Less Frequent ECHO Screening of Childhood Cancer Survivors

Janis C. Kelly

May 21, 2014

The frequency of cardiac screening could be reduced in survivors of childhood cancer who were treated with anthracyclines, suggest 2 independent research groups writing in the Annals of Internal Medicine. However, an expert contacted for comment was not convinced.

Because anthracyclines are notoriously cardiotoxic, survivors of childhood cancers who received these drugs as part of their treatment face a lifetime of echocardiography (ECHO) screening to detect asymptomatic left ventricular dysfunction (ALVD) and then drug intervention to reduce the risk for progression to congestive heart failure (CHF).

Currently, the Children's Oncology Group's (COG's) Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers recommends that this screening be carried out every 1 to 5 years, depending on several risk factors (eg, lifetime anthracycline dose, age at cancer diagnosis, history of chest irradiation, etc).

However, the 2 research groups concluded from computer modeling studies that less frequent screening (typically at 5 years and 10 years) could be as effective as annual screening for detecting ALVD and cuts costs by half.

Julia Steinberger, MD, a pediatric cardiologist and a member of the COG's long-term follow-up guidelines cardiovascular task force, was also not convinced that these 2 computer modeling studies should be the basis for dumping the COG guidelines recommendations.

"I don't believe that these studies are sufficient to support changing to 5- or 10-year assessment," Dr. Steinberger told Medscape Medical News. Dr. Steinberger is professor in the Division of Cardiology, Department of Pediatrics, University of Minnesota; director, Pediatric Lipid Clinic and Preventive Cardiology Program, University of Minnesota; and director, Pediatric Echocardiography Services, University of Minnesota Amplatz Children's Hospital Heart Center, in Minneapolis.

Less Frequent Screenings More Cost-effective

In the first study, F. Lennie Wong, PhD, and colleagues conclude, "Although routine echocardiography may reduce incidence of heart failure, less frequent screenings every 1 to 5 years are more cost-effective and maintain most of the health benefits." Dr. Wong is from the Department of Population Sciences, City of Hope Medical Center, Duarte, California.

Dr. Wong's group used a computer model to simulate the life histories of 10 million childhood cancer survivors from 5 years after cancer diagnosis until their death. Included in the model were the 12 risk profiles outlined in the COG guidelines. Lifetime costs, quality-adjusted life-years (QALYs), and total risks for heart failure for different screening intervals based on risk profile were compared with no screening.

The researchers found that increasing the screening interval could provide similar health benefits at about half the cost of the COG guidelines.

"After death from malignancies, cardiotoxicity from anthracycline therapies used for the primary cancer is the leading cause of death in survivors of childhood cancer," Dr. Wong told Medscape Medical News.

The risk of cardiotoxicity increases as this population ages. "Routine cardiac screening with echocardiography enables identification of survivors of childhood cancer at increased risk for heart failure," Dr. Wong explained, "and early identification of these high-risk populations allows employment of preventive strategies that may reduce the incidence of heart failure in survivors."

"Tailored echocardiographic screening matched to risk, as recommended by this paper, may be more cost-effective than current screening guidelines while maintaining most health benefits," Dr. Wong concluded.

"A more cost-effective strategy involving less frequent screening, and hence less patient burden, could provide similar health benefits at half of the cost," the group writes in their article. "On the basis of our modeling using the CCSS [Childhood Cancer Survivor Study] cohort, annual screening recommended by the guidelines for more than 50% of survivors could be decreased to every 2 to 4 years. The biennial screening recommended for more than 30% of survivors may be decreased to every 5 years. Screening every 5 years, recommended for 3% of survivors, could be maintained, but the frequency could be reduced to 10 years for an additional 12% of the survivors."

Dr. Wong urged clinicians to maintain long-term vigilance for appropriate implementation of screening guidelines, both to reduce excessive testing and to maintain the therapeutic efficacy of preventive strategies.

In the second study, Jennifer M. Yeh, PhD, and colleagues used a computer model and a similar hypothetical patient population to compare risks for CHF, QALYs, and total costs for different screening intervals on the basis of risk for CHF. Persons were categorized as low- or high-risk on the basis of cumulative anthracycline dose. Dr. Yeh is from the Center for Health Decision Science, Harvard School of Public Health, Boston, Massachusetts.

Outcome measures were lifetime systolic CHF risk, lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs).

Dr. Yeh reported that the lifetime risk for systolic CHF among 5-year childhood cancer survivors aged 15 years was 18.8% without routine cardiac assessment. This lifetime risk was reduced by routine ECG to 2.3% with assessment every 10 years and to 8.7% with annual assessment.

The ICER was $111,600 per QALY for assessment every 10 years compared with no assessment, and $117,900 for assessment every 5 years compared with no assessment. The ICERs for more frequent assessment exceeded $165 000 per QALY.

"The probability that assessment every 10 or 5 years was preferred at a $100,000-per-QALY threshold was 0.33 for the overall cohort," the authors write.

"Our findings suggest that current recommendations for cardiac assessment may reduce systolic CHF incidence, but less frequent screening than currently recommended may be preferred and possible revision of current recommendations is warranted," they conclude.

Other Experts Less Convinced

Other experts are less convinced. In an accompanying editorial, Richard M. Steingart, MD, Jennifer E. Liu, MD, and Kevin C. Oeffinger, MD, from Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York City, write, "Both studies used a societal perspective, which represents the public interest rather than that of any group or the person. Analyses are intended to inform decisions at the level of broad resource allocation and may provide little guidance about optimal management of persons."

Both studies used a societal perspective, which represents the public interest. Dr. Richard Steingart, Dr. Jennifer E. Liu, and Dr. Kevin C. Oeffinger

The editorial writers also point out that both groups made several assumptions in their computer models. Because there are few data on the natural progression from ALVD to CHF in young cancer survivors, the computer models assumed CHF progression on the baiss of extrapolations from patients without cancer who developed CHF secondary to hypertension, coronary disease, and myocardial infarction. In addition, the magnitude of ALVD ejection fraction (EF) reduction was not considered in predicting CHF risk, and neither analysis included clinical information such as hypertension and vascular disease in the cancer survivor, which affect ALVD development and progression to CHF.

Also, the assumed effectiveness of the treatments that prevent ALVD from progressing to CHF was based on a clinical trial in patients with hypertension and coronary disease who had an EF less than 35%. The editorialists say that regular cardiac screening in cancer survivors will likely result in earlier detection of ALVD and initiation of cardioprotective treatment at an earlier stage when EF is greater than 35%. Therefore, it is likely that more survivors would have to be treated longer to demonstrate the effectiveness of therapy, they suggest.

The 2 new computer studies highlight the many variables that should be explored, the editorialists comment.

"The clinician and patient should be assured that screening for ALVD is a valuable undertaking and that state-of-the-art CE [cost effectiveness] analyses allow for variation in their choices based on the details of the clinical presentation, patient preference, and local imaging experience," they write.

The authors, the editorialists, and Dr. Steinberger have disclosed no relevant financial relationships.

Ann Intern Med. 2014;160:661-671, 672-683, 731-732. Published online May 19, 2014. Abstract, Abstract, Editorial


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