Children with high-risk neuroblastoma — a type of cancer that typically affects young children — who are being treated on a clinical trial tend to have poorer outcomes if they are non-white Hispanic or on public insurance, according to an analysis of data from multiple Children’s Oncology Group (COG) trials.

Lead author Dr. Puja J. Umaretiya, a clinical fellow in pediatric hematology/oncology at Dana-Farber Cancer Institute and Boston Children’s Hospital, in Massachusetts, presented the findings at a press briefing ahead of the 2022 ASCO Annual Meeting. She said that the results suggest that equal access to care does not necessarily translate into equitable outcomes.

“Our data show that Hispanic children with high-risk neuroblastoma have inferior overall survival compared with other children,” she said. “This is despite having access to the same clinical trials and receiving the same uniform plan treatment and after controlling for disease associated factors.

“We acknowledge that describing disparities is simply not enough, we must strive to identify mechanisms that cause inequitable outcomes,” she said. “And in this cohort, we begin to do so by looking at things like stopping a trial, early delays in therapy, or increased rates of relapse, none of which seem to explain the survival differences that we see by race and ethnicity.”

In the study analysis, average five-year overall survival was approximately 47% for Hispanic children compared with 50% for other non-Hispanic children, 61% for white non-Hispanic children, and 63% for Black non-Hispanic children.

Umaretiya said that existing data have shown that Black children with neuroblastoma are more likely to experience late relapse. Furthermore, children with public insurance, a proxy for household poverty, are more likely to relapse and more likely to die when treated on immunotherapy trials.

The causes for these disparities are unknown. Investigators felt that a clinical trial was the ideal setting to explore the question because care is highly standardized. They sought to identify the associations between survival and race, ethnicity and socioeconomic status. Investigators also wanted to explore associations between those factors and possible mechanisms for poorer survival like early trial discontinuation, delays in induction chemotherapy and relapsed disease.

Umaretiya and her team conducted a retrospective cohort study on data from 699 children with high-risk neuroblastoma treated in three upfront COG trials from 2007 to 2016: ANBL0532, evaluating two high-dose chemotherapy regimens followed by a stem cell transplant; ANBL0P1, evaluating induction therapy followed by meta-iodobenzylguanidine labeled with iodine-131 and chemotherapy in treating patients undergoing stem cell transplant, radiation therapy and maintenance therapy with isotretinoin; and ANBL12P1 evaluating busulfan, melphalan and stem cell transplant following chemotherapy.

Five-year overall survival was lower among children who used only public insurance compared to others (53% vs 63%) and among children living in neighborhood level poverty compared to others (54% vs 62%). However, Umaretiya added that proxy poverty measures did not remain significantly associated with survival after adjusting for other factors including race, ethnicity and disease-associated factors.

“We looked at mean duration of induction by days and found that overall, by race and ethnicity, there were no significant differences. We also found that there was no difference in who stopped trial participation early by race and ethnicity,” she said. “A little over one-third of patients stopped the trial early, regardless of racial or ethnic group. We also found that there were no differences in the frequency of relapse by race and ethnicity, and that about half of patients relapse, regardless of race or ethnicity.”

Umaretiya and her team also observed no difference in overall survival rural vs urban areas.

Investigators will next examine the interaction of survival and race, ethnicity and poverty, acknowledging the intersectionality of these factors due to structural racism in the United States.

“Our data also suggests that even though we relapse occurs at the same frequency across racial and ethnic groups, the rates of death do not,” Umaretiya said. “Our next steps will focus on this post-relapse period and (we will) specifically look at enrollment on early-phase trials as a proxy for access to life extending therapy as well as the causes of death, looking at whether these children die of disease or toxicity.”

ASCO President Dr. Everett E. Vokes, chair of the department of medicine at the University of Chicago said that children in these trials should have had similar outcomes and that they did not raises important questions.

“We see discrepancies here in overall survival … of 8% to 10% at the longer terms of follow up,” he said. “They seem to correlate with socioeconomic factors and race, but the specific causes of death, or increased death, in those groups are not elucidated yet. And I think that that will be important work moving forward.”

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