiol Exp 4:18 Di Leo G, Sardanelli F (2020) Statistical significance: p value, 0.05 threshold, and applications to radiomics—reasons for a conservative approach. Eur Radiol Exp 4:18
20.
go back to reference Rosenquist KJ, Pedley A, Massaro JM et al (2013) Visceral and Subcutaneous Fat Quality and Cardiometabolic Risk. JACC Cardiovasc Imaging 6:762–771CrossRef Rosenquist KJ, Pedley A, Massaro JM et al (2013) Visceral and Subcutaneous Fat Quality and Cardiometabolic Risk. JACC Cardiovasc Imaging 6:762–771CrossRef
21.
go back to reference Alvey NJ, Pedley A, Rosenquist KJ, et al (2014) Association of Fat Density With Subclinical Atherosclerosis. J Am Heart Assoc 3(4):e000788CrossRef Alvey NJ, Pedley A, Rosenquist KJ, et al (2014) Association of Fat Density With Subclinical Atherosclerosis. J Am Heart Assoc 3(4):e000788CrossRef
22.
go back to reference Neuhouser ML, Aragaki AK, Prentice RL et al (2015) Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk. JAMA Oncol 1:611CrossRef Neuhouser ML, Aragaki AK, Prentice RL et al (2015) Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk. JAMA Oncol 1:611CrossRef
23.
go back to reference Antonopoulos AS, Antoniades C (2017) The role of epicardial adipose tissue in cardiac biology: classic concepts and emerging roles. J Physiol 595:3907–3917CrossRef Antonopoulos AS, Antoniades C (2017) The role of epicardial adipose tissue in cardiac biology: classic concepts and emerging roles. J Physiol 595:3907–3917CrossRef
24.
go back to reference Romero SAD, Brown JC, Bauml JM et al (2018) Barriers to physical activity: a study of academic and community cancer survivors with pain. J Cancer Surviv 12:744–752CrossRef Romero SAD, Brown JC, Bauml JM et al (2018) Barriers to physical activity: a study of academic and community cancer survivors with pain. J Cancer Surviv 12:744–752CrossRef
25.
go back to reference Becker K, Erckenbrecht JF, Häussinger D, Fueling T (1999) Cardiotoxicity of the antiprolif erative compound fluorouracil. Drugs 57(4):475–484CrossRef Becker K, Erckenbrecht JF, Häussinger D, Fueling T (1999) Cardiotoxicity of the antiprolif erative compound fluorouracil. Drugs 57(4):475–484CrossRef
26.
go back to reference Baba S, Jacene HA, Engles JM, Honda H, Wahl RL (2010) CT Hounsfield units of brown adipose tissue increase with activation: preclinical and clinical studies. J Nucl Med 51:246–250CrossRef Baba S, Jacene HA, Engles JM, Honda H, Wahl RL (2010) CT Hounsfield units of brown adipose tissue increase with activation: preclinical and clinical studies. J Nucl Med 51:246–250CrossRef
27.
go back to reference Mittelman SD, Orgel E (2018) Adipocyte metabolism of the chemotherapy daunorubicin. Oncoscience 5:146–147CrossRef Mittelman SD, Orgel E (2018) Adipocyte metabolism of the chemotherapy daunorubicin. Oncoscience 5:146–147CrossRef
28.
go back to reference Ma R, Ties D, van Assen M et al (2020) Towards reference values of pericoronary adipose tissue attenuation: impact of coronary artery and tube voltage in coronary computed tomography angiography. Eur Radiol 30:6838–6846CrossRef Ma R, Ties D, van Assen M et al (2020) Towards reference values of pericoronary adipose tissue attenuation: impact of coronary artery and tube voltage in coronary computed tomography angiography. Eur Radiol 30:6838–6846CrossRef
29.
go back to reference Craig LA, Ekert PG, Conyers R, Elliott DA (2017) Genetic determinants of anthracycline cardiotoxicity – ready for the clinic? Br J Clin Pharmacol 83:1141–1142CrossRef Craig LA, Ekert PG, Conyers R, Elliott DA (2017) Genetic determinants of anthracycline cardiotoxicity – ready for the clinic? Br J Clin Pharmacol 83:1141–1142CrossRef
30.
go back to reference Yaqub F (2013) Mechanism of action of anthracycline drugs. Lancet Oncol 14:e296CrossRef Yaqub F (2013) Mechanism of action of anthracycline drugs. Lancet Oncol 14:e296CrossRef
Metadata
Title
Potential role of epicardial adipose tissue as a biomarker of anthracycline cardiotoxicity
Authors
Caterina Beatrice Monti
Simone Schiaffino
Maria Del Mar Galimberti Ortiz
Davide Capra
Moreno Zanardo
Elena De Benedictis
Alberto Gianluigi Luporini
Pietro Spagnolo
Francesco Secchi
Francesco Sardanelli
Publication date
01-12-2021
Publisher
Springer International Publishing
Published in
Insights into Imaging / Issue 1/2021
Electronic ISSN: 1869-4101
DOI
https://doi.org/10.1186/s13244-021-01069-4

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