Cardiovascular Disease in Survivors of Childhood Cancer: Insights Into Epidemiology, Pathophysiology, and Prevention

Saro H. Armenian, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.Follow
Gregory T. Armstrong, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.Follow
Gregory Aune, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Eric J. Chow, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Matthew J. Ehrhardt, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Bonnie Ky, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Javid Moslehi, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Daniel A. Mulrooney, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Paul C. Nathan, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Thomas D. Ryan, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Helena J. van der Pal, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Elvira C. van Dalen, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Leontien C. Kremer, Saro H. Armenian, City of Hope, Duarte, CA; Gregory T. Armstrong, Matthew J. Ehrhardt, and Daniel A. Mulrooney, St Jude Children's Research Hospital, Memphis; Javid Moslehi, Vanderbilt School of Medicine, Nashville, TN; Gregory Aune, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX; Eric J. Chow, Fred Hutchinson Cancer Research Center, Seattle, WA; Bonnie Ky, University of Pennsylvania, Philadelphia, PA; Paul C. Nathan, The Hospital for Sick Children, Toronto, Ontario, Canada; Thomas D. Ryan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Helena J. van der Pal and Leontien C.M. Kremer, Princess Máxima Center for Pediatric Oncology, Utrecht; and Elvira C. van Dalen and Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.

Abstract

Cardiovascular disease (CVD), which includes cardiomyopathy/heart failure, coronary artery disease, stroke, pericardial disease, arrhythmias, and valvular and vascular dysfunction, is a major concern for long-term survivors of childhood cancer. There is clear evidence of increased risk of CVD largely attributable to treatment exposures at a young age, most notably anthracycline chemotherapy and chest-directed radiation therapy, and compounded by traditional cardiovascular risk factors accrued during decades after treatment exposure. Preclinical studies are limited; thus, it is a high priority to understand the pathophysiology of CVD as a result of anticancer treatments, taking into consideration the growing and developing heart. Recently developed personalized risk prediction models can provide decision support before initiation of anticancer therapy or facilitate implementation of screening strategies in at-risk survivors of cancer. Although consensus-based screening guidelines exist for the application of blood and imaging biomarkers of CVD, the most appropriate timing and frequency of these measures in survivors of childhood cancer are not yet fully elucidated. Longitudinal studies are needed to characterize the prognostic importance of subclinical markers of cardiovascular injury on long-term CVD risk. A number of prevention trials across the survivorship spectrum are under way, which include primary prevention (before or during cancer treatment), secondary prevention (after completion of treatment), and integrated approaches to manage modifiable cardiovascular risk factors. Ongoing multidisciplinary collaborations between the oncology, cardiology, primary care, and other subspecialty communities are essential to reduce therapeutic exposures and improve surveillance, prevention, and treatment of CVD in this high-risk population.

Publication Title

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

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