Changing Hearts and Minds: Improving Outcomes in Cancer Treatment-Related Cardiotoxicity
- 57 Downloads
Purpose of Review
Cardiovascular effects from cancer treatment remains a leading cause of treatment-associated morbidity and mortality among cancer survivors. The National Cancer Institute and National Heart, Lung, and Blood Institute convened a Workshop in June 2018 entitled “Changing Hearts and Minds: Improving Outcomes in Cancer Treatment-Related Cardiotoxicity” to highlight progress, ongoing work, and update scientific priorities since the 2013 Workshop. Here we will describe these advances and provide an overview of the research priorities identified.
Since 2013, the National Institutes of Health has increased its support of cancer treatment-related cardiotoxicity research through the funding of grants and coordination of internal and external working groups. Workshop participants identified knowledge gaps and recommended over 20 new promising opportunities in basic and clinical cardiotoxicity research.
Significant progress on mechanisms, detection, management, and prevention of cardiotoxicity has been made over the past 5 years, yet some critical gaps remain.
KeywordsCardiotoxicity Cancer treatment Cardiovascular disease Cardio-oncology
The authors thank the workshop speakers and attendees and Sarah Fagan for her logistics and support work.
This work was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute and contract no. HHSN261201400011.
Compliance with Ethical Standards
Conflict of Interest
Nonniekaye Shelburne, Naoko I. Simonds, Bishow Adhikari, Michael Alley, Patrice Desvigne-Nickens, Eileen Dimond, Kelly Filipski, Lisa Gallicchio, and Lori Minasian declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Mertens AC, Yasui Y, Neglia JP, Potter JD, Nesbit ME Jr, Ruccione K, et al. Late mortality experience in five-year survivors of childhood and adolescent cancer: the childhood Cancer survivor study. J Clin Oncol. 2001;19(13):3163–72. https://doi.org/10.1200/JCO.2001.19.13.3163.CrossRefPubMedGoogle Scholar
- 7.Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med. 375(15):1457–67. https://doi.org/10.1056/NEJMra1100265.
- 8.Shelburne N, Adhikari B, Brell J, Davis M, Desvigne-Nickens P, Freedman A, et al. Cancer treatment-related cardiotoxicity: Current state of knowledge and future research priorities. JNCI. 2014;106(9). https://doi.org/10.1093/jnci/dju232.
- 9.NIH, 2015a. https://grants.nih.gov/grants/guide/pa-files/PA-18-003.html. Accessed 03 Dec 2018.
- 10.NIH, 2015b. https://grants.nih.gov/grants/guide/pa-files/PA-18-013.html. Accessed 03 Dec 2018.
- 11.NCI, 2018a. https://epi.grants.cancer.gov/events/cardiotoxicity/improving-outcomes.html. Accessed 03 Dec 2018.
- 12.• Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893–911. https://doi.org/10.1200/JCO.2016.70.5400. This review provides evidence based clinical practice guidelines for cardiotoxicity prevention and management in adult patients with cancer. Guidelines were developed by an expert panel and highlights existing evidence and knowledge gaps. CrossRefPubMedGoogle Scholar
- 13.• Armenian SH, Hudson MM, Mulder RL, et al. Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: A report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol. 2015;16(3):e123–36. https://doi.org/10.1016/S1470-2045(14)70409-7. This review provides evidence based clinical practice guidelines for identifying pediatric cancer survivors at risk for treatment related cardiomyopathy, including surveillance and management modalities. Guidelines were developed by an international expert panel and highlights existing evidence and knowledge gaps. CrossRefPubMedPubMedCentralGoogle Scholar
- 14.DuBois VFS, Casarotto E, Danhof M, Della PO. Pharmacokinetic-pharmacodynamic modelling of drug-induced QTc interval prolongation in man: prediction from in vitro human ether-à-go-go-related gene binding and functional inhibition assays and conscious dog studies. Br J Pharmacol. 2016;173:2819–32.CrossRefGoogle Scholar
- 18.• Sharma A, Burridge PW, WL MK, et al. Sci Transl Med. 2017;9(377). https://doi.org/10.1126/scitranslmed.aaf2584. This study utilized induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients treated with tyrosine kinase inhibitors (TKI) to generate a cardiac safety index based on cardiomyocyte viability, contractility, electrophysiology, calcium handling and signaling. The cardiac safety index and HiPSC-CMs can play an important role in assessing novel TKI cardiotoxicity during toxicology testing.
- 20.Lipshultz SE, Adams MJ, Colan SD, Constine LS, Herman EH, Hsu DT, et al. Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions—a scientific statement from the American Heart Association. Circulation. 2013;128:1927–95. https://doi.org/10.1161/CIR.0b013e3182a88099.CrossRefPubMedGoogle Scholar
- 21.Mertens AC, Liu Q, Neglia JP, Wasilewski K, Leisenring W, Armstrong GT, et al. Cause-specific late mortality amont 5-year survivors of childhood cancer: the childhood Cancer survivor study. J Natl Cancer Inst. 2008;100:1368–79. https://doi.org/10.1093/jci/djn310.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Murtagh G, Lyons T, O’Connell E, Ballot J, Geraghty L, Fennelly D, et al. Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up. Breast Cancer Res Treat. 2016;156:501–6. https://doi.org/10.1007/s10549-016-3781-4.CrossRefPubMedGoogle Scholar
- 27.•• Moslehi JJ, Salem J, Sosman JA, et al. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018;391:933. https://doi.org/10.1016/S0140-6736(18)30533-6. This is the first analysis to describe the clinical features of myocarditis in patients with cancer receiving immune check point inhibitors. The analysis of the World Health Organization’s database of individual case safety reports identified early onset and increasing incidence of myocarditis, immune related adverse events and fatalities. CrossRefPubMedGoogle Scholar
- 28.•• Khouri MG, Ky B, Dunn G, et al. Echocardiography Core Laboratory Reproducibility of Cardiac Safety Assessments in Cardio-Oncology. J Am Soc Echocardiogr. 2017;31(3):361–71. https://doi.org/10.1016/j.echo.2017.11.018. This is the first study to evaluate reproducibility between echocardiography core labs when conducting multi-site cardio-oncology studies. While high reproducibility within core labs was demonstrated, notable differences between labs existed. Improved echocardiogram reproducibility was seen with the institution of standard operating procedures and the application of measurement conventions across core labs, similar to processes when comparing blood assays between laboratories. CrossRefGoogle Scholar
- 29.FDA, 2018. https://www.fda.gov/downloads/drugs/guidances/ucm268555.pdf. Accessed 27 Dec 2018.
- 30.University of Pennsylvania, 2018. https://rt19.pmacs.upenn.edu/crcu_html/radcomp/website/index.html. Accessed 27 Dec 2018.
- 31.van Dalen EC, Caron HN, Dickenson HO, Kremer LCM. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Syst Rev. 2011. https://doi.org/10.1002/14651858.CD003917.pub4.
- 32.Schuchter LM, Hensley ML, Meropol NJ, Winer EP. Update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society for Clinical Oncology. J Clin Oncol. 2002;20:2895–903. https://doi.org/10.1200/JCO.2002.04.178.CrossRefPubMedGoogle Scholar
- 35.Seicean S, Seicean A, Plana JC, Budd GT, Marwick TH. Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. J Am Coll Cardiol. 2012;60:2384–90. https://doi.org/10.1016/j.jacc.2012.07.067.CrossRefPubMedGoogle Scholar
- 37.Pituskin E, Mackey JR, Koshman S, Jassal D, Pitz M, Haykowsky MJ, et al. Multidisciplinary approach to novel therapies in cardio-oncology research (MANTICORE 101-breast): a randomized trial for the prevention of trastuzumab-associated cardiotoxicity. J Clin Oncol. 2017;35(8):870–7. https://doi.org/10.1200/JCO.2016.68.7830.CrossRefPubMedGoogle Scholar
- 38.Lipshultz SE, Scully RE, Lipsitz SR, et al. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukemia: long-term follow-up of a prospective, randomized, multicentre trial. Lancet Oncol. 2010;11(10):950–61. https://doi.org/10.1016/S1470-2045(10)70204-7.CrossRefPubMedPubMedCentralGoogle Scholar
- 39.Asselin BL, Devidas M, Chen L, Franco VI, Pullen J, Borowitz MJ, et al. Cardioprotection and safety of dexrazoxane in patients treated for newly diagnosed T-cell acute lymphoblastic leukemia or advanced-stage lymphoblastic non-Hodgkin lymphoma: a report of the Children’s oncology group randomized trial pediatric oncology group 9404. J Clin Oncol. 2016;34(8):854–62. https://doi.org/10.1200/JCO.2015.60.8851.CrossRefPubMedGoogle Scholar
- 41.Guglin ME. Lisinopril or carvedilol for prevention of trastuzumab induced cardiotoxicity- lisinopril or carvedilol for cardiotoxicity. 2018. Presented at the American College of Cardiology Annual Scientific Session, Orlando, FL, March 11, 2018.Google Scholar
- 44.Miller TP, Li Y, Kavcic M, et al. Accuracy of adverse event ascertainment in clinical trials for pediatric acute myeloid leukemia. Alexandria: ASCO; 2015.Google Scholar
- 46.NCI, 2018b. https://healthcaredelivery.cancer.gov/pro-ctcae.