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      Precision cardio-oncology: understanding the cardiotoxicity of cancer therapy

      , 1 , 2 , 3

      NPJ Precision Oncology

      Nature Publishing Group UK

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          Abstract

          Current oncologic treatments have brought a strong reduction in mortality in cancer patients. However, the cancer therapy-related cardiovascular complications, in particular chemo-therapy and radiation therapy-induced cardiotoxicities are a major cause of morbidity and mortality in people living with or surviving cancer. The simple fact is that all antineoplastic agents and radiation therapy target tumor cells but also result in collateral damage to other tissues including the cardiovascular system. The commonly used anthracycline chemotherapy agents can induce cardiomyopathy and congestive heart failure. Targeted therapies with human epidermal growth factor antibodies, tyrosine kinase inhibitors or vascular endothelial growth factor antibodies, and the antimetabolites also have shown to induce cardiomyopathy and myocardial ischemia. Cardiac arrhythmias and hypertension have been well described with the use of tyrosine kinase inhibitors and antimicrotubule agents. Pericarditis can happen with the use of cyclophosphamide or cytarabine. Mediastinal radiation can cause constrictive pericarditis, myocardial fibrosis, valvular lesions, and coronary artery disease. Despite significant progresses in the understanding of the molecular and pathophysiologic mechanisms behind the cardiovascular toxicity of cancer therapy, there is still lack of evidence-based approach for the monitoring and management of patients. This review will focus mainly on the recent advances in the molecular mechanisms of cardiotoxicity related to common cancer therapies while introducing the concept of cardio-oncology service. Applying the general principles of multi-disciplinary approaches toward the diagnosis, prevention, monitoring, and treatment of cancer therapy-induced cardiomyopathy and heart failure will also be discussed.

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          Most cited references 124

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          Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.

          Since sunitinib malate has shown activity in two uncontrolled studies in patients with metastatic renal-cell carcinoma, a comparison of the drug with interferon alfa in a phase 3 trial is warranted. We enrolled 750 patients with previously untreated, metastatic renal-cell carcinoma in a multicenter, randomized, phase 3 trial to receive either repeated 6-week cycles of sunitinib (at a dose of 50 mg given orally once daily for 4 weeks, followed by 2 weeks without treatment) or interferon alfa (at a dose of 9 MU given subcutaneously three times weekly). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, patient-reported outcomes, and safety. The median progression-free survival was significantly longer in the sunitinib group (11 months) than in the interferon alfa group (5 months), corresponding to a hazard ratio of 0.42 (95% confidence interval, 0.32 to 0.54; P<0.001). Sunitinib was also associated with a higher objective response rate than was interferon alfa (31% vs. 6%, P<0.001). The proportion of patients with grade 3 or 4 treatment-related fatigue was significantly higher in the group treated with interferon alfa, whereas diarrhea was more frequent in the sunitinib group (P<0.05). Patients in the sunitinib group reported a significantly better quality of life than did patients in the interferon alfa group (P<0.001). Progression-free survival was longer and response rates were higher in patients with metastatic renal-cell cancer who received sunitinib than in those receiving interferon alfa (ClinicalTrials.gov numbers, NCT00098657 and NCT00083889 [ClinicalTrials.gov]). Copyright 2007 Massachusetts Medical Society.
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            2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

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              Cancer treatment and survivorship statistics, 2014.

              The number of cancer survivors continues to increase due to the aging and growth of the population and improvements in early detection and treatment. In order for the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborated to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results (SEER) program registries. In addition, current treatment patterns for the most common cancer types are described based on information in the National Cancer Data Base and the SEER and SEER-Medicare linked databases; treatment-related side effects are also briefly described. Nearly 14.5 million Americans with a history of cancer were alive on January 1, 2014; by January 1, 2024, that number will increase to nearly 19 million. The 3 most common prevalent cancers among males are prostate cancer (43%), colorectal cancer (9%), and melanoma (8%), and those among females are cancers of the breast (41%), uterine corpus (8%), and colon and rectum (8%). The age distribution of survivors varies substantially by cancer type. For example, the majority of prostate cancer survivors (62%) are aged 70 years or older, whereas less than one-third (32%) of melanoma survivors are in this older age group. It is important for clinicians to understand the unique medical and psychosocial needs of cancer survivors and to proactively assess and manage these issues. There are a growing number of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. © 2014 American Cancer Society.
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                Author and article information

                Affiliations
                [1 ]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Reid Health, , Indiana University School of Medicine, ; Richmond, IN 47374 USA
                [2 ]ISNI 0000 0001 2189 3846, GRID grid.207374.5, Professor of Medicine and Director, Cancer Center of Henan Provincial People’s Hospital, , Zhengzhou University, ; Zhengzhou, Henan China
                [3 ]ISNI 0000 0000 9277 8602, GRID grid.412098.6, Professor of Biochemistry and Director, Zhengzhou Central Laboratory of Antibody Research, , Henan University of Traditional Chinese Medicine, ; Zhengzhou, Henan China
                Contributors
                +765-962-1337 , Xinqhan@iupui.edu
                Journal
                NPJ Precis Oncol
                NPJ Precis Oncol
                NPJ Precision Oncology
                Nature Publishing Group UK (London )
                2397-768X
                12 September 2017
                12 September 2017
                2017
                : 1
                : 1
                34
                10.1038/s41698-017-0034-x
                5871905
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                © The Author(s) 2017

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