The vast majority of children and adolescents treated for Hodgkin’s lymphoma will survive into adulthood. But according to a recent study developed at St. Jude Children’s Research Hospital, adult survivors of childhood Hodgkin’s lymphoma are more likely to experience cardiovascular events than the general population.
The study, “Cumulative burden of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin’s lymphoma: an analysis from the St. Jude Lifetime Cohort Study,” published in The Lancet Oncology, suggests that Hodgkin’s lymphoma survivors will benefit from individualized screening and treatment plans to decrease their risk for cardiovascular events.
Today, nearly 90 percent of patients with pediatric and adolescent Hodgkin’s lymphoma survive into adulthood. But because these patients are treated with chest radiotherapy and anthracyclines, both of which known to increase the risk for cardiovascular disease, survivors may develop severe cardiovascular health disorders, resulting in an increased risk for premature death compared to the general population.
“With cure rates for pediatric cancer at historic highs, the question becomes: What is the legacy of that cure?” Dr. Nickhill Bhakta, MD, hematology-oncology fellow at St. Jude Children’s Research Hospital, said in a press release. “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?”
In this study, Bhakta and colleagues assessed whether adult Hodgkin’s lymphoma survivors had worse cardiovascular health conditions than general population controls. The researchers applied a new metric, called the cumulative burden method, that quantified the total cardiovascular burden of young survivors by considering all the cardiovascular conditions observed during the patient’s lifetime.
“Cumulative burden is a new tool for studying chronic illness in childhood cancer survivors or any population with significant morbidity, such as diabetes or HIV/AIDS,” Bhakta said.
The study included 670 survivors with a median age at diagnosis of 14.6 years who reached the age of 18 and survived for at least 10 years following the diagnosis of primary Hodgkin’s lymphoma. Data from survivors was obtained from two ongoing cohort studies at St. Jude Children’s Research Hospital.
The St. Jude Lifetime Cohort Study (SJLIFE), which follows health outcomes of childhood cancer survivors treated at the hospital, included data from 348 patients; and the St. Jude Long-term Follow-up Study (SJLTFU), a study initiated in 2000 to collect outcome and late toxicity data for all patients treated at the hospital for childhood cancer, which included 322 Hodgkin’s lymphoma survivors.
All SJLIFE participants were assessed for 22 chronic cardiovascular health conditions, including hypertension, arrhythmias, heart attack, cardiovascular dysfunctions, and structural heart defects, and 272 age and sex frequency-matched SJLIFE community controls were used for comparison.
Results revealed that survivors who reached age 50 were significantly more likely to exhibit severe (grade 3 to grade 5) cardiovascular conditions than healthy controls, with cumulative incidence of 45.5 percent in survivors compared to 15.7 percent in community controls.
The total cumulative burden at age 50 was found to be twice as high, with survivors having 430.6 cardiovascular events in every 100 patients, and community controls having 227.4 events per 100 controls. Cumulative burden for severe events, however, was five times higher than that of community controls (100.8 events per 100 survivors versus 17 events per 100 controls).
The cardiovascular events that contributed the most to the increased cumulative burden in survivors were heart attacks and structural heart defects. In addition, researchers found that although the radiation dose given upon chest radiotherapy influenced the number of severe cardiovascular events, treatment with anthracyclines did not.
“Survivors tended to have more severe disease across the lifespan and likely need an individualized screening and treatment plan,” Bhakta said. “Cumulative burden provides us with a global view of trade-offs between different treatment late effects that must be considered when designing new interventions.”
“Predictions based on the cumulative disease burden might also provide an appropriate method for assessing the socioeconomic cost of progressive chronic heart conditions when evaluating the potential effect of using novel, and hopefully less toxic, cancer treatments,” Marianne C. Aznar, PhD; Sarah Darby, PhD; Graham P. Collins, MA, MBBS, MRCP, FRCPath, DPhil; and David Cutter, MRCP, FRCR, DPhil, all of the University of Oxford, wrote in an accompanying editorial.
“Prioritizing access to these treatments requires reliable clinical data on their effectiveness and relevant predictions of the future risks they might present (or avoid) to quantify the impact for each individual patient,” they wrote.
