ReviewLong-term cardiovascular health 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.
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