Childhood Cancer Research Articles

Feasibility of telehealth exercise and nicotinamide riboside supplementation in survivors of childhood cancer at risk for diabetes: A pilot randomized controlled trial.

Childhood cancer survivors (CCS) have a 50% higher risk of diabetes mellitus (DM) compared with the general population. Interventions in survivors with prediabetes (fasting glucose 100-125mg/dL or hemoglobin A1c 5.7%-6.4%) may mitigate the development of DM and its attendant morbidity, but there is limited information on the feasibility of secondary prevention in this setting. This 6-week pilot feasibility 1:1 randomized controlled trial enrolled 20 CCS on a structured telehealth exercise program±nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor. Feasibility metrics were: (1)≥50% of eligible CCS enrolled onto study; (2)≥70% of participants completed baseline and end-of-study assessments; (3)≥70% compliance with exercise and NR. Secondary endpoints included changes in biomarkers associated with glucose homeostasis and muscle health. Median age (years) at cancer diagnosis was 16.5 (range, 1.5-21.5) and 35.5 (range, 18.0-67.0) at study enrollment. Enrollment rate was 87%, and 85% of participants completed baseline and end-of-study assessments. The mean percentage of exercise sessions completed was 86.6%; NR compliance was>90%. There were no severe adverse events attributable to study interventions. Secondary endpoints were not significantly different between study arms at study completion. Myostatin decrease was observed in participants who completed a higher median number of exercise sessions and was associated with decreased intramuscular adipose tissue and increased lower extremity muscle cross-sectional area. A telehealth exercise intervention±NR supplementation was feasible in CCS with prediabetes. Future studies in larger cohorts may be needed to evaluate their beneficial effects on muscle health and DM risk among CCS.

Association of Family-Centered Care With Psychological Distress Among Caregivers of Children With Cancer at a Tertiary-Level Hospital in Ethiopia: Cross-Sectional Study.

Psychological distress (PD) is a common mental health problem faced by caregivers of children with cancer. The involvement of families in childcare was found to be associated with lower levels of distress. The study aims to determine the associations between family-centered care (FCC) and PD among caregivers of children with cancer receiving treatment at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. An institution-based, cross-sectional study was conducted from June to December 2022. Caregivers of children with cancer aged 0-14 years receiving cancer treatment at the pediatric oncology unit completed a face-to-face, interviewer-administered, structured questionnaire during a routine inpatient or outpatient visit. The questionnaire included questions on the characteristics of the child and caregiver, PD (measured by the Kessler Psychological Distress Scale [K10]), FCC (measured by the Measure of Processes of Care [MPOC-20]), and social support (measured by the Oslo-3 Social Support Scale [OSS-3]). Data were collected using the Kobo toolbox and exported to SPSS (version 26; IBM Corp) for cleaning and analysis. A multivariable logistic regression model was used. An odds ratio with a 95% CI was calculated, and a P value less than .05 was considered statistically significant. A total of 384 caregivers of children with cancer participated in the study. The total PD score ranged from 10 to 50, with a mean score of 17.30 (SD 8.96; 95% CI 16.84-18.60). The proportion of caregivers found to have mild, moderate, and severe levels of PD was 43 (11.2%), 35 (9.1%), and 51 (13.3%), respectively. The overall prevalence of mild to severe PD symptoms was 33.6% (95% CI 28.9%-38.3%). A statistically significant negative association was found between FCC and PD (adjusted odds ratio [AOR] 0.68, 95% CI 0.53-0.86). In addition, having no formal education (AOR 2.87, 95% CI 1.28-6.45), having a history of relapse (AOR 3.24, 95% CI 1.17-9.02), beginning cancer treatment at TASH (AOR 2.82, 95% CI 1.4-4.85), beginning treatment within the last 3 months (AOR 3.99, 95% CI 1.73-9.23), and beginning treatment within the last 4 to 18 months (AOR 2.68, 95% CI 1.25-5.76) were significantly associated with higher level of PD. A total of 1 in 3 caregivers have reported PD. FCC was found to be protective of PD. The finding of this study suggests the need for FCC intervention to improve the mental health condition of caregivers. In addition, the intervention needs to consider the educational status of the caregivers, the time since the cancer diagnosis, and the history of relapse.

Frequency of polymorphisms in the IKZF1 and CDKN2A/2B genes and descriptive analysis in pediatric patients with acute lymphoblastic leukemia: a multicenter hospital-based prevalence study in Rio De Janeiro

BackgroundAcute lymphoblastic leukemia (ALL) is the most common childhood cancer, and B-cell ALL (B-ALL) is the most common subtype. The understanding of ALL has advanced significantly in recent years due to genomic sequencing, which has made it possible to identify genetic variants and detect the association between “single nucleotide polymorphisms” (SNP) and certain diseases.MethodsWe evaluated 126 patients diagnosed with B-ALL in hospitals in Rio de Janeiro. We described the frequency of polymorphisms in the IKZF1, CDKN2A/2B genes, the contribution of these genetic variants in pediatric ALL, and compared them with the general population of Rio de Janeiro.ResultsWe demonstrated that the SNPs rs3731217, rs4132601, and rs11978267 were more frequent in patients with B-ALL.ConclusionsThese findings contribute to a more complete understanding of B-ALL. They can guide future studies, bringing new perspectives on personalized therapies with reduced side effects and optimization efficacy of B-ALL treatment in children.

The implementation of molecular tumor profiling in the practice of pediatric cancer pathology: The pathologists' experience.

The increased accessibility and utilization of molecular testing including next-generation sequencing (NGS) has impacted the practice of pediatric pathology, with diagnostic, prognostic, and therapeutic implications for our patients. This survey is the first to describe the utilization of molecular testing in the routine practice of pediatric pathology for the care of children with known or suspected solid tumors. The Society for Pediatric Pathology Practice Committee distributed a survey to our membership asking 25 questions about training, practice setting, molecular ordering practices, and barriers to testing. Seventy-five pathologists responded to the survey. The survey provides valuable insight into the current use of molecular testing for the care of children with known or suspected solid tumors. Most respondents reported that they are increasingly using a variety of molecular techniques, with increased use over time, and that NGS is useful. These results highlight a variety of barriers to molecular testing, including cost, insurance coverage, turnaround time, limitations of available assays (including limited coverage of pediatric-specific alterations), and difficulty in determining the most appropriate test to order. These data may be useful in supporting pediatric pathologists in their practice.

The Effects of Having a Child with Cancer on Parental Psychology: A Cross-Sectional Study

Objective: In childhood cancers, parents are affected psychologically as well as children. We aimed to evaluate the effect of childhood cancer type and stage, as well as elapsed time from diagnosis, on the anxiety and stress indicators among parents. Materials and Methods: Patients aged between 0–18 years and diagnosed with cancer who were receiving chemotherapy (0–1 month, 1–6 month, 6–12 month) and completed treatment were included. Parents of those children (mother or father) who agreed to participate this study were also included. The personal information form and three psychological assessment scales (Beck Hopelessness Scale (PSS), Psychological Resilience Scale (PRS), Uncertainty Intolerance Scale (IUS)) were used for assessment of mental health of the parents. Scores of the scales and clinical features of the children with cancer were compared statistically. Results: The study included 84 parents (57 mothers, 27 fathers) and 84 children. The rate of children with solid tumors was 60% (n:50) and 40% of them were metastatic, which means advanced stage. The rate of the children with leukemia was 40% (n:34) and 23% of them were in high-risk group. According to the type (leukemia vs. solid tumors) and stage (high risk/advanced stage vs. others) of the cancer, there was no statistical difference among parents in the psychological scales (p > 0.05). Additionally, results of the psychological scales showed no significant difference between mothers and fathers (p > 0.05). The hopelessness scores are significantly higher among parents whose child’s treatment is terminated compared with those whose active therapy is ongoing, and resilience scores are higher among parents who have less than 1 month since diagnosis of childhood cancer than later periods. Conclusions: The regular assessment of mental health among parents of children with cancer across all the survivorship trajectory: at the time of diagnosis, during active therapy, and after treatment.

Building a machine learning-assisted echocardiography prediction tool for children at risk for cancer therapy-related cardiomyopathy

BackgroundDespite routine echocardiographic surveillance for childhood cancer survivors, the ability to predict cardiomyopathy risk in individual patients is limited. We explored the feasibility and optimal processes for machine learning-enhanced cardiomyopathy prediction in survivors using serial echocardiograms from five centers.MethodsWe designed a series of deep convolutional neural networks (DCNNs) for prediction of cardiomyopathy (shortening fraction ≤ 28% or ejection fraction ≤ 50% on two occasions) for at-risk survivors ≥ 1-year post initial cancer therapy. We built DCNNs with four subsets of echocardiographic data differing in timing relative to case (survivor who developed cardiomyopathy) index diagnosis and two input formats (montages) with differing image selections. We used holdout subsets in a 10-fold cross-validation framework and standard metrics to assess model performance (e.g., F1-score, area under the precision-recall curve [AUPRC]). Performance of the input formats was compared using a combined 5 × 2 cross-validation F-test.ResultsThe dataset included 542 pairs of montages: 171 montage pairs from 45 cases at time of cardiomyopathy diagnosis or pre-diagnosis and 371 pairs from 70 at-risk survivors who didn’t develop cardiomyopathy during follow-up (non-case). The DCNN trained to distinguish between non-case and time of cardiomyopathy diagnosis or pre-diagnosis case montages achieved an AUROC of 0.89 ± 0.02, AUPRC 0.83 ± 0.03, and F1-score: 0.76 ± 0.04. When limited to smaller subsets of case data (e.g., ≥ 1 or 2 years pre-diagnosis), performance worsened. Model input format did not impact performance accuracy across models.ConclusionsThis methodology is a promising first step toward development of a DCNN capable of accurately differentiating pre-diagnosis versus non-case echocardiograms to predict survivors more likely to develop cardiomyopathy.Graphical

Repurposing of c-MET Inhibitor Tivantinib Inhibits Pediatric Neuroblastoma Cellular Growth

Background: Dysregulation of receptor tyrosine kinase c-MET is known to promote tumor development by stimulating oncogenic signaling pathways in different cancers, including pediatric neuroblastoma (NB). NB is an extracranial solid pediatric cancer that accounts for almost 15% of all pediatric cancer-related deaths, with less than a 50% long-term survival rate. Results: In this study, we analyzed a large cohort of primary NB patient data and revealed that high MET expression strongly correlates with poor overall survival, disease progression, relapse, and high MYCN levels in NB patients. To determine the effects of c-MET in NB, we repurposed a small molecule inhibitor, tivantinib, and found that c-MET inhibition significantly inhibits NB cellular growth. Tivantinib significantly blocks NB cell proliferation and 3D spheroid tumor formation and growth in different MYCN-amplified and MYCN-non-amplified NB cell lines. Furthermore, tivantinib blocks the cell cycle at the G2/M phase transition and induces apoptosis in different NB cell lines. As expected, c-MET inhibition by tivantinib inhibits the expression of multiple genes in PI3K, STAT, and Ras cell signaling pathways. Conclusions: Overall, our data indicate that c-MET directly regulates NB growth and 3D spheroid growth, and c-MET inhibition by tivantinib may be an effective therapeutic approach for high-risk NB. Further developing c-MET targeted therapeutic approaches and combining them with current therapies may pave the way for effectively translating novel therapies for NB and other c-MET-driven cancers.

RELATO DE EXPERIÊNCIA: UM OLHAR HUMANIZADO COM PACIENTES ONCOLÓGICOS PEDIÁTRICOS NO SETOR DA ENFERMARIA

The objective of this work is to report the experience and describe the monitoring of pediatric oncology patients during their hospitalization carried out during the Mandatory Supervised Curricular Internship I. This is a descriptive, qualitative study of the experience report type, about the experience of the student covering the description of the discipline, internship field, activities carried out, challenges and personal and professional impact during the monitoring of pediatric oncology patients during their hospitalization, in the Mandatory Curricular Internship (ECS) l in the ninth period of the Nursing degree. The practice of supervised internship in health is a crucial stage in the academic training and professional development of students. Provides valuable opportunities to develop practical skills and apply theoretical knowledge in real situations. The work experience in the pediatrics sector also contributed to broadening their perspectives for a possible follow-up in the area and improving skills such as critical and reflective reasoning, decision-making and leadership, which are important for success in professional life.

A hybrid detection model for acute lymphocytic leukemia using support vector machine and particle swarm optimization (SVM-PSO).

Leukemia, a hematological disease affecting the bone marrow and white blood cells (WBCs), ranks among the top ten causes of mortality worldwide. Delays in decision-making often hinder the timely application of suitable medical treatments. Acute lymphoblastic leukemia (ALL) is one of the primary forms, constituting approximately 25% of childhood cancer cases. However, automated ALL diagnosis is challenging. Recently, machine learning (ML) has emerged as an important tool for building detection models. In this study, we present a hybrid detection model that improves the accuracy of the detection process by combining support vector machine (SVM) and particle swarm optimization (PSO) approaches to automatically identify ALL. We use SVM to represent a two-dimensional image and complete the classification process. PSO is employed to enhance the performance of the SVM model, reducing error rates and enhancing result accuracy. The input images are obtained from two public datasets (ALL-IDB1 and ALL-IDB2), and public online datasets are utilized for training and testing the proposed model. The results indicate that our hybrid SVM-PSO model has high accuracy, outperforming stand-alone algorithms and demonstrating superior performance, an enhanced confusion matrix, and a higher detection rate. This advancement holds promise for enhancing the quality of technical software in the medical field using machine learning.

BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas.

Pediatric diffuse midline gliomas (pDMG) are an aggressive type of childhood cancer with a fatal outcome. Their major epigenetic determinism has become clear, notably with the identification of K27M mutations in histone H3. However, the synergistic oncogenic mechanisms that induce and maintain tumor cell phenotype have yet to be deciphered. In 20 to 30% of cases, these tumors have an altered BMP signaling pathway with an oncogenic mutation on the BMP type I receptor ALK2, encoded by ACVR1. However, the potential impact of the BMP pathway in tumors non-mutated for ACVR1 is less clear. By integrating bulk, single-cell, and spatial transcriptomic data, we show here that the BMP signaling pathway is activated at similar levels between ACVR1 wild-type and mutant tumors and identify BMP2 and BMP7 as putative activators of the pathway in a specific subpopulation of cells. By using both pediatric isogenic glioma lines genetically modified to overexpress H3.3K27M and patients-derived DIPG cell lines, we demonstrate that BMP2/7 synergizes with H3.3K27M to induce a transcriptomic rewiring associated with a quiescent but invasive cell state. These data suggest a generic oncogenic role for the BMP pathway in gliomagenesis of pDMG and pave the way for specific targeting of downstream effectors mediating the K27M/BMP crosstalk.

BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas

Pediatric diffuse midline gliomas (pDMG) are an aggressive type of childhood cancer with a fatal outcome. Their major epigenetic determinism has become clear, notably with the identification of K27M mutations in histone H3. However, the synergistic oncogenic mechanisms that induce and maintain tumor cell phenotype have yet to be deciphered. In 20 to 30% of cases, these tumors have an altered BMP signaling pathway with an oncogenic mutation on the BMP type I receptor ALK2, encoded by ACVR1. However, the potential impact of the BMP pathway in tumors non-mutated for ACVR1 is less clear. By integrating bulk, single-cell, and spatial transcriptomic data, we show here that the BMP signaling pathway is activated at similar levels between ACVR1 wild-type and mutant tumors and identify BMP2 and BMP7 as putative activators of the pathway in a specific subpopulation of cells. By using both pediatric isogenic glioma lines genetically modified to overexpress H3.3K27M and patients-derived DIPG cell lines, we demonstrate that BMP2/7 synergizes with H3.3K27M to induce a transcriptomic rewiring associated with a quiescent but invasive cell state. These data suggest a generic oncogenic role for the BMP pathway in gliomagenesis of pDMG and pave the way for specific targeting of downstream effectors mediating the K27M/BMP crosstalk.

Common viral respiratory infections in children with cancer during the COVID-19 pandemic: a multicenter study from Türkiye.

Microbiologic confirmation of respiratory tract infections gained importance during the coronavirus disease 2019 (COVID-19) pandemic. This study retrospectively evaluated seasonal distribution, clinical presentation, and complications of respiratory viral infections (RVIs) other than COVID-19 in children with cancer during and after the pandemic lockdown. Two hundred and sixty-five inpatient and outpatient RVI episodes in 219 pediatric cancer patients confirmed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) panels from 13 centers were enrolled. Eighty-six (32.5%) of the total 265 episodes occurred in 16 months corresponding to the lockdowns in Türkiye, and the remaining 67.5% in 10 months thereafter. Human rhinovirus/enterovirus (hRE) (48.3%) was the most common agent detected during and after lockdown. Parainfluenza virus (PIV) (23.0%), influenza virus (9.8%), and respiratory syncytial virus (RSV) (9.1%) were the other common agents. The 28.7% of episodes were lower respiratory tract infections (LRTIs), and complications and mortality were higher than upper respiratory tract infections (URTIs) (25.0% vs 5.3%). Bacteremia was identified in 11.5% of culture-drawn episodes. Treatment delay in one-third and death within four weeks after RVI in 4.9% of episodes were observed. During the pandemic, fewer episodes of RVIs occurred during the lockdown period. Respiratory viruses may cause complications, delays in treatment, and even death in children with cancer. Therefore, increased awareness of RVIs and rapid detection of respiratory viruses will benefit the prevention and, in some cases, abrupt supportive and some antiviral treatment of RVI in children with cancer.

Self-Reported Late Effects in Childhood Cancer Survivors in Kenya

Background: The number of children surviving cancer in low and middle-income countries is expected to grow in the coming years. Knowledge about late effects and follow-up preferences in Kenya is lacking.Objectives: This study assessed self-reported late effects in Kenyan childhood cancer survivors and explored their preferences for survivorship care.Methods: Childhood cancer survivors, having successfully completed treatment for at least one year, were interviewed using semi-structured questionnaires during clinic or home visits between 2021-2022. Medical records were reviewed for patient and treatment characteristics.Results: Twenty-six survivors of hematological malignancies (n=19, 73%), solid tumors (n=6, 23%), unknown tumor type (n=1, 4%), were interviewed. Most survivors (n=19, 73%) solely received chemotherapy and one survivor (4%) was irradiated. Median time since treatment completion was seven years. Fifteen survivors (58%) were previously lost to follow-up. Many survivors (n=19; 73%) self-reported late effects, predominantly pain and fatigue. Survivors (n=11, 42%) were limited in daily life activities: physical work (n=10, 38%), personal care (n=6, 23%), social activities (n=6, 23%). Eight survivors (31%) recalled being informed about late effects. Some survivors experienced a negative attitude toward cancer in regional hospitals. Follow-up duration was longer among informed patients (p=0.043). Survivors recommended education and survivor meetings and preferred their follow-up to be done at the referral center.Conclusions: Kenyan childhood cancer survivors self-report late effects, comparable in frequency, nature and severity to other survivors worldwide. Survivors and healthcare providers require education about the lifelong impact of childhood cancer and should have access to survivorship expertise to continue follow-up. Keywords: Pediatrics; survivorship; neoplasms; aftercare.

Quality of life and late therapy effects in pediatric non-Hodgkin lymphoma survivors: Insights from a single-institution study.

The survival outcomes of pediatric patients with mature B-non-Hodgkin lymphoma (NHL) have improved due to advances in treatment. We aimed to assess the frequency and severity of late effects and their impact on quality of life among pediatric NHL survivors. This retrospective study included patients diagnosed with mature B-NHL at Children's Cancer Hospital of Egypt (CCHE) 57357 from January 2012 through December 2015. Patients received treatment according to the modified LMB 96 protocol. The minimum follow-up period was 5years. Assessments for toxicity and quality of life were conducted at regular intervals during and after treatment. Patients were assessed for toxicity including pulmonary dysfunction, cardiac dysfunction, lipid profile abnormalities, endocrine dysfunction (thyroid function, vitamin D levels, growth curves), and cognitive function (intelligence quotient [IQ] level using Stanford-Binet Intelligence Scales-5th Edition, and quality of life (QoL) assessment (PedsQoL). A total of 273 patients were eligible, and 206 were evaluable. Median age was 5.45 (range: 2.4-18), with a male-to-female ratio 4:1. Pulmonary function abnormalities were detected in 119/203 (58.6%); most had mild dysfunction (72/119, 60.5%), while 17% had severe dysfunction. Cardiac toxicity occurred in 10% of the patients (n=20). IQ testing showed that 52 patients had a low average IQ score, while 151 patients had either average or above average scores. The total mean QoL score was 99±0.058 classified as "satisfactory." However, significant impairment of the physical domain of quality of life was observed among group C patients compared to A/B (p=.033), older age at diagnosis (p=.042), and those with pulmonary dysfunction (p<.001). Total score of quality of life was significantly impaired among patients with pulmonary dysfunction (p=.009), likewise older age at diagnosis (p=.017) and those with low average IQ scores (p=.033). Childhood mature B-NHL survivors are at significant risk for late effects; pulmonary dysfunction and low average IQ that can subsequently impact QoL.

Metagenomic characterization of viruses in the serum of children with newly diagnosed cancer

Background and ObjectivesA large cohort of pediatric patients with various forms of childhood cancer was investigated for the presence of viruses using metagenomics. A total of 476 patient samples, collected between 1989 and 2018, were analyzed, representing various pediatric oncological diagnoses and a control group of non-malignant diagnoses. Study designThe study was carried out using metagenomic sequencing of serum samples. Viruses were identified and analyzed using bioinformatics methods, followed by Polymerase chain reaction (PCR) confirmation ResultsThe results indicate that a wide range of viruses can be detected in the bloodstream of children with newly diagnosed cancer. Nine viral genomes were identified: Human Pegivirus (HPgV), Hepatitis C virus, Parechovirus 1, Rhinovirus C, Human papillomavirus 116, Human polyomavirus 10, Parvovirus B19, and different variants of Torque Teno Virus (TTV). In this study, a previously unknown virus was found belonging to the Iflavirdae family in the order Picornavirales. HPGV was significantly more common in patients with leukemia compared to other conditions. ConclusionsThese results highlight the abundance of systemic virus infections in children, and the value of metagenomic sequencing for hypothesis forming regarding the associations between virus infections and cancer.

The economic costs of precision medicine for clinical translational research among children with high-risk cancer

Embedding precision medicine in paediatric oncology shows promise to have a positive impact on how children with cancer will be treated in the future. While there are a number of studies of precision medicine in childhood cancer, there is limited evidence available on the cost of implementing the related testing. This is the first Australian study that systematically measures the cost of using precision medicine in the care of high-risk childhood cancers, through the Zero Childhood Cancer Precision Medicine Programme. In 2021 Australian dollars, the estimated costs inclusive of genomic and preclinical testing were: (A) $12,743 per patient for access; (B) $14,262 per identification of molecular cause; and (C) $21,769 per MTB recommendation. The information gained supports the understanding of the cost of reporting clinically significant outcomes relevant to the biology of the tumour, diagnosis, prognosis and potentially improving clinical management for a child.

6471 Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone

Abstract Disclosure: N.I. Pollock: None. M. Song: None. A. Wolf: None. Y. Li: None. C. Hawkes: None. N. Motamedi: None. M.R. Denburg: None. S. Mostoufi-Moab: None. Title: Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone Objectives: Aromatase inhibitor (AI) therapy in combination with growth hormone (GH), or as monotherapy, may have a role in improving height outcomes in male pediatric patients with GH deficiency (GHD). The effectiveness of AI therapy in the childhood cancer survivors is not known. In this retrospective study, we assess adult height (AH) in childhood cancer survivors treated with AI combined with GH therapy compared to those treated with GH alone. Methods: This was a single center retrospective cohort study of male survivors of childhood cancer treated with GH for diagnosis of GHD between 2007 and 2023. We compared AH outcomes in males treated with GH alone or in combination with off-label use of AI. Demographic and clinical characteristics, including anthropometric measurements, endocrinopathies, and cancer history, were obtained from the medical record. AH was noted as height documented at fusion of growth plates or following 18 years of age. Differences in demographic, clinical, and treatment characteristics were assessed using univariate tests of association. Multivariable regression with stepwise selection was used to examine risk factors associated with AH. All statistical analyses were performed using Stata 18.0. Results: Ninety-two patients were included; 70 were treated with GH monotherapy and 22 with combination AI/GH. Median age at AI initiation was 13.6 years (IQR 12.3-14.3) versus 11.2 years (IQR 8.6-12.9) for GH (unpaired t-test p-value &amp;lt;0.01; 95% CI -4.01, -1.91). A greater proportion of patients in the AI/GH group had been treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (Fisher’s exact p-value &amp;lt;0.01). There was no statistically significant difference in AH or AH Z-score between treatment groups, with the median AH Z-score in the AI/GH group -1.95 (IQR -3.11, -0.75) versus -1.39 (IQR -2.65, 0.11) in the GH group. In multivariable linear regression, history of radiation to the spine (β= -5.9, 95% CI -11.2, -0.6), height Z-score (β= 0.3, 95% CI 0.11, 0.46), BMI Z-score (β= 3.2, 95% CI 0.95, 5.5), and advanced bone age at GH or AI treatment initiation (β= -10.1, 95% CI -17.3, -2.9) were significantly associated with AH. Conclusions: Adjunctive treatment with AI and GH was not associated with increased AH outcomes in male survivors of childhood cancer compared to GH monotherapy. Future work is needed to determine optimal adjunctive medical therapy to maximize FAH impacted by cancer therapy for this patient population. Presentation: 6/3/2024

Temporal trends in pediatric cancer mortality: rare cancers lag behind more common cancers

Temporal trends demonstrate improved survival for many types of common pediatric cancer. Studies have not examined improvement in very rare pediatric cancers or compared these improvements to more common cancers. In this cohort study of the Surveillance, Epidemiology, and End Results (SEER) registry, we examined patients from 1975 to 2016 who were 0–19 years of age at the time of diagnosis. Cancers were grouped by decade of diagnosis and 3 cancer frequency groups: Common, Intermediate, and Rare. Trends in mortality across decades and by cancer frequency were compared using Kaplan–Meier curves and adjusted Cox proportional hazards models. A total of 50,222 patients were available for analysis, with the top 10 cancers grouped as Common (67%), 13 cancers grouped with Intermediate (24%), and 37 cancers as Rare (9%). Rare cancers had higher rates of children who were older and Black. 5-year survival increased from 63% to 86% across all cancers from the 1970s to the 2010s. The hazard ratio (HR) for mortality decreased from the reference point of 1 in the 1970s to 0.27 (95% CI: 0.25-0.30) in the 2010s in Common cancers, while the HR only dropped to 0.60 (0.49–0.73) over that same period for rare cancers. Pediatric oncology patients have experienced dramatic improvement in mortality since the 1970s, with mortality falling by nearly 75% in common cancers. Unfortunately, rare pediatric cancers continue to lag behind more common and therefore better studied cancers, highlighting the need for a renewed focus on research efforts for children with these rare diseases.

General context and relevant public datasets available for improving pathways in Paediatric Cancer applying Artificial Intelligence. A review

Due to the promise of transforming healthcare and medicine that Artificial Intelligence (AI) has posed, the number of applications has increased exponentially. These applications range from screening and disease diagnosis to prognosis, treatment planning, and follow-up. In complex topics such as childhood cancer, these techniques are being expanded with the ambition of improving the quality of care by allowing healthcare professionals to make more informed decisions. However, the adequate application of such techniques heavily depends on the data, which creates a set of challenges including collection, bias, and scarcity among others. Furthermore, ethical, legal, and regulatory frameworks increase even more the difficulties to develop AI-powered solutions. In this paper, we present an exhaustive literature review to identify and analyse public datasets targeting two common childhood cancer types, such as neuroblastoma and nephroblastoma. Moreover, the complex context for the development of AI- based software solutions is outlined. It includes the description of the most relevant techniques to address problems associated with data sharing and training. Finally, a set of code snippets is provided to perform exploratory analysis for the available data.

6715 Short Adult Height in Childhood Cancer Survivors: Prevalence, Risk Factors, and Genetic Contribution

Abstract Disclosure: T. Yoshida: None. J. Baedke: None. F. Wang: None. W. Moon: None. Y. Sapkota: None. J. Miguel Martínez: None. T.E. Merchant: None. C.L. Wilson: None. K.K. Ness: None. M.M. Hudson: None. Y. Yasui: None. A. Delaney: None. Background: Survivors of childhood cancer are at elevated risk for short adult height (SAH) due to cancer and/or its treatment. In the general population, height is a highly polygenic trait; heritability is estimated to be 70-80%. However, the contribution of genetic factors to SAH among childhood cancer survivors is unknown. In addition, the contribution of chemotherapy agents to risk of SAH among survivors has not been established. We assessed: 1) prevalence of SAH; 2) contribution of genetic factors; and 3) impact of cancer therapy including chemotherapy, on SAH in a large cohort of childhood cancer survivors. Methods: Participants included 4461 childhood cancer survivors aged ≥18 years (female 47.5%, mean age 33.2 years old) with measured height information. SAH was defined as height &amp;lt;3rd percentile for age and sex based on the Centers for Disease Control growth charts. Cancer and treatment history were extracted from medical records. We calculated multi-ancestry height polygenic score (PGS) using the latest methodology developed from 5.4 million individuals of diverse ancestries with more than 1 million variants, where lower score associates with shorter height. With a random sample of 75% of survivors, we fit a multivariable logistic regression model for SAH with the PGS, chemotherapy exposures/doses, corticosteroid exposures/doses, and established risk factors for SAH (e.g., age at cancer diagnosis, radiotherapy exposure) as covariates (main model). The remaining 25% of survivors served for validation of the main model and for the calculation of the population attributable fractions (PAF) of the PGS and cancer treatments. Results: The prevalence of SAH was 8.9% among all survivors (9.3% in males; 8.5% in females) and differed widely by primary cancer diagnosis. SAH was associated with lower PGS [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.40-0.55 for a one standard deviation increase], alkylating agent exposure of &amp;gt;12000 mg/m2 (OR 2.19, 95% CI 1.41-3.38, vs. non-exposure), and spinal radiotherapy (OR 3.65, 95% CI 2.23-6.00, vs. non-exposure). Radiotherapy exposure to the hypothalamic-pituitary region and younger age at cancer diagnosis was also associated with SAH in a dose-response manner. The area under the ROC curve of the main model in the validation dataset was 0.80 (95% CI 0.74-0.87), suggesting good predictive ability for SAH by the model. The PAF of SAH calculated from the multiplicative logistic regression model of SAH was 85.7% for cancer treatments and 30.2% and 60.2% for having PGS below the median and the 90th percentile, respectively. Conclusions: Cancer treatments are the primary contributor to SAH risk among survivors with a PAF of 85.7%. Exposure to high-dose alkylating agents contributes to this along with radiotherapy. Inherited genetic factors also affect SAH among survivors but to a much lesser degree than cancer treatments. Presentation: 6/3/2024