Cardiac Diseases Following Childhood Cancer Treatment

Haddy, Nadia; Diallo, Stéphanie; El‐Fayech, Chiraz; Schwartz, Boris; Pein, F; Hawkins, Michael M.; Veres, Cristina; Oberlin, Odile; Guibout, Catherine; Pacquement, Hélène; Munzer, Martine; Nguyen, Tan Dat; Bondiau, Pierre‐Yves; Berchery, Delphine; Laprie, Anne; Scarabin, Pierre‐Yves; Jouven, Xavier; Bridier, A.; Koscielny, Serge; Deutsch, Éric; Diallo, Ibrahima; Vathaire, Florent de

doi:10.1161/circulationaha.115.016686

Cited by 97 publications

(66 citation statements)

References 26 publications

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“…Thirdly, studies on cardiac biomarkers regarding other relevant cancer therapy‐related side effects such as an increased risk for coronary artery disease or other forms of cardiotoxic cancer therapy such as radiotherapy were not available for the present analysis. Patients who received high‐dose anthracyclines and chest radiotherapy have an up to 61.5‐fold increased risk and a cumulative incidence for overall cardiac disease of 11.0% at the age of 40 years . Therefore, evaluation of cardiac biomarkers in the detection of cardiovascular adverse events other than heart failure is needed in future studies.…”

Section: Discussionmentioning

confidence: 99%

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer—a meta‐analysis

et al. 2020

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Aims Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients. Methods and results PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT-proBNP (OR = 7.1; 95% CI = 2.0-25.5; n = 350; P = 0.003). The sensitivity of BNP/NT-proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1-6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5-13.2; n = 179; P = 0.53). Conclusions BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer—a meta‐analysis

et al. 2020

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“…Mulrooney et al reported health outcomes in a cohort of just over 14,000 survivors of childhood and adolescent cancer and found that this population was at substantial risk for cardiovascular disease, with a two-to six-fold increased relative risk for coronary events in patients who had received >15 Gy to the heart compared to non-irradiated survivors [157]. Moreover, the relative risk of cardiovascular events was reported up to 60-fold higher in childhood cancer survivors that received a higher cardiac mean dose of >30 Gy compared to patients who received either no RT or a dose to the heart of 0.1 Gy or less [158]. While some studies report exposure at an older age may also be a risk factor for more severe normal tissue toxicity [159,160], a rodent study reported increased mortality rates and incidence of RT pneumonitis compared to geriatric rats after 13 Gy partial body irradiation [161].…”

Section: Preclinical Models To Study Cardiac Radiation Toxicities: Anmentioning

confidence: 98%

Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity

Schlaak

SenthilKumar

Boerma

et al. 2020

Cancers

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Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short-and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance.

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“…For instance, in a French cohort of 3162 childhood cancer survivors, in those patients who did not receive anthracyclines, at median follow-up of 26 years after estimated average doses to the heart ≥30 Gy, the risk of heart disease was increased several fold compared to patients who had received doses to the heart <0.1 Gy [11]. …”

Section: Cardiac Injury Of High-dose Radiationmentioning

confidence: 99%

Effects of ionizing radiation on the heart

Boerma

Sridharan

Mao

et al. 2016

Mutation Research/Reviews in Mutation Research

122

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This article provides an overview of studies addressing effects of ionizing radiation on the heart. Clinical studies have identified early and late manifestations of radiation-induced heart disease, a side effect of radiation therapy to tumors in the chest when all or part of the heart is situated in the radiation field. Studies in preclinical animal models have contributed to our understanding of the mechanisms by which radiation may injure the heart. More recent observations in human subjects suggest that ionizing radiation may have cardiovascular effects at lower doses than was previously thought. This has led to examinations of low-dose photons and low-dose charged particle irradiation in animal models. Lastly, studies have started to identify noninvasive methods for detection of cardiac radiation injury and interventions that may prevent or mitigate these adverse effects. Altogether, this ongoing research should increase our knowledge of biological mechanisms of cardiovascular radiation injury, identify non-invasive biomarkers for early detection, and potential interventions that may prevent or mitigate these adverse effects.

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Cardiac Diseases Following Childhood Cancer Treatment

Abstract: Survivors of childhood cancers treated with radiotherapy and anthracycline run a high dose-dependent risk of developing CD. CDs develop earlier in patients treated with anthracycline than in those treated without it.

Cited by 97 publications

References 26 publications

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer—a meta‐analysis

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer—a meta‐analysis

Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity

Effects of ionizing radiation on the heart

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