Nickhill Bhakta, MD

Photo courtesy of St. Jude

Children’s Research Hospital

and Seth Dixon

New research has shown that survivors of pediatric Hodgkin lymphoma (HL) are more likely to have chronic cardiovascular conditions than adults who did not have cancer in childhood.

And cardiovascular conditions are more severe among HL survivors than the general population.

Investigators believe this research, published in The Lancet Oncology, should aid efforts to reduce and better manage the late effects of cancer treatment.

For this study, the investigators used a measurement called “cumulative burden” to better capture the distribution and magnitude of chronic disease in childhood cancer survivors.

The metric showed that, by age 50, HL survivors had more than twice as many cardiovascular problems as adults who had not had cancer as children. HL survivors were also 5 times more likely to have severe, life-threatening, or fatal heart conditions.

“With cure rates for pediatric cancer at historic highs, the question becomes, ‘What is the legacy of that cure?’” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“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? 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.”

Unlike statistical methods that count health conditions once at diagnosis, cumulative burden tracks individuals’ multiple, recurring treatment-related health conditions.

Dr Bhakta and his colleagues focused on calculating the cumulative burden of cardiovascular disease in 670 pediatric HL survivors. The subjects were at least 18 years old and had survived at least 10 years beyond their cancer diagnoses.

The participants had been assessed for 22 chronic cardiovascular conditions, including heart attacks, hypertension, arrhythmias, and structural heart defects. Investigators used those and other clinical findings to calculate the cumulative burden by tracking the incidence and severity of cardiovascular disease.

The team also determined the cumulative burden for a comparison group of 272 community volunteers who underwent the same health assessments. The volunteers were similar in age and gender to the HL survivors but had no history of childhood cancer.

The analysis showed that the cumulative burden of cardiovascular disease, including severe and life-threatening conditions, was greater among HL survivors at 30 and 50 years of age than among the comparison group. In fact, the cumulative burden of the most serious heart problems, including heart attacks, was similar for 30-year-old HL survivors and 50-year-old community volunteers.

At age 50, 45.5% of HL survivors had developed at least one grade 3-5 cardiovascular condition, compared to 15.7% of the control subjects.

The HL survivors had a cumulative burden of 430.6 grade 1-5 cardiovascular conditions per 100 individuals and 100.8 grade 3-5 cardiovascular conditions per 100 individuals. In comparison, controls had 227.4 grade 1-5 conditions and 17.0 grade 3-5 conditions per 100 individuals.

The investigators noted that severe, chronic heart conditions became more common with age in both groups, but serious problems accumulated more rapidly in HL survivors.

“Survivors tended to have more severe disease across the lifespan and likely need an individualized screening and treatment plan,” Dr Bhakta said.

He added that the results of this study highlight trade-offs to consider in designing future clinical trials. For example, the investigators found that reducing the dose of anthracyclines will lower the rate, but not the severity, of cardiovascular disease in pediatric and young adult HL survivors.

In contrast, lowering the heart radiation dose will not significantly 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,” Dr Bhakta concluded.

Long-term health burden of Hodgkin lymphoma treatment