ACADEMIA

Simulations find improved outcomes but suggest less frequent screening may be as beneficial

One of the first studies to analyze the effectiveness of screening survivors of childhood cancer for early signs of impending congestive heart failure (CHF) finds improved health outcomes but suggests that less frequent screening than currently recommended may yield similar clinical benefit. The researchers, in a study published in the Annals of Internal Medicine, utilized a simulation-based model to estimate the long-term benefits associated with routine screening.

The study's findings suggest that the current CHF screening guidelines for survivors of pediatric cancer should be re-examined. The current guidelines recommend that survivors treated with chemotherapy agents known to affect long-term heart health be screened as often as every year, with a schedule dependent on their level of CHF risk. The new study suggests that screening survivors less often may be nearly as effective in detecting heart disease early. Some survivors might be better served by a different method of screening than the one currently used.

"It is important to monitor survivors so we can reduce the late effects of treatment whenever possible, but we may be asking them to be tested too often, which burdens both individuals and the health care system," says senior author Lisa Diller, MD, chief medical officer of Dana-Farber/Boston Children's Cancer and Blood Disorders Center. "We think it is worthwhile to review the current CHF screening guidelines."

"Our findings suggest that there is a long-term benefit in screening survivors at elevated risk for CHF," says lead author Jennifer Yeh, PhD, of the Center for Health Decision Science at Harvard School of Public Health. "Yet less frequent screening than currently recommended may be reasonable when other factors are considered. We hope these results can help inform the ongoing discussion about screening childhood cancer survivors."

As cure rates of pediatric cancers have risen, increasing numbers of survivors are at a substantially higher risk of heart disease, including congestive heart failure, compared to the general population. The increase in risk varies depending on several factors, including whether a patient was treated with anthracyclines, a class of drugs known to cause heart disease, and/or radiation to the heart. For instance, those who received no or low (<250 mg/m2) cumulative doses of anthracyclines have a relatively low lifetime risk of developing CHF, while those who received large (≥250 mg/m2) cumulative doses are at higher risk.

The Children's Oncology Group (COG) currently recommends that survivors undergo screening by echocardiography for asymptomatic left ventricular dysfunction (ALVD). If left untreated, this clinically silent condition can progress to CHF, so clinicians typically prescribe beta blockers and ACE inhibitors to patients with signs of ALVD. COG recommends that patients at high risk of developing CHF be screened every year or two and those at low risk be screened every two or five years.

"Survivors are screened for decades and face risks for other late effects, as well," Diller says. "We need to consider carefully how often we ask survivors to be screened over the course of their lives, given the substantial cumulative economic impact and anxiety that screening may cause."

To estimate the clinical benefits and cost-effectiveness of the current heart screening guidelines, Diller, Yeh and their co-author, cardiologist Anju Nohria, MD, of Brigham and Women's Hospital, constructed a supercomputer model of a virtual cohort of 15-year-olds who had survived cancer at least five years. Using data from the Childhood Cancer Survivors Study and the Framingham Heart Study, the researchers modeled the cohort's CHF risk and clinical progression over the course of survivors' lifetimes. Their analysis suggests that routine screening may prevent as many as one in 12 cases of CHF.

The authors then used Medicare data to estimate the costs and value (expressed in cost per quality-adjusted life year [QALY]) of different screening schedules (i.e., every 1, 2, 5 or 10 years) and methods (echocardiography versus cardiac magnetic resonance imaging [cMRI]) for the different CHF risk groups (i.e., low, high).

At a cost-effectiveness threshold of $100,000/QALY, the model's results indicate that echocardiographic screening might not be the best value for resources invested to reduce lifetime CHF risk among survivors at low risk of developing the disease. On the other hand, the data suggest that biennial echocardiography screening may be a high-value strategy for high-risk survivors.

The simulation's data also suggested that cMRI may be preferable to echocardiography as a screening method, with cMRI's greater cost per test balanced by its greater sensitivity. According to the model, cMRI-based screening of low-risk survivors every 10 years and high-risk survivors every five years was more cost effective than any echocardiography-based schedule.

Lastly, the data suggest that it may be most beneficial to treat high-risk survivors before signs of ALVD even appear. For instance, proactively treating all high-risk patients in the virtual cohort with ACE inhibitors and beta blockers reduced their lifetime CHF risk more than if they received an echocardiograph every two years, although additional clinical studies on the benefit of the treatments are needed to support this strategy in practice.

The researchers relied on simulation modeling using the best available clinical and epidemiologic data because of the immense logistical obstacles to conducting prospective randomized clinical studies of survivors' long-term cardiovascular outcomes. The number of survivors that clinical studies would need to enroll and follow for years is challenging given how rare childhood cancers are. Yet guidance on the health benefits associated with current recommendations is needed.

"Our findings suggest that current recommendations for cardiac assessment may reduce systolic CHF incidence, but less frequent screening than currently recommended may be preferred," the study concludes. "Possible revision of current recommendations is warranted."