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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.

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.

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 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: Integratedbehavioral health models have been proposed as care delivery approaches to mitigate mental health disparities in primary care settings. However, these models have not yet been widely adopted or evaluated in pediatric oncology medical homes. Methods: We conducted a retrospective cohort study of 394 children with newly diagnosed cancer at Dana-Farber/Boston Children's Cancer and Blood Disorders Center (DF/BCH) from April 2013 to January 2017. Baseline sociodemographic characteristics and psychiatry utilization outcomes at 12 months following diagnosis were abstracted from the medical record. The severity of household material hardship (HMH), a concrete poverty exposure, at diagnosis and race/ethnicity were characterized by parent report using the Psychosocial Assessment Tool 2.0 (PAT). Associations between sociodemographic characteristics and receipt of psychiatry consultation were assessed with multivariable logistic regression models. Results: Among 394 children, 29% received a psychiatric consultation within 12 months postdiagnosis. Of these, 88% received a new psychiatric diagnosis, 76% received a psychopharmacologic recommendation, and 62% received a new behavioral intervention recommendation. In multivariable logistic regression adjusting for age, cancer diagnosis, and PAT total score, there was no statistically significant association between HMH severity or household income and psychiatry utilization. Children who identified as racial/ethnic minorities were significantly less likely to receive a psychiatry consultation (OR = 0.48, 95% CI = 0.27–0.84). Conclusions: In a pediatric oncology medical home with an integrated behavioral health model, socioeconomic status was not associated with disparate psychiatry utilization. However, there remained a profound racial/ethnic disparity in psychiatry utilization, highlighting the need for additional research and care delivery intervention.

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 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.

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

Background: The American Academy of Pediatrics and the National Academy of Medicine recommend vitamin D supplementation for breastfeeding infants. However, compliance with this recommendation is poor. Maternal supplementation with vitamin D is a safe and effective alternative to achieving vitamin D sufficiency in breastfeeding infants, and mothers have indicated a preference for self-supplementation over infant supplementation. Research aim: We sought to explore Family Medicine clinicians’ knowledge, attitudes, and practices regarding vitamin D supplementation recommendations for breastfeeding dyads. Methods: Fifty-six Family Medicine clinicians (including faculty physicians, resident physicians, and nurse practitioners/physician assistants) completed an online, anonymous survey regarding their knowledge and practices concerning vitamin D supplementation for breastfeeding infants. Results: The vast majority of clinicians (92.9%) correctly identified the American Academy of Pediatrics’ 2008 recommended dose for vitamin D supplementation in breastfeeding infants and estimated recommending vitamin D supplementation of exclusively breastfeeding infants 70.1% of the time. If all options were equivalent, clinicians would prefer to offer maternal or infant supplementation (50%) or maternal supplementation (37.5%) over infant supplementation (12.5%). Most (69.6%) preferred daily over monthly supplementation regimens. Conclusion: Family Medicine clinicians are knowledgeable regarding current recommendations for vitamin D supplementation in breastfeeding infants. They are also open to recommending maternal supplementation or offering parents a choice of maternal or infant vitamin supplementation.

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.

Asthma is independently associated with HLA-DR3 and increased risks of pneumococcal diseases. We aimed to determine whether HLA-DR polymorphism (HLA-DRB1*03), sensitization to house dust mite (HDM), or their interaction affects humoral immune responses to pneumococcal polysaccharide and protein antigens of intact pneumococci. Induction of serum titers of anti-pneumococcal polysaccharide and anti-surface protein IgM and IgG in response to immunization with intact pneumococci (Pn) serotype 14 was determined using humanized HLA-DR3 and DR2 transgenic mice. Transgenic mice were sensitized by injecting HDM and challenged with intranasal HDM. Mice were subsequently immunized with heat-killed Pn14 at day 24. Serum titers of anti-phosphorylcholine (PC) IgM and IgG, anti-pneumococcal polysaccharide, capsular type 14 (PPS14) IgM and IgG, and anti-pneumococcal surface protein A (PspA) IgG were measured. We included a total of 44 mice (22 DR3 and 22 DR2 mice) and half of mice in each group were sensitized with HDM (i.e. 22 HDM-sensitized and 22 control mice). HDM-sensitized mice, irrespective of HLA-DR polymorphism, had significantly lower humoral immune responses. HLA-DR3 mice, irrespective of HDM sensitization, elicited a significantly lower anti-PC IgG response. In contrast, the anti-PspA IgG response was higher in DR3 relative to DR2 mice. The effect of HDM sensitization on lowering humoral immune responses to Pn14 was observed in DR3 mice regardless of the nature of the antigen, whereas such decreases were observed only for the anti-PPS14 IgG and anti-PC IgM responses in DR2 mice. HDM sensitization lowered humoral immune responses to intact pneumococcus and this effect was significantly modified by the HLA-DR polymorphism.

51 Background: Cancer remains the leading cause of childhood death beyond infancy. Though growing subspecialty palliative care provides expertise in caring for dying children, all pediatricians encounter dying patients and should feel adequately prepared to participate in their care. Clinicians who feel insufficiently trained in communication or end-of-life care are more likely to distance themselves from seriously ill patients and report higher levels of distress and burnout. Pediatric residents are often responsible for the frontline care of dying children in the hospital and yet, most pediatric residencies lack a formal end-of-life curriculum. Here, we aim to understand the experience of pediatric residents caring for dying patients. Methods: A thirty-four item survey instrument was administered to residents in a large pediatric residency program at a tertiary care center at Rising Junior Orientation and Rising Senior Orientation in spring 2018. All residents present completed the survey. Results: Seventy-six residents completed surveys including 46 rising juniors and 30 rising seniors. Only 19 residents (25%) reported receiving any training in caring for dying children; most of which was by noon/morning conferences or informal teaching. Nearly all (70/74; 95%) residents felt that their training in caring for dying children was not sufficient. A majority of residents reported minimal to no comfort with discussion of goals of care (73%) or resuscitation status (69%), managing pain (76%), anxiety (79%), and dyspnea (80%) at the end-of-life, performing a death exam (81%), and reaching out to families after the death of a child (85%). A majority of residents anticipate continuing to care for dying children after residency (50/76; 66%). Conclusions: Pediatric residents are uncomfortable with caring for dying patients and receive minimal training, suggesting that end-of-life care is a large gap in the pediatric residency training experience.

Daily vitamin D supplementation is recommended for breastfed infants, but alternative methods include enriching breast milk with vitamin D through maternal supplementation or intermittent high-dose vitamin D. We determined maternal preferences for vitamin D supplementation in 140 mothers with exclusively breastfed infants, and 44 who used both breast and formula milk. Only 101 (55%) supplemented their infants with vitamin D. One hundred sixty (88%) preferred supplementing themselves rather than their infants, and 102 (57%) preferred daily to monthly supplementation. Safety was most important in choosing a method of supplementation. Taking maternal preferences into consideration may improve adequate intakes of vitamin D in breastfed infants.

BACKGROUND We recently reported a more rapid waning of vaccine-induced humoral immunity (measles vaccine) in children with asthma. It is unknown if asthma affects susceptibility to vaccine-preventable diseases. OBJECTIVE To determine whether asthma is associated with an increased risk of vaccine-preventable disease, e.g., breakthrough varicella infection. METHODS This was a retrospective population-based case-control study that examined cases of breakthrough varicella among children between 2005 and 2011. Children with a diagnosis of breakthrough varicella infection in Olmsted County, Minnesota (infection of >42 days after vaccination) between 2005 and 2011 and two age- and sex-matched controls were enrolled for each case. Asthma status was determined by using predetermined criteria. Conditional logistic regression models were used to calculate matched odds ratios (OR) and their corresponding 95% confidence intervals (CI). RESULTS Of the 165 cases and their 330 matched controls, 48% were boys and the mean (standard deviation) age at the index date was 6.6 ± 3.5 years for both cases and controls. Of the 330 controls, 80 (24%) had two doses of the varicella vaccine compared with only 23 (14%) of the 165 cases (OR 0.29 [95% CI, 0.14-0.61]; p = 0.001). Children with a history of asthma ever had a higher risk of developing breakthrough varicella compared with those without a history of asthma (adjusted OR 1.63 [95% CI, 1.04-2.55]; p = 0.032) when adjusting for elapsed time since the first varicella vaccination and the number of varicella vaccine doses. CONCLUSIONS A history of asthma might be an unrecognized risk factor for breakthrough varicella infection. Children with asthma should follow the two-dose varicella vaccine policy.

Cannabinoids have been well established as mediators of tumor cell proliferation in several cancer models. The activity of cannabinoid receptor 1 (CB1) agonists as well as cannabinoid receptor 2 (CB2) agonists have been extensively studied over the last decade, though their mechanisms of action have yet to be defined in the context of attenuating tumor proliferation. CB1 is abundant in the central nervous system with a low level of expression in the periphery, while CB2 exists primarily on cells of the immune system. Due to the lack of neuronal expression of CB2 receptors, compounds acting at CB2 receptors do not produce the psychotropic effects associated with CB1 receptor compounds. Although CB1 and CB2 compounds have yielded similar antiproliferative results in some tumor cells in vitro, CB2 receptors are markedly upregulated in many tumor cell lines for unknown reasons. Therefore, we focused on compounds selective for the CB2 receptor, including the CB2 selective agonists JWH-015 and AM1241. We show here that CB2 agonists and antagonists alike attenuate the proliferation of mouse and human breast cancer cells in a concentration dependent manner. CB2 agonist induced breast cancer anti-proliferation is not blocked by pretreatment with pertussis toxin, the CB1 cannabinoid receptor antagonist SR141716, or the transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonist capsazepine. The CB1 and CB2 receptors are classified as G-protein coupled receptors (GPCRs) that are generally linked to Gai or Gaq. Agonists and antagonists of G protein coupled receptors are typically defined based on their Ga mediated effect on intracellular cAMP levels. This method of classification is not entirely effective: it ignores the possibility of differential effects on alternative kinases and the bg subunit activity. The anti-proliferative activity of both JWH-015 and SR144528 may be explained by alternative receptor coupling pathways, changes in constitutive activity, or activity at a separate receptor. Here, we show a dose and time dependent decrease in phosphorylated ERK in cells treated with either JWH-015 (CB2 agonist) or SR144528 (CB2 antagonist). Together, these data along with the absence of a pertussis toxin effect suggest that the CB2 compounds are acting in a non-Gai coupled manner, and are attenuating a pro-survival pathway. Further studies are necessary to identify the binding partner responsible for the antiproliferative effects of CB2 compounds. We advance the idea that CB2 receptors on breast cancer cells constitutively activate the MAP/ERK pro-survival pathway and that by preventing constituitive activity of the CB2 receptor, CB2 compounds downregulate phosphorylation of the MAPK/ERK pathway to promote apoptosis of breast cancer cells. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-23.

Katherine E Hanlon,1,2 Alysia N Lozano-Ondoua,1 Puja J Umaretiya,1 Ashley M Symons-Liguori,1 Anupama Chandramouli,1 Jamie K Moy,1 William K Kwass,1 Patrick W Mantyh,1 Mark A Nelson,3 Todd W Vanderah,11Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA; 2Department of Biomedical Sciences, University of New England College of Osteopathic Medicine, Biddeford, ME, USA; 3Department of Pathology, University of Arizona College of Medicine, Tucson, AZ, USA Introduction: Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems. The mechanism of this modulation remains only partially delineated, and activity induced via the CB1 and CB2 receptors may be distinct despite significant sequence homology and structural similarity of ligands. Methods: The CB2-selective agonist JWH-015 was used to investigate mechanisms downstream of CB2 activation in mouse and human breast cancer cell lines in vitro and in a murine mammary tumor model. Results: JWH-015 treatment significantly reduced primary tumor burden and metastasis of luciferase-tagged murine mammary carcinoma 4T1 cells in immunocompetent mice in vivo. Furthermore, JWH-015 reduced the viability of murine 4T1 and human MCF7 mammary carcinoma cells in vitro by inducing apoptosis. JWH-015-mediated reduction of breast cancer cell viability was not dependent on Gαi signaling in vitro or modified by classical pharmacological blockade of CB1, GPR55, TRPV1, or TRPA1 receptors. JWH-015 effects were calcium dependent and induced changes in MAPK/ERK signaling. Conclusion: The results of this work characterize the actions of a CB2-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor.Keywords: cannabinoid receptor-2, CB2, breast cancer, JWH-015, MAPK/ERK, apoptosis, calcium&nbsp

Nigerian toddlers with low dietary calcium intakes increased forearm bone mineral density (BMD) after 18 months of calcium supplementation compared with placebo. However, it is not known if this bone mineral accretion is sustained after calcium supplement withdrawal. We therefore investigated the influence of prior calcium supplementation on forearm BMD 12 months after withdrawal of the supplement.Nigerian toddlers aged 12-18 months from three urban communities were enrolled in a controlled trial of calcium supplementation. Two communities received daily calcium supplements, one as calcium carbonate (400mg), and the other as ground fish (529±109 mg), for a duration of 18 months, and all three communities received vitamin A (2500 IU daily) as placebo. Forearm BMD was measured 5 times during 18 months of calcium supplementation and at 12 months after supplement withdrawal.Of 647 children enrolled, 390 completed the trial of calcium supplementation and 261 of these returned for the final follow-up 12 months after discontinuation of supplementation. During the 18 months of supplementation, an adjusted model demonstrated that the increase in both distal and proximal forearm BMD over time was significantly greater in the calcium supplemented groups than in the placebo group (P0.04). However, after supplement withdrawal, the increase in BMD over time was largely attenuated and only remained significant at the proximal forearm in the ground fish group (P=0.03).The benefit of calcium supplementation on forearm BMD in young Nigerian children is not sustained after supplement withdrawal.