Increased Cardiac Risk After a Second Malignant Neoplasm Among Childhood Cancer Survivors: A FCCSS Study.

Background: Childhood cancer survivors (CCS) are at an elevated risk of developing both a second malignant neoplasm (SMN) and cardiac disease.
Objectives: This study sought to assess the excess of occurrence of cardiac disease after a SMN among CCS.
Methods: Analyses included 7,670 CCS from the French Childhood Cancer Survivors Study cohort diagnosed between 1945 and 2000. To account for the time dependence of the occurrence of a SMN, we employed a landmark approach, considering an additive regression model for the cumulative incidence of cardiac disease. We estimated the effect of a SMN on the instantaneous risk of cardiac disease using a proportional cause-specific hazard model, considering a SMN as a time-dependent exposure. In both models, we adjusted for demographic and treatment information and considered death as a competing event.
Results: In 7,670 CCS over a median follow-up of 30 years (IQR: 22-38 years), there were 378 cases of cardiac disease identified, of which 49 patients experienced a SMN. Patients who survived 25 years after their childhood cancer diagnosis and had a SMN in that time frame had a significantly increased cumulative incidence of cardiac disease, which was 3.8% (95% CI: 0.5% to 7.1%) higher compared with those without a SMN during this period. No SMN-induced excess of cardiac disease was observed at subsequent landmark times. SMNs were associated with a 2-fold increase (cause-specific HR: 2.0; 95% CI: 1.4-2.8) of cardiac disease.
Conclusions: The occurrence of a SMN among CCS is associated with an increased risk of cardiac disease occurrence and risk at younger ages.
Competing Interests: This work was supported and funded by the Gustave Roussy Foundation (Pediatric Program "Guérir le Cancer de l’Enfant"), the ITMO (Instituts thématiques multiorganismes) Cancer d’Aviesan Program (RadioPrediTool project no. 20CM112-00), the INCa (Institut national du cancer)/ARC (Foundation ARC for Cancer Research) foundation (CHART project), the Foundation ARC for Cancer Research (grant no. Pop-HaRC 201401208), the "START" PAIR Research Program (grant no. INCa-Fondation ARC-LNCC 11902), and the Ligue Nationale Contre le Cancer association. These funding agencies had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, and approval of the manuscript. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2023 The Authors.)