Battling Pediatric Cancer Outcome Disparities, New Interventions Aim to Close Gaps

Pediatric oncologist Lena Winestone, MD, recalls treating a 2-year-old leukemia patient who underwent a bone marrow transplant as her only chance for a cure.

The girl's family, who spoke only Spanish and struggled with literacy, could not pay their rent or afford the girl's weekly transportation to the hospital for after-transplant care. The family had three other children and lived more than 2 hours from the transplant center, remembers Dr. Winestone, an assistant professor of pediatrics in the division of malignancies and bone & marrow transplant at the University of California, San Francisco.

The hospital's social worker was able to secure grant support for the family's housing and worked with the patient's insurance to arrange for transportation. However, the departure times were rigid, Dr. Winestone said, and the family sometimes had to leave the hospital before the child's graft vs. host disease (GvHD) treatment was complete for the day.

"If we had not finished her treatment, we had to disconnect her from the machine early," Dr. Winestone said. "Her mother also had to load her oxygen tanks [three of them], her BiPAP machine, and her tube feeds into the transportation every week in order to make sure she could be safely transported. She was treated for GvHD for almost 2 years, but unfortunately, her GvHD started to affect her lungs and ultimately, she passed away."

Dr. Winestone says it's difficult to know whether the girl's death was directly related to her socioeconomic status, but that it certainly made all aspects of the child's care more complicated and forced health care providers to adapt her cancer care to accommodate the family's circumstances.

This story is one of countless cases where socioeconomic status impacted a young patient's cancer care and likely contributed to a worse outcome. A plethora of data has demonstrated that children with cancer who are Black, Hispanic, or of lower socioeconomic status are more likely to relapse and die even when treated uniformly on clinical trials.

A 2022 study for example, found that children from marginalized racial/ethnic groups and those living in poverty were more likely to have inferior 5-year overall survival, compared with other children, even when assigned to receive the same initial treatment. Of 696 children with high-risk neuroblastoma, 47% of Hispanic children had a 5-year overall survival (OS), compared with 50% for other non-Hispanic children, and 61% for white non-Hispanic patients. Children on public health insurance (a proxy for household poverty) had a 53% 5-year OS, compared with 63% for children unexposed to household poverty. Pediatric patients exposed to neighborhood poverty had a 54% 5-year OS, compared with 62% for unexposed children.

In another study, children with acute lymphoblastic leukemia who lived in high-poverty areas were more likely to experience early relapse than other patients, despite having the same treatment. Of the 575 children studied, 92% of children from high-poverty areas who relapsed, experienced early relapse, defined as less than 36 months after remission. By comparison, only 48% of other children who relapsed experienced early relapse.

Reasons behind the relapse and survival disparities are multifold, which has led to challenges in addressing the gaps and improving cancer outcomes for poverty-stricken children. A research infrastructure that is largely based on biological, rather than social determinants of health, acts as another barrier, oncologists say.

Historically, interventions to address disparities in pediatric oncology have never been evaluated, said Kira Bona, MD, MPH, a pediatric oncologist at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. This is in large part because the body of literature illustrating the disparities is relatively new, said Dr. Bona, whose research focuses on poverty-associated outcome disparities in childhood cancer.

However, new efforts aim to change this landscape by using the growing data to develop and analyze possible interventions. A set of three novel interventions led by Dr. Bona and her research team are in the works, some of which have shown promise in early studies.

"Now is the time to begin to actively intervene on disparities in childhood cancer," Dr. Bona said. "We're really good at studying genetic mutations in cancer cells that might lead to a risk of relapse, and when we identify those mutations, what we do is intervene. We try new chemotherapy agents, new ways of delivering therapy. We are now at the point where we have identified that social determinants of health may be equally 'risky' but we haven't taken the next step to begin intervening in the same way."

What is causing disparities in pediatric cancer outcomes?

Lack of access to the health care system is a top contributor to the disparities, although there is no single root cause, said Sharon Castellino, MD, director of the Leukemia and Lymphoma Program at the Aflac Cancer & Blood Disorders Center of Children's Healthcare of Atlanta, and a professor in the department of pediatrics at Emory University, Atlanta.

Even before cancer diagnosis, Dr. Castellino notes that many children of color and/or of lower socioeconomic status are not receiving regular health care, leading to sicker children and more advanced-stage cancer by the time they are diagnosed.

Lack of insurance is a primary barrier to this access, adds Xu Ji, PhD, MSPH, an assistant professor in the department of pediatrics at Emory University and a member of the Cancer Prevention and Control Research Program at the university's Winship Cancer Institute.

Studies have long shown that uninsured children are more likely to go without needed care, compared with those with private insurance. Patients of color are at much higher risk of being uninsured than White patients, with the uninsured rates for Hispanic, American Indian, and Alaska Native patients being more than 2.5 times higher than that of White patients.

"We all know that insurance is a strong predictor of health outcomes," said Dr. Ji, whose research focuses on insurance disparities and gains among cancer patients. "Lack of insurance coverage and therefore lack of access to care along the pediatric cancer continuum from early detection to early diagnosis to timely initiation of treatment to receipt of high-quality treatment to access to recommended survivorship care and even access to palliative and end-of-life care are all very important constructs in the pathway from poverty to ultimate cancer outcomes for children."

Unstable housing, employment difficulties, and lack of family support can also come into play. Dr. Castellino remembers the case of a 12-year-old cancer patient who entered treatment with advanced-stage Hodgkin Lymphoma. The girl came from a low-income, single-parent household without stable housing. Dr. Castellino said when the child was granted a wish from the Make-a-Wish Foundation, she asked for her own bed.

"We had been working with her every week for 6 months when that request came up," she recalled. "We said, 'You don't have to wait for your make-a-wish, we can get you a bed now.' We don't even know the extent of what happens at home for many of these children."

The impact of toxic stress on child cancer patients is an emerging area of research, said Dr. Winestone, whose research explores racial, ethnic, and socioeconomic disparities in access to care and outcomes of leukemia and lymphoma treatment. For example, Dr. Winestone's research includes understanding how exposure to poverty or adverse experiences in childhood may influence a patient's biological response to chemotherapy.

Other contributors to disparities include transportation issues, lack of childcare for other children, literacy, and language barriers. A 2016 study suggests that language barriers negatively impact the quality of informed decision-making and the care experience for Spanish-speaking parents of pediatric cancer patients with limited English proficiency.

Such access issues are also compounded by systemic factors, including a shortage of physicians of color who may be able to forge better trust relationships with families of similar race and ethnicity, Dr. Castellino adds. Lower enrollment of pediatric cancer patients with higher social vulnerabilities in clinical trials is another problem.

"In childhood cancer, I believe our improvements have been built on the backs of prior generations of families and children who have enrolled in trials. We learn things, and the next generation of therapy improves," Dr. Castellino said. "If you have a whole group of the population not represented in trials, you don't know what's driving the fact they may or may not improve."

Working toward solutions

With such a diverse set of factors fueling outcome gaps, a similarly diverse approach is needed to help bridge the divide, say disparity researchers.

To this end, Dr. Bona and her research team are currently building the first portfolio of health equity interventions, each designed to address a different adverse social determinant of health differently.

The Pediatric Cancer Resource Equity (PediCARE) intervention is a centrally delivered, household material hardship (HMH)–targeted intervention that provides transportation and groceries to low-income pediatric oncology families. The intervention was recently studied in a pilot, randomized, controlled trial at Dana-Farber Cancer Institute and the University of Alabama between May 2019 and August 2021.

Families were first screened for HMH and randomized into receiving either the intervention or usual care for 6 months. The intervention group received groceries via Instacart and transportation to and from the hospital coordinated through the Ride Health platform using Uber or Lyft. For families with their own cars, gas cards were provided. Of the families offered the chance to participate, 100% agreed to participate in the program, and there was 0% attrition in either arm of the program during the 6 months, according to the study findings, which were presented at the 2023 American Society of Clinical Oncology annual meeting in June.

Among families who received the PediCARE intervention, 100% successfully received grocery and transportation resources, 100% reported that it was "easier to buy food for my family," 85% reported it was easier to get to and from the hospital, and 95% reported they would be "very likely to recommend the intervention to other families," according to the results.

"The key takeaway is that we had excellent feasibility outcomes," said Haley Newman, MD, lead author of the study and an attending physician in the division of oncology at The Children's Hospital of Philadelphia. "From this study, we learned that PediCARE is accessible and feasible in very diverse settings. From this, what we really took away is that PediCARE could be successfully rolled out in a phase 3 randomized trial, which would be the best way to examine efficacy."

Another initiative in its early stages is Pediatric RISE, a guaranteed income intervention being developed with support from the Children's Cancer Research Fund, the American Cancer Society, and other donors. The intervention will provide unrestricted cash transfers to low-income families during the early months of chemotherapy, Dr. Bona said. Families are currently being enrolled in a pilot study with a goal of refining the intervention before it's tested for feasibility and efficacy.

"The goal here is ultimately to evaluate the question: If we are able to successfully provide income support to low-income families going through childhood cancer treatment, might we be able to ameliorate some of the disparities associated with living in poverty that we have already described in childhood cancer," Dr. Bona said.

Pediatric Assist, a developing intervention centering on benefits, is a third initiative that will soon be evaluated. The intervention will provide newly diagnosed families with systemic access to a centralized benefits counselor who can help them determine which existing government benefits they might be eligible for and assist them in navigating the application process.

"The idea here is that we know many lower-income families in the U.S. are eligible for existing supports, but may not be accessing them because of how incredibly difficult the system is to navigate," Dr. Bona said. "For example, we know that low-income families may be eligible for SNAP benefits, but figuring out if you are eligible and then applying for SNAP involves multiple, complicated steps that are often infeasible for a parent when their child is admitted to the hospital with a newly diagnosed, life-threatening illness."

Pilot refinement of the intervention is expected in the fall of 2023.

Overcoming barriers, addressing challenges

Investigators are also making headway in proving that collecting social determinants of health (SDoH) data during existing clinical trials is easily achievable.

Past Children's Oncology Group trials have collected only race, ethnicity, insurance, and zip code data as proxies for exposure to adverse SDoH. Dr. Winestone and her colleagues recently investigated the feasibility and acceptability of the first COG trial to prospectively embed SDoH data collection.

Of eligible participants, 360 of 413 opted-in to the embedded SDOH aim across 101 COG sites (87.2% consent rate). Among participants, 316 surveys (87.8%) were completed a median of 11 days post enrollment, according to the findings, which were presented at the ASCO annual meeting.

"We've come to realize the importance of the social determinants of health [as it pertains] to outcomes, but it has been a process to learn how to effectively collect that data in a large collaborative environment," said Dr. Winestone. "This abstract demonstrates that patients are very willing to provide this data, and they're able to do it in an efficient way. People think of these questions as very sensitive and that families may not want to share the answers, but this study demonstrates those presumptions are false."

The authors hope the findings fuel incorporation of SDoH data collection in future National Clinical Trials Network trials to inform impactful health equity research.

While such research and intervention efforts are gaining momentum, challenges to do the work remain. A lack of research funding and support are among the obstacles, Dr. Winestone said.

To date, much of pediatric cancer work has focused on developing new therapeutic approaches to reach a cure for more patients, she explained.

"While that's incredibly essential, if we're creating these approaches that only work for a subset of patients that have resources, we're contributing to the inequities in the system," Dr. Winestone said. "Really, [we need] dedicated support to studying how to make sure the interventions we know are effective are reaching all populations, and that the patients are poised to benefit from those interventions by setting them up for success."

A strong research infrastructure exists to evaluate and support clinical drug trials in pediatric oncology, but the same does not exist for health equity interventions, Dr. Bona adds. A significant question that needs to be addressed is how best to integrate health equity evaluation into existing infrastructure or whether to build a parallel infrastructure.

Despite the challenges, Dr. Bona believes now is exactly the right time to investigate and intervene in poverty as a risk factor for childhood cancer relapse and outcomes. What has led to success in childhood cancer is how pediatric oncology has collaborated across the country to operate clinical drug trials at various centers, all in the same way, to identify which treatments work best, she said.

"We have an opportunity now in pediatrics to take advantage of this highly successful clinical trials research infrastructure to integrate interventions to address disparities in a way that has not been done previously," she said. "The opportunity to significantly improve survival in childhood cancer by reducing disparities exists if we take this head on from a research and funding perspective and approach social risk factors just as we already know how to approach tumor genomic risk factors."

This article originally appeared on MDedge.com, part of the Medscape Professional Network.