In a French study of more than 7,000 childhood cancer survivors, published in JACC: CardioOncology, Thibaud Charrier, PhD, of the Université Paris-Saclay, Villejuif, France, and colleagues reported that the occurrence of a second malignant neoplasm among these childhood cancer survivors seemed to be associated with an increased risk of cardiac disease occurrence and risk at younger ages.1
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. Data were collected from self-reported questionnaires, hospital-based databases or registries, and from long-term clinical follow-up. 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.
Thibaud Charrier, PhD
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 the diagnosis of 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%).
The investigators found 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.”
DISCLOSURE: Dr. Charrier and his coauthors reported no conflicts of interest.
REFERENCE
1. Charrier T, Haddy N, Schwartz B, et al: Increased cardiac risk after a second malignant neoplasm among childhood cancer survivors, a FCCSS study. JACC CardioOncol 5:792-803, 2023.
