In a study reported in JAMA Oncology, Glele et al identified potential risk factors for valvular heart disease (VHD) in a European cohort of long-term childhood cancer survivors.
Study Details
The nested case-control study used data from the PanCareSurFup (PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies) and ProCardio cohorts, including radiation dose reconstruction and chemotherapy exposure, for 5-year childhood cancer survivors from seven European countries diagnosed between 1940 and 2009. Case patients with symptomatic VHD (grade ≥ 3) were matched 1:2 with controls according to subcohort, sex, age at cancer diagnosis, and calendar year of initial diagnosis.
Key Findings
A total of 225 cases and 442 controls were included in the analysis. Of 225 cases, 195 (86.7%) were diagnosed with VHD ≥ 20 years after diagnosis of childhood cancer.
Survivors receiving a mean heart radiation therapy (RT) dose of 5 to < 15 Gy had increased risk of VHD (odds ratio [OR] = 4.7, 95% confidence interval [CI] = 2.1–10.7) vs those without heart RT; risk of VHD was higher in those with exposure to more than half the heart. The heart RT dose appeared to be associated with an exponential increase in risk, with an OR for VHD of 104.1 (95% CI = 27.8–389.6) for mean heart doses of ≥ 30 Gy. Risk increased over follow-up, from 6.0 (95% CI = 1.4–26.5) after 5 to 19 years to 71.4 (95% CI = 20.4–250.0) after ≥ 30 years.
Cumulative anthracycline doses of ≥ 400 mg/m2 were associated with increased VHD risk (OR = 3.8; 95% CI, 1.4–10.3), with an exponential dose-response pattern being observed. Cumulative exposure to platinum agents was associated with a linear increase in VHD risk.
No statistically significant associations were found for VHD risk with other chemotherapy agents or with radiation to the spleen.
The investigators concluded: “In this case-control study, heart RT, anthracyclines, and platinum agents were associated with increased VHD risk in childhood cancer survivors. Risks from both RT and anthracyclines were amplified with age and follow-up, underscoring the need for long-term cardiac surveillance.”
Brice Fresneau, MD, PhD, of the Department of Children and Adolescents Oncology, Gustave Roussy, Villejuif, France, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the Ligue Nationale Contre le Cancer, Dutch Cancer Society, and others. For full disclosures of all study authors, visit jamanetwork.com.
