Survivors of Hodgkin lymphoma face high cardiovascular toxicity burden
Cardiovascular toxicities occurred more frequently and severely among adult survivors of pediatric, adolescent and young adult Hodgkin lymphoma than in the general population, according to study results published in The Lancet Oncology.
Nearly 90% of children and adolescents treated for Hodgkin lymphoma will survive into adulthood.
“With cure rates for pediatric cancer at historic highs, the question becomes: What is the legacy of that cure?” 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?”
Bhakta and colleagues applied the cumulative burden metric — which tracks chronic, ongoing treatment-related health conditions — to compare chronic cardiovascular conditions in survivors of pediatric Hodgkin lymphoma with disease-free controls.
“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 data from 670 survivors (53% male; median age at diagnosis, 14.6 years) who reached the age of 18 years and survived for 10 years or longer after a pathologically confirmed Hodgkin lymphoma diagnosis.
Researchers identified these survivors using data from two ongoing cohort studies at St. Jude Children’s Research Center: The St. Jude Lifetime Cohort Study (SJLIFE; n = 348) — which follows health outcomes of childhood cancer survivors treated at the hospital — and the St. Jude Long-term Follow-up Study, a system-based administrative study that collects outcomes and late toxicity data. All SJLIFE study participants underwent assessment for 22 chronic cardiovascular health conditions, including myocardial infarction, hypertension, arrhythmias, cardiovascular dysfunctions and structural heart defects.
A comparison group of 272 community controls served as an age- and sex-matched comparison group.
The cumulative incidence of grade 3 to grade 5 chronic cardiovascular health conditions by age 50 years was 45.5% (95% CI, 36.6-54.3) among adult survivors of childhood Hodgkin lymphoma, compared with 15.7% (95% CI, 7-24.4) of community controls.
By age 50 years, the cumulative burden of any-grade chronic cardiovascular condition was twice as high among survivors than controls (430.6 events per 100 survivors vs. 227.4 events per 100 controls).
The cumulative burden of grade 3 to grade 5 events was five times higher among Hodgkin lymphoma survivors (100.8 events per 100 survivors vs. 17 events per 100 controls). Survivors had a higher total cumulative burden of chronic cardiovascular conditions at age 30 years and 50 years.
Although the researchers observed no meaningful difference in the overall burden of dyslipidemia or essential hypertension, other chronic conditions had greater contributions to the cumulative burden among Hodgkin lymphoma survivors. Myocardial infarction and structural defects caused the highest contribution to the cumulative differences between survivors and controls.
A multivariate analysis showed that high-dose cardiac radiation ( 35 Gy) contributed to an increase in grade 3 to grade 5 cardiovascular burden, although treatment with anthracyclines did not.
The researchers acknowledged limitations to their study, such as the inclusion of survivors who did not participate in the SJLIFE study and the mixed use of prospective and retrospective data.
“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 tradeoffs between different treatment late effects that must be considered when designing new interventions.”
The use of cumulative burden metrics may lead to better and more economically sound treatment choices, Marianne C. Aznar, PhD; Sarah Darby, PhD; Graham P. Collins, MA, MBBS, MRCP, FRCPath, DPhil; and David Cutter, MRCP, FRCR, DPhil, all of University of Oxford, wrote in an accompanying editorial.
“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,” Aznar and colleagues wrote. “However, some of the new treatments proposed are expensive. For example, proton radiotherapy has been suggested as an alternative to standard photon-based radiotherapy for some patients because it promises to reduce the exposure of healthy tissue and hence the risk of late side-effects, including cardiovascular disease and second malignancies. As of today, proton radiotherapy is still substantially more expensive than photon-based radiotherapy and access remains limited either by the number of proton treatment facilities in the patient’s country or by reimbursement issues.
“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 added.– by Cameron Kelsall
Disclosure: The researchers and Aznar and colleagues report no relevant financial disclosures.