Childhood Cancer Survivors: Risk of Second Cancer and Heart Disease

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In a French study of more than 7,000 childhood cancer survivors published by Charrier et al in JACC: CardioOncology, researchers reported that the occurrence of a second malignant neoplasm among these survivors seemed to be associated with an increased risk of cardiac disease occurrence and risk at younger ages.

As stated by the investigators: “In the present study, we aim to quantify both the increased risk and increased cumulative incidence of cardiac disease after a second malignant neoplasm among childhood cancer survivors.”

Study Details

The French Childhood Cancer Survivors Study cohort included 7,670 childhood cancer survivors diagnosed between 1945 and 2000 at five cancer centers in France. Approximately half (54.8%) of the individuals included in the study were female, and nearly half (48.6%) were younger than age 5 at their first childhood cancer diagnosis. Data were collected from self-reported questionnaires, hospital-based databases or registries, and from long-term clinical follow-ups.

The investigators used a landmark approach to account for the time dependence of the occurrence of a second malignant neoplasm. They also considered an additive regression model to assess the cumulative incidence of cardiac disease.

In terms of exposure to cancer therapy during childhood, the study authors abstracted from medical records details on chemotherapy, surgery, and radiotherapy. In addition, for external-beam radiotherapy and/or brachytherapy, they used patient-specific voxel phantoms to retrospectively reconstruct the radiation dose distributions to the heart for individual treatment information.

Key Findings

Over a median follow-up of 30 years (interquartile range [IQR] = 22–38 years), 795 individuals developed a second malignant neoplasm, 329 developed cardiac disease with a second malignant neoplasm, and 49 developed cardiac disease after a second malignant neoplasm.

The median time to a cardiac disease was 23 years (IQR = 15–32 years), with a median age at event of 32 years (IQR = 21–40 years).

Among those with and without a second malignant neoplasm, the cardiac diseases identified were heart failure (51.3%), valvular heart disease (14.6%), arrhythmia (12.2%), pericardial disease (7.4%), ischemic heart disease (7.4%), and other heart diseases (7.1%). Of the second malignant neoplasms, the most common were breast cancer (11.3%), thyroid cancer (10.3%), bone cancer (8.8%), and skin epitheliomas and cancer (8.5%).

There was a significantly increased cumulative incidence of cardiac disease in patients who survived 25 years after their childhood cancer diagnosis and had a second malignant neoplasm; it was 3.8% (95% confidence interval [CI] = 0.5%–7.1%) higher than that in those without a second malignant neoplasm during this period. In addition, the investigators reported that second malignant neoplasms were associated with a twofold increase (cause-specific hazard ratio = 2.0, 95% CI = 1.4–2.8) of cardiac disease.

The investigators concluded, “Our study shows that childhood cancer survivors diagnosed with a second malignant neoplasm have both a higher cause-specific hazard of cardiac disease and cumulative incidence of cardiac disease, likely related to the cardiotoxicity of second malignant neoplasm treatments. Our findings provide important insights for clinical practice guidelines concerning second malignant neoplasms and cardiac disease post-therapy surveillance and risk-reducing strategies.”

Thibaud Charrier, MD, of the Université Paris-Saclay, Villejuif, France, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit

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