{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T15:38:50Z","timestamp":1785598730522,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/17\/47\/32805"],"award-info":[{"award-number":["FS\/17\/47\/32805"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CS-2015-15-003"],"award-info":[{"award-number":["CS-2015-15-003"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["AA\/18\/4\/34221"],"award-info":[{"award-number":["AA\/18\/4\/34221"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["FS\/17\/47\/32805"],"award-info":[{"award-number":["FS\/17\/47\/32805"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["CS-2015-15-003"],"award-info":[{"award-number":["CS-2015-15-003"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["AA\/18\/4\/34221"],"award-info":[{"award-number":["AA\/18\/4\/34221"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"The University of Manchester","doi-asserted-by":"publisher","award":["FS\/17\/47\/32805"],"award-info":[{"award-number":["FS\/17\/47\/32805"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"The University of Manchester","doi-asserted-by":"publisher","award":["CS-2015-15-003"],"award-info":[{"award-number":["CS-2015-15-003"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"The University of Manchester","doi-asserted-by":"publisher","award":["AA\/18\/4\/34221"],"award-info":[{"award-number":["AA\/18\/4\/34221"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>High dose interleukin-2 (IL-2) is known to be associated with cardiopulmonary toxicity. The goal of this study was to evaluate the effects of high dose IL-2 therapy on cardiopulmonary structure and function. Combined cardiopulmonary magnetic resonance imaging (MRI) was performed in 7 patients in the acute period following IL-2 therapy and repeated in 4 patients in the chronic period. Comparison was made to 10 healthy volunteers. IL-2 therapy was associated with myocardial and pulmonary capillary leak, tissue oedema and cardiomyocyte injury, which resulted in acute significant left ventricular (LV) dilatation, a reduction in LV ejection fraction (EF), an increase in LV mass and a prolongation of QT interval. The acute effects occurred irrespective of symptoms. In the chronic period many of the effects resolved, but LV hypertrophy ensued, driven by focal replacement and diffuse interstitial myocardial fibrosis and increased cardiomyocyte mass. In conclusion, IL-2 therapy is ubiquitously associated with acute cardiopulmonary inflammation, irrespective of symptoms, which leads to acute LV dilatation and dysfunction, increased LV mass and QT interval prolongation. Most of these effects are reversible but IL-2 therapy is associated with chronic LV hypertrophy, driven by interstitial myocardial fibrosis and increased cardiomyocyte mass. The findings have important implications for the monitoring and long term impact of newer immunotherapies. Future studies are needed to improve risk stratification and develop cardiopulmonary-protective strategies.<\/jats:p>","DOI":"10.3390\/diagnostics12061352","type":"journal-article","created":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T10:05:14Z","timestamp":1653905114000},"page":"1352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Acute and Chronic Cardiopulmonary Effects of High Dose Interleukin-2 Therapy: An Observational Magnetic Resonance Imaging Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Jakub","family":"Lagan","sequence":"first","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK"},{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine H.","family":"Naish","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christien","family":"Fortune","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK"},{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Campbell","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shien","family":"Chow","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK"},{"name":"The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, Bebingtonm CH63 4JY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Pillai","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0958-7392","authenticated-orcid":false,"given":"Joshua","family":"Bradley","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK"},{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenin","family":"Francis","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Clark","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Macnab","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-440X","authenticated-orcid":false,"given":"Gaetano","family":"Nucifora","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Dobson","sequence":"additional","affiliation":[{"name":"Liverpool Heart and Chest Hospital NHS Foundation Trust, Thomas Drive, Liverpool L14 3PE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik B.","family":"Schelbert","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, PA 15213, USA"},{"name":"Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK"},{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hawkins","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK"},{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK"},{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester M13 9PL, UK"},{"name":"Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology & Regenerative Medicine, School of Biology, Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S0140-6736(15)00046-X","article-title":"Renal cancer","volume":"387","author":"Capitanio","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.eururo.2018.08.036","article-title":"Epidemiology of Renal Cell Carcinoma","volume":"75","author":"Capitanio","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.3816\/CGC.2008.s.002","article-title":"Current algorithms and prognostic factors in the treatment of metastatic renal cell carcinoma","volume":"6","author":"Molina","year":"2008","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s40425-016-0174-5","article-title":"High-dose interleukin2\u2014A 10-year single-site experience in the treatment of metastatic renal cell carcinoma: Careful selection of patients gives an excellent outcome","volume":"4","author":"Chow","year":"2016","journal-title":"J. Immunother. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s00262-016-1854-1","article-title":"Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2","volume":"65","author":"Stenehjem","year":"2016","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1097\/00000658-198910000-00008","article-title":"Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients","volume":"210","author":"Rosenberg","year":"1989","journal-title":"Ann. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1002\/1097-0142(19941115)74:10<2850::AID-CNCR2820741018>3.0.CO;2-T","article-title":"Cardiotoxicity as a dose-limiting factor in a schedule of high dose bolus therapy with interleukin-2 and alpha-interferon. An unexpectedly frequent complication","volume":"74","author":"Kruit","year":"1994","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/00002371-199603000-00006","article-title":"Isolated left ventricular filling abnormalities may predict interleukin-2-induced cardiovascular toxicity","volume":"19","author":"Citterio","year":"1996","journal-title":"J. Immunother. Emphasis Tumor Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/CJI.0b013e318177a4ba","article-title":"Toxicity and activity of a twice daily high-dose bolus interleukin 2 regimen in patients with metastatic melanoma and metastatic renal cell cancer","volume":"31","author":"Acquavella","year":"2008","journal-title":"J. Immunother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/cncr.23552","article-title":"High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: A retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006","volume":"113","author":"Klapper","year":"2008","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1002\/1097-0142(19941215)74:12<3212::AID-CNCR2820741221>3.0.CO;2-I","article-title":"Cardiopulmonary toxicity of treatment with high dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma","volume":"74","author":"Schwartzentruber","year":"1994","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s40425-017-0307-5","article-title":"Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: Data from the PROCLAIMSM registry","volume":"5","author":"Curti","year":"2017","journal-title":"J. Immunother. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0046-8177(90)90005-P","article-title":"Pathologic findings associated with interleukin-2-based immunotherapy for cancer: A postmortem study of 19 patients","volume":"21","author":"Kragel","year":"1990","journal-title":"Hum. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/1097-0142(19901001)66:7<1513::AID-CNCR2820660713>3.0.CO;2-X","article-title":"Myocarditis or acute myocardial infarction associated with interleukin-2 therapy for cancer","volume":"66","author":"Kragel","year":"1990","journal-title":"Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s10554-021-02496-6","article-title":"Cardiac involvement in cystic fibrosis evaluated using cardiopulmonary magnetic resonance","volume":"38","author":"Lagan","year":"2022","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1007\/s10554-020-02091-1","article-title":"Myocardial involvement in eosinophilic granulomatosis with polyangiitis evaluated with cardiopulmonary magnetic resonance","volume":"37","author":"Lagan","year":"2021","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_17","first-page":"63","article-title":"Reference ranges (\u201cnormal values\u201d) for cardiovascular magnetic resonance (CMR) in adults and children: 2020 update","volume":"22","author":"Hetzel","year":"2020","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1161\/CIRCIMAGING.112.000192","article-title":"Comprehensive validation of cardiovascular magnetic resonance techniques for the assessment of myocardial extracellular volume","volume":"6","author":"Miller","year":"2013","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12968-017-0389-8","article-title":"Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI)","volume":"19","author":"Messroghli","year":"2017","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1002\/mrm.21814","article-title":"Modeling of contrast agent kinetics in the lung using T1-weighted dynamic contrast-enhanced MRI","volume":"61","author":"Naish","year":"2009","journal-title":"Magn. Reson. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/RLI.0b013e318281057d","article-title":"Quantitative and semiquantitative measures of regional pulmonary microvascular perfusion by magnetic resonance imaging and their relationships to global lung perfusion and lung diffusing capacity: The multiethnic study of atherosclerosis chronic obstructive pulmonary disease study","volume":"48","author":"Hueper","year":"2013","journal-title":"Investig. Radiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1161\/JAHA.116.003555","article-title":"Automated Extracellular Volume Fraction Mapping Provides Insights Into the Pathophysiology of Left Ventricular Remodeling Post-Reperfused ST-Elevation Myocardial Infarction","volume":"5","author":"Bulluck","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.4049\/jimmunol.137.5.1735","article-title":"Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2","volume":"137","author":"Rosenstein","year":"1986","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11906","DOI":"10.1073\/pnas.1002569107","article-title":"Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells","volume":"107","author":"Krieg","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1200\/JCO.2005.03.206","article-title":"Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma","volume":"23","author":"McDermott","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/jnci\/80.3.177","article-title":"Increased vascular permeability in organs mediated by the systemic administration of lymphokine-activated killer cells and recombinant interleukin-2 in mice","volume":"80","author":"Ettinghausen","year":"1988","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1161\/01.CIR.87.4.1340","article-title":"Cardiotoxicity of human recombinant interleukin-2 in rats. A morphological study","volume":"87","author":"Zhang","year":"1993","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1080\/10976640500452000","article-title":"Cardiac magnetic resonance appearance of myocarditis caused by high dose IL-2: Similarities to community-acquired myocarditis","volume":"8","author":"Ingkanisorn","year":"2006","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1200\/JCO.1989.7.1.7","article-title":"Cardiorespiratory effects of immunotherapy with interleukin-2","volume":"7","author":"Lee","year":"1989","journal-title":"J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1136\/hrt.71.2.166","article-title":"Impaired left ventricular filling rate induced by treatment with recombinant interleukin 2 for advanced cancer","volume":"71","author":"Fragasso","year":"1994","journal-title":"Br. Heart J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1388-9842(00)00073-8","article-title":"Negative inotropic effects of recombinant interleukin 2 in patients without left ventricular dysfunction","volume":"2","author":"Tio","year":"2000","journal-title":"Eur. J. Heart Fail."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/eurheartj\/eht193","article-title":"Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission","volume":"35","author":"Wong","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1001\/jamacardio.2017.2511","article-title":"Temporal Relation Between Myocardial Fibrosis and Heart Failure With Preserved Ejection Fraction: Association With Baseline Disease Severity and Subsequent Outcome","volume":"2","author":"Schelbert","year":"2017","journal-title":"JAMA Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1200\/JCO.1989.7.4.486","article-title":"Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: Analysis of toxicity and management guidelines","volume":"7","author":"Margolin","year":"1989","journal-title":"J. Clin. Oncol."},{"key":"ref_35","first-page":"212","article-title":"The Toxicity and Benefit of Various Dosing Strategies for Interleukin-2 in Metastatic Melanoma and Renal Cell Carcinoma","volume":"6","author":"Pachella","year":"2015","journal-title":"J. Adv. Pract. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/ejhf.1631","article-title":"Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: A meta-analysis","volume":"22","author":"Michel","year":"2020","journal-title":"Eur. J. Heart Fail."},{"key":"ref_37","first-page":"14","article-title":"Immune checkpoint inhibitor-induced myocarditis in cancer patients: A case report and review of reported cases","volume":"7","author":"Matzen","year":"2021","journal-title":"Cardiooncology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40425-014-0026-0","article-title":"High dose interleukin-2 (Aldesleukin)\u2014Expert consensus on best management practices-2014","volume":"2","author":"Dutcher","year":"2014","journal-title":"J. Immunother. Cancer"},{"key":"ref_39","first-page":"100420","article-title":"Cardiotoxicity from immune checkpoint inhibitors","volume":"25","author":"Michel","year":"2019","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.jacc.2018.02.037","article-title":"Myocarditis in Patients Treated with Immune Checkpoint Inhibitors","volume":"71","author":"Mahmood","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1200\/JCO.2016.72.1985","article-title":"Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study","volume":"35","author":"Hammers","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.critrevonc.2018.10.004","article-title":"Second-line cabozantinib versus nivolumab in advanced renal cell carcinoma: Systematic review and indirect treatment comparison","volume":"139","author":"Porta","year":"2018","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/jmri.1880070112","article-title":"Physiologic measurements by contrast-enhanced MR imaging: Expectations and limitations","volume":"7","author":"Roberts","year":"1997","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1532-429X-15-35","article-title":"Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing","volume":"15","author":"Bluemke","year":"2013","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jcf.2015.11.009","article-title":"Preliminary comparison of normalized T1 and non-contrast perfusion MRI assessments of regional lung disease in cystic fibrosis patients","volume":"16","author":"Donnola","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.media.2007.06.004","article-title":"Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brain","volume":"12","author":"Avants","year":"2008","journal-title":"Med. Image Anal."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/6\/1352\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:21:54Z","timestamp":1760138514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/6\/1352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,30]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["diagnostics12061352"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12061352","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,30]]}}}