Late-onset lymphopenia during radiation is associated with an increased risk of tumor recurrence in newly diagnosed pediatric medulloblastoma.

BACKGROUND: Recent data found a correlation between lymphopenia occurring early during craniospinal radiation therapy (RT) and risk of disease recurrence in newly diagnosed childhood medulloblastoma. However, the population included patients who received chemotherapy prior to or during RT. Here, we investigate the effect of lymphopenia during RT in patients with newly diagnosed pediatric medulloblastoma who were chemotherapy-naïve. PROCEDURE: We analyzed 79 patients with newly diagnosed medulloblastoma (ages 2-21 years) treated between 1997 and 2013 with craniospinal RT. Log-rank tests were used to determine survival differences, and Cox proportional hazards regression was used to assess associations between patient characteristics and lymphopenia with disease recurrence risk. RESULTS: Eighty-three percent of patients (62/75) had grade ≥3 lymphopenia by RT Week 3, with 95% developing grade ≥3 lymphopenia at some point during therapy. There was no difference in incidence of lymphopenia between those who received proton beam RT (93%) versus photon (97%). Twenty-four of 79 (30%) patients developed disease recurrence at an average 27.0 months after diagnosis. There was higher risk of disease recurrence in patients with grade ≥3 lymphopenia during RT Week 4 (log-rank p = .016; Cox p = .03) and Week 5 (log-rank p = .024; Cox p = .032); after adjusting for clinical risk group, only grade ≥3 lymphopenia at Week 4 remained prognostic (Cox p = .04). No correlation was found between risk of tumor recurrence and early lymphopenia (RT Weeks 0-3) or absolute lymphocyte count (ALC) below the median at any time during RT. CONCLUSIONS: Lymphopenia during RT Weeks 4 and 5 correlates with increased risk of tumor recurrence in pediatric patients with newly diagnosed medulloblastoma.

Germline Genetic Testing and Survival Outcomes Among Children With Rhabdomyosarcoma: A Report From the Children's Oncology Group.

Importance: Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma. Objective: To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma. Design, Setting, and Participants: In this cohort study, data were obtained for individuals, aged 0.01-23.23 years, newly diagnosed with rhabdomyosarcoma who were treated across 171 Children's Oncology Group sites from March 15, 1999, to December 8, 2017. Data analysis was performed from June 16, 2021, to May 15, 2023. Exposure: The presence of a CPV in 24 rhabdomyosarcoma-associated cancer-predisposition genes (CPGs) or an expanded set of 63 autosomal-dominant CPGs. Main Outcomes and Measures: Overall survival (OS) and event-free survival (EFS) were the main outcomes, using the Kaplan-Meier estimator to assess survival probabilities and the Cox proportional hazards regression model to adjust for clinical covariates. Analyses were stratified by tumor histology and the fusion status of PAX3 or PAX7 to the FOXO1 gene. Results: In this study of 580 individuals with rhabdomyosarcoma, the median patient age was 5.9 years (range, 0.01-23.23 years), and the male-to-female ratio was 1.5 to 1 (351 [60.5%] male). For patients with CPVs in rhabdomyosarcoma-associated CPGs, EFS was 48.4% compared with 57.8% for patients without a CPV (P = .10), and OS was 53.7% compared with 65.3% for patients without a CPV (P = .06). After adjustment, patients with CPVs had significantly worse OS (adjusted hazard ratio [AHR], 2.49 [95% CI, 1.39-4.45]; P = .002), and the outcomes were not better among patients with embryonal histology (EFS: AHR, 2.25 [95% CI, 1.25-4.06]; P = .007]; OS: AHR, 2.83 [95% CI, 1.47-5.43]; P = .002]). These associations were not due to the development of a second malignant neoplasm, and importantly, patients with fusion-negative rhabdomyosarcoma who harbored a CPV had similarly inferior outcomes as patients with fusion-positive rhabdomyosarcoma without CPVs (EFS: AHR, 1.35 [95% CI, 0.71-2.59]; P = .37; OS: AHR, 1.71 [95% CI, 0.84-3.47]; P = .14). There were no significant differences in outcome by CPV status of the 63 CPG set. Conclusions and Relevance: This cohort study identified a group of patients with embryonal rhabdomyosarcoma who had a particularly poor outcome. Other important clinical findings included that individuals with TP53 had poor outcomes independent of second malignant neoplasms and that patients with fusion-negative rhabdomyosarcoma who harbored a CPV had outcomes comparable to patients with fusion-positive rhabdomyosarcoma. These findings suggest that germline CPV testing may aid in clinical prognosis and should be considered in prospective risk-based clinical trials.

Adaptive, behavioral, and emotional outcomes following postoperative pediatric cerebellar mutism syndrome in survivors treated for medulloblastoma.

OBJECTIVE: Patients who experience postoperative pediatric cerebellar mutism syndrome (CMS) during treatment for medulloblastoma have long-term deficits in neurocognitive functioning; however, the consequences on functional or adaptive outcomes are unknown. The purpose of the present study was to compare adaptive, behavioral, and emotional functioning between survivors with and those without a history of CMS. METHODS: The authors examined outcomes in 45 survivors (15 with CMS and 30 without CMS). Comprehensive neuropsychological evaluations, which included parent-report measures of adaptive, behavioral, and emotional functioning, were completed at a median of 2.90 years following craniospinal irradiation. RESULTS: Adaptive functioning was significantly worse in the CMS group for practical and general adaptive skills compared with the group without CMS. Rates of impairment in practical, conceptual, and general adaptive skills in the CMS group exceeded expected rates in the general population. Despite having lower overall intellectual functioning, working memory, and processing speed, IQ and related cognitive processes were uncorrelated with adaptive outcomes in the CMS group. No significant group differences or increased rates of impairment were observed for behavioral and emotional outcomes. CONCLUSIONS: Survivors with CMS, compared with those without CMS, are rated as having significant deficits in overall or general adaptive functioning, with specific weakness in practical skills several years posttreatment. Findings from this study demonstrate the high risk for ongoing functional deficits despite acute recovery from symptoms of CMS, highlighting the need for intervention to mitigate such risk.

Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis.

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor ß1, adipsin, fetuin-A, interleukin-1 ß, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.

PM2.5, vegetation density, and childhood cancer: a case-control registry-based study from Texas 1995-2011.

BACKGROUND: Air pollution is positively associated with some childhood cancers while greenness is inversely associated with some adult cancers. The interplay between air pollution and greenness in childhood cancer etiology is unclear. We estimated the association between early life air pollution and greenness exposure and childhood cancer in Texas (1995-2011). METHODS: We included 6,101 cancer cases and 109,762 controls (aged 0-16 years). We linked residential birth address to census tract annual average particulate matter ≤2.5 µg/m³ (PM2.5) and Normalized Difference Vegetation Index (NDVI). We estimated odds ratios (OR) and 95% confidence intervals (95% CI) between PM2.5/NDVI interquartile range increases and cancer. We assessed statistical interaction between PM2.5 and NDVI (likelihood ratio tests). RESULTS: Increasing residential early life PM2.5 exposure was associated with all childhood cancers (OR 1.10, 95% CI: 1.06-1.15), lymphoid leukemias (OR: 1.15, 95% CI: 1.07-1.23), Hodgkin lymphomas (OR: 1.27, 95% CI: 1.02-1.58), non-Hodgkin lymphomas (OR: 1.24, 95% CI: 1.02-1.51), ependymoma (OR: 1.27, 95% CI: 1.01-1.60) and others. Increasing NDVI exposure was inversely associated with ependymoma (0-4-year-old OR: 0.75, 95% CI: 0.58-0.97) and medulloblastoma (OR: 0.75, 95% CI: 0.62-0.91), but positively associated with malignant melanoma (OR: 1.75, 95% CI: 1.23-2.47) and Langerhans cell histiocytosis (OR: 1.56, 95% CI: 1.07-2.28). There was evidence of statistical interaction between NDVI and PM2.5 (p < .04) for all cancers. DISCUSSION: Increasing early life exposure to PM2.5 increased the risk of childhood cancers. NDVI decreased risk of two cancers yet increased risk of others. These findings highlight the complexity between PM2.5 and NDVI in cancer etiology.

Impact of environment on pediatric and adult brain tumors: The 2023 Brain Tumor Epidemiology Consortium meeting report.

The Brain Tumor Epidemiology Consortium (BTEC) is an international organization with membership of individuals from the scientific community with interests related to brain tumor epidemiology including surveillance, classification, methodology, etiology, and factors associated with morbidity and mortality. The 2023 annual BTEC meeting entitled "Impact of Environment on Pediatric and Adult Brain Tumors" was held in Lexington, KY, USA on May 22 - 24, 2023. The meeting gathered scientists from the United States, Canada, Australia, and Europe and included four keynote sessions covering genomic, epigenomic, and metabolomic considerations in brain tumor epidemiology, cancer clusters, environmental risk factors, and new approaches to cancer investigation. The meeting also included three abstract sessions and a brainstorming session. A summary of the meeting content is included in this report.

Risk factors for childhood brain tumours: A systematic review and meta-analysis of observational studies from 1976 to 2022.

BACKGROUND: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention. METHODS: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, during pregnancy and/or during post-natal period. Random effects meta-analysis was used to estimate summary effect sizes (ES) and 95% confidence intervals (CIs). We also quantified heterogeneity (I2) across studies. FINDINGS: A total of 4040 studies were identified, of which 181 studies (85 case-control and 96 cohort studies) met our criteria for inclusion. Of all eligible studies, 50% (n = 91) were conducted in Europe, 32% (n = 57) in North America, 9% (n = 16) in Australia, 8% (n = 15) in Asia, 1% (n = 2) in South America, and none in Africa. We found associations for some modifiable risk factors including childhood domestic exposures to insecticides (ES 1.44, 95% CI 1.20-1.73) and herbicides (ES 2.38, 95% CI 1.31-4.33). Maternal domestic exposure to insecticides (ES 1.45, 95% CI 1.09-1.94), maternal consumption of cured meat (ES 1.51, 95% CI 1.05-2.17) and coffee ≥ 2 cups/day (ES 1.45, 95% 95% CI 1.07-1.95) during pregnancy, and maternal exposure to benzene (ES 2.22; 95% CI 1.01-4.88) before conception were associated with CBTs in case-control studies. Also, paternal occupational exposure to pesticides (ES 1.48, 95% CI 1.23-1.77) and benzene (ES 1.74, 95% CI 1.10-2.76) before conception and during pregnancy were associated in case-control studies and in combined analysis. On the other hand, assisted reproductive technology (ART) (ES 1.32, 95% CI 1.05-1.67), caesarean section (CS) (ES 1.12, 95% CI 1.01-1.25), paternal occupational exposure to paint before conception (ES 1.56, 95% CI 1.02-2.40) and maternal smoking > 10 cigarettes per day during pregnancy (ES 1.18, 95% CI 1.00-1.40) were associated with CBT in cohort studies. Maternal intake of vitamins and folic acid during pregnancy was inversely associated in cohort studies. Hormonal/infertility treatment, breastfeeding, child day-care attendance, maternal exposure to electric heated waterbed, tea and alcohol consumption during pregnancy were among those not associated with CBT in both case-control and cohort studies. CONCLUSION: Our results should be interpreted with caution, especially as most associations between risk factors and CBT were discordant between cohort and case-control studies. At present, it is premature for any CBT to define specific primary prevention guidelines.

Self-Sampling for Human Papillomavirus Testing: Acceptability in a U.S. Safety Net Health System.

INTRODUCTION: Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system. METHODS: A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to date on screening. Participants were asked about barriers to provider-performed screening. Kit users and nonusers were asked about their experiences. RESULTS: Prevalent barriers to provider-performed screening included perceived discomfort of pelvic examination (69.4%), being uncomfortable with male providers (65.4%), and embarrassment (57.0%). Among participants who reported using the mailed kit (n=164), most reported good experiences (84.8%). Most reported self-sampling as more/equally convenient (89.0%), less/equally embarrassing (99.4%), and less/equally stressful (95.7%) than provider-performed screening. Among kit nonusers (n=43), reasons for not using the kit included forgetting about it (76.7%), preferring provider-performed screening (76.7%), and fearing cancer (67.4%). CONCLUSIONS: Prospective Evaluation of Self-Testing to Increase Screening trial participants generally had a positive experience with self-sampling for human papillomavirus testing. Increased comfort and reduced embarrassment/anxiety with self-sampling are relevant attributes because these were the most prevalent reported barriers to provider-performed screening. High acceptability suggests potentially high uptake when self-sampling for human papillomavirus testing receives regulatory approval and is available in safety net health systems.

A comprehensive analysis of neuroblastoma incidence, survival, and racial and ethnic disparities from 2001 to 2019.

BACKGROUND: We characterize the incidence and 5-year survival of children and adolescents with neuroblastoma stratified by demographic and clinical factors based on the comprehensive data from United States Cancer Statistics (USCS) and the National Program of Cancer Registries (NPCR). METHODS: We analyzed the incidence of neuroblastoma from USCS (2003-2019) and survival data from NPCR (2001-2018) for patients less than 20 years old. Incidence trends were calculated by average annual percent change (AAPC) using joinpoint regression. Differences in relative survival were estimated comparing non-overlapping confidence intervals (CI). RESULTS: We identified 11,543 primary neuroblastoma cases in USCS. Age-adjusted incidence was 8.3 per million persons [95% CI: 8.2, 8.5], with an AAPC of 0.4% [95% CI: -0.1, 0.9]. Five-year relative survival from the NPCR dataset (n = 10,676) was 79.7% [95% CI: 78.9, 80.5]. Patients aged less than 1 year had the highest 5-year relative survival (92.5%). Five-year relative survival was higher for non-Hispanic White patients (80.7%) or Hispanic patients (80.8%) compared to non-Hispanic Black patients (72.6%). CONCLUSION: Neuroblastoma incidence was stable during 2003-2019. Differences in relative survival exist by sex, age, race/ethnicity, and stage; patients who were male, older, non-Hispanic Black, or with distant disease had worse survival. Future studies could seek to assess the upstream factors driving disparities in survival, and evaluate interventions to address inequities and improve survival across all groups.

Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Role of non-chromosomal birth defects on the risk of developing childhood Hodgkin lymphoma: A Children's Oncology Group study.

BACKGROUND: Non-chromosomal birth defects are an important risk factor for several childhood cancers. However, these associations are less clear for Hodgkin lymphoma (HL). Therefore, we sought to more fully elucidate the association between non-chromosomal birth defects and HL risk. PROCEDURE: Information on cases (n = 517) diagnosed with HL (ages of 0-14) at Children's Oncology Group Institutions for the period of 1989-2003 was obtained. Control children without a history of cancer (n = 784) were identified using random digit dialing and individually matched to cases on sex, race/ethnicity, age, and geographic location. Parents completed comprehensive interviews and answered questions including whether their child had been born with a non-chromosomal birth defect. To test the association between birth defects and HL risk, conditional logistic regression was applied to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Children born with any non-chromosomal birth defect were not more likely to be diagnosed with HL at 0-14 years of age (aOR: 0.91; 95% CI: 0.69-1.21). No associations were detected between major or minor birth defects and HL (aOR: 1.34; 95% CI: 0.67-2.67 and aOR: 0.88; 95% CI: 0.57-1.34, respectively). Similarly, no association was observed for children born with any birth defect and EBV-positive HL (aOR: 0.57; 95% CI: 0.25-1.26). CONCLUSIONS: Previous assessments of HL in children with non-chromosomal birth defects have been limited. Using data from the largest case-control study of HL in those <15 years of age, we did not observe strong associations between being born with a birth defect and HL risk.

Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease.

BACKGROUNDKaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown.METHODSThis was a cross-sectional study. All cases were confirmed by IHC for KS-associated herpesvirus (KSHV) LANA protein. Baseline blood samples were profiled for HIV and KSHV genome copy numbers by qPCR and secreted cytokines by ELISA. Biopsies were characterized for viral and human transcription, and KSHV genomes were determined when possible.RESULTSSeventy participants with pediatric KS were enrolled between June 2013 and August 2019 in Malawi and compared with adult patients with KS. They exhibited high KSHV genome copy numbers and IL-6/IL-10 levels. Four biopsies (16%) had a viral transcription pattern consistent with lytic viral replication.CONCLUSIONThe unique features of pediatric KS may contribute to the specific clinical manifestations and may direct future treatment options.FUNDINGUS National Institutes of Health U54-CA-254569, PO1-CA019014, U54-CA254564, RO1-CA23958.

Incidental detection of FGFR3 fusion via liquid biopsy leading to earlier diagnosis of urothelial carcinoma.

The rising utilization of circulating tumor DNA (ctDNA) assays in Precision Oncology may incidentally detect genetic material from secondary sources. It is important that such findings are recognized and properly leveraged for both diagnosis and monitoring of response to treatment. Here, we report a patient in whom serial cell-free DNA (cfDNA) monitoring for his known prostate adenocarcinoma uncovered the emergence of an unexpected FGFR3-TACC3 gene fusion, a BRCA1 frameshift mutation, and other molecular abnormalities. Due to the rarity of FGFR3 fusions in prostate cancer, a workup for a second primary cancer was performed, leading to the diagnosis of an otherwise-asymptomatic urothelial carcinoma (UC). Once UC-directed treatment was initiated, the presence of these genetic abnormalities in cfDNA allowed for disease monitoring and early detection of resistance, well before radiographic progression. These findings also uncovered opportunities for targeted therapies against FGFR and BRCA1. Overall, this report highlights the multifaceted utility of longitudinal ctDNA monitoring in early cancer diagnosis, disease prognostication, therapeutic target identification, monitoring of treatment response, and early detection of emergence of resistance.

A novel tailed primer nucleic acid test for detection of HPV 16, 18 and 45 DNA at the point of care.

Cervical cancer is a leading cause of death for women in low-resource settings despite being preventable through human papillomavirus (HPV) vaccination, early detection, and treatment of precancerous lesions. The World Health Organization recommends high-risk HPV (hrHPV) as the preferred cervical cancer screening strategy, which is difficult to implement in low-resource settings due to high costs, reliance on centralized laboratory infrastructure, and long sample-to-answer times. To help meet the need for rapid, low-cost, and decentralized cervical cancer screening, we developed tailed primer isothermal amplification and lateral flow detection assays for HPV16, HPV18, and HPV45 DNA. We translated these assays into a self-contained cartridge to achieve multiplexed detection of three hrHPV genotypes in a disposable cartridge. The developed test achieves clinically relevant limits of detection of 50-500 copies per reaction with extracted genomic DNA from HPV-positive cells. Finally, we performed sample-to-answer testing with direct lysates of HPV-negative and HPV-positive cell lines and demonstrated consistent detection of HPV16, HPV18, and HPV45 with 5000-50,000 cells/mL in < 35 min. With additional optimization to improve cartridge reliability, incorporation of additional hrHPV types, and validation with clinical samples, the assay could serve as a point-of-care HPV DNA test that improves access to cervical cancer screening in low-resource settings.

Assessing Risk for Complications in Acute Hematogenous Osteomyelitis in Children: Validation of 2 Predictive Scores.

BACKGROUND: Acute hematogenous osteomyelitis (AHO) can be associated with severe complications which can be difficult to predict in the clinical setting. The previously published predictive acute complication score ("A-SCORE") and chronic complication score ("C-SCORE") show promise, however, further external validation is needed. METHODS: We performed a retrospective study of 418 children with AHO and analyzed the performance of A-SCORE (variables included bone abscess, fever after 48 h of starting antibiotics, suppurative arthritis, disseminated disease, and delayed source control) to predict risk for acute complicated course (treatment failure, prolonged admission, and/or need for ≥2 bone debridements) and C-SCORE (includes disseminated disease, bone debridement, and CRP ≥10 mg/dL at 2-4 days after starting antibiotics) to predict chronic complications (growth restriction, pathologic fracture, chronic osteomyelitis, avascular necrosis, joint deformity, and/or frozen joint). RESULTS: An acute complicated course occurred in 106/418 (25.4%); 51/380 (13.5%) with complete follow-up data had a chronic complication. The A-SCORE performed with similar specificity (78%) and negative predictive value (NPV) (92%), and higher sensitivity (81%) and increased area under the receiver operating curve (AUC) (0.87) in our population. The C-SCORE performed with similar sensitivity (64%) and NPV (94%) but had lower specificity (86%) and AUC (0.71) than originally reported. Other variables associated with development of complications such as tibia involvement and bacteremia ≥2 days were identified but did not result in significantly improved predictive scores. CONCLUSIONS: Predictive A-SCORE and C-SCORE for AHO complications in children may help guide acute management and long-term follow-up decisions. Prospective studies are needed to determine their applicability.

Bringing CAR T cell therapy trials to underserved populations.

There is a critical need for equitable access to cell therapies in cancer treatment, particularly within public safety-net healthcare systems that serve minority and socioeconomically disadvantaged populations. We discuss how the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine is piloting a cell therapy program aimed at addressing cancer care disparities and has the potential to serve as a national model for enhancing health equity in cancer care.

Acute and chronic kidney injury during therapy for pediatric acute leukemia: A report from the Leukemia Electronic Abstraction of Records Network (LEARN).

Children with acute leukemia are at increased risk of kidney injury. Using electronic health record data from three centers between 2010 and 2018, this study retrospectively described acute kidney injury (AKI) and chronic kidney disease (CKD) prevalence in children with acute lymphoblastic or myeloid leukemia (ALL, AML) using Common Terminology Criteria for Adverse Events (CTCAE) and Kidney Disease Improving Global Outcomes (KDIGO) definitions. AKI during therapy was 25% (ALL) and 32% (AML) using CTCAE, versus 84% (ALL) and 74% (AML) using KDIGO. CKD prevalence was low and Grade 1/Stage 2. Further investigation is needed to optimally define kidney injury in acute leukemia.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

PURPOSE: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. METHODS: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. RESULTS: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. CONCLUSION: Our data suggest that breastfeeding does not protect against CBT.

Children's Oncology Group's 2023 blueprint for research: Epidemiology.

The Children's Oncology Group (COG) Epidemiology Committee has a primary focus on better understanding the etiologies of childhood cancers. Over the past 10 years, the committee has leveraged the Childhood Cancer Research Network, and now more recently Project:EveryChild (PEC), to conduct epidemiologic assessments of various childhood cancers, including osteosarcoma, neuroblastoma, germ cell tumors, Ewing sarcoma, rhabdomyosarcoma, and Langerhans cell histiocytosis. More recent studies have utilized questionnaire data collected as part of PEC to focus on specific characteristics and/or features, including the presence of congenital disorders and the availability of stored cord blood. Members of the COG Epidemiology Committee have also been involved in other large-scale National Institutes of Health efforts, including the Childhood Cancer Data Initiative and the Gabriella Miller Kids First Pediatric Research Program, which are improving our understanding of the factors associated with childhood cancer risk. Future plans will focus on addressing questions surrounding health disparities, utilizing novel biospecimens in COG epidemiology studies, exploring the role of environmental factors on the etiologies and outcomes of childhood cancer, collaborating with other COG committees to expand the role of epidemiology in childhood cancer research, and building new epidemiologic studies from the Molecular Characterization Initiative-all with the ultimate goal of developing novel prevention and intervention strategies for childhood cancer.