INTRODUCTION:We sought to identify racial/ethnic and neighborhood disparities in acute kidney injury (AKI) in children with acute lymphoblastic or myeloid leukemia (ALL, AML). METHODS:Electronic health record data were retrospectively collected from patients treated for de novo pediatric ALL or AML in the multicenter Leukemia Electronic Abstraction of Records Network. AKI was defined by modified Kidney Disease Improving Global Outcomes criteria. Neighborhood-level resources were defined by the Child Opportunity Level (COL). Prevalence ratios (PRs) for AKI at diagnosis by race/ethnicity and COL were calculated using modified Poisson regression. Cox regression was used to calculate hazard ratios (HRs) of first AKI after initiation of chemotherapy (i.e., "during therapy"). RESULTS:Of 952 ALL patients, Non-Hispanic Black (NHB) ALL patients had significantly increased prevalence of AKI at leukemia diagnosis compared to Non-Hispanic White (NHW) patients in the adjusted model (PR 1.50); there were no significant differences by COL. During ALL therapy overall, NHB patients did not have any significant differences in hazard of AKI by race/ethnicity or COL in adjusted models. Among 168 AML patients, there were no significant differences in AKI at diagnosis by race/ethnicity or COL in AML. During AML therapy overall, NHB patients had significantly higher risk of AKI in both unadjusted (HR 1.95) and adjusted (HR 2.68) models, but no differences by COL. CONCLUSION:NHB patients with ALL had increased risk of AKI at the time of leukemia diagnosis, and NHB patients with AML had significantly increased risk of AKI during therapy. Further studies to identify drivers and interventions that mitigate AKI risk are warranted.

Pediatric brain tumor survivors are known to be at risk for long-term deficits in psychosocial and executive functioning. Few studies focus on patients treated with surgery alone, with sparsely reported long-term outcomes. We aimed to characterize clinical factors that predict adverse outcomes in this population. We identified patients diagnosed with a brain tumor at Texas Children’s Hospital from 2012 to 2019 who were treated with surgical resection alone. Initial assessment occurred within six months of diagnosis and were repeated annually thereafter for three years. We examined the parent-report Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC), including the sub-indices of Behavioral Regulation (BRI) and Metacognition (MI). Furthermore, we examined the parent-report Behavior Assessment System for Children (BASC): Behavioral Symptoms Index (BSI), Externalizing Symptoms (ES), Internalizing Symptoms (IS). Multi-variate analysis was completed with linear mixed modeling to assess the impact of gross total resection (GTR) on our outcome measures. Our analysis included 44 patients aged 3 to 17 years (mean 9.5 years). The most common diagnosis was low grade glioma (29/44, 66%) and the majority underwent GTR of their tumor (37/44, 84%). After controlling for tumor location, pathology, age, sex, and baseline FSIQ, patients who underwent GTR, compared to those who did not, had significantly higher levels of impairment across all time points for global executive function, behavioral regulation, behavioral symptoms, and externalizing symptoms (all comparisons p ≤ 0.01). There was no significant interaction identified over time. Although the medical needs of patient who receive GTR as curative therapy are typically low, children undergoing GTR experience increased executive and behavioral symptoms long-term compared to children undergoing subtotal resections. Our findings highlight the importance of increased psychosocial and neurocognitive monitoring in this vulnerable population to facilitate earlier access to psychological intervention and mitigate these long-term deficits.

Methotrexate is a critical component of pediatric acute lymphoblastic leukemia (ALL) therapy that can result in neurotoxicity which has been associated with an increased risk of relapse. We leveraged machine learning to develop a neurotoxicity risk prediction model in a diverse cohort of children with ALL. We included children (age 2-20 years) diagnosed with ALL (2005-2019) and treated in Texas without pre-existing neurologic disease. Clinical information was obtained by medical record review. Neurotoxicity occurring post-induction and prior to maintenance therapy was defined as neurologic episodes occurring within 21 days of methotrexate. Suspected cases were independently confirmed by 2 pediatric oncologists. Demographic and clinical factors were compared using logistic regression. The dataset was randomly split (80/20) for training and testing. random forest (RF) with boosting and downsampling using 5-repeat, 10-fold cross-validation was used to construct a predictive model. Neurotoxicity developed in 115 (8.7%) of 1325 eligible patients. Several factors including older age at diagnosis (OR = 1.19, 95% CI: 1.15-1.24) and Latino ethnicity (OR = 2.79, 95% CI: 1.83-4.35) were associated with neurotoxicity. The RF had an area under the curve of 0.77 with a train error rate of 0.29 and a test error rate of 0.24. The overall sensitivity was 0.73, and specificity was 0.69. In one of the largest studies of its kind, we developed a novel risk prediction model of methotrexate-related neurotoxicity. Ultimately, a validated model may help guide the development of personalized treatment strategies to reduce the burden of neurotoxicity in children diagnosed with ALL.

Childhood cancer survivors (CCSs) are at increased risk for chronic health issues due to late effects of cancer and its treatment. We address the impact of environmental exposures, such as air pollution, tobacco smoke, extreme weather events, and pesticides, on the health and survival of CCSs. These environmental hazards have been associated with worsening health outcomes and decreased survival among CCSs on a global scale. We also highlight that providers at a major pediatric cancer center in the United States have limited knowledge and practical skills about environmental risk factors and how to reduce exposures. Our survey results show that pediatric oncology providers would find an environmental referral service helpful and useful in their department. Integrating environmental health into pediatric cancer care can empower patients and families, promote healthier behaviors, and potentially reduce morbidity and mortality in this vulnerable population.

There are limited data on the effectiveness of mailed self-collection to increase cervical cancer screening (CCS) participation in underresourced health care settings. To compare the effectiveness of mailed self-collection kits, with and without patient navigation, to telephone reminders to increase CCS in a safety-net health system. This pragmatic, parallel, single-blinded, randomized clinical trial within a publicly funded safety-net health system in Houston, Texas, compared (1) telephone reminder (TR) for clinic-based screening, (2) TR with mailed self-collection (SC), and (3) TR with mailed SC and patient navigation among a random sample of CCS-eligible patients not up to date with CCS, including those with no CCS on record. The trial was conducted from February 20, 2020, to August 31, 2023. All groups received a TR by a patient navigator to attend clinic-based CCS. In the SC and SC with patient navigation groups, participants were additionally mailed a self-collection kit to their home as an alternative to clinic-based CCS. In the SC with patient navigation group, the mailed kit was followed by a patient navigation telephone call. CCS participation was defined as attendance for clinic-based screening or return of a mailed self-collection kit within 6 months of randomization and determined through electronic health record review. Of the 2474 participants in the intent-to-screen analyses (median [IQR] age, 49 [39-57] years), 2325 (94.0%) were from racial or ethnic minoritized populations (1655 [66.9%] identifying as Hispanic or Latino, 82 [3.3%] as non-Hispanic Asian, 535 [21.6%] as non-Hispanic Black or African American, and 53 [2.1%] as other or unknown race, including American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander), and 1388 (56.1%) were covered by the county’s publicly funded financial assistance program. At 6 months, 144 of 828 participants (17.4%) in the TR group, 340 of 828 (41.1%) in the SC group, and 381 of 818 (46.6%) in the SC with patient navigation group had participated in CCS. Compared to TR, relative participation was 2.36 (95% CI, 1.99-2.80) times higher for SC and 2.68 (95% CI, 2.27-3.16) times higher for SC with patient navigation; screening difference was 23.7% (95% CI, 19.4%-27.9%) for SC and 29.2% (95% CI, 24.9%-33.5%) for SC with patient navigation. In this randomized clinical trial in a safety-net health system, SC was effective for increasing CCS participation among underscreened patients; there were modest additional gains from SC with patient navigation. The large increase in CCS participation using SC compared to TR suggest that SC should be considered in safety-net settings with suboptimal CCS coverage. ClinicalTrials.gov Identifier: NCT03898167

BACKGROUND:Children born with a congenital anomaly have a higher risk of developing a brain tumor during childhood or adolescence, but the co-occurrence between specific types of congenital anomalies and specific types of childhood brain tumors (CBTs) is not well described. This study characterized the associations between specific congenital anomalies and CBTs. METHODS:We leveraged a population-based registry linkage study of births (1990-2018), congenital anomalies, and cancer from 9 states (n = 22,599,099 births). Congenital anomalies were classified as major structural without a known chromosomal or genetic syndrome, chromosomal, neurofibromatosis, and/or tuberous sclerosis complex. CBT classification was based on the International Classification of Childhood Cancer for children diagnosed < 20 years. Cox regression analyses were conducted separately by congenital anomaly for anomaly-CBT combinations with at least 5 co-occurring cases. We conducted analyses for any CBT and separately for astrocytoma, atypical teratoid/rhabdoid tumor, ependymoma, medulloblastoma, mixed and unspecified gliomas, and primitive neuroectodermal tumors. RESULTS:There were 6,247 children diagnosed with a CBT. Having any major structural anomaly was associated with risk of any CBT and across all subgroups (aHR range: 1.48-3.69) except ependymoma, particularly among children diagnosed with a tumor by 1 year of age. Of the 66 anomaly-CBT combinations analyzed, 42 were significant (P < .05), including 25 in an earlier version of this study and 16 novel associations (aHR range: 1.46-525). Anomaly-CBT associations also differed by astrocytoma histology. CONCLUSIONS:We observed consistent evidence that having a structural congenital anomaly increases risk of developing a CBT, particularly in infancy, which may provide insights into etiology.

ABSTRACT:Hepatotoxicity is a well-documented complication of induction chemotherapy for acute lymphoblastic leukemia (ALL), but our understanding of its biological mechanisms is limited. We identified 314 patients with ALL (aged 1-19 years) treated at Texas Children's Hospital (2008-2019) with diagnostic bone marrow plasma available for metabolomic profiling: 234 for discovery and 80 for replication. Hepatotoxicity during induction was defined as follows: (1) transaminitis: grade ≥3 aspartate aminotransferase or alanine aminotransferase or (2) conjugated hyperbilirubinemia: conjugated bilirubin (c.bili) >3 mg/dL. Untargeted profiling detected 519 metabolites. Adjusted odds ratios (aORs) for each metabolite were calculated with logistic regression, accounting for sex, age, body mass index, race/ethnicity, and treatment intensity. The population was 56% Latino, 57% male, 92% B-ALL, 25% overweight/obese, and 57% National Cancer Institute standard-risk at a median age of 5 years. Transaminitis was observed in 34% of the discovery and 24% of the replication cohort. Seven instances of c.bili >3 mg/dL were observed in the discovery cohort, with none in the replication cohort. Furthermore, 12 metabolites were associated with transaminitis (P < .05) in the discovery cohort, including 2 that replicated (P < .05): 1,2-dipalmitoyl-glycerophosphocholine (GPC) (aOR combined = 1.88 [95% confidence interval [CI], 1.26-2.79], P = .002) and 1-(1-enyl-palmitoyl)-2-palmitoleoyl-GPC (aOR combined = 1.56 [95% CI: 1.17-2.09], P = .003). In the discovery cohort, 34 metabolites were associated with c.bili >3 mg/dL, including the top association of 1,2-dipalmitoyl-GPC (aOR = 5.76 [95% CI: 2.20-23.16], P = .002). We observed and replicated associations between phosphatidylcholine metabolites at ALL diagnosis and hepatotoxicity during induction therapy, suggesting a potential role for lipid dysregulation in the development of hepatotoxicity.

The 4th Symposium on Childhood Cancer Health Disparities was held at Texas Children's Hospital in Houston, Texas, on September 26, 2023. The symposium registered 94 attendees from different backgrounds (e.g. clinicians, epidemiologists, exposure assessment scientists, geospatial experts) with an interest in environmental health disparities of pediatric cancer susceptibility and treatment outcomes. The focus of the symposium was to provide an overview of the role of environmental risk factors in studies of pediatric cancer, introduce novel exposure assessment tools that can be applied to the field, and highlight opportunities to study the impact of environmental health disparities in pediatric cancer susceptibility and outcomes. This report summarizes the scientific content of the symposium and highlights priorities to advance the field.

HPV self-collection was recently FDA-approved for cervical cancer screening. In the PRESTIS trial, we recently demonstrated a 2.5-fold increase in screening participation among underscreened women in a public safety net health system who received a mailed at-home HPV self- collection kit compared to those who received a standard telephone reminder. However, receipt of clinical follow up among participants with a positive HPV test has not been described. We used data from the PRESTIS randomized clinical trial (n=2,464). Bilingual (English/Spanish) patient navigation was provided to assist participants with a positive HPV test result with scheduling and attending follow up appointments (colposcopy if positive for HPV 16 or 18; triage Pap test if positive for other high-risk types). We summarized receipt of follow-up care in regard to timeliness and demographic characteristics using descriptive and bivariable statistics. Among participants with a positive HPV test result (n=90), 83.3% scheduled a follow up test and 70.0% completed clinical follow up. Among those who attended follow up (n=63), 65.1% received timely follow up within 3 months of their test result; 15.9% and 19.1%, respectively, received follow up between 3-6 months and after 6 months of their test result. Patients who needed colposcopy (n=16) had a higher proportion of follow up (93.8%) compared to those triaged to Pap testing (64.9% of n= 74). Fewer non-Hispanic Black participants (58.6%) attended clinical follow up compared to Hispanic (76.4%) and non-Hispanic White (66.7%) participants. A higher proportion of those with county-funded financial assistance (75.5%) and commercial insurance (65.2%) attended follow up compared with those covered by Medicaid, Medicare, or other insurance plans (53.9%). While mailed self-collection kits can increase cervical screening participation, almost one-third of participants with a positive HPV test did not complete clinical follow-up, despite patient navigation. This underscores the need for additional strategies to address barriers among screen-positive patients to ensure they receive timely and appropriate follow-up care. Graciela Nogueras, Trisha Amboree, Susan Parker, Antonia Marinoni, Matthew Anderson, Susan Hilsenbeck, Shaun Bulsara, Maria Daheri, Maria Jibaja-Weiss, Kathleen Schmeler, Ashish Deshmukh, Elizabeth Chiao, Michael Scheurer, Jane Montealegre. Follow up after a positive HPV test result: Results from the PRESTIS study [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B025.

Emerging evidence suggests genetic ancestry may influence childhood cancer outcomes, but its impact on pediatric rhabdomyosarcoma (RMS) is unknown. We explored genetic ancestry's impact on survival among children with RMS. This multi-center observational cohort study is a secondary analysis of previously collected biobanking, genomic, and clinical data. The study included 920 individuals with newly diagnosed RMS under 40 years of age enrolled from 2005 to 2017 under the COG soft tissue sarcoma biobanking protocol D9902. The primary endpoints were (1) event-free survival (EFS), defined as the time from study enrollment to tumor recurrence/progression, secondary malignancy, or death from any cause; and (2) overall survival (OS), defined as the time from study enrollment to death from any cause. Genetic ancestry was estimated using Grafpop software, and Cox regression assessed the association between genetic ancestry and EFS and OS, considering RMS overall, by fusion status, and by histological subtype. Covariates included sex, age at diagnosis, tumor stage, and histology, except during stratified analyses. In embryonal RMS and PAX3/7:FOXO1 fusion-negative RMS, individuals with South Asian or Asian-Pacific Islander ancestry showed worse EFS (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.07-3.97, p = 0.03 and HR 2.01, 95% CI 1.07-3.76, p = 0.03, respectively) and OS (HR 2.30, 95% CI 1.09-4.84, p = 0.03 and HR 2.33, 95% CI 1.15-4.70, p = 0.020, respectively) compared to those with primarily European genetic ancestry. These findings suggest that genetic ancestry influences survival outcomes within RMS subtypes, and further understanding may improve precision-medicine-based efforts.

Importance:There are limited data on the effectiveness of mailed self-collection to increase cervical cancer screening (CCS) participation in underresourced health care settings. Objective:To compare the effectiveness of mailed self-collection kits, with and without patient navigation, to telephone reminders to increase CCS in a safety-net health system. Design, Setting, and Participants:This pragmatic, parallel, single-blinded, randomized clinical trial within a publicly funded safety-net health system in Houston, Texas, compared (1) telephone reminder (TR) for clinic-based screening, (2) TR with mailed self-collection (SC), and (3) TR with mailed SC and patient navigation among a random sample of CCS-eligible patients not up to date with CCS, including those with no CCS on record. The trial was conducted from February 20, 2020, to August 31, 2023. Interventions:All groups received a TR by a patient navigator to attend clinic-based CCS. In the SC and SC with patient navigation groups, participants were additionally mailed a self-collection kit to their home as an alternative to clinic-based CCS. In the SC with patient navigation group, the mailed kit was followed by a patient navigation telephone call. Main Outcomes and Measures:CCS participation was defined as attendance for clinic-based screening or return of a mailed self-collection kit within 6 months of randomization and determined through electronic health record review. Results:Of the 2474 participants in the intent-to-screen analyses (median [IQR] age, 49 [39-57] years), 2325 (94.0%) were from racial or ethnic minoritized populations (1655 [66.9%] identifying as Hispanic or Latino, 82 [3.3%] as non-Hispanic Asian, 535 [21.6%] as non-Hispanic Black or African American, and 53 [2.1%] as other or unknown race, including American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander), and 1388 (56.1%) were covered by the county's publicly funded financial assistance program. At 6 months, 144 of 828 participants (17.4%) in the TR group, 340 of 828 (41.1%) in the SC group, and 381 of 818 (46.6%) in the SC with patient navigation group had participated in CCS. Compared to TR, relative participation was 2.36 (95% CI, 1.99-2.80) times higher for SC and 2.68 (95% CI, 2.27-3.16) times higher for SC with patient navigation; screening difference was 23.7% (95% CI, 19.4%-27.9%) for SC and 29.2% (95% CI, 24.9%-33.5%) for SC with patient navigation. Conclusions and Relevance:In this randomized clinical trial in a safety-net health system, SC was effective for increasing CCS participation among underscreened patients; there were modest additional gains from SC with patient navigation. The large increase in CCS participation using SC compared to TR suggest that SC should be considered in safety-net settings with suboptimal CCS coverage. Trial Registration:ClinicalTrials.gov Identifier: NCT03898167.

Kaposi sarcoma (KS) is a common childhood cancer in Malawi, but few studies have explored clinical characteristics of relapsed disease. We aimed to characterize clinical patterns of relapse to improve treatment and, ultimately, long-term survival in patients with pediatric KS. A retrospective cohort study was conducted among patients ages <19 years of age at time of KS diagnosis in Lilongwe, Malawi between August 1, 2010 and March 15, 2020. Specifically, emphasis was placed on patients who had relapsed disease and excluded patients with refractory disease or those who died whilst receiving front-line treatment. Salvage therapy typically involved an intensified chemotherapy regimen compared to front-line therapy - namely nonliposomal doxorubicin plus bleomycin/vincristine or paclitaxel monotherapy. One-hundred and ninety patients with pediatric KS were included in this analysis, 50 of whom experienced relapse (26%). Older median age was associated with occurrence of relapse (10 vs. 6.7 years, p-value = 0.004). Median time from diagnosis to first relapse was 10.6 months (range 2.3-49 months). Three-year post-relapse overall survival (OS) for the entire cohort was 60% with a median follow-up time of 4.7 years after relapse. Survival was significantly higher for patients who relapsed with the woody edema clinical phenotype of pediatric KS versus those with visceral/disseminated disease - 3-year OS 79% (95% CI 62-100) vs. 29% (14-61). These data demonstrate potential for continued survival after KS relapse in the pediatric population and identify subsets of high-risk patients. The higher mortality observed in patients with visceral/disseminated KS highlights the need for improved therapeutic strategies.

Purpose Molecular markers increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection. Methods Clinical variables and somatic mutation data for 20 genes from 641 patients with RMS in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The Baseline Clinical (BC) model included treatment location, age, fusion status, and risk group. The Gene Enhanced 2 (GE2) model added TP53 and MYOD1 mutations to the BC predictors. The Gene Enhanced 6 (GE6) model further included NF1, MET, CDKN2A, and MYCN mutations, selected through least absolute shrinkage and selection operator regression. Model performance was assessed using likelihood ratio tests and optimism-adjusted, bootstrapped validation and calibration metrics. Results The GE6 model demonstrated superior predictive performance compared with the BC model (P < .001) and GE2 model (P < .001). The GE6 model achieved the highest discrimination with a time-dependent area under the receiver operating characteristic curve of 0.766. Mutations in TP53, MYOD1, CDKN2A, MET, and MYCN were associated with higher hazards, while NF1 mutation correlated with lower hazard. Individual prognosis predictions varied between models in ways that may suggest different treatments for the same patient. For example, the 5-year EFS for a 10-year-old patient with high-risk, fusion-negative, NF1-positive disease was 50.0% (95% CI, 39 to 64) from BC but 76% (64 to 90) from GE6. Conclusion Incorporating molecular markers into RMS prognosis models improves prognosis predictions. Individualized prognosis predictions may suggest alternative treatment regimens compared with traditional risk-classification schemas. Improved clinical variables and external validation are required before implementing these models into clinical practice.

BACKGROUND:Candida species are the most common cause of invasive fungal disease, and children with hematologic malignancy are at increased risk. Non- albicans Candida (NAC) now account for more than half of all invasive candidiasis (IC) and carry a worse prognosis. We aimed to compare the epidemiology, risk factors, organ dissemination, biomarkers and outcomes in IC based on the species implicated and evaluate trends in antifungal resistance over time. METHODS:Patients 0-18 years of age with hematologic malignancy and IC at 2 centers were included. Fifty-three patients from 2011 to 2022 were identified. Information related to demographics, host and risk factors, Candida species and antifungal susceptibilities, treatment and outcomes was collected via retrospective chart review. Data were analyzed at the species level. RESULTS:The incidence rate of IC was 29 per 1000 patients with leukemia and lymphoma. The median time to infection from diagnosis of malignancy was 38 days. Candida tropicalis (n = 17; 30%) was the most identified species followed by Candida albicans (n = 14; 25%). Patients with C. tropicalis infection were more likely to have dissemination to the eyes ( P = 0.035), spleen ( P = 0.001) and skin ( P = 0.003) than patients with C. albicans or other NAC. Of the 34 patients who underwent dilated retinal examination, 24% (n = 8) had evidence of intraocular candidiasis. Seven of the 8 patients with intraocular disease had prolonged candidemia (3 or more days; P = 0.003). The 12-week crude mortality rate was 16.9%. CONCLUSIONS:NAC, specifically C. tropicalis , accounted for most of the IC in children with hematological malignancies. Screening for intraocular candidiasis continues to play an important role in patients with IC, and future studies are needed to determine if screening can be limited to patients with select risk factors.