Study Calls for Revisiting Guidelines for Screening Childhood Cancer Survivors at Risk of Congestive Heart Failure
May 20, 2014
Simulations find improved
outcomes but suggest less frequent screening may be as beneficial
BOSTON — 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
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 Centerfor 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 computer 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,
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.”
The study was supported by the National Cancer Institute (grant number