Childhood Cancer Research Articles

Effect of peppermint inhalation versus Swedish massage on chemotherapy induced-nausea and vomiting in children with leukemia: Multi-arm randomised trial design

BackgroundChemotherapy is the foremost treatment for children with leukemia, while causing different serious side-effects. Chemotherapy-induced nausea and vomiting are the most common deliberating side effects and critical concerns of pediatric oncology nurses among those children. AimTo investigate the effect of peppermint inhalation versus Swedish massage on chemotherapy-induced nausea and vomiting in children with leukemia. DesignA multi-arm randomised trial design with three parallel groups. SettingThis study was conducted at outpatient and inpatient Hematology/leukemia Units at Alexandria University Children's Hospital at Smouha. MethodsSeventy-five children with leukemia received the first chemotherapy session. They were randomly allocated into three equal groups, 25 children in each group (control, peppermint inhalation, and Swedish massage groups). Every child is assessed for nausea and vomiting before chemotherapy administration and after for three days for consecutive three sessions of treatment. ResultsStudy findings revealed that children in peppermint inhalation and Swedish massage groups showed significant reduction in mean total score of chemotherapy-induced nausea and vomiting among peppermint inhalation and Swedish groups (15.120 ± 4.585 and 14.680 ± 3.158, respectively) was observed on third chemotherapy session than in control group (45.680 ± 5.793) (p < 0.001). ConclusionIt can be concluded that Swedish massage and peppermint inhalation therapies may have significant antiemetic effects as alleviating the chemotherapy induced nausea and vomiting for children with leukemia. Practice implicationsThis study directs the pediatric oncology nurses to incorporate peppermint inhalation and Swedish massage therapies besides antiemetic drugs in pediatric oncology unit protocols for management of chemotherapy induced nausea and vomiting.

Characterization of transcriptional heterogeneity and novel therapeutic targets using single cell RNA-sequencing of primary and circulating Ewing sarcoma cells.

Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. Single cell RNA-sequencing and immunofluorescence of circulating tumor cells at the time of diagnosis identified TSPAN8 as a novel therapeutic target.

Genetic risk of second malignant neoplasm after childhood cancer treatment: A systematic review.

Second malignant neoplasm (SMN) is one of the most severe long-term risks for childhood cancer survivors (CCS), significantly impacting long-term patient survival. While radiotherapy and chemotherapy are known risk factors, the observed inter-individual variability suggests a genetic component contributing to the risk of SMN. This article aims to conduct a systematic review of genetic factors implicated in the SMN risk among CCS. Searches were performed in PubMed, Scopus, and Web of Sciences. Eighteen studies were included (eleven candidate gene studies, three genome-wide association studies, and four whole exome/genome sequencing studies). The included studies were based on different types of first cancers, investigated any or specific types of SMN, and focused mainly on genes involved in drug metabolism and DNA repair pathways. These differences in study design and methods used to characterize genetic variants limit the scope of the results and highlight the need for further extensive and standardized investigations. However, this review provides a valuable compilation of SMN risk-associated variants and genes, facilitating efficient replication and advancing our understanding of the genetic basis for this major risk for CCS.

Addressing heart health in survivors of childhood cancers.

Addressing heart health in survivors of childhood cancers.

ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА ПРИОБРЕТЕННОЙ АПЛАСТИЧЕСКОЙ АНЕМИИ У ДЕТЕЙ: АНАЛИЗ ДАННЫХ РЕГИСТРОВОГО ИССЛЕДОВАНИЯ

Acquired aplastic anemia (AA) is still the diagnosis of exclusion. The purpose of the research was to identify clinical and laboratory signs that do not correspond to acquired AA allowing to diagnose other diseases accompanied by cytopenia. Materials and methods used: Authors represent the results of diagnostic search in pediatric patients (0 to 18 y/o) with a suspected diagnosis of acquired AA who underwent remote diagnosis in the laboratories of the National Scientific and Practical Center for Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev (Moscow, Russia) as part of the Register Study in Sep. 1, 2017-May 1, 2022. Results: in retrospective analysis of 523 children records, 104 (20%) patients had other diagnoses. In 29 (27.9%) patients were diagnosed with inherited bone marrow failure syndromes (IBMFS), in 11 (10.6%) with myelodysplastic syndrome, in 11 (10.6%) with deficiency anemia, in 10 (9.6%) with congenital unspecified AA, in 7 (6.7%) with immune cytopenia, in 7 (6.7%) with inborn defects of immunity, in 6 (5.8%) with secondary AA, in 6 (5.8%) with acute leukemia, in 2 (1.9%) with paroxysmal nocturnal hemoglobinuria and in 15 (14.4%) cases with other unspecified diseases. Fanconi anemia (n=15/29 patients) was the most common disease in the IBMFS group; this group had also included: dyskeratosis congenita (n=9), Schwachman-Diamond syndrome (n=2), amegakaryocytic thrombocytopenia (n=2), Diamond-Blackfan anemia in combination with congenital neutropenia (n=1). Conclusion: differential diagnosis of acquired AA can be difficult though it is undoubtedly must-do for successful treatment. Verification of other alternative diseases, including genetically determined syndromes, contributes to the choice of optimal patient management tactics.

ОЦЕНКА БЕЗОПАСНОСТИ И ЭФФЕКТИВНОСТИ МЕТОДИКИ МОБИЛИЗАЦИИ И СБОРА ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК У ДЕТЕЙ РАЗНЫХ ВОЗРАСТНЫХ ГРУПП СО ЗЛОКАЧЕСТВЕННЫМИ НОВООБРАЗОВАНИЯМИ: ОПЫТ ОДНОГО ЦЕНТРА

High dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is used currently as a consolidating stage in cancer treatment protocols for children from different age groups with various malignant neoplasms. Auto-HSCT can improve both progression-free survival and overall survival of such patients. At the same time the optimization of the collection of autologous hematopoietic stem cells (HSCs) seems to be an important factor in the successful implementation of auto-HSCT. The purpose of this research was to evaluate the safety and effectiveness of the HSCs mobilization and collection method in children from different age groups with various malignancies. Materials and methods used: a single-center retrospective cohort study of 258 pediatric patients (median body weight 20.0 [13.8; 42.0] (7.0-95.0) kg and median height 116 [97; 155] (55.0-189) cm) with various cancers aged 1 to 18 y/o (median 78.0 [36; 144] (3-215) months old) who received treatment in Jan. 2020-Jan. 2023 at the Research Institute of Pediatric Oncology and Hematology named after Academician L.A. Durnov with the N.N. Blokhin Russian Cancer Research Center (Moscow, Russia). Patients were divided into 3 age groups: younger than 1 y/o, 1 to 10 y/o and 11 to 18 y/o. Results: 242 (93.8%) of HSC apheresis procedures were successful on the first attempt, 16 patients underwent repeated apheresis (a total of 274 procedures were performed). The median number of CD34+ cells obtained was 110.95 [45.6; 276.4] (0.70-2338.2) cells/µl, median apheresis duration was 253.5 [189; 338] (82-575) min. No serious complications were observed during the HSCs mobilization and collection in any patient. None of the patients developed hemodynamic disturbances. The main criteria for effectiveness was the CD34+/kg level, the median of which was 5.1 [2.4; 12.7] (0.01-95.6)•106. One of the safety criteria for the patients from all the three age groups was the absence of hemodynamic disorders and citrate reactions in the form of numbness, cyanosis of the skin and respiratory disorders. Another important safety criteria were the absence of a significant decrease in both platelet and hemoglobin levels. The median platelet levels prior to the procedure was 125.5 [68; 210] (14.0-815)•109/l and 129 [73; 210] (17.0-823)•109/l at the end of the procedure (p&lt;0.001). Hemoglobin levels before and after the procedure were 100 [94; 110] (75-242) g/l and 99 [93; 109] (70-142) g/l, respectively (p&lt;0.001). Considering it safe to reduce hemoglobin (g/l) and/or platelets (•109/l) by no more than 10 units in each measurement, in 87.6±4.1% (83.0-91.1) of observed cases the procedure was safe without statistically significant differences in all age groups. The effectiveness of the HSCs mobilization and collection method proposed by the Authors in children of the older age group (11 to 18 y/o) was the lowest and was statistically significantly different from the effectiveness in the group of children aged 1 to 10 y/o (p&lt;0.001) with cancer and amounted to 84.5±4.4% (79.6-88.4). Conclusion: with the multidisciplinary team of practitioners, HSC apheresis in children is a safe and effective technique used as part of the complex cancer treatment in patients from poor prognosis groups. The apheresis algorithm that the Authors have proposed allows high-quality collection of CD34+ positive cells in amounts sufficient for further auto-HSCT.

Knowledge, Attitudes, and Practices regarding Pain Assessment among Nurses Working at Public-Sector Pediatric Oncology Units in Pakistan

Abstract Introduction Pain in pediatric oncology patients is often undertreated due to a lack of timely assessment and inefficient communication between health care workers. Improper pain assessment is a leading cause of poorly managed pain in children. In high-income countries, pediatric oncology nurses play a key role in developmentally appropriate pain assessment measures to identify potential management strategies. However, nurses in low- and middle-income countries (LMICs) face a deficit of knowledge about pain assessment tools and management. Owing to differences in availability of resources, a disparity exists between health-related quality of life of cancer patients treated at public- and private-sector hospitals in Pakistan. Methodology The Indus Hospital and Health Network partnered with nine public-sector hospitals nationwide to improve pediatric oncology practices. Supported by the My Child Matters grant, training sessions were conducted for nurses at each public-sector pediatric oncology unit (POU) from March to December 2021. Pain assessment tools were provided. To assess retention and implementation of practices, a knowledge, attitudes, and practices questionnaire was distributed online to nurses at each POU. All responses remained anonymous. Results Fifty-four responses were recorded, 85% were female and most were between 26 and 30 years of age. Most of the participants held a diploma in nursing and were designated charge nurses with more than 6 years of experience. Forty nurses reported routinely assessing pain; the most common reason for not doing so was increased workload. Correlations were observed between routinely performing pain assessment and the number of patients per nurse, availability of formal credentialing or certifications at the institution and routinely performing pain assessment, availability of trainings focused on pain assessment and routinely performing pain assessment, and qualification of nurses and knowledge of nonpharmacological pain assessment methods. Conclusion Strategies to improve pain assessment knowledge and practices among pediatric oncology nurses in LMICs must be developed to improve patient care and clinical outcomes.

Healthcare professional perspectives following implementation of an infection management care pathway for pediatric patients with cancer: a qualitative study.

The Pediatric Oncology Group of Ontario (POGO) supported an effort to implement infection management care pathways based on clinical practice guidelines, to improve the consistency of infection management in pediatric cancer patients. The objective of this qualitative study was to describe the perspective of healthcare professionals (HCPs) following implementation. Four tertiary pediatric oncology centers in Ontario, Canada, implemented the pathways. We randomly identified three HCPs per group (clinical pharmacists; nurse case managers, educators or practitioners and physician assistants; pediatric oncology fellows; or pediatric oncology staff physicians) per site and invited them to participate in a qualitative interview. One-on-one interviews were conducted remotely, followed by thematic analysis of interview transcripts. A total of 66 invitations were extended and 42 HCPs participated. Identified themes were: (1) implementation approach, (2) access and navigation, (3) engagement, (4) concerns, (5) workplace benefits, (6) reception, and (7) provincial harmonization. HCPs preferred in-person implementation strategies over e-mail communication. They identified teaching/educational utility and benefits to non-oncology departments and non-tertiary centers participating in shared care of patients. Other positive aspects related to evidence-based practice, safety, supporting oncology HCPs, and benefits to patients and families. Concerns included need to ensure users applied clinical judgement and loss of autonomy. Provincial harmonization of practice was viewed positively, although potential logistical and institutional cultural barriers were raised. Following infection management care pathway implementation, HCPs described educational utility and benefits to non-oncology departments, oncology HCPs, patients, and families. Our findings may facilitate future infection management care pathway provincial harmonization.

Focused cancer pathway analysis revealed unique therapeutic targets in retinoblastoma.

Retinoblastoma (RB) is a pediatric cancer of the eye that occurs in 1/15000 live births worldwide. Albeit RB is initiated by the inactivation of RB1 gene, the disease progression relies largely on transcriptional alterations. Therefore, evaluating gene expression is vital to unveil the therapeutic targets in RB management. In this study, we employed an RT2 Profiler™ PCR array for a focused analysis of 84 cancer-specific genes in RB. An interaction network was built with gene expression data to identify the dysregulated pathways in RB. The key transcript alterations identified in 13 tumors by RT2 Profiler™ PCR array was further validated in 15 tumors by independent RT-qPCR. Out of 84 cancer-specific genes, 68 were dysregulated in RB tumors. Among the 68 genes, 23 were chosen for further analysis based on statistical significance and abundance across multiple tumors. Pathway analysis of altered genes showed the frequent perturbations of cell cycle, angiogenesis and apoptotic pathways in RB. Notably, upregulation of MCM2, MKI67, PGF, WEE1, CDC20 and downregulation of COX5A were found in all the tumors. Western blot confirmed the dysregulation of identified targets at protein levels as well. These alterations were more prominent in invasive RB, correlating with the disease pathogenesis. Our molecular analysis thus identified the potential therapeutic targets for improving retinoblastoma treatment. We also suggest that PCR array can be used as a tool for rapid and cost-effective gene expression analysis.

When Lightning Strikes Twice: Routes to Second Malignancies in Young Patients.

Given the rarity of cancer in childhood, it should be even more uncommon for pediatric cancer survivors to develop a second, independent malignancy, yet they incur a greatly elevated risk after initial remission. In this issue of Cancer Discovery, Sánchez-Guixé and colleagues unpick the origins of second tumours in four children, and the potential role platinum-based chemotherapy may play in subsequent tumorigenesis. See related article by Sánchez-Guixé et al., p. 953 (8).

Cancer predisposing syndromes in childhood and adolescence pose several challenges necessitating interdisciplinary care in dedicated programs.

Genetic disposition is a major etiologic factor in childhood cancer. More than 100 cancer predisposing syndromes (CPS) are known. Surveillance protocols seek to mitigate morbidity and mortality. To implement recommendations in patient care and to ascertain that the constant gain of knowledge forces its way into practice specific pediatric CPS programs were established. We retrospectively analyzed data on children, adolescents, and young adults referred to our pediatric CPS program between October 1, 2021, and March 31, 2023. Follow-up ended on December 31, 2023. We identified 67 patients (30 male, 36 female, 1 non-binary, median age 9.5 years). Thirty-five patients were referred for CPS surveillance, 32 for features suspicious of a CPS including café-au-lait macules (n = 10), overgrowth (n = 9), other specific symptoms (n = 4), cancer suspicious of a CPS (n = 6), and rare neoplasms (n = 3). CPS was confirmed by clinical criteria in 6 patients and genetic testing in 7 (of 13). In addition, 6 clinically unaffected at-risk relatives were identified carrying a cancer predisposing pathogenic variant. A total of 48 patients were eventually diagnosed with CPS, surveillance recommendations were on record for 45. Of those, 8 patients did not keep their appointments for various reasons. Surveillance revealed neoplasms (n = 2) and metachronous tumors (n = 4) by clinical (n = 2), radiological examination (n = 2), and endoscopy (n = 2). Psychosocial counselling was utilized by 16 (of 45; 35.6%) families. The diverse pediatric CPSs pose several challenges necessitating interdisciplinary care in specified CPS programs. To ultimately improve outcome including psychosocial well-being joint clinical and research efforts are necessary.

Longitudinal changes of psychological distress among childhood cancer survivors: The Swiss Childhood Cancer Survivor Study.

Childhood cancer survivors may experience psychological distress due to the disease, cancer treatments, and potential late effects. Limited knowledge exists regarding longitudinal changes in psychological distress after childhood cancer. We aimed to determine changes in psychological distress over time and explore determinants of changes. The Swiss Childhood Cancer Survivor Study collected data at baseline (2007-2009) and follow-up (2010-2012). Psychological distress was measured using the Brief Symptom Inventory 18 (BSI-18), including three symptom scales (somatization, depression, anxiety) and an overall distress index (Global Severity Index, GSI). Sum-scores were T-standardized (mean=50; standard deviation [SD]=10). Survivors with a score ≥57 on the GSI or two symptom scales were classified as cases with distress. We used linear mixed effects regression to identify potential sociodemographic and clinical determinants of change in psychological distress. We analyzed 696 survivors at baseline (mean age=24years [SD=4], 49% females, mean time since diagnosis=16years [SD=4]). On follow-up (2.4years, SD=1), 317 survivors were analyzed, including 302 participants with repeated measures. We found that 13% (39/302) were cases at baseline, and 25% (76/302) were cases on follow-up. Those older at study and longer since diagnosis, females, diagnosed with central nervous system (CNS) tumors, and those reporting late effects were more likely to experience higher levels of distress. Females and unemployed are at higher risk for developing or persisting psychological distress than males and those who are employed or in training. We observed an increase in psychological distress score over time, with higher proportion of psychological distress on follow-up. Anticipatory guidance and screening should be implemented in regular follow-up care.

Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantation or comorbidities.

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.

Harmonizing cancer care delivery for AYAs with osteosarcoma: Comparison of pediatric and medical oncology approaches in a single center.

10039 Background: Osteosarcoma (OS) has a peak incidence amongst adolescents and young adults (AYA). Nuances in chemotherapeutic regimens are largely influenced by the training of pediatric or medical oncologists. MAP is the standard chemotherapy regimen used by pediatric oncologists. Chemotherapy regimens used by medical oncologists vary; our center uses preoperative doxorubicin/cisplatin (AP) followed by either doxorubicin/ifosfamide (AI) or a combination of HD methotrexate and HD ifosfamide. We undertook this analysis to characterize the treatment response, toxicity, and survival outcomes for AYAs with OS treated with pediatric vs medical oncology regimens as an initial step towards harmonizing our institutional approach to the treatment of AYA patients with bone sarcomas. Methods: We retrospectively reviewed the records of AYAs with OS receiving primary treatment at our center. Clinicopathologic characteristics and outcomes for patients treated with MAP vs. AP+ were compared. Progression-free survival (PFS) was defined as the time from either MAP/AP+ initiation or surgery to the time of first recurrence or death. Overall survival was defined as the time from MAP/AP+ initiation or surgery to death. The distributions of PFS and overall survival were estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups. Regression analyses of survival data based on the Cox proportional hazard (PH) model were conducted on the time to event outcomes. Results: Between 2016-2022, 209 OS patients were seen at our center for initial diagnosis and treatment recommendations including 124 AYAs (59%). Amongst AYAs, 41 patients (median age 22y, range 14-38y) initiated and received the majority of their chemotherapy at our center and were included in analysis. Of the 41 AYAs, 17 were treated on MAP; 24 were treated using AP+. Ten patients &lt; 20 years received MAP; one patient &gt;30 years received MAP. The median time from initiation of therapy to surgery for those receiving MAP was 87.5 days vs 95.5 days for AP (p = 0.0052). Percent tumor necrosis varied widely with both regimens (range 0-99%) and was not statistically different (p = 0.11). There was no statistically significant difference in PFS between AYAs treated with MAP as compared to AP+ (Three-year PFS rates 80% vs 66%, p = 0.40). Evaluation of treatment related toxicity and late effects is ongoing. Conclusions: We had insufficient data to compare survival outcomes in this limited retrospective series. This limited retrospective study did not show a statistically significant difference in PFS for AYA patients with OS treated with a standard pediatric vs. adult type regimen containing at least 3-drug chemotherapy. Further study is needed to refine treatment for this patient population. These data support prospective efforts to harmonize AYA treatment paradigms in osteosarcoma.

A comprehensive analysis of minimally differentially methylated regions common to pediatric and adult solid tumors

Cancer is the second most common cause of death in children aged 1–14 years in the United States, with 11,000 new cases and 1200 deaths annually. Pediatric cancers typically have lower mutational burden compared to adult-onset cancers, however, the epigenomes in pediatric cancer are highly altered, with widespread DNA methylation changes. The rarity of pediatric cancers poses a significant challenge to developing cancer-type specific biomarkers for diagnosis, prognosis, or treatment monitoring. In the current study, we explored the potential of a DNA methylation profile common across various pediatric cancers. To do this, we conducted whole genome bisulfite sequencing (WGBS) on 31 recurrent pediatric tumor tissues, 13 normal tissues, and 20 plasma cell-free (cf)DNA samples, representing 11 different pediatric cancer types. We defined minimal focal regions that were differentially methylated across samples in the multiple cancer types which we termed minimally differentially methylated regions (mDMRs). These methylation changes were also observed in 506 pediatric and 5691 adult cancer samples accessed from publicly available databases, and in 44 pediatric cancer samples we analyzed using a targeted hybridization probe capture assay. Finally, we found that these methylation changes were detectable in cfDNA and could serve as potential cfDNA methylation biomarkers for early detection or minimal residual disease.

Childhood Cancer in Cameroon and Kenya: Preliminary findings of an implementation effectiveness study for early detection of childhood cancer.

e23096 Background: Early childhood cancer detection reduces mortality, particularly in LMIC contexts where an improved understanding of early warning signs and symptoms (EWSS) and integration of vital referral pathways into existing health systems are crucial to improved childhood cancer outcomes. Our project seeks to adapt and implement a Ghanaian-developed EWSS intervention for Kenya and Cameroon using implementation science frameworks to move beyond the common but ineffective train-and-hope approach. Cameroon operates on a three-tiered sub-sector health system, with the intermediate level consisting of regional delegations that support districts1. In Kenya a six-tiered health system delivers primary care (1-2), mid-level care (3-4), advanced care with centers of excellence (5-6) 2. Health system contexts will inform implementation planning and execution. Methods: Health system stakeholders convened in each country to launch their EWSS initiative. Two-day meetings were collaboratively led by local stakeholders and the research team, guided by The Implementation Roadmap3, a multi-implementation framework resource. They discussed l) local barriers to childhood cancer detection, 2) referral pathways, 3) leadership and operational implementation teams, 4) sustainable EWSS training, and 4) target settings. Results: Stakeholders endorsed the EWSS program and identified individuals to form implementation teams to plan and execute implementation reflective of health system organization and realities. Both countries engaged in an evidence-based implementation planning process, reviewed EWSS core components and training logistics, and endorsed a sustainable tiered training model targeting clinicians and oncologists across system levels and institutional providers. Training content will be adapted for country, region, and county contexts. Both countries endorsed and identified district childhood cancer champions to facilitate training and coordinate timely referrals. Common implementation barriers identified included high healthcare worker turnover, transportation logistics for in-person training, and remuneration options for trainees. Conclusions: Health system leaders in Kenya and Cameroon endorsed an evidence-based EWSS implementation and sustainment approach and identified adaptations responsive to the health system contexts. Implementation will be locally led to ensure effectiveness, sustainability, and appropriate cultural EWSS adaptation. Moving forward, local implementation teams will work with researcher-facilitators to implement EWSS toward improved cancer detection rates.

Statistical fragility of findings from randomized phase 3 trials in pediatric oncology.

e23003 Background: The fragility index (FI) and survival-inferred fragility index (SIFI) have been proposed as adjunctive metrics to facilitate interpretation of p-values in clinical trials. FI/SIFI is the number of patients on a positive (p &lt; 0.05) trial’s experimental arm who would need to switch from “responder/non-event” to “non-responder/event” to cause p &gt; 0.05. Fragility indices have been reported previously in medical oncology, with median values &lt; 10 often seen in the literature. This metric has not been studied in pediatric oncology trials. Methods: PubMed was used to identify randomized phase 3 pediatric oncology trials published between 1980-2020. We report trial characteristics and calculate FI for trials with a binary outcome and SIFI for trials with a time-to-event outcome. We also report the fragility quotients (FQ and SFQ) to normalize FI and SIFI relative to trial size. Results: 113 trials included sufficient data for analysis. The median FI for trials with a binary outcome (n = 40) was 4.5 (range: 1-33). The median SIFI for trials with a time-to-event outcome (n = 73) was 13 (range: 0-61). The FI or SIFI was less than the number of patients lost to follow-up in 25% of 36 trials. Median FQ = 0.026 and SFQ = 0.03, indicating that revised outcome in 2.6% or 3% of trial participants would be sufficient to alter the trial conclusion. FQ and SFQ did not significantly vary according to trial characteristics. While sample sizes increased over time (mean 187, 1980s; mean 437, 2010s), FQ and SFQ remained stable between 2-3%. Conclusions: The statistical conclusions of pediatric oncology phase 3 trials hinge on a relatively small number and proportion of patients. Despite sample size limitations of low prevalence diseases, pediatric cancer trials appear similarly or less fragile than adult oncology trials. Fragility was similar for large versus small trials and remained constant over four decades. [Table: see text]

The science of getting published: Key factors influencing publication in pediatric oncology.

11024 Background: Childhood cancer is rare, with an annual global incidence of 400,000 cases. Research articles play a crucial role in disseminating significant advancements in this rare field; however, it often experiences delays. We investigated the key factors influencing the transition from abstracts presented at the American Society of Clinical Oncology (ASCO) Annual Meetings to publication of articles in the pediatric oncology field. Methods: We analyzed oral (OA), poster (PA), and publication-only abstracts (PO) presented during pediatric oncology sessions at ASCO Annual Meetings from 2017 to 2023. We cross-referenced abstract titles and authors with PubMed-indexed journals. Each predictor was assessed for its correlation with the publication status using the chi-square test. Additionally, logistic regression was performed to understand the influence of each predictor while controlling for other variables. Results: A total of 521 abstracts were identified. Among these, 93 were OA, 270 were PA, and 158 were PO. Of these, 67%, 60%, and 32% were eventually published, respectively. The mean time to publication was 21.3 months for OA, 17.15 months for PA, and 23.4 months for PO. Female authors comprised 56% of the first authors. Funding was provided for 96% of OA, 87.7% of PA, and 63% of PO. Only 7% of all abstracts were from low-middle-income countries (LMICs). A significant correlation was found between the likelihood of publication and the income level of the authors' country of affiliation (p&lt;0.0001), the number of authors (p=0.001), presentation type (p&lt;0.0001), availability of funding (p&lt;0.0001), and the number of institutions involved (p=0.0001). The gender of the first author was not a significant predictor of publication (p=0.46). However, according to the logistic regression model, only the availability of funding and presentation type had a significant impact on the likelihood of publication (p&lt;0.05), while the other variables were found to be insignificant. Conclusions: Our study underscores the critical role of funding as a driver in the publication process. Researchers from LMICs are less likely to publish, likely due to a lack of funding. Furthermore, we observed a delay in publication, with an average time exceeding a year and a half. These findings emphasize the importance of equitable funding access and enhanced publication processes to improve research dissemination.

Inpatient healthcare utilization in the first year following a childhood cancer diagnosis: A population-based analysis.

11138 Background: Children with cancer may require substantial healthcare resources during treatment, including inpatient care. Hospital utilization patterns at the population level, and factors associated with higher utilization, are not well-described. Methods: We conducted a retrospective cohort analysis of Washington State (WA) cancer registry data (1992-2013) linked to state birth (1974-2013), death (1992-2013), and hospital discharge (1992-2013) records to identify all WA children diagnosed with cancer &lt;20 years. We examined hospitalization frequency and total inpatient bed days in the year after cancer diagnosis. To evaluate factors associated with outcomes of interest, we constructed multivariable negative binomial regression models of children with ≥1 inpatient admission, calculating incidence rate ratios (IRR). Covariates included rural residence (binary; census tract rural-urban commuting area codes), high neighborhood deprivation (binary; state-normative census block group Area Deprivation Index [ADI]), sex, race/ethnicity, diagnosis age, birth year, and cancer type (per International Classification of Childhood Cancer). Due to differences in utilization by cancer type, we also examined children in subanalyses with acute lymphoblastic leukemia (ALL), lymphomas, and solid (including central nervous system [CNS]) tumors. Results: 2,231 children (mean diagnosis age 7.2 years; 68% diagnosed since 2000) had 12,833 inpatient encounters. In the year after diagnosis, children had a median of 4 (IQR 2-8) hospitalizations/year at-risk, and 21 (IQR 8-54) inpatient days (median length of stay 4 days [IQR 2-6]). In multivariable analysis, high ADI (IRR 1.11, 95% CI 1.01-1.21), but not rural residence (IRR 0.95, 95% CI 0.85-1.05), was associated with greater hospitalization frequency. Female sex was associated with lower frequency (IRR 0.94, 95% CI 0.88-1.00). In analysis of total inpatient days, high ADI (IRR 1.15, 95% CI 1.02-1.29) and Hispanic ethnicity (IRR 1.31, 95% CI 1.13-1.51) were independently associated with greater inpatient days. In subanalysis of patients with ALL (N=497), associations between inpatient days and ADI (IRR 1.18, 95% CI 0.99-1.40) and Hispanic ethnicity (IRR 1.01, 0.84-1.23) were no longer significant. For lymphoma (N=259), associations were similar but also no longer significant (ADI IRR 1.14, 95% CI 0.78-1.71; Hispanic IRR 1.26, 95% CI 0.79-2.10). Among patients with solid/CNS tumors (N=1,151), associations with Hispanic ethnicity remained significant (IRR 1.46, 95% CI 1.19-1.80), but not ADI (IRR 1.11, 95% CI 0.95-1.30). Conclusions: Children with cancer spend considerable time inpatient during the year after diagnosis. Disparities in hospital utilization mirror some known disparities in childhood cancer survival. Initiatives to alleviate systemic disadvantages may reduce inpatient utilization for some groups.

Pediatric cancer registry in Turkey 2002-2023: 22 years of achievement (TPOG &amp; TPHD).

10051 Background: The survival rates for childhood cancer have seen significant improvements in high-income countries over the past few decades. However, in low- and middle-income countries, it remains a substantial challenge. Access to care remains a significant barrier to improving survival rates in low- and middle-income countries (LMICs). The pediatric cancer registry is a crucial component of pediatric cancer control efforts. In this context, we present the findings from 22 years of the pediatric cancer registry in Turkey. Methods: The present pediatric cancer registry was established by Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association in 2002. The childhood cancer cases registered between 2002-2023 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 22 years from 2002 to 2023, 50887 cases were registered. For all cases, median age was 6.5 year (0-19; M/F 28641/22233, 6 hermaphrodite, 7 unknown). Age distribution was 0-4 yrs, 41.1%; 5-9 yrs, 24.7%; 10-14 yrs, 23.1%; 15-19 yrs, 11.0%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (14633, 28.8%, 5.6, 8510/6123); Lymphoma &amp; other RES tumors (8958, 17.6%, 9.2, 5956/3000, 2 unknown); CNS [brain &amp; spinal] (7299, 14.3%, 7.0, 4066/3232, 1 unkown); Sympathetic system (3783, 7.4%, 2.4, 1951/1831, 1 hermaphrodite); Retinoblastoma (1444, 2.8%, 1.5, 752/692); Renal (2310, 4.5%, 3.1, 1140/1168, 1 hermaphrodite &amp; 1 unknown); Liver (732, 1.4%, 2.1, 428/304); Malignant bone (3122, 6.1%, 12.5, 1747/1375); Soft tissue sarcomas (3675, 7.2%, 7.3, 2047/1628); Germ cell (2933, 5.8%, 8.9, 1077/1849, 4 hermaphrodite, 3 unknown); Carcinoma &amp; other malignant epithelial (1628, 3.2%, 13.1, 783/845); Other/non-specific malignant (370, 0.7%, 7.8, 184/186). Five-year survival rate was found as 71.1%. Conclusions: The survival rates for children and adolescents have improved to 70%, a figure comparable to that of other middle-income countries and reflective of the quality of pediatric cancer care in Turkey. This represents a successful pediatric cancer registry from a middle-income country, covering a period of over 20 years. It has become a valuable resource for stakeholders at both the national and international levels.