Elevating the Research and Treatment Needs of Latino Children, Adolescents, and Young Adult Survivors

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This content is from the “Advancing the Science of Cancer in Latinos: 2024 Conference Proceedings.”

Increasing Diversity in Pediatric Cancer Clinical Trials

Dr. Paula Aristizabal is Associate Professor of Pediatrics in the Division of Pediatric Hematology and Oncology, Medical Director of the International Outreach Program, and Quality Improvement Lead at the University of California San Diego and Rady Children’s Hospital.

Disparities in pediatric cancer

Dr. Aristizabal’s presentation covered the demographic shift in the US, disparities in pediatric cancer, inequities in clinical trial participation in pediatric cancer research, barriers to clinical trial participation in Latinos, and strategies to improve recruitment of Latinos to clinical trials. The Latino population will likely become the most populous demographic in the US in the next few decades. Texas and California have the largest Latino populations, with San Antonio in particular being 65.8% Latino. Latinos are already California’s largest ethnic group, and are projected to comprise 43% of the population by 2030. Clearly, it is imperative to provide the best care possible to this growing population.

Although childhood cancer is the leading cause of death by disease past infancy in the US, with 17,000 children younger than 21 years diagnosed annually, survival has improved dramatically, and is now greater than 80%. Because of unequal access to services and poorer health outcomes, however, disparities in overall survival exist. Latino children have higher incidence of certain cancers, for example lymphoma and leukemia, and poorer survival rates than non-Hispanic White children (74% vs. 81%, p<0.001).

Phases of disparities research

In Dr. Aristizabal’s view there are three phases of disparities research. The first phase is “Detecting,” meaning defining and measuring cancer disparities such as ethnic disparities in acute lymphoblastic leukemia (ALL) survival, racial disparities in acute myeloid leukemia (AML) survival, and minority underrepresentation in clinical trials. The second phase is “Understanding,” or identifying the mechanisms of cancer disparities such as the presence of high-risk biologic features, decreased access to stem cell transplantation, and adverse social determinants of health (e.g., limited health literacy, poverty, and language barriers). The third phase is “Reducing,” meaning the development and evaluation of interventions such as dose adjustments for genetic polymorphisms, interventions to improve treatment adherence, interventions to improve participation in clinical trials, and interventions to address poverty.

Some of Dr. Aristizabal’s work in the “Understanding” phase of disparities research involves understanding the role of social determinants of health in influencing Latino participation in clinical trials. Minorities are generally under-represented in research, with Latino participants constituting only 1-7% of overall participation. This disparity is even worse in adult cancer clinical trials, with Latino individuals making up only 0.4%-2.2% of overall participation. In fact, only 2% of approximately 10,000 National Cancer Institute (NCI) clinical trials have representative minority participants. This means that cancer outcomes data are largely based on data from non-Hispanic White participants, and there is incomplete information to adequately assess treatment benefits for minorities.

This trend is also present in pediatric cancer clinical trials, with 53% of Latino parents declining participation compared to 20% of non-Hispanic White parents. Dr. Aristizabal’s work focused on the role of health literacy, culture, and language in this discrepancy. Beginning with the informed consent process, barriers exist. First, there are no mandates to ensure comprehension, and informed consent forms are complex and difficult to understand. This leaves parents with an incomplete understanding of risks, procedures, randomization, alternative treatments, and the voluntary nature of trial participation. Furthermore, pediatric cancer often requires urgent treatment, leaving little time for decision-making.

COMPRENDO

Based on this limited health literacy among Latino families, Dr. Aristizabal and colleagues developed COMPRENDO (ChildhOod Malignancy Peer REsearch NavigatiOn), a peer-navigation intervention to improve research literacy and diversity in pediatric cancer clinical trials. In the program, peer-navigators provide in-hospital support, telephone support, and in-home support. The goals of the program are to improve parents’ informed consent experience and comprehension of informed consent for cancer treatment, to explain to parents terms and concepts to be discussed by the oncologist during the treatment conference, to introduce to parents concepts of clinical trials, and to facilitate and empower shared decision-making. In fact, this intervention showed increased comprehension of therapeutic trials, particularly in Latino parents and Spanish-speaking parents.

In closing, Dr. Aristizabal shared strategies to increase clinical trial enrollment of Latino individuals. First, not only should the demographics of patients enrolled in clinical trials be comparable to the US population, but approaches to improve enrollment must also be tailored to specific settings. Structural barriers for Latino participation should be considered during study design and informed consent design. Provider-level training focused on patient-provider communication is also important, with linguistically appropriate tools and culturally-aware staff. Finally, key factors at the patient-level include building trust; education and awareness of clinical trials; culture, language, and health literacy-focused interventions; and initiatives to address socio-economic barriers.

Treatment-Related Toxicity and Pediatric Cancer

Dr. Allison Grimes is Associate Professor of Pediatrics and Director of the Adolescent and Young Adult Cancer Program at the University of Texas Health San Antonio Mays Cancer Center and the Greehey Children’s Cancer Research Institute.

Disparities in pediatric cancer

The central objective of Dr. Grimes’s presentation was to recognize disparities specific to Latino children, related to short- and long-term toxicities of cancer therapy. Although pediatric cancer survival in the US now exceeds 80%, survival disparities exist for Latino and Black children, children with low socioeconomic status, and children in underserved areas. Latino children also have higher incidence of several cancers, including leukemia and lymphoma, and have lower 5-year overall survival than non-Hispanic White children (74% vs. 81%). Furthermore, Latino children have more frequent and more severe treatment-related toxicities with several common key drugs utilized in pediatric cancer regimens.

Survival improvements are largely driven by multicenter clinical trials by national and international cooperative groups (e.g., Children’s Oncology Group) to improve risk stratification, treatment intensity, and supportive care reducing toxicity. Treatment-related toxicities contribute to significant morbidity, decreased quality of life, and mortality in some. Accurate measurement and reporting of toxicities are critical to understanding the scope of the problem but are routinely under-captured and data is not always linked to race/ethnicity. High-quality, large, multicenter trials are needed to determine if certain approaches can mitigate risk. However, there are obstacles to the development of supportive care trials, including funding and limited participant access.

Late effects and toxicities experienced by pediatric cancer patients may be categorized by organ system. The brain, for example, may experience neurocognitive deficits in association with the use of methotrexate. Alternatively, toxicities may be organized by cancer type, with Ewing sarcoma patients often experiencing cardiomyopathy associated with the use of anthracyclines. A significantly higher number of Latino patients with Ewing sarcoma (82%) experience grade 3/4 toxicity compared to non-Hispanic White patients (56%).

Latino children with acute lymphoblastic leukemia (ALL) experience increased toxicities associated with several common treatments. Latino patients undergoing CAR-T cell therapy, for example, experience more severe cytokine release syndrome compared with non-Hispanic White patients, even adjusting for disease burden and age. Hispanic ethnicity was also found to be associated with an increased risk for creatinine elevation associated with high-dose methotrexate use. In fact, Latino children experienced a nearly 6-fold increase in neurotoxicity odds with serum creatinine elevation ≥50% compared with creatinine elevation <25%. Non-White minorities experience more frequent and more severe hyperglycemia and are more likely to require insulin in association with corticosteroids, mercaptopurine, and asparaginase. Finally, Hispanic ethnicity was identified as a strong predictor of hepatotoxicity associated with asparaginase.

Strategies for reducing toxicity in pediatric cancer patients can include the following approaches: therapy reduction, including reduction of exposure duration, cumulative dosing caps, and risk-adapted therapy plans; the use of less toxic drugs including immunotherapy and CAR-T; the use of pharmacogenomics to drive drug dosing decisions; and increasing the number of supportive care trials.

An example of a supportive care intervention

It is imperative to design supportive care interventions that target treatment toxicities in pediatric cancer. In light of this need, Dr. Grimes and colleagues have recently undertaken a randomized controlled trial studying the impact of continuous glucose monitoring (CGM) on glycemic control in pediatric, adolescent and young adult (PAYA) ALL patients. Treatment-related hyperglycemia (TRH) associated with corticosteroids and asparaginase affects up to 1/3 of ALL youth, a disproportionate amount of which are Black and Latino. TRH is associated with increased bacterial and fungal infections and diminished survival in ALL patients. However, no standardized approach exists for detecting, monitoring, or managing TRH in this population.

The primary objective of the trial is to determine whether use of unblinded CGM, over standard of care, improves glycemic control as measured by glucose percent time in range (TIR, 70-180 mg/dL), among PAYA patients (age 10-39 years) with newly diagnosed ALL during the initial six weeks of therapy. Dr. Grimes and colleagues hypothesize that access to continuous, real-time glucose measurements obtained via wearable CGM devices will lead to improved glycemic control, as measured by increased TIR, over standard of care. Such practical, supportive care interventions could have great influence in eliminating disparities in the treatment-related toxicity experienced by Latino pediatric cancer patients.

Improving Cancer Survivorship Care for Latino AYA Survivors

Dr. Jacqueline Casillas is a Professor in the Department of Pediatrics at the David Geffen School of Medicine at the University of California Los Angeles (UCLA), Director of the Pediatric, Adolescent and Young Adult (AYA) Survivorship Program at UCLA, and Medical Director of the Jonathan Jaques Children’s Cancer Institute at Miller’s Women and Children’s Hospital.

Adolescent and young adult survivors

Dr. Casillas’s presentation focused on three main topics: the epidemiology of AYA survivorship, the cost of cure and late effects, and improving care for AYA survivors. In 2020 there were 89,500 new cancer cases in AYA patients, defined as individuals between 15 and 39 years. Although the overall 5-year survival rate in this demographic is 83-86%, survival is lower for racial/ethnic minorities. Currently, there are approximately 675,000 AYA survivors overall.

Cancer is the leading cause of death in the Latino population, accounting for 20% of overall deaths. Although there is limited data for Latino AYAs, cancer mortality rates for patients aged 15-19 declined from 2010 to 2019 by 2% per year. Survival disparities exist for the most common types of cancer for adolescents. Latino patients with leukemia, for example, have survival rates of 71% compared with 82% for non-Hispanic White patients. For Latino adolescents, the most common cancer types are brain, leukemia, lymphoma and germ cell tumors.

Late effects

Cancer survival comes with the risk of late effects, defined as any chronic or late occurring outcome, physical or psychosocial, that persists or develops beyond 5 years from the diagnosis of cancer. For AYA cancer survivors, late effects are an emerging area of research since this is an understudied population. AYA clinical trials tend to have lower enrollment compared with well-established childhood cancer survivorship studies or survivorship studies done in older adults.

Unique risks exist for AYA survivors, including increased risk of secondary cancers, increased risk of chronic comorbidities, and increased risk of mortality as survivors. AYAs have a higher excess risk for secondary malignant neoplasms than either children or older adults. The cumulative incidence for developing a secondary neoplasm continues to increase over time for AYA survivors is 15 years, highlighting the need for long-term survivorship care. Increased risk of chronic comorbidities are also present, with 40% of AYA survivors experiencing multiple comorbidities at 10 years after index date, compared with 20% of AYAs without cancer. The most common comorbidities were dyslipidemia, hypertension, thyroid disorders, and severe depression or anxiety.

Clinical trial participation

There is a dearth of data for Latino AYA survivors, partially due to Latino underrepresentation in cancer clinical trials. Factors that contribute to this underrepresentation include a lack of awareness of clinical trials, fear of toxicities and mistrust, transportation issues, a lack of access to academic centers or specialized cancer centers, high rates of uninsured or underinsured, language and communication barriers, the complexity of clinical trial design (particularly for low literacy patients and families), and the unconscious bias of providers.

Given the increased risk for morbidity and mortality in AYA survivors, survivorship care must include several considerations. First, cancer prevention and health promotion counseling must be provided for risk reduction, including counseling on tobacco exposure and cessation, alcohol use, diet, exercise, and obesity prevention. Next, screening must be prioritized for early detection of late effects including medical and psychosocial outcomes. Hereditary genetic predispositions and appropriate genetic counseling should also be considered. Finally, assessment of cultural beliefs, environment, and inclusion of Latinos in research should be prioritized in order to develop interventions to achieve health equity in cancer survivorship care.

Interventions

Because of the developmental stage of AYA survivors, cancer diagnosis may disrupt their independence from their parents and healthy peers. These survivors may wish to identify with a peer support group for others diagnosed and treated for cancer, which could optimize health outcomes. Survivorship care may be seen as intrusive and they may want to re-immerse themselves with healthy peers. Furthermore, since this population is very mobile, attendance at follow-up visits may be sporadic. Two interventions developed by Dr. Casillas and colleagues included a photonovela, used for educational intervention, and a text messaging system, used to remind and educate AYA survivors on their risk for late effects and the importance of survivorship care planning and healthy lifestyles. Such interventions can help clinicians interact with AYA survivors more effectively, and help survivors to be engaged in seeking survivorship care.

Minorities are less likely than non-Hispanic White individuals to be confident in a survivorship care plan, which can prepare survivors to be more self-assured in being their own health advocates. Latinos in particular can benefit from inclusion of the nuclear family in survivorship care discussions. However, a cancer stigma associated with survivorship discussions exists in the Latino community, resulting in continued emotional distress related to discussions regarding cancer diagnosis and treatment. Interventions targeting de-stigmatization of survivorship care in AYA-appropriate ways can make a difference in Latino cancer outcomes.