Objective: Describe the healthcare utilization in the last 60 days of life in pediatric patients with cancer who died at home under hospice care and those that died in the hospital. Methods: Retrospective chart review of the medical records of those children with cancer diagnosis with palliative care consult and died either under hospice care at home or in the hospital. Results: Patients dying under hospice care spent a median of 44 days at home. Patients dying in the hospital spent a median of 30.5 days in the hospital, 10.5 days in the intensive care unit, and underwent 3.5 procedures requiring anesthesia. 45% of those that died in the hospital were compassionately extubated. Conclusion: For those dying with a cancer diagnosis, hospice care can allow for significant time at home with minimal healthcare while those dying in the hospital do spend a significant time in the hospital. This provides more information to both providers and families about end-of-life healthcare utilization.

Abstract BACKGROUND BrainChild-04 is a first-in-human clinical trial of quad-chimeric antigen receptor (CAR) T cell therapy for children and young adults with central nervous system (CNS) tumors. This trial administers repeated locoregional CAR T cells targeting B7-H3, EGFR, HER2, and IL-13Ralpha2 (“quad-CAR T cells”), leveraging multi-antigen targeting to address the tumor heterogeneity of high-grade CNS tumors. METHODS The primary endpoints are feasibility and safety, and secondary endpoints are disease response and correlative studies of CAR T cell activity. The trial utilized a Bayesian Optimal Interval (BOIN) statistical design with three planned dose regimens(DR). There are 2 arms with weekly delivery for 3 weeks of a 4-week cycle:(A) –diffuse intrinsic pontine glioma (DIPG), (B) –non-pontine diffuse midline glioma (DMG) or other relapsed CNS tumors. RESULTS Enrolled patients include DMG N=6, DIPG N=5, other CNS tumors N=4. Of the 15 enrolled patients, 7 have been infused with 8 awaiting infusions. A total of 33 intracranial CAR T doses have been delivered, including Arm A DR 1 (N=1), Arm B DR 1 (N=3), DR2 (N=3). The most common adverse events have been grade 1-2 fever (7/7 patients), grade 1-3 headache (6/7), and grade 1-2 nausea/vomiting (6/7). There have been no DLTs and no cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity (ICANS). CTCAE and tumor inflammation-associated neurotoxicity are both being captured. All treated patients are alive with median follow up time post-initial infusion of 93(14-198) days. CAR T cells were detected by flow cytometric analysis of CSF post-infusion in 14/24 CSF samples. Radiographic response, CSF circulating tumor DNA, targeted mass spectrometry, and cytokine analysis will be presented. CONCLUSIONS Our preliminary experience suggests tolerability of locoregional delivery of quad-CAR T cells at doses currently evaluated. The trial remains ongoing and these data support continued evaluation of this product to better assess anti-tumor activity in patients with CNS tumors, including DIPG/DMG.

Background:Effective therapy for medulloblastoma at the time of relapse is limited. The objective of this study is to review outcomes from the Seattle Children's Hospital (SCH) institutional standard therapy for relapsed medulloblastoma, modified from the published ACNS0821 regimen. Methods:Retrospective review of patients treated for relapsed medulloblastoma from 2012-2024 treated with modified ACNS0821 therapy, including combination bevacizumab, irinotecan, and temozolomide, referred to as "TIB." Each TIB cycle includes oral temozolomide (200 mg/m2/day) for the first 5 days, intravenous (IV) bevacizumab (10 mg/kg/dose), and IV irinotecan (125 mg/m2/dose or 340 mg/m2) on days 1 and 15 of each cycle. Patient medical history, prior treatment, therapy toxicity, response, and outcome were collected. The analysis included Kaplan-Meier estimates of 3-year overall survival (OS) and 3-year progression-free survival. Results:Fifteen patients were treated with TIB for relapsed medulloblastoma at SCH (median age 5.81 (0.21-23.6) years, 60% male). Twelve patients completed planned therapy. Therapy was discontinued for toxicity (n = 1) and family preference (n = 1). The most common toxicities were thrombocytopenia (n = 7), neutropenia (n = 4), nausea (n = 5), vomiting (n = 5), and diarrhea (n = 3). Five patients required dose modification of one agent for toxicity. Median follow-up from TIB therapy start was 1.61 (0.47-7.66) years. Three-year OS was 48% (95% CI: 18%-74%) and 3-year event-free survival was 16% (95% CI: 1%-49%). Conclusions:TIB was well-tolerated in pediatric patients with relapsed medulloblastoma, and outcomes were similar to those published in clinical trials. TIB therapy should be considered for patients with relapsed medulloblastoma, especially patients with limited access to care due to travel barriers.

Abstract BACKGROUND Childhood brain tumors remain a leading cause of death with significant treatment-related morbidity and mortality, including disproportionate rates of altered metabolism, neuropathy, and poor quality-of-life. Growth Differentiation Factor 15 (GDF15), a circulating cytokine released by tissue injury, mediates nausea, vomiting, and anorexia, and promotes tumor growth, angiogenesis, and metastasis in adult cancers, predicting worse progression-free survival in adults with low-grade gliomas. Despite adult cancer data, GDF15 remains unexplored in children. Published pilot data demonstrate higher circulating GDF15 in children with cancer compared to healthy controls, but GDF15 expression has not been studied in pediatric brain tumors. We present GDF15 tumor tissue expression with tumor type, grade, metastasis, and progression to inform future study of GDF15’s role in pediatric brain tumors. METHODS Single-center retrospective review of 64 pediatric brain tumor specimens collected through our Precision Genomics Program. GDF15 RNA expression (normalized to ß-actin tissue expression) was log-transformed. Mean GDF15 expression based on diagnosis was compared (using ANOVA) and two-sample t-tests were used to compare metastatic, progressive, and high-grade disease. RESULTS Highest mean GDF15 expression was seen in medulloblastoma (1.96+0.66, N=3) and lowest in low-grade glioma (0.79+0.26, N=27), but groups were not statistically different (p=0.29). GDF15 expression was higher in progressive (1.46+0.22) versus non-progressive disease (0.76+0.24, p=0.04). Although not statistically different, GDF15 expression was higher in high-grade (1.43+0.27) compared to low-grade (1.03+0.21, p=0.24) and metastatic (1.80+0.44) versus non-metastatic disease (1.06+0.17, p=0.08). CONCLUSIONS This ongoing work suggests variable GDF15 expression in different pediatric brain tumors and may suggest GDF15 mediates disease progression. GDF15 may play a role in metastatic or high-grade disease, but further study is needed with larger disease-specific cohorts. We demonstrate feasibility of utilizing existing genomic data and are pursuing further characterizing these potential differences through international public databases (i.e., Children’s Brain Tumor Network).

Abstract Disclosure: D. Chatila: None. L.A. DiMeglio: None. D. Runco: None. N.G. Haddad: None. Introduction Excessive weight gain in childhood brain tumor (CBT) survivors has been documented. We characterized changes in body mass index (BMI) in CBT survivors and studied possible risk factors for excessive weight gain. Objectives 1) Compare BMI z-score at CBT diagnosis to that at time of last clinical follow up, and 2) Correlate BMI and BMI z-score changes with age at diagnosis; tumor location; treatment including radiation therapy (RT), chemotherapy (CT), or both; presence of endocrinopathies. Methods Following IRB approval, we conducted a retrospective chart review of children with CBTs diagnosed between 2005 and 2017. We excluded children with craniopharyngiomas due to their known high risk of obesity. Results 311 patients (177 female) were identified (median age at diagnosis 6y [range 0-18 y], median follow-up duration 6y [range 1-15 y]. Gliomas were the most common CBT type (69%) then medulloblastomas (18%) and germinomas (6%). 77 (25%) of CBTs were suprasellar. 137 patients received RT, 167 had CT, 110 had both, 7 had only surgery. 95 (30%) of children were ultimately diagnosed with a concomitant endocrinopathy. Baseline BMI and BMI z-scores (18.6 ± 4.8; 0.45 ± 1.52) correlated with mean BMI and BMI z-scores at last follow up [22.5 ± 6.4 (r=0.15, p=0.005); 0.67 ± 1.26, (r=0.11, p=0.048)]. BMI z-scores increased significantly over time. Age at diagnosis was not correlated with change in BMI or BMI z-scores. There were no differences in BMI z-scores at last follow-up or change in BMI z-scores between patients who had suprasellar tumors vs those with other tumor locations (BMI z-scores 0.94 ± 1.53 vs 0.60 ± 1.17, p=0.06; change in BMI z-score 0.36 ± 1.95 vs 0.18 ± 1.84, p=0.47). However, patients with a suprasellar tumor location had a lower mean age at diagnosis (5.6 ± 4.2 years vs 7.2 ± 4.2 years p=0.01). There were no differences in BMI z-scores at last follow-up or change in BMI z-score by type of treatment (CT, RT, or surgery alone) nor were there differences in BMI z-scores at last follow-up or change in BMI z-score between patients who did and did not have endocrinopathies (BMI z-score 0.61 ± 1.29 vs 0.70 ± 1.25, p=0.57; change in BMI z-score 0.03 ± 1.95 vs -0.33 ± 1.817, p=0.11) although children with endocrinopathies were older at CBT diagnosis (8.1 ± 4.9 years vs 6.3 ± 4.5 years, p=0.002) and had a longer duration of follow up than patients without endocrinopathies (7.5 ± 3.4 vs 5.7± 3.0 years, p< 0.001). Conclusions In CBT survivors, BMI z-scores increased over time however this change did not correlate with age at diagnosis of CBT, tumor location, type of intervention received, or presence of endocrinopathies. Future studies are needed to evaluate additional risk factors underlying increases in BMI. Presentation: Thursday, June 15, 2023

PURPOSE The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation. MATERIALS AND METHODS Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration. RESULTS In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics. CONCLUSION The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.

BackgroundGrowth differentiation factor 15 (GDF15), an inflammatory marker and mediator of adult cancer cachexia, remains largely unexplored in children. GDF15 increases nausea, vomiting, and anorexia in cancer and contributes to malnutrition, with the potential to be a cachexia therapeutic target. No studies have examined GDF15 in children with newly diagnosed cancer. Our pilot study compares GDF15 in children with newly diagnosed cancer to age- and sex-matched controls and correlates levels with anthropometric measurements and quality of life (QOL).MethodsChildren with newly diagnosed cancer aged 2-21 years were enrolled with serum GDF15 ELISA, anthropometric measures [height, weight, and mid-upper arm circumference (MUAC)], and QOL assessments (using PedsQL™ Core and Gastrointestinal Modules), which were collected at baseline and repeated 3 months later. Serum GDF15 levels were obtained from age- and sex-matched controls for comparison.ResultsA total of 57 participants enrolled (N=30, cancer group; N=27, control group) with a median age of 8.8 years (IQR 5.6-15.9 years). The participants were primarily male (54.4%), white (82.5%), and non-Hispanic (82.5%). Cancer diagnoses included acute lymphoblastic leukemia (N=8), lymphoma (N=8), neuroblastoma (N=5), soft tissue tumors (N=4), acute myeloid leukemia (N=2), and single participants with brain, kidney, and bone tumors. Baseline GDF15 was higher in the cancer cohort compared to the control cohort (median=614.6pg/mL and 320.5pg/mL, respectively; p<0.001). When examining participants with evaluable baseline and 3-month follow-up GDF15 levels (N=18), GDF15 was not statistically different (median=657.1pg/mL and 675.3pg/mL, respectively; p=0.702). A total of 13 of the 30 participants and 21 caregivers completed the PedsQL™ Core and Gastrointestinal symptom modules. QOL scores did not differ significantly at 3-month follow-up compared to baseline, but diarrhea worsened (p=0.017). Median participant response for diarrhea at baseline was 92.9 (IQR=92.9-96.4; N=13), which was significantly better than the follow-up (median=78.6; IQR= 71.4-92.9; p=0.017). There were no correlations between change in height, weight, or MUAC and change in GDF15 levels (p=0.351, 0.920, and 0.269 respectively).ConclusionGDF15 was elevated in children with cancer at diagnosis compared to controls but did not correlate with anthropometric measurements or QOL. This pilot study will inform future prospective studies to better describe the natural history of GDF15 and its role in cachexia and as a potential therapeutic target.

Abstract Purpose Effective, empathic communication is crucial for pediatric oncology clinicians when discussing palliative and end-of-life (PC/EOL) care with parents of children with cancer. Unfortunately, many parents report inadequate communication at these distressing times. This study evaluates the communication skills training (CST) clinicians received to deliver a PC/EOL communication intervention as part of a multi-site randomized-controlled trial (RCT). Methods Clinicians from eight sites formed dyads (one physician and one nurse [RN] or advanced practice provider [APP]) and were trained over 3 days (in-person or virtually). Training was adapted from VitalTalkTM and included didactic instruction, videos, visual aids, and dedicated time to practice with simulated patients. Study participants completed a confidential, post-training online evaluation survey. A self-reported quality assurance checklist was used to measure fidelity to the communication protocol when delivered to parents during the RCT. Results Thirty clinicians completed training; 26 completed post-training surveys including twelve (46.1%) physicians, 8 (30.8%) RNs and 6 (23.1%) APPs. Most were female (65.4%); white (80.8%), not Latinx (88.5%); 40-50 years old (53.9%); and in practice over 10 years (65.4%). Nine (34.6%) trained in-person; the rest trained virtually. Ninety-two percent reported the course was valuable or very valuable for developing their PC/EOL communication skills and 96% reported learning something new. Dyads trained virtually had similar fidelity to those trained in-person (95% and 90% respectively) when delivering the PC/EOL communication intervention to parents. Conclusion This PC/EOL CST was valuable for improving pediatric oncology clinicians’ communication skills, successfully implemented in-person and virtually, and translated effectively into practice.

ObjectivesDespite continued development of targeted therapies for children with cancer, patients continue to experience an array of unwanted side effects. Children with solid tumours may experience constipation as a result of vinca alkaloid therapy, psychological stressors, periods of inactivity and opioid use. Our objective was to investigate the prevalence and treatment of constipation in hospitalised children with solid tumours treated with chemotherapy.MethodsWe retrospectively analysed data from 48 children’s hospitals in the Pediatric Health Information System, extracting patients 0–21 years of age with a solid tumour diagnosis hospitalised from October 2015 through December 2019.ResultsWe identified 13 375 unique patients with a solid tumour diagnosis receiving chemotherapy. Constipation was the most common gastrointestinal complaint with 8658 (64.7%; 95% Cl: 63.9% to 65.5%) having a constipation diagnosis or having received at least two laxatives during admission. Bone cancers had the highest percentage (69.9%) of patients with constipation, while Hodgkin’s lymphoma had the lowest, although 52.1% of patients were affected. A total of 44% (n=35 301) of encounters received an opioid at some point during admission. Of patients receiving constipation medications, the most commonly prescribed was polyethyl glycol (n=25 175, 31.7%), followed by docusate (n=11 297, 14.2%), senna (n=10 325, 13.0%) and lactulose (n=5501, 6.9%).ConclusionsConstipation is the most common gastrointestinal issue that children with solid tumours experience while receiving chemotherapy in the inpatient setting. Increased attention should be given to constipation prophylaxis and treatment in children with solid tumours undergoing chemotherapy, particularly those identified as high risk.

Clinical care and research around cancer cachexia in children is lacking. Cachexia increases treatment-related toxicity and long-term morbidity and potentially affects mortality. We highlight the urgent need for specific focus on childhood cancer cachexia and discuss potential solutions to inform cachexia therapeutics for children.

Background Malnutrition and cachexia during pediatric cancer treatment worsen toxicity and quality-of-life. Clinical practice varies with lack of standard malnutrition definition and nutrition interventions. This scoping review highlights available malnutrition screening and intervention data in childhood cancer and the need for standardizing assessment and treatment. Methods Ovid Medline, CINAHL, and Cochrane Library were searched for studies containing malnutrition as the primary outcome with anthropometric, radiographic, or biochemical measurements. Secondary outcomes included validated nutritional assessment or screening tools. Two authors reviewed full manuscripts for inclusion. Narrative analysis was chosen over statistical analysis due to study heterogeneity. Results The search yielded 234 articles and 17 articles identified from reference searching. Nine met inclusion criteria with six nutritional intervention studies (examining appetite stimulants, nutrition supplementation, and proactive feeding tubes) and three nutritional screening studies (algorithms or nutrition support teams) each with variable measures and outcomes. Both laboratory evaluations (albumin, prealbumin, total protein) and body measurement (weight loss, mid-upper arm circumference) were used. Studies demonstrated improved weight, without difference between formula or appetite stimulant used. Screening studies yielded mixed results on preventing weight loss, weight gain, and survival. Conclusion Our review demonstrated a paucity of evidence for malnutrition screening and intervention in pediatric cancer treatment. While a variety of malnutrition outcomes, interventions, and screening tools exist, nutritional interventions increased weight and decreased complications. Screening tools decreased malnutrition risk and may improve weight gain. Potential age- and disease-specific nutritional benefits and toxicities also exist, further highlighting the benefit of standardizing malnutrition definitions, screening, and interventions.

Clinical care and research around cancer cachexia in children is lack-ing. Cachexia increases treatment -related toxicity and long-term morbidity and potentially affects mortality. We highlight the urgent need for specific focus on childhood cancer cachexia and discuss po-tential solutions to inform cachexia therapeutics for children.

Background Malnutrition during cancer treatment increases treatment-related morbidity and mortality. Our study better characterizes variability in malnutrition identification and treatment by examining nutrition-related diagnoses and support for children with central nervous system (CNS) and non-CNS solid tumors during therapy. We examined diagnosis of malnutrition, use of tube feeding or parenteral nutrition (PN), and appetite stimulants. Methods We retrospectively reviewed 0 to 21-year-old patients in the Pediatric Health Information System from 2015 to 2019. Patients were classified as having (1) billed malnutrition diagnosis, (2) malnutrition diagnosis or using PN and enteral nutrition ("functional malnutrition"), and (3) any previous criteria or prescribed appetite stimulants ("possible malnutrition"), as well as associated risk factors. Results Among 13,375 unique patients, CNS tumors were most common (24.4%). Overall, 26.5% of patients had malnutrition diagnoses, 45.4% met functional malnutrition criteria, and 56.0% had possible malnutrition. Patients with adrenal tumors had highest billed, functional, and possible malnutrition (36.6%, 64.1%, and 69.4%, respectively) followed by CNS tumors (29.1%, 52.4%, and 64.1%). Patients with adrenal tumors had highest rates of PN use (47.4%) and those with CNS tumors had the highest tube feeding use (26.8%). Hospital admissions with malnutrition had a longer hospital length of stay (LOS) (6 vs 3 days, P < 0.0001), more emergency department admissions (24.4% vs 21.8%, P < 0.0001), and more opioid use (58.6% vs 41.4%, P < 0.0001). Conclusions Variability in malnutrition diagnoses hinders clinical care and nutrition research in pediatric oncology. Improving disease-specific recognition and treatment of malnutrition can target nutrition support, ensure appropriate reimbursement, and potentially improve outcomes for children with solid tumors.

Features associated with malnutrition are poorly elucidated in pediatric cancer care. We aimed to better understand characteristics associated with weight-for-height (WHZ) and height-for-age (HAZ) changes for infants and young children during cancer treatment. This retrospective study included 434 patients diagnosed < 3 years old from 2007 to 2015 at a large pediatric cancer center. Patients starting treatment outside our center, those with relapsed or secondary malignancies, or with inaccurate information were excluded. Abstracted weights and heights for a 24-month period after treatment initiation were converted to sex-specific and age-specific z scores. Although not statistically different at baseline, patients with hematologic malignancies gained weight over time, while other tumor types did not. Higher treatment intensity and younger age at diagnosis increased odds of clinically significant weight loss. Older children had higher HAZ at diagnosis and HAZ also significantly decreased over time for all examined risk factors, which is distinctly different from patterns in WHZ over time. In conclusion, WHZ and HAZ are affected differently by cancer treatment in infants and young children. We identify key risk factors for weight loss and growth stunting which will be necessary to develop prospective trials to examine anthropometric, bio-chemical, and patient recorded outcomes around nutrition.

BACKGROUND:Various measures and definitions for undernutrition are used in pediatrics. Younger children treated for cancer are at high risk, but lack well-defined risk-based screening and intervention. METHODS:A retrospective study collected weight longitudinally for patients less than three years-old over two years after initiating cancer treatment. We included those diagnosed 2007-2015 at a large pediatric cancer center. Exclusion criteria included treatment starting outside our system, secondary or relapsed malignancy, or incomplete information. A decrease ≥1 in weight-for-age or weight-for-height z-score signified clinically significant weight loss. Univariate and multivariate models assessed hazards for developing first episode of clinically significant weight loss. RESULTS:Of 372 patients, only 24.6% of patients lost 10% of weight, but 58.6% lost weight-for-age z-score ≥1 and 64.8% lost ≥1 weight-for-height z-score within two years of treatment initiation. Patients who lost weight were younger (median age 15 vs. 24 months, p < 0.001). Compared to patients diagnosed in the first year of life, those diagnosed 24-35 months were less likely to lose weight (HR 0.62, p < 0.001) and lost weight later (median time to weight loss 144 vs. 35 days). Higher treatment intensity increased weight loss risk (HR 2.30, p < 0.001) and decreased time to weight loss (35 vs. 154 days). No differences were found based on sex, diagnosis, enteral or parenteral nutrition, gastroenterology consults, or intensive care admissions. CONCLUSIONS:Using normalized z-scores is more sensitive for identifying weight loss. Younger children are more likely to lose weight with higher intensity cancer therapy. Patient and treatment specific information should be used in risk stratifying weight loss screening and nutritional interventions.