A new statistical method created by investigators to quantify the total cardiovascular burden of adults who had Hodgkin lymphoma (HL) as children found that these pediatric HL survivors had more and more serious cardiovascular problems by age 50 than others their age without this type of childhood cancer.
The study, “Cumulative burden of disease: a relevant measure of the late side-effects of cancer treatment,” published in the journal The Lancet Oncology, points to the importance of considering this burden when clinically evaluating these adults, and of developing new treatment approaches for young HL patients that might improve their overall health in adulthood.
Researchers at St. Jude Children’s Research Hospital developed a “cumulative burden” measurement to provide both descriptive and inferential insights into the health of adult survivors of pediatric cancers. Applying the metric to people with HL as children, they found that these adults had more than twice the cardiovascular problems of other adults, and were five times more likely to have serious, even life-threatening, heart conditions.
“With cure rates for pediatric cancer at historic highs, the question becomes what is the legacy of that cure? We are doing a better job of keeping patients alive, but are we doing a better job at addressing the chronic diseases that are sometimes the price of that cure,” Nickhill Bhakta, MD, a St. Jude hematology-oncology fellow and the study’s first author, said in a news release. “Cumulative burden is a new tool for studying chronic illness in childhood cancer survivors or any patient population with significant morbidity, such as diabetes or HIV/AIDS.”
Therapy-related exposures and cardiovascular disease in childhood cancer survivors is a risk well-estabished and characterized. Investigators have prediction models for congestive heart failure, and optimized screening guidelines for survivors based on disease-specific, toxicity-related tradeoffs and exposure risk profiles.
Much of what is known, however, is based on the cumulative incidence — or, in some cases, the absolute number — of chronic cardiovascular conditions among individuals in a particular cohort. The total magnitude of cardiovascular morbidity in survivors, capturing the severity of different conditions and of recurrent events, has not been accurately described.
Cumulative burden is a metric that tracks multiple and recurring treatment-related conditions among individuals. It may help researchers to refine screening guidelines for survivors, and to design clinical trials aimed at both achieving high cure rates and reducing the late effects of treatment. Pediatric Hodgkin lymphoma patients are among the possible beneficiaries.
For the past 40 years, children and adolescents diagnosed with Hodgkin’s lymphoma have experienced a five-year relative survival above 80 perecent. Extended survival into adulthood exceeds 90 percent today; for example, the U.S. has about 36,000 pediatric and adolescent Hodgkin’s lymphoma survivors. As a consequence of treatments that include chest radiotherapy and anthracyclines, however, these people can develop lifelong cardiovascular disorders and be at greater risk of premature death.
The researchers calculated the cumulative burden of cardiovascular disease in 670 pediatric Hodgkin lymphoma survivors, based on a detailed health analysis of 348 individuals enrolled in the St. Jude Lifetime Cohort Study (St. Jude LIFE). Patients who reached age 18 and were at least 10 years post-diagnosis of Hodgkin’s lymphoma were included. Outcomes in these survivors were compared with a sample of 272 SJLIFE community control participants who never had childhood cancer, ages 18 years or older at the time of assessment. All SJLIFE participants underwent assessment for 22 chronic cardiovascular conditions.
Results showed that the cumulative burden of cardiovascular disease was greater among survivors at 30 and 50 years of age compared with control participants. In fact, the cumulative burden of the most serious heart problems, including heart attacks, was similar for 30-year-old survivors and 50-year-old community members.
While severe, chronic heart conditions became more common with age in both groups, serious problems accumulated more rapidly in survivors.
“Survivors tended to have more severe disease across the lifespan and likely need an individualized screening and treatment plan,” Bhakta said.
The findings also emphasized adjustments that should be considered in future clinical trials. For example, the researchers found that reducing the dose of anthracyclines will lower the rate, but not the severity, of cardiovascular disease in younger adult HL survivors. Conversely, lowering the heart radiation dose will not lower the rate of cardiovascular disease, but it will reduce the severity.
“Cumulative burden provides us with a global view of tradeoffs between different treatment late effects that must be considered when designing new interventions,” Bhakta said.