In a study reported in the Journal of Clinical Oncology, Ehrhardt et al identified intervals of screening for heart failure that were cost-effective among survivors of childhood cancer, according to heart failure risk defined by International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) guidelines.  

As stated by the investigators, “Survivors of childhood cancer treated with anthracyclines and/or chest-directed radiation are at increased risk for heart failure…. The … IGHG recommends risk-based screening echocardiograms, but evidence supporting its frequency and cost-effectiveness is limited.

Study Details

In the study, a microsimulation model of the clinical course of heart failure was developed using data from the Childhood Cancer Survivor Study and St. Jude Lifetime Cohort. Long-term health outcomes and economic impact of screening according to IGHG-defined risk groups were analyzed.

Risk groups are defined according to doxorubicin-equivalent anthracycline dose and/or radiotherapy dose as follows: low = 1 to 99 mg/m² and/or < 15 Gy; moderate = 100 to < 250 mg/m² or 15 to < 35 Gy; and high = ≥ 250 mg/m² or ≥ 35 Gy or both ≥ 100 mg/m² and ≥ 15 Gy. Screening intervals of 1, 2, 5, and 10 years were compared with no screening.

Screening performance and treatment effectiveness were estimated from published studies. Costs and quality-of-life weights were based on national averages and published reports. Strategies with incremental cost-effectiveness ratios (ICERs) < $100,000 per quality-adjusted life-years gained were considered cost-effective.

Cost-Effectiveness Outcomes

The investigators found that among a cohort representative of the Childhood Cancer Survivor Study, cumulative lifetime risks of heart failure according to IGHG risk group were 36.7% for high risk, 24.7% for moderate risk, and 16.9% for low risk.

Routine screening reduced risk of heart failure by 4% (for 10-year intervals) to 11% (for 1-year intervals), depending on screening frequency. Screening delayed the average age of heart failure onset by as much as 1.6 to 2.0 years with screening at 1-year intervals.

Screening high-risk survivors at 1-, 2-, 5-, and 10-year intervals averted 1 case of heart failure for every 1,012, 667, 445, and 383 screening echocardiograms, respectively. For moderate-risk survivors, 1 case was averted for every 1,660, 1,103, 745, and 654 echocardiograms, respectively, at these intervals. No interval strategy resulted in averting 1 case with < 1,000 echocardiograms in low-risk survivors.

Strategies meeting the cost-effectiveness threshold of < $100,000 per quality-adjusted life-year gained were: screening every 2 (ICER = $77,880), 5 ($37,700), and 10 years ($34,600) for high-risk survivors and screening every 5 ($94,580) and 10 years ($79,310) for moderate-risk survivors. ICERs per quality-adjusted life-year gained were > $175,000 for all screening frequencies for low-risk survivors, with this population constituting approximately 40% of survivors for whom screening currently is recommended.

The investigators concluded: “Our findings suggest that refinement of recommended screening strategies for IGHG high- and low-risk survivors is needed, including careful reconsideration of discontinuing asymptomatic left-ventricular dysfunction and [heart failure] screening in low-risk survivors.”

Matthew Ehrhardt, MD, MS, of the Departments of Oncology and Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Institutes of Health and the American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit ascopubs.org.