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PURPOSE To report the incidence and risk factors for secondary neoplasm after transplantation for sickle cell disease. METHODS Included are 1,096 transplants for sickle cell disease between 1991 and 2016. There were 22 secondary neoplasms. Types included leukemia/myelodysplastic syndrome (MDS; n = 15) and solid tumor (n = 7). Fine-Gray regression models examined for risk factors for leukemia/MDS and any secondary neoplasm. RESULTS The 10-year incidence of leukemia/MDS was 1.7% (95% CI, 0.90 to 2.9) and of any secondary neoplasm was 2.4% (95% CI, 1.4 to 3.8). After adjusting for other risk factors, risks for leukemia/MDS (hazard ratio, 22.69; 95% CI, 4.34 to 118.66; P = .0002) or any secondary neoplasm (hazard ratio, 7.78; 95% CI, 2.20 to 27.53; P = .0015) were higher with low-intensity (nonmyeloablative) regimens compared with more intense regimens. All low-intensity regimens included total-body irradiation (TBI 300 or 400 cGy with alemtuzumab, TBI 300 or 400 cGy with cyclophosphamide, TBI 200, 300, or 400 cGy with cyclophosphamide and fludarabine, or TBI 200 cGy with fludarabine). None of the patients receiving myeloablative and only 23% of those receiving reduced-intensity regimens received TBI. CONCLUSION Low-intensity regimens rely on tolerance induction and establishment of mixed-donor chimerism. Persistence of host cells exposed to low-dose radiation triggering myeloid malignancy is one plausible etiology. Pre-existing myeloid mutations and prior inflammation may also contribute but could not be studied using our data source. Choosing conditioning regimens likely to result in full-donor chimerism may in part mitigate the higher risk for leukemia/MDS.

Background: Oral chemotherapy nonadherence is a challenge in clinical oncology. During therapy for acute lymphoblastic leukemia (ALL), poor adherence to 6-mercaptopurine (6MP) increases relapse risk. Clinically significant nonadherence is reported in 30% of children treated for ALL on Children's Oncology Group (COG) trials. Whether nonadherence rates vary across regimens with different treatment schedules and modes of administration is unknown. Methods: We conducted an exploratory, cross-sectional survey study on parents of children (1–18 years) receiving continuation therapy on, or as per Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 11-001. Treatment required weekly visits to the clinic and 14 days of oral 6MP every 3 weeks. Survey assessed self-reported sociodemographics, medication-taking, chemotherapy comprehension, and 6MP adherence; adherence survey items were developed from published surveys. Patients were grouped as nonadherent if they endorsed missing one 6MP dose during the last cycle, or more than one dose during prior cycles, for nonmedical reasons. Results: Sixty-two families completed the surveys, all of whom had evaluable adherence data. In total, 25% of patients met the study definition of nonadherence. Twenty-three percent reported that it was “not easy” to follow administration guidelines around the dairy intake and 57% requested more teaching and educational resources. Conclusion: Self-reported nonadherence to oral 6MP in the DFCI ALL Consortium is high, with rates similar to those observed in the COG. This suggests that the additional contact during weekly infusions on the DFCI is insufficient to address barriers affecting oral chemotherapy adherence.

Black and Hispanic children with leukemia experience inferior survival compared to non-Hispanic White (NHW) children. Identifying modifiable social determinants of health can inform intervention targets to address inequities. We characterized the frequency of income poverty and household material hardship (HMH) by race/ethnicity in a clinical trial cohort with de novo acute lymphoblastic leukemia. Compared to NHW families, Black and Hispanic families reported more frequent HMH (19% vs. 47% vs. 68% respectively); low-income (27% vs. 52% vs. 74%), and combined low-income and HMH (12% vs. 37% vs. 52%) poverty exposures. Disparate poverty exposures are interventional targets to address racial/ethnic outcome inequities.

Adolescents and young adults (AYAs) with advanced cancer identify normalcy as an important component of quality end-of-life care. We sought to define domains of normalcy and identify ways in which clinicians facilitate or hinder normalcy during advanced cancer care.This was a secondary analysis of a qualitative study that aimed to identify priority domains for end-of-life care. Content analysis of semi-structured interviews among AYAs aged 12-39 years with advanced cancer, caregivers, and clinicians was used to evaluate transcripts. Coded excerpts were reviewed to identify themes related to normalcy.Participants included 23 AYAs with advanced cancer, 28 caregivers, and 29 clinicians. Participants identified five domains of normalcy including relationships, activities, career/school, milestones, and appearance. AYAs and caregivers identified that clinicians facilitate normalcy through exploration of these domains with AYAs, allowing flexibility in care plans, identification of short-term and long-term goals across normalcy domains, and recognizing losses of normalcy that occur during cancer care.AYAs with cancer experience multiple threats to normalcy during advanced cancer care. Clinicians can attend to normalcy and improve AYA quality of life by acknowledging these losses through ongoing discussions on how best to support domains of normalcy and by reinforcing AYA identities beyond a cancer diagnosis.

Children living in poverty experience excessive relapse and death from newly diagnosed acute lymphoblastic leukemia (ALL). The influence of household poverty and neighborhood social determinants on outcomes from chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory (r/r) leukemia is poorly described. We identified patients with r/r CD19+ ALL/lymphoblastic lymphoma treated on CD19-directed CAR T-cell clinical trials or with commercial tisagenlecleucel from 2012 to 2020. Socioeconomic status (SES) was proxied at the household level, with poverty exposure defined as Medicaid-only insurance. Low-neighborhood opportunity was defined by the Childhood Opportunity Index. Among 206 patients aged 1 to 29, 35.9% were exposed to household poverty, and 24.9% had low-neighborhood opportunity. Patients unexposed to household poverty or low-opportunity neighborhoods were more likely to receive CAR T-cell therapy with a high disease burden (>25%), a disease characteristic associated with inferior outcomes, as compared with less advantaged patients (38% vs 30%; 37% vs 26%). Complete remission (CR) rate was 93%, with no significant differences by household poverty (P = .334) or neighborhood opportunity (P = .504). In multivariate analysis, patients from low-opportunity neighborhoods experienced an increased hazard of relapse as compared with others (P = .006; adjusted hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.3-4.1). There was no difference in hazard of death (P = .545; adjusted HR, 1.2; 95% CI, 0.6-2.4). Among children who successfully receive CAR T-cell therapy, CR and overall survival are equitable regardless of proxied SES and neighborhood opportunity. Children from more advantaged households and neighborhoods receive CAR T-cell therapy with a higher disease burden. Investigation of multicenter outcomes and access disparities outside of clinical trial settings is warranted.

Social determinants of health (SDoH) are associated with stark disparities in cancer outcomes, but systematic SDoH data collection is virtually absent from oncology clinical trials. Trial-based SDoH data are essential to ensure representation of marginalized populations, contextualize outcome disparities, and identify health-equity intervention opportunities. We report the feasibility of a pediatric oncology multicenter therapeutic trial-embedded SDoH investigation. Among 448 trial participants, 392 (87.5%) opted-in to the embedded SDoH study; 375 (95.7%) completed baseline surveys, with high longitudinal response rates (88.9-93.1%) over 24 months. Trial-embedded SDoH data collection is feasible and acceptable and must be consistently included within future oncology trials.

Social determinants of health (SDoH) are associated with stark disparities in cancer outcomes, but systematic SDoH data collection is currently absent from oncology clinical trials. Trial-based SDoH data are essential to ensure representation of marginalized populations, contextualize outcomes, and identify health-equity intervention opportunities. We report the feasibility of the first pediatric oncology multicenter trial-embedded SDoH investigation. Among 448 trial participants, 392 (87.5%) opted-in to the embedded SDoH study; 375 (95.7%) completed baseline surveys, with high longitudinal response rates (87.2-92.8%) over 24-months of therapy. Trial-embedded SDoH data collection is feasible and acceptable, and must be consistently included within future oncology trials.

Background Single patient Investigational New Drug (IND) applications are one mechanism through which experimental therapies are accessed for children with cancer. The landscape of use, outcomes, and toxicity from single patient INDs remains unknown in pediatric oncology. Methods We performed a retrospective analysis of all single patient INDs requested and prescribed at a single institution between 1/1/2007 and 5/1/2019. We report aggregate data from the US Food and Drug Administration (FDA) on single patient IND applications over the final two years of the study (2017–2019). We report an overview of all IND applications, as well as clinical descriptions of patients, treatments, outcomes, and toxicity. Results Over the 2‐year period, the FDA approved all 171 submitted single patient IND requests for pediatric oncology. We identified 56 requests from our center during the 12‐year study period, and all were approved (median time from FDA submission to approval: 1 day (range 0–12)). 71% of requests were based on disease histology. Lack of pediatric clinical trial (65%) was the most common reason for use. 48 approved requests were ultimately administered. The median duration of treatment was 84 days (range: 4–1590), with 3 patients remaining on treatment at time of analysis. Only 7% discontinued treatment due to toxicity. Three‐year overall survival was 50% (95% CI, 35–64). Conclusions Single patient INDs in pediatric oncology were universally approved in our national and single‐center analysis. In our cohort, single patient INDs were primarily utilized based on disease histology, rather than genomics, for agents that lacked a clinical trial., Single patient Investigational New Drug (IND) applications in pediatric oncology are universally approved in a timely fashion in our analysis. Single patient IND therapy is pursued for a range of reasons, with few patients discontinuing therapy due to toxicity.

Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age ≤18 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (≥20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.

Background Food insecurity (FI) is an adverse social determinant of health (SDoH) prevalent among pediatric cancer patients and associated with poorer health outcomes in general pediatrics. Receipt of federal SNAP benefits reduces FI in general pediatrics, and is thus a marker of appropriate resource support to mitigate adverse SDoH. Dana-Farber Cancer Institute (DFCI) Acute Lymphoblastic Leukemia (ALL) Consortium Trial 16-001 is the first pediatric oncology clinical trial to prospectively collect parent-reported SDoH, including income, SNAP receipt, and FI. We investigated whether income-eligible pediatric ALL families were successfully receiving SNAP benefits, and whether SNAP receipt was associated with FI. Methods Secondary analysis of children aged 1-17 years with de novo ALL enrolled on the DFCI 16-001-embedded SDoH cohort study at 6 US centers from 2017-2022. We utilized parent-reported SDoH data at diagnosis (T0) and 6-mos (T1) into therapy to identify families as (1) SNAP-eligible, proxied as household income Citation Format: Rahela Aziz-Bose, Yael Flamand, Puja J. Umaretiya, Lenka Ilcisin, Ariana Valenzuela, Peter D. Cole, Lisa M. Gennarini, Justine M. Kahn, Kara M. Kelly, Bruno Michon, Thai-Hoa Tran, Jennifer J. G. Welch, Lewis B. Silverman, Kira Bona. Food insecurity and receipt of Supplemental Nutrition Assistance Program (SNAP) benefits among income-eligible US pediatric acute lymphoblastic leukemia patients enrolled on a multi-center clinical trial [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B096.

BACKGROUND: Our previous study to understand end-of-life care of adolescents and young adults (AYAs) had a suboptimal survey response rate by bereaved caregivers. OBJECTIVE: To identify sociodemographic factors associated with caregiver nonparticipation. DESIGN/SETTING/SUBJECTS: Post hoc analysis of a retrospective multicenter cohort study of caregivers of deceased AYAs from 2013 to 2016. MEASUREMENTS: Exposures: race, ethnicity, area-, and household-poverty. Primary outcome: survey participation. Secondary outcomes: loss to follow-up at each recruitment step. RESULTS: Thirty-five of 263 eligible caregivers participated in the survey (13.3%). Caregivers of AYAs living in high-poverty zip codes were significantly more likely to have a disconnected or incorrect phone number (odds ratio [OR] 2.12; 95% confidence interval [CI] 1.04–4.58; p = 0.03). Caregivers of nonwhite AYAs were significantly less likely to participate (OR 0.35; 95% CI 0.12–0.87; p = 0.01). CONCLUSIONS: Caregivers of patients living in poverty are less likely to be reached by traditional recruitment efforts. Caregivers of racial/ethnic minority patients are less likely to participate overall.

Background Off‐label drug prescribing is common in pediatric clinical medicine, though the extent and impact of this practice in pediatric oncology has not yet been characterized. Methods We completed a retrospective single‐institution cohort study evaluating prevalence, characteristics, and clinical outcomes of off‐label prescribing of 108 FDA‐approved targeted anticancer drugs in patients, Off‐label prescribing patterns and outcomes with targeted anticancer agents have not been previously described in pediatric oncology. In this analysis from a large pediatric cancer center, off‐label prescribing of FDA‐approved targeted therapies was common, increasing, encompassed a broad sample of targeted agents, and was tolerable.

Context Parents of patients with a serious illness experience psychological distress, which impacts parents' wellbeing and, potentially, their ability to care for their children. Parent psychological distress may be influenced by children's symptom burden and by families' financial difficulty. Objectives This study examined the associations among parent psychological distress, parent-reported patient symptoms, and financial difficulty, seeking to determine the relative association of financial difficulty and of patient symptoms to parent psychological distress. Methods Cross-sectional study of baseline data for 601 parents of 532 pediatric palliative care patients enrolled in a prospective cohort study conducted at seven US children's hospitals. Data included self-reported parent psychological distress and parent report of child's symptoms and family financial difficulty. We used ordinary least squares multiple regressions to examine the association between psychological distress and symptom score, between psychological distress and financial difficulty, and whether the degree of financial difficulty modified the relationship between psychological distress and symptom score. Results The majority of parents were moderately to severely distressed (69%) or severely distressed (17%) and experienced some degree of financial difficulty (65%). While children's symptom scores and family financial difficulty together explained more of the variance in parental psychological distress than either variable alone, parental distress was associated more strongly, and to a larger degree, with financial difficulty than with symptom scores alone. Conclusions Parent psychological distress was associated with parent-reported patient symptoms and financial difficulty. Future work should examine these relationships longitudinally, and whether interventions to improve symptom management and ameliorate financial difficulties improve parental outcomes.

Adult cancer disparities have been documented for decades and continue to persist despite clinical advancements in cancer prevention, detection, and treatment. Pediatric cancer survival has improved significantly in the United States for the past 5 decades to over 80%; however, disparate outcomes among children and adolescents with cancer still affect many populations in the United States and globally, including racial and ethnic minorities, populations with low socioeconomic status, and residents of underserved areas. To achieve equitable outcomes for all children and adolescents with cancer, it is imperative that concerted multilevel approaches be carried out to understand and address health disparities and to ensure access to high-quality cancer care. Addressing social determinants of health, such as removing barriers to health care access and ensuring access to social supports, can reduce pediatric cancer disparities. Nevertheless, public health policy, health system interventions, and innovative delivery of evidence-based services are critically needed. Partnerships among patients, caregivers, and health care providers, and among health care, academic, and governmental institutions, have a pivotal role in reducing cancer disparities and improving outcomes in the 21st century.

BACKGROUND Modern therapeutic advances in high-risk neuroblastoma have improved overall survival (OS), but it is unclear whether these survival gains have been equitable. This study examined the relationship between socioeconomic status (SES) and overall survival (OS) in children with high-risk neuroblastoma and whether SES-associated disparities have changed over time. PROCEDURE In this population-based cohort study, children

Background Racial and ethnic minority children with cancer disproportionately receive intensive care at the end of life (EOL). It is not known whether these differences are goal-concordant or disparities. The authors sought to explore patterns of pediatric palliative care (PPC) and health care utilization in pediatric oncology patients receiving subspecialty palliative care at the end-of-life (last 6 months) and to examine goal-concordance of location of death in a subset of these patients. Methods This was a retrospective cohort study of pediatric oncology patients receiving subspecialty palliative care at a single large tertiary care center who died between January 2013 and March 2017. Results A total of 115 patients including 71 White, non-Hispanic patients and 44 non-White patients (including 12 Black patients and 21 Hispanic patients) were included in the analytic cohort. There were no significant differences in oncologic diagnosis, cause of death, or health care utilization in the last 6 months of life. White and non-White patients had similar PPC utilization including time from initial consult to death and median number of PPC encounters. Non-White patients were significantly more likely to die in the hospital compared to White patients (68% vs 46%, P = .03). Analysis of a subcohort with documented preferences (n = 45) revealed that 91% of White patients and 93% of non-White patients died in their preferred location of death. Conclusions Although non-White children with cancer were more likely to die in the hospital, this difference was goal-concordant in our cohort. Subspecialty PPC access may contribute to the achievement of goal-concordant EOL care.

7013 Background: CD19-directed chimeric antigen receptor T cell (CART) therapy has dramatically improved survival for children with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). While significant socioeconomic (SES) outcome disparities exist for children with newly diagnosed B-ALL, the impact of SES on CART access and outcomes is poorly described. Using the largest single-center pediatric CART experience, we investigated the hypothesis that poverty-exposed children would have inferior survival outcomes compared to unexposed children. Methods: Retrospective cohort study of US pediatric patients treated on CD19 CART clinical trials or with commercial tisagenlecleucel at Children's Hospital of Philadelphia from 2012-2020. Poverty was the primary exposure, defined at the household-level by insurance status (public vs private). Neighborhood opportunity was defined by census-derived Childhood Opportunity Index (COI) (low [q1-2] vs high [q3-4]). Overall survival (OS) and relapse-free survival (RFS) were evaluated by Kaplan Meier methods, and association with exposures by Cox regression models. Results: Among 206 patients, 36% were household poverty exposed, 24.9% low COI, 21.4% identified as Hispanic, 7.3% non-Hispanic Black, 63.6% non-Hispanic White, and 7.7% non-Hispanic Other. Household-poverty exposure was similar between local and referred patients (32.4% vs 36.7%). Patients unexposed to poverty at the household level or with high COI presented to CART with high disease burden (37.1% vs 26%, p = 0.049, 37.9% vs. 29.7%, p = 0.002). In multivariate analysis adjusting for age, race/ethnicity, disease burden, relapse status, and inotuzumab exposure, there were no significant differences in OS by householdverty (HR 0.86, 95%CI 0.50-1.48, p = 0.575) or low COI (HR 1.03, 95%CI 0.53-1.99, p = 0.932). Low COI was associated with inferior RFS (HR 2.26, 95%CI 1.34-8.80, p = 0.002). There was no significant difference in RFS by household-poverty (HR 0.84, 95%CI 0.48-1.44, p = 0.520). Conclusions: Household poverty was not associated with inferior survival outcomes in pediatric patients who received CART for r/r B-ALL. Patients with low neighborhood opportunity had increased hazard of relapse, a finding that requires investigation of the COI components underlying this association. Patients of higher proxied SES were more likely to have high disease burden, an access inequity potentially reflecting referral pattern bias or greater ability of advantaged families to advocate for CART. Future institutional and multi-center studies should utilize patient-reported social determinants of health to investigate mechanisms driving these disparities and guide care delivery interventions to improve equity in access and outcomes. Clinical trials: NCT01626495, NCT02435849, NCT02374333, NCT02228096, NCT02906371

10005 Background: Racial and socioeconomic disparities have not been comprehensively investigated in high-risk neuroblastoma (HR NBL). Prior Children’s Oncology Group (COG) investigations have demonstrated population-based disparities in late relapse rates among Black children, and trial-based disparities in relapse and survival among children living in poverty receiving post-consolidation immunotherapy. It is unknown whether these disparities persist in upfront trials for newly diagnosed patients. We leveraged COG data to investigate race, ethnicity, and socioeconomic disparities in a cohort of children with HR NBL treated on upfront clinical trials from 2007-2016. Methods: Retrospective cohort study of children enrolled on upfront COG HR NBL trials ANBL0532, ANBL09P1, and ANBL12P1. Race and ethnicity were the primary exposures categorized as: Black Non-Hispanic (BNH); Hispanic; Other Non-Hispanic (ONH); or White Non-Hispanic (WNH). Poverty was the secondary exposure, defined as household (public insurance only vs others), area (census-defined high-poverty ZIP code with >20% of population living below 100% Federal Poverty Level (FPL) vs

6546 Background: Concrete resource needs (CRN: insecurity of food, utilities, and/or housing) are important and modifiable indicators of poverty. Prior work among adults with chronic cardiometabolic diseases demonstrates that CRN-targeted interventions improve health outcomes. Poverty is associated with inferior health outcomes among patients with cancer. Frailty is a recognized state of increased vulnerability and is associated with increased toxicities from cancer therapies and reduced survival. The prevalence of CRN among older adults with cancer and its role in modifying the risk of frailty remains unknown. We aimed to (1) describe the prevalence of CRN and (2) examine the association between CRN and frailty among older adults with cancer. Methods: The CARE registry prospectively enrolls older adults (≥60y) with cancer seen at UAB as new patients. Single-item screening measures captured food, housing and utility insecurity in addition to the baseline CARE geriatric assessment beginning 8/2020. The 44-item CARE Frailty Index (based on the principles of deficit accumulation) was used to define frailty. Multivariable analysis examined association of CRN with frailty, adjusting for age, race, sex, education, employment, marital status, and cancer type and stage. Results: The cohort included 485 participants with a mean age at enrollment of 69y; 63.7% were male; 20.4% were non-Hispanic Black. The most prevalent cancer types included colorectal (33.0%), pancreatic (16.3%) and hepatobiliary (12.2%) cancers. Median time from cancer diagnosis to study enrollment was 35 days. The overall prevalence of CRN was 6.6% (insecurity of housing [2.9%], food [4.3%], and utilities [4.1%]). Participants with CRN were less educated ( < HS: 21.9% vs. 9.9%, p= 0.01), more often widowed/divorced (53.1% vs. 35.1%, p= 0.003) and more likely to be disabled (43.8% vs. 12.4%, p< 0.001). Overall, 33.8% of patients were frail. In multivariable analysis, patients with CRN had a 6.24 higher odds of frailty (95% CI 1.72-22.7, p= 0.005) compared to those without CRN after adjustment for above-mentioned covariates. Conclusions: CRN represents a novel exposure that is independently associated with frailty. In order to inform a CRN-targeted intervention for the growing number of older adults with cancer, future work is warranted to examine the CRN construct in this population, including examination of more detailed screening measures and CRN-associated cancer outcomes.

10004 Background: Children living in poverty and those who identify as a race/ethnicity other than non-Hispanic White experience higher rates of relapse and lower overall survival across many pediatric cancers. Racial, ethnic and socioeconomic disparities have not been comprehensively investigated in osteosarcoma. We leveraged data from US-enrolled patients on the recent international EURAMOS-1 trial to investigate disparities in survival outcomes. Aim: Identify if race/ethnicity, household or neighborhood poverty exposure are associated with event-free survival (EFS) or overall survival (OS) in patients with non-metastatic osteosarcoma enrolled at a US-center on EURAMOS-1. Methods: Retrospective cohort study of US patients aged 5-21 years enrolled on EURAMOS-1 with a diagnosis of non-metastatic, primary osteosarcoma. Poverty was the primary exposure defined at the household- (sole coverage with Medicaid or CHIP public insurance versus other) and neighborhood- (Census-defined high-poverty ZIP code with >20% of residents living at

Background Whether social determinants of health are associated with survival in the context of pediatric oncology–targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials. Methods We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children’s Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided. Results In multivariable Cox regressions adjusted for disease and treatment factors, household poverty–exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P < .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P < .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P < .001) compared with the unexposed group. Conclusions Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.

Poor adherence to 6-mercaptopurine during acute lymphoblastic leukemia (ALL) therapy increases relapse risk. Clinically-significant non-adherence has been documented in up to 30% of children treated for ALL on Children’s Oncology Group trials. Whether non-adherence rates vary across regimens with different chemotherapy schedules and modes of administration is not known. In a cross-sectional survey study of N= 61 children treated on, or as per Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 11-001, 25% (95% CI 14 – 37%) of respondents self-reported non-adherence to 6MP, suggesting that the frequency of non-adherence may be similar across different Consortia regimens.

This quality improvement study examines disparities in proton radiotherapy use in patients enrolled in Children’s Oncology Group Trials

BACKGROUND Children with advanced cancer experience high symptom distress, which negatively impacts their health-related quality of life (HRQOL). To the authors' knowledge, the relationship between income and symptom distress and HRQOL is not well described. METHODS The Pediatric Quality of Life and Symptoms Technology (PediQUEST) multisite clinical trial evaluated an electronic patient-reported outcome system to describe symptom distress and HRQOL in children with advanced cancer via repeated surveys. The authors performed a secondary analysis of PediQUEST data for those children with available parent-reported household income (dichotomized at 200% of the Federal Poverty Level and categorized as low income [

Background: The “Promoting Resilience in Stress Management” intervention is a skills-based, early palliative care intervention with demonstrated efficacy in adolescents and young adults with cancer. Aim: Utilizing data from a randomized clinical trial of Promoting Resilience in Stress Management versus Usual Care, we examined whether response to Promoting Resilience in Stress Management differed across key sociodemographic characteristics. Design: Adolescents and young adults with cancer completed patient-reported outcome measures of resilience, hope, benefit-finding, quality of life, and distress at enrollment and 6 months. Participants were stratified by sex, age, race, and neighborhood socioeconomic disadvantage based on home address (Area Deprivation Index scores with 8–10 = most disadvantaged). Differences in the magnitude of effect sizes between stratification subgroups were noted using a conservative cutoff of d > 0.5. Setting/participants: Participants were 12 to 25 years old, English-speaking, and receiving cancer care at Seattle Children’s Hospital. Results: In total, 92 adolescents and young adults (48 Promoting Resilience in Stress Management, 44 Usual Care) completed baseline measures. They were 43% female, 73% 12 to 17 years old, 64% White, and 24% most disadvantaged. Effect sizes stratified by sex, age, and race were in an expected positive direction and of similar magnitude for the majority of outcomes with some exceptions in magnitude of treatment effect. Those who lived in less disadvantaged neighborhoods benefited more from Promoting Resilience in Stress Management, and those living in most disadvantaged neighborhoods benefited less. Conclusion: The “Promoting Resilience in Stress Management” intervention demonstrated a positive effect for the majority of outcomes regardless of sex, age, and race. It may not be as helpful for adolescents and young adults living in disadvantaged neighborhoods. Future studies must confirm its generalizability and integrate opportunities for improvement by targeting individual needs.

The Inaugural Symposium on Childhood Cancer Health Disparities was held in Houston, Texas, on November 2, 2016. The symposium was attended by 109 scientists and clinicians from diverse disciplinary back-grounds with interests in pediatric cancer disparities and focused on reviewing our current knowledge of disparities in cancer risk and out-comes for select childhood cancers. Following a full day of topical sessions, everyone participated in a brainstorming session to develop a working strategy for the continued expansion of research in this area. This meeting was designed to serve as a springboard for examination of childhood cancer disparities from a more unified and systematic approach and to enhance awareness of this area of need.

Introduction: Health disparities are major issue for racial, ethnic, and socioeconomically disadvantaged groups. Though outcomes in childhood acute lymphoblastic leukemia (ALL) have steadily improved, identifying persistent disparities is critical. Prior studies evaluating ALL outcomes by race or ethnicity have noted narrowing disparities or that residual disparities are secondary to differences in leukemia biology or socioeconomic status (SES). We aimed to identify persistent inequities by race/ethnicity and SES in childhood ALL in the largest cohort ever assembled for this purpose. Methods: We identified a cohort of newly-diagnosed patients with ALL, age 0-30.99 years who were enrolled on COG trials between 2004-2019. Race/ethnicity was categorized as non-Hispanic white vs. Hispanic vs. non-Hispanic Black vs. non-Hispanic Asian vs. Non-Hispanic other. SES was proxied by insurance status: United States (US) Medicaid (public health insurance for low-income individuals) vs. US other (predominantly private insurance) vs. non-US patients (mainly jurisdictions with universal health insurance). Event-free and overall survival (EFS, OS) were compared across race/ethnicity and SES. The relative contribution of disease prognosticators (age, sex, white blood cell count, lineage, central nervous system status, cytogenetics, end Induction minimal residual disease) was examined with Cox proportional hazard multivariable models of different combinations of the three constructs of interest (race/ethnicity, SES, disease prognosticators) and examining hazard ratio (HR) attenuation between models. Results: The study cohort included 24,979 children, adolescents, and young adults with ALL. Non-Hispanic White patients were 13,872 (65.6%) of the cohort, followed by 4,354 (20.6%) Hispanic patients and 1,517 (7.2%) non-Hispanic Black patients. Those insured with US Medicaid were 6,944 (27.8%). Five-year EFS (Table 1) was 87.4%±0.3% among non-Hispanic White patients vs. 82.8%±0.6% [HR 1.37, 95 th confidence interval (95CI) 1.26-1.49; p Table 2 shows the multivariable models and illustrates different patterns of HR adjustment among specific racial/ethnic and SES groups. Inferior EFS among Hispanic patients was substantially attenuated by the addition of disease prognosticators (HR decreased from 1.37 to 1.17) and further (but not fully) attenuated by the subsequent addition of SES (HR 1.11). In contrast, the increased risk among non-Hispanic Black children was minimally attenuated by both the addition of disease prognosticators and subsequent addition of SES (HR 1.45 to 1.38 to 1.32). Similarly, while the superior EFS of non-US insured patients was substantially attenuated by the addition of race/ethnicity and disease prognosticators (HR 0.79 to 0.94), increased risk among US Medicaid patients was minimally attenuated by the addition of race/ethnicity or disease prognosticators (HR 1.21 to 1.16). OS disparities followed similar patterns but were consistently worse than in EFS, particularly among patients grouped as non-Hispanic other. Conclusions: Substantial disparities in survival outcomes persist by race/ethnicity and SES in the modern era. Our findings suggest that reasons for these disparities vary between specific disadvantaged groups. Additional work is required to identify specific drivers of survival disparities that may be mitigated by targeted interventions. Figure 1 Figure 1. Disclosures Gupta: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Teachey: NeoImmune Tech: Research Funding; Sobi: Consultancy; BEAM Therapeutics: Consultancy, Research Funding; Janssen: Consultancy. Zweidler-McKay: ImmunoGen: Current Employment. Loh: MediSix therapeutics: Membership on an entity's Board of Directors or advisory committees.

We aimed to explore the predictive value of screening for distress alone, hope alone, or a combination of both. In a multi-center prospective study, 37 English-speaking Adolescents and Young Adults (AYAs) with cancer and 40 parents completed validated instruments at diagnosis (“baseline”) and 3–6 months later (“follow-up”). Correlated regression models described associations. Within each instrument, baseline and follow-up scores were associated. However, only a composite hope/distress score predicted all three patient-centered outcomes. Multi-dimensional screens incorporating positive and negative psychosocial constructs may predict patient-centered outcomes better than isolated, single-construct instruments.

10025 Background: Poverty is associated with inferior psychosocial function among parents of children with cancer. Severe parental distress during treatment predicts future poor mental health for both parents and children. It is also associated with impaired parental cognitive bandwidth and executive function, which may have implications for treatment adherence. Efforts to identify poverty-exposures amenable to intervention are essential to improving survivorship quality of life for the > 90% of children with acute lymphoblastic leukemia (ALL) who will be long-term survivors. Household material hardship (HMH) is a targetable poverty exposure defined as at least 1 of 3 unmet basic needs including food, housing, or utilities. Dana-Farber Cancer Institute (DFCI) ALL Consortium trial 16-001 is the first pediatric oncology clinical trial to systematically evaluate HMH. We investigated the hypothesis that HMH exposure independently predicts severe parent psychological distress during ALL therapy. Methods: Patients with newly diagnosed ALL ages 1-17 years were enrolled on the DFCI 16-001 embedded HMH cohort study at 8 U.S. and Canadian centers. Secondary interim analyses used baseline (within 32-days of trial enrollment) and 6-mos parent-reported sociodemographic data, the Kessler-6 (K6) Psychological Distress scale, and trial-collected child and disease data. Severe psychological distress was defined as a K6 > = 13. Multivariable cox regression evaluated baseline HMH-exposure and parent distress at baseline and 6-mos adjusting for child’s initial ALL risk group (Very High Risk (VHR) vs other) and marital status (single vs dual parent). Results: Among 258 families with evaluable data, 34% reported baseline HMH. Families were predominantly English-speaking (54%) dual parent households (71%). Children were a median of 5.7 years (IQR 1.0-17.99) at diagnosis and predominantly non-Hispanic white (66%) with expected disease distribution by immunophenotype (84% B-cell). HMH (odds ratio (OR) 2.18, 95% confidence interval (CI) 1.0-4.31, p = 0.025) and VHR initial risk group (OR 2.32; 95% CI 1.06-5.06, p = 0.035) were independently associated with baseline severe psychological distress. Only HMH was independently associated with 6-mos severe psychological distress (OR 4.93, 95% CI 1.80-13.48, p = 0.002). Future analyses will investigate race and ethnicity associations with parental distress pending trial accrual for statistical power. Conclusions: HMH, a modifiable poverty exposure, is significantly associated with severe parent psychological distress at diagnosis that persists 6-months into pediatric ALL therapy. These findings identify a cohort at high risk of inferior mental health outcomes, and affirm the need for HMH-targeted interventions to support children and parents during cancer treatment to reduce poverty-associated outcome disparities in survivorship.

The aim of this analysis was to explore intra-family longitudinal relationships in psychosocial well-being among Adolescent and Young Adults (AYAs, Mage=17, SD=2.1) with cancer and their mothers using data from a multi-site, prospective, survey-based study. AYA-mother dyads (n=14 dyads) completed validated Patient Reported Outcomes (PROs) measures of self-perceived resilience [Connor-Davidson Resilience Scale (CD-RISC-10)] and distress [Kessler-6 psychological distress scale (K6)] at baseline (14–60 days following diagnosis) and follow-up (3–6 months later). Higher AYA distress predicted better maternal resilience, whereas higher maternal distress predicted worse AYA resilience. Thus, processes of resilience between AYAs and their mothers may differ.

Context In our increasingly multicultural society, providing sensitive and respectful pediatric palliative care is vital. Objectives We held a one-day workshop conference with stakeholders and pediatric clinicians to identify suggestions for navigating conflict when cultural differences are present and for informing standard care delivery. Methods Participants explored cases in one of four workshops focused on differences based on race/ethnicity, economic disparity, religion/spirituality, or family values. Each workshop was facilitated by two authors; separate transcriptionists recorded workshop discussions in real time. We used content analyses to qualitatively evaluate the texts and generate recommendations. Results Participants included 142 individuals representing over six unique disciplines, 25 of the U.S., and three nations. Although the conference focused on pediatric palliative care, findings were broadly generalizable to most medical settings. Participants identified key reasons cultural differences may create tension and then provided frameworks for communication, training, and clinical care. Specifically, recommendations included phrases to navigate emotional conflict, broken trust, unfamiliar family values, and conflict. Suggested approaches to training and clinical care included the development of core competencies in communication, history taking, needs assessment, and emotional intelligence. Important opportunities for scholarship included qualitative studies exploring diverse patient and family experiences, quantitative studies examining health disparities, and randomized clinical trials testing interventions designed to improve community partnerships, communication, or child health outcomes. Conclusion Taken together, findings provide a foundation for collaboration between patients, families, and clinicians of all cultures.

Background Population-based evidence suggests that lower socioeconomic status (SES) negatively impacts the overall survival (OS) of children with leukemia; however, the relationships between SES and treatment-related mortality, relapse, and timing of relapse remain unclear. Procedure We examined OS, event-free survival (EFS) and cumulative incidence (CI) and timing of relapse by community-level poverty for 575 children aged 1–18 years with newly diagnosed acute lymphoblastic leukemia (ALL) treated on consecutive phase III multicenter Dana-Farber Cancer Institute ALL Consortium Protocols between 2000 and 2010. Children were categorized into high- and low-poverty areas for the analysis using aggregate U.S. Census data linked to zip code. Results Children living in high-poverty areas experienced a 5-year OS of 85% as compared with 92% for those in low-poverty areas (P = 0.02); poverty remained marginally significant (P = 0.07) after adjustment for immunophenotype, age, and white blood cell count. There were no differences detected in EFS or CI relapse by poverty area. However, 92% of the relapses observed in children from high-poverty areas occurred

Family financial hardship has emerged as a burden of pediatric cancer treatment with negative implications for family well-being. As part of an extensive project to create evidence-based standards for the psychosocial care of children with cancer, we performed a literature review of pediatric cancer-associated financial hardship utilizing six databases, and identified 24 publications for incorporation into this review. Financial hardship during childhood cancer was found to affect a significant proportion of the population and to negatively impact family well-being. Existing literature supports a strong recommendation for assessment of financial hardship as a component of comprehensive psychosocial care in pediatric oncology.

Introduction: Income, education, and health insurance coverage have been shown to influence access to appropriate oncology care, impacting detection and treatment. We sought to evaluate the role of area-based measures of socioeconomic status in contributing to outcome disparities on the two most recent Children's Oncology Group (COG) Phase 3 clinical trials for acute myeloid leukemia (AML), AAML0531 and AAML1031. We hypothesized that pediatric AML patients from low income and low education zip codes have inferior five-year overall survival (OS) and event-free survival (EFS) relative to patients from middle income and more educated zip codes. Methods: Patients enrolled on AAML0531 and AAML1031 were included. Patients with Down syndrome (n=5), FLT3/ITD high allelic ratio (n=264), in AAML1031 Arm D (n=332), and patients whose zip code was not able to be mapped to a US Census area were excluded (n=60). Patients were observed from enrollment on study through last available follow up. Zip code level median annual household income was the primary exposure and was categorized as follows: Poverty: $56,516. Secondary exposures of interest included zip code level educational attainment and insurance type (Medicaid Only vs other insurance) at AML diagnosis. Standard descriptive statistics were used to compare patient characteristics by levels of exposure; the Kaplan Meier method was used to estimate OS (defined as time from study entry to death) and EFS (time from study entry until failure to achieve CR during induction, relapse, or death). Cox proportional hazards models were used to estimate hazard ratios (HR) for OS and EFS. Measures of association were adjusted for known risk factors for mortality including cytogenetic/mutation risk group, gemtuzumab (GO) receipt, race, and age. Logistic regression analyses were used to estimate odds ratios (OR) for early mortality (defined as death during induction). Results: Of 2387 patients enrolled on AAML0531 and AAML1031, 1726 met inclusion criteria for the overall analysis. Due to missing covariate data, 1467 patients were included in the final model. Race/ethnicity differed significantly by area-based income, area-based education, and insurance type with a higher proportion of Black and Hispanic patients living in poverty, low income, and low education areas, and having Medicaid only insurance. Lower area-based income was associated with lower OS (43% in poverty vs. 61% in low income vs. 68% in middle/high income; p = 0.004) and EFS (34% in poverty vs. 46% in low income vs. 54% in middle/high income; p = 0.005), shown in Figure 1. Lower area-based educational attainment was also associated with lower OS (58% in Quartile 4 (lower education) vs. 70% in Quartile 1 (higher education); p = 0.005 across quartiles) and EFS (44% in Q4 vs. 54% in Q1; p = 0.03 across quartiles). Patients with Medicaid Only insurance had lower OS (59 ± 5% vs. 66 ± 3%: p = 0.01) but similar EFS (48 ± 5% vs. 50 ± 3%: p = 0.33). In a full multivariable model, differences in survival by area-based educational attainment and insurance type resolved suggesting that observed crude associations were explained by confounding by area-based income combined with established risk factors. Patients from middle/high income areas experienced 25% lower risk of mortality compared to patients from low income areas (OS: crude HR 0.74 95% CI 0.62, 0.89; adjusted HR 0.79 95% CI 0.63, 0.99) with similar differences in EFS (crude HR 0.79 95% CI 0.69, 0.92; adjusted HR 0.77 95% CI 0.65, 0.89). There was no meaningful confounding of the income-survival association detected as evidenced by unchanged magnitudes of association following adjustment for area-based education, insurance, and established risk factors. Area-based low income was associated with both higher risk of early death (crude OR: 2.43 95% CI 1.04, 5.69) and treatment-related mortality on therapy (11.1 ± 10.5% vs. 3.7 ± 2.5%, p = 0.03) compared to area-based middle/high income. Conclusions: Lower area-based income and education were associated with significantly inferior EFS and OS among patients with AML on the last two Phase 3 COG trials. Moreover, zip-code based low SES is an independent risk factor for mortality in pediatric AML. Additional studies to understand mechanisms of observed socioeconomic disparities in treatment outcomes will inform interventions that may mitigate these inequities. Disclosures Fisher: Pfizer: Research Funding; Astellas: Other: Data Safety Monitoring Board Chair for an antifungal study; Merck: Research Funding.

INTRODUCTION Pediatric acute myeloid leukemia (AML) requires intensive chemotherapy that results in prolonged periods of neutropenia, placing patients at significant risk for life threatening infection. Current supportive care guidelines strongly recommend hospitalization after chemotherapy completion until neutrophil recovery. While approximately 70% of United States (US) centers adhere to this recommendation, there are little data to support inpatient over outpatient management. Therefore, we compared clinical outcomes (Aim 1), patient experiences (Aim 2), and patient quality of life (QoL) (Aim 3), between the two strategies in a nationally representative sample of newly diagnosed AML patients METHODS Aim 1 employed retrospective, standardized chart abstraction for AML patients treated between 2011 and 2019 at 17 centers in the US. Patients were observed from their first course of chemotherapy through treatment completion, stem cell transplant, site transfer, relapse, or death. The unit of analysis was chemotherapy courses, the primary exposure was inpatient versus outpatient management, and primary outcomes were bacteremia and time to next treatment course. Only courses in which the patient met "discharge eligible" criteria were included (Figure 1). Analyses excluded Induction I given the low rate of outpatient management. Log-binomial regression was used to compare the bacteremia incidence and generalized linear regression was used to compare time to next course. Generalized estimating equations were used in overall analyses to account for correlation between courses from the same patient. For Aim 2, patients/ families at 9 centers underwent semi-structured interviews that were transcribed and analyzed using a conventional content analysis approach (InVivo). For Aim 3, parent proxies at 14 centers completed a PedsQL before the start of chemotherapy and then after neutrophil recovery but prior to the start of the subsequent course. Only one chemotherapy course per patient was considered. Only "discharge eligible" patients were included. Parent-proxy generic core QoL scores at the end of the chemotherapy cycle were compared by exposure group using analysis of covariance accounting for baseline scores. RESULTS 573 patients contributed 1188 treatment courses for Aim 1 (Figure 1). Mean age was 9 ±6 years, 47% were female, and AML was classified as low, intermediate, and high risk, respectively in 65%, 4%, and 31%, respectively. Overall rates of bacteremia were not significantly different in patients receiving outpatient versus inpatient management (23.8% vs 29.0%, RR 0.76, 95% CI: 0.56, 1.03; p=0.07). Days to next course also did not differ between the groups (30.2 vs. 31.6, adjusted difference -1.6, 95% CI: -3.2, 0.5; p=0.17). In Aim 2, 86 interviews in 57 families (39 inpatient, 18 outpatient) were performed. 86% of families receiving inpatient management expressed satisfaction and 85% receiving outpatient management expressed satisfaction. Dissatisfaction with inpatient management was driven by concerns for hospital acquired infections and separation from family. Dissatisfaction with outpatient management stemmed from stress of caring for a neutropenic child at home. Patients/families reporting satisfaction with outpatient management emphasized that the approach would not be appropriate for all families. For Aim 3, mean (±SD) parent proxy PedsQL score did not differ between outpatient (74.3 ±18.3) and inpatient management (70.3 ±19.2), adjusted mean difference 3.95, 95% CI: -5.57, 13.5. CONCLUSION In this nationally representative sample of AML patients, outpatient management had bacteremia rates similar to inpatient management, with no difference in time to the start of next treatment course or patient QoL. Semi-structured interviews revealed strong alignment between patient/family satisfaction and center discharge practice. However, families experiencing outpatient management note high stress in caring for profoundly neutropenic patients at home and that this strategy would not be suitable for all families. These clinical and patient-centered results suggest that outpatient management during neutropenia is a viable approach without excess risk for children with AML. However, implementation studies are needed to identify patient/family characteristics that portend a positive experience with an outpatient strategy. Disclosures Raetz: Pfizer: Research Funding. Rubnitz:AbbVie: Research Funding. Fisher:Pfizer: Research Funding; Astellas: Other: Data Safety Monitoring Board Chair for an antifungal study; Merck: Research Funding.

Three domains of parental social distress across the pediatric cancer care trajectory are the focus of this chapter: employment, financial hardship, and social supports. Prevalence of social distress and potential disparities in the delivery of high-quality palliative care are discussed. Literature review, expert opinion, clinical pearls, and case vignettes are utilized to highlight elements within each domain that can be targeted for intervention. Concrete recommendations for incorporation of these domains into pediatric cancer care are provided.

* Abbreviations: EOL — : end of life PPC — : pediatric palliative care The importance of pediatric palliative care (PPC) for children with cancer has been broadly embraced over the last 2 decades in response to compelling evidence of high symptom burden and suffering throughout the continuum of care.1–3 Yet, how best to evaluate the impact of PPC remains a methodological challenge in a field focused on patient-reported outcomes, including symptom alleviation and goal-concordant care. In adult oncology, the benchmarking of palliative care has been facilitated by data demonstrating that end-of-life (EOL) care intensity (which is evaluable with administrative data, such as hospitalization and receipt of ICU care) is discordant with the wishes of adult patients with cancer.4,5 Similar benchmarking in pediatrics has been limited by an unknown correlation of care intensity with family goals and an absence of methodology for pediatric-specific administrative data. In this issue of Pediatrics , Johnston et al6 provide the first US population-based data … Address correspondence to Kira Bona, MD, MPH, Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115. E-mail: kira.bona{at}childrens.harvard.edu