Is Cardio-Oncology a Rapidly Growing Field of Precision Medicine?

«ἀρχὴ παιδϵύσϵως ἡ τῶν ὀνομάτων ἐπίσκϵψις» (“The beginning of education is the examination of names”) Antisthenes Greek philosopher, c.445 – c.365 BC Cardio-oncology (CO) is a recently introduced but rapidly evolving field of cardiovascular (CV) medicine. It involves the CV evaluation, follow-up and management of cancer patients and survivors, aiming at the prevention, timely diagnosis and effective management of CV disease in these patients. One specific aim of CO is to render cancer patients fit to receive the best available anticancer therapy without any compromises or interruptions because of CV problems.1 Some anticancer therapies are quite effective against cancer, such as anthracyclines for breast cancer or haematological malignancies or the recently introduced immune checkpoint inhibitors for metastatic melanoma and other malignancies.2, 3 However, these favourable antitumour effects often come at the expense of an increased risk for CV complications. CO aims at ensuring optimal cancer outcomes without the expense of CV complications. An overview of the concept and aims of CO and how these fit in the cancer patient's journey is outlined in Figure 1. In the current issue of the Journal, Zamorano and colleagues provide a comprehensive description of what CO is all about with specific details on the cardiotoxicity profile of different anticancer therapies and the strategies for risk stratification, early diagnosis, prevention and treatment of cardiotoxicity in patients with cancer.4 Grammatically speaking, the term ‘cardio-oncology’ would typically be applied to describe the ‘oncology of the heart’; in other words, the domain of oncology dealing with the management of the primary or metastatic tumours that invade the heart, which are generally rare entities. In contrast, if one would seek a proper term to describe the ‘cardiology of cancer patients’, that is what CO is actually about, it would rather use the term ‘onco-cardiology’. This term actually appeared in earlier reports in the field.5, 6 Despite this minor grammatical misuse, the term ‘cardio-oncology’ has now been widely used and accepted. The need for CO was dictated by the continuously growing number of cancer survivors and the increasing impact of CV disease in the outcome of patients with malignancies. Both cancer patients and cancer survivors are increasing. In 2019, there were more than 17 million cancer survivors in the US and this number is expected to exceed 22 million in 2030 due to population aging and the advances in early detection and treatment of malignancies.7 Heart disease seems to have an important impact on these patients. Women with breast cancer, 10 years after the diagnosis and treatment of these malignancies, have a higher risk of dying of heart disease than of cancer.8 In the same line, adult survivors of childhood or adolescence cancer have an eight-fold higher CV mortality compared to their non-cancer counterparts.9 The previously encountered beliefs, still expressed by some CO opposers that ‘cancer patients die anyway so why would somebody care about their CV health’ or that ‘cancer patients would be lucky if they eventually die of heart disease instead of cancer’, have been well overcome by the impressive outcomes accomplished by anticancer therapies over the recent years. For example, the 3-year survival rate of patients with advanced melanoma has climbed to 58% with the use of combined immune checkpoint inhibitor therapy.10 Despite the fact that cancer patients were always being treated by cardiologists, their CV approach was mostly limited to the baseline evaluation of specific patients scheduled for few cardiotoxic therapies such as anthracyclines and the acute management of arising CV complications. In contrast, the CO discipline constitutes a very recent concept, in the sense of a structured and comprehensive CV approach, consisting of baseline evaluation, subsequent monitoring and long-term follow-up that aim at CV prevention and that are tailored to the particular characteristics and needs of patients with malignancies. In addition, this is a very rapidly growing discipline, as indicated by the bursting development of dedicated CO clinics around the world, the increasing number of relative publications and the introduction of dedicated journals, all encountered over the past 5 years. It became clear quite early that CO should evolve according to the principle of precision medicine in order to become successful and truly useful for the cancer patient. Precision medicine aims at tailoring treatment and prevention to the particular characteristics of each patients, moving away from the one-size-fits-all approach, in which disease interventions target the average patient. In same context, CO aims at identifying among cancer patients those who will benefit from systematic CV follow-up and treatment, in parallel to the oncological management, and at targeting these specific patients with tailored monitoring protocols, biomarker and imaging-guided early interventions and, upon achievement of cancer remission, tailored long-term follow-up protocols (Figure 1). These are actually the tools that CO has yet to develop to fulfil its mission. Towards this direction, the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology have already published a series of position papers on baseline risk stratification as well as the role of serum biomarkers and imaging in the monitoring of cancer patients receiving potentially cardiotoxic anticancer therapies.11-13 These documents provide useful guidance to clinicians on the above areas based on the hitherto accumulated bulk of evidence. Today, CO is a field of important challenges but also of opportunities. Given the increasing number of cancer cases and survivors and the growing impact of CV disease in these patients, it is expected that there will be a continuously increasing demand for CO services in the near future, which renders CO a promising professional field. At the same time, it constitutes a dynamic area of basic and clinical research. The continuous progress in anticancer therapeutics will keep providing new grounds for the investigation of their CV effects and potential toxicities, while exploring the complex pathways that link cancer and heart disease, and their potential implications for the prevention and management of cancer and CV disease offer quite an attractive field of research.14 One of the current challenges that CO faces concerns the delineation of primordial prevention strategies that would prevent cardiotoxicity. A number of studies have tested and continue to test several cardioactive and other agents in this regard, but data remain still limited for any firm conclusions or recommendations. Sensitive imaging techniques and biomarkers are able to detect early signs of subtle cardiotoxicity and potentially guide primary prevention strategies.15, 16 However, their integration in clinically relevant monitoring protocols that would determine what to measure, when and how to react to the results in each patient, needs further refinement. The attending oncologist or haematologist remain the central physician in the management of cancer patients, but a multidisciplinary approach in the context of a culture of close collaboration among all implicated physicians is still to be developed. Finally, the proper training of physicians in CO remains to be delineated through the description of curriculum, the development of courses and the establishment of certification and accreditation processes. The key issues for the successful development of the field of CO with the corresponding implicated stakeholders are summarized in Figure 2. Conflict of interest: none declared.