Elsevier

Maturitas

Volume 105, November 2017, Pages 37-45
Maturitas

Review
Long-term cardiovascular health in adult cancer survivors

https://doi.org/10.1016/j.maturitas.2017.05.014Get rights and content

Highlights

  • Cancer treatment can have long-term detrimental cardiovascular side-effects.

  • Awareness of these long-term side-effects is of crucial value in the management of these patients.

  • Prospective information is needed to fill the current gaps in knowledge (in particular regarding the long-term side-effects of non-anthracyclines).

  • Multidisciplinary efforts will reduce the impact of the side-effects of anticancer treatments.

Abstract

The number of cancer survivors has tremendously increased over the past decades as a result of aging of the population and improvements in early cancer detection and treatment. Ongoing successes in cancer treatment are expected to result in a further increase in the number of long-term survivors. However, cancer treatment can have detrimental cardiovascular side-effects that impact morbidity and mortality, reducing quality of life in cancer survivors. The spectrum of radiotherapy- and chemotherapy-induced cardiovascular disease is broad, varying from subclinical valvular dysfunction to overt congestive heart failure, and such effects may not be apparent for more than twenty years after the initial cancer treatment. Awareness of these long-term side-effects is of crucial value in the management of these patients, in order to reduce the impact of cardiovascular morbidity and mortality. This review provides a comprehensive overview of the long-term cardiovascular complications of cancer treatments (radiotherapy and chemotherapy) in adult cancer survivors.

Introduction

Over the past decades, improvements in early cancer detection and treatment have significantly improved survival rates of many malignancies [1]. Furthermore, the incidence of cancer patients has increased (and will increase further) due to aging of the population [2]. As a result of these two trends, the population of cancer survivors is growing rapidly in the Western world. In 2012, nearly fourteen million cancer survivors were alive in the United States and it has been postulated that this will increase to eighteen million by 2022 [2]. A similar trend is observed in Europe [3].

Within the population of cancer survivors, the awareness for health problems that can occur after cancer survival is increasing. Besides the risk of recurrent or secondary malignancies, functional disabilities and psychosocial distress, cancer survivors are prone to develop cardiovascular disease (CVD) [4], [5]. Fig. 1 provides an example on the characteristic survival pattern observed in survivors of Hodgkin’s disease [6]. Compared to people without a cancer history, CVD risk is 30% higher in adult cancer survivors [7]. In addition, CVD is the most common cause of non-cancer death among cancer survivors and significantly reduces the eight-year overall survival from 81% to 60% compared to cancer survivors without CVD [8], [9].

Traditionally, cancer and CVD were considered two different entities. However, there is growing evidence that there might be a common biological pathway, as cancer and CVD share common risk factors such as ageing, smoking and obesity [10]. Patients with these pre-existing risk factors at baseline are also more likely to develop CVD during and after anticancer treatment [11]. Finally, preliminary evidence suggests that subclinical myocardial damage can occur prior to anticancer treatment, implicating an effect on cardiac function by the malignant process itself [12].

The spectrum of anticancer treatment-induced CVD is wide, varying from valvular heart disease (VHD) and constrictive pericarditis to ischaemic heart disease and overt congestive heart failure (CHF) [13]. The first clinical manifestations may appear more than twenty years after exposure [4]. Awareness of these long-term side effects is therefore of importance in the follow-up and management of these patients. This review provides a comprehensive overview of the long-term cardiovascular (CV) complications of anticancer treatments (radiotherapy, chemotherapy and targeted therapy) in adult cancer survivors. Acute CV complications of anticancer treatments in adults [14], as well as long-term side effects in childhood cancer survivors will be discussed elsewhere in this issue and are out of the scope of this review.

Section snippets

Long-term radiotherapy-induced cardiovascular disease

Radiotherapy (RT) is an integral component of anticancer treatment in nearly 50% of cancer patients [15]. Exposure of the heart to RT has been associated with severe long-term CV complications in cancer survivors. In the 1960’s, it was first recognised that thoracic RT might induce severe CV sequelae [16], which led to drastic refinements in RT techniques over the past decades. As a result, acute complications (i.e. acute pericarditis) have become rare and most RT-induced complications manifest

Long-term systemic therapy-induced cardiovascular disease

Exposure to systemic therapy (chemotherapy or targeted therapy) may pose a threat for CV health in cancer survivors in many ways. The most notorious long-term adverse effect is systemic therapy-related cardiac dysfunction. Table 1 provides an overview of current publications on long term cardiovascular complication in systemic therapy. We would like to emphasize that long-term follow-up data on CV complications are lacking in the majority of (modern) systemic therapy agents and that several of

Future perspectives

In the past decades, significant improvements have been made in early cancer detection and treatment leading to improved prognosis in cancer patients. However, cancer treatment has detrimental long-term effects on CV health and early recognition of unwanted side effects is needed to initiate preventive treatment at an early stage in high-risk patients. Fig. 5 provides a schematic overview of the available literature we set out in this overview article.

To answer the specific clinical problems

Contributors

WRN, ML and AJT performed the literature search and wrote the manuscript.

AdG, AvR, MJC, FWA and AHEMM were co-authors who reviewed and revised the manuscript.

All authors saw and approved the final version.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

No funding was received for this article.

Provenance and peer review

This article has undergone peer review.

Acknowledgements

Folkert W. Asselbergs is supported by a Dekker scholarship-Junior Staff Member 2014T001–Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre.

References (77)

  • K. Murbraech et al.

    Valvular dysfunction in lymphoma survivors treated with autologous stem cell transplantation: a national cross-sectional study

    JACC. Cardiovasc. Imaging.

    (2016)
  • D. Hering et al.

    Echocardiographic features of radiation-associated valvular disease

    Am. J. Cardiol.

    (2003)
  • L. Krapf et al.

    Anatomical features of rheumatic and non-rheumatic mitral stenosis: potential additional value of three-dimensional echocardiography

    Arch. Cardiovasc. Dis.

    (2013)
  • R.L. Larsen et al.

    Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults

    Am. J. Cardiol.

    (1992)
  • J.C. Rehammar et al.

    Risk of pacemaker or implantable cardioverter defibrillator after radiotherapy for early-stage breast cancer in Denmark, 1982–2005

    Radiother. Oncol.

    (2017)
  • M. Lotrionte et al.

    Review and meta-analysis of incidence and clinical predictors of anthracycline cardiotoxicity

    Am. J. Cardiol.

    (2013)
  • J.R. Mackey et al.

    Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial

    Lancet. Oncol.

    (2013)
  • N.F. Ponde et al.

    Twenty years of anti-HER2 therapy-associated cardiotoxicity

    ESMO Open

    (2016)
  • H. Abdel-Qadir et al.

    Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: a systematic review and meta-analysis

    Cancer Treat. Rev.

    (2017)
  • P. Vejpongsa et al.

    Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities

    J. Am. Coll. Cardiol.

    (2014)
  • D. Cardinale et al.

    Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy

    J. Am. Coll. Cardiol.

    (2010)
  • N. Fallah-Rad et al.

    The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with a

    J. Am. Coll. Cardiol.

    (2011)
  • H. Abdel-Qadir et al.

    The risk of myocardial infarction with aromatase inhibitors relative to tamoxifen in post-menopausal women with early stage breast cancer

    Eur. J. Cancer

    (2016)
  • J.C. Voog et al.

    Cardiovascular mortality following short-term androgen deprivation in clinically localized prostate cancer: an analysis of RTOG 94-08

    Eur. Urol.

    (2016)
  • E.C. de Haas et al.

    The metabolic syndrome in cancer survivors

    Lancet Oncol.

    (2010)
  • K.D. Miller et al.

    Cancer treatment and survivorship statistics 2016

    CA Cancer J. Clin.

    (2016)
  • J.S. de Moor et al.

    Cancer survivors in the United States: prevalence across the survivorship trajectory and implications for care

    Cancer Epidemiol. Biomark. Prev.

    (2013)
  • F.E. van Leeuwen et al.

    Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment

    Hematol. Am. Soc. Hematol. Educ. Progr.

    (2016)
  • M.R. Keats et al.

    Cardiovascular disease and physical activity in adult cancer survivors: a nested, retrospective study from the Atlantic PATH cohort

    J. Cancer Surviv.

    (2017)
  • S.H. Armenian et al.

    Cardiovascular disease among survivors of adult-onset cancer: a community-based retrospective cohort study

    J. Clin. Oncol.

    (2016)
  • R.J. Koene et al.

    Shared risk factors in cardiovascular disease and cancer

    Circulation

    (2016)
  • H. Abdel-Qadir et al.

    A population-based study of cardiovascular mortality following early-stage breast cancer

    JAMA Cardiol.

    (2017)
  • N. Pavo et al.

    Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality

    Heart

    (2015)
  • J.L. Zamorano et al.

    ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: the Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)

    Eur. Heart J.

    (2016)
  • M.S. Ewer et al.

    Cardiotoxicity of anticancer treatments

    Nat. Rev. Cardiol.

    (2015)
  • M. Boerma et al.

    Pharmacological induction of transforming growth factor-beta1 in rat models enhances radiation injury in the intestine and the heart

    PLoS One

    (2013)
  • K.E. Cohn et al.

    Heart disease following radiation

    Medicine (Baltimore)

    (1967)
  • F.C. 3rd Brosius et al.

    Radiation heart disease. Analysis of 16 young (aged 15–33 years) necropsy patients who received over 3,500 rads to the heart

    Am. J. Med.

    (1981)
  • Cited by (0)

    View full text