Search

BackgroundAutoimmune diseases have been linked to an increased risk of pregnancy-related complications. A family history of autoimmune diseases may be related to the risk of childhood cancer based on similar histocompatibility antigens. We utilized data from national registries in Denmark to examine associations between maternal autoimmune disease and cancer in their offspring.MethodsWe linked data from several national registries in Denmark to identify childhood cancer cases in children

BackgroundMaternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer.MethodsThe present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy.Results1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74).ConclusionsOverall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

Background and aims: Cancer and its treatments may cause neurocognitive impairments in preschool children, but there is limited research on the neurocognitive outcomes of this population. This study, which assessed the neurocognitive function of preschool children with cancer and analyzed various influencing factors of neurocognitive functioning, is of significant importance. We aimed to investigate neurocognitive function and related risk factors in preschool children with cancer to inform preventive and intervention strategies. Methods: From September 2023 to May 2024, we recruited 100 preschool children with cancer. The Chinese version of the Ages & Stages Questionnaires, the Spence Preschool Anxiety Scale Chinese Version, and the Sleep Disturbance Scale for Children were used to collected data. Binary logistic stepwise regression analysis was used to explore the influencing factors of neurocognitive function in preschool children with cancer. Results: 49% of the preschool children with cancer had abnormalities in at least one neurocognitive dimension. The majority of children had abnormalities in gross motor dimension, accounting for 30%, which was related to age and frequency of participation in neurocognitive activities. Communication dimension was related to father's education level, dietary habit, and frequency of participation in activities. Fine motor dimension was associated with age, sex, and father's education level. Problem-solving dimension was associated with age and dietary habit. Personal-social dimension was related to age and radiotherapy. Conclusions: Nearly half of preschool children with cancer experienced neurocognitive impairment. The Chinese version of the Ages & Stages Questionnaires is a simple and effective tool for screening children with possible neurocognitive impairment. It was found that children's neurocognitive function was significantly influenced by family environment, dietary habit, cognitive activities, and cancer treatment. Therefore, it is recommended to strengthen family and social support, and to formulate personalized intervention such as cognitive therapy and dietary adjustment based on children's age and family background, which are important for promoting neurocognitive recovery. [ABSTRACT FROM AUTHOR]

Cancer immunotherapies produce remarkable results in B cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor and normal tissues to identify biologically relevant cell surface immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer. Proteogenomic analyses reveal sixty high-confidence candidate immunotherapeutic targets, and we prioritize delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlates with a super-enhancer. Immunofluorescence, flow cytometry, and immunohistochemistry show robust cell surface expression of DLK1. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells results in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), shows potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Since high DLK1 expression is found in several adult and pediatric cancers, our study demonstrates the utility of a proteogenomic approach and credentials DLK1 as an immunotherapeutic target. [Display omitted] • Multi-omic data integration prioritizes DLK1 as an immunotherapeutic target • DLK1 expression is driven by a super-enhancer • DLK1 silencing in neuroblastoma cells results in cellular differentiation • DLK1-directed ADC shows potent and specific cytotoxicity in preclinical models Hamilton et al. perform proteogenomic analyses to discover high-confidence candidate immunotherapeutic targets in neuroblastoma. Delta-like canonical notch ligand 1 (DLK1) is prioritized and validated. A DLK1-directed antibody-drug conjugate (ADCT-701) is developed and shows potent and specific in vivo cytotoxicity, supporting a phase 1 first-in-human clinical trial (ClinicalTrials.gov: NCT06041516). [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Design Methods Results Conclusion Implications for the Profession and/or Patient Care Impact Reporting Method Patient or Public To analyse how adolescents and young adults who survived childhood cancer experience their quality of life and to explore their meanings and conceptualisations of quality of life.Narrative design following Squire's method.In‐person and virtual recruitment, due to the global COVID‐19 pandemic, was carried out in Brazil between May and November 2021. Eighteen semi‐structured virtual interviews were conducted with childhood cancer survivors. These data were analysed using reflexive thematic analysis and employing a triangulation of investigators.Four subthemes were identified, encompassing participants' perceptions and meanings of quality of life. Through the reflection and synthesis of these subthemes, a central theme emerged entitled ‘New self’, capturing the profound impact of the cancer and survival experience on every aspect of the self, along with participants' sense of having gained ‘a new life’ and a ‘second chance’.The study provides a rich and nuanced understanding of quality of life for childhood cancer survivors. The results highlight that after all the changes in life due to cancer, integrating the new self becomes a central aspect of quality of life for survivors.Recognising the profound shifts in self‐perception that survivors of childhood cancer undergo, nurses should engage early in empowering patients and families, offering education, space and support to help adolescents and young adults grow throughout their journey.The richness and depth inherent in qualitative data on quality of life can inform the development of care standards and health policies for survivors, guide the allocation of strategic resources and shape the development of plans and interventions focusing on childhood cancer survivors.The COREQ checklist was used.No patient or public contribution. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Survival rates from childhood cancer continue to increase, with an ongoing interest in long‐term survivorship. Although infertility and gonadal failure are well recognized in Hodgkin lymphoma (HL) survivors, sexual dysfunction is less studied. The objective of this study was to compare the prevalence of sexual dysfunction in HL survivors with that in matched community controls.Long‐term survivors of HL (n = 186; female, 51.61%; mean age at diagnosis. 14.41 years [range, 3.01–22.60 years]; current mean ± standard deviation age, 36.73 ± 7.93 years) and matched community controls (n = 182; female, 50.55%; mean ± standard deviation age, 36.41 ± 9.02 years) completed a comprehensive, in‐person clinical assessment, laboratory battery, and the International Index of Erectile Function or the Female Sexual Function Index questionnaire.Male survivors had increased levels of erectile dysfunction (18.89% vs. 6.67%; p = .0239) but indicated no difference in sexual desire. Female survivors had a higher prevalence of sexual dysfunction compared with female controls (46.88% vs. 15.22%; p < .0001) and an increased prevalence of moderate‐to‐severe loss of sexual desire (38.04% vs. 23.26%; p = .0361). Female survivors with sexual dysfunction indicated increased levels of anxiety (p = .0184), depression (p = .0153), and worse physical and mental health (p = .0141 and p = .0419, respectively). Male survivors with erectile dysfunction had higher rates of anxiety and impaired physical health (p = .0147 and p = .0266, respectively).Sexual dysfunction was prevalent in this childhood and adolescent Hodgkin lymphoma survivor cohort and was associated with effects on quality of life. Health care providers must recognize the need for screening and intervention in this group to hopefully contribute to improved overall quality of life. [ABSTRACT FROM AUTHOR]

Objective: This research aims to explore parents' cognitive beliefs, specifically illness cognitions, in response to their children being diagnosed with cancer. This study is an initial step toward providing regular psychosocial assessment as a standard for psychosocial care for children with cancer and their families in Latvia. Methods: Data were collected from 120 parents (mostly mothers, n = 109) as an initial evaluation of the psychosocial risks faced by families participating in the support program "Holistic and Multidisciplinary Support for Children with Functional Disabilities and Their Family Members," which was managed by the Children's Hospital Foundation at the Children's Clinical University Hospital in Riga (Latvia) from 2020 to 2023. The patients comprised 66 boys and 54 girls (M age = 7.1, SD = 4.7, range: 0–17 years) with diverse cancer diagnoses. The parents completed the Latvian version of the Psychosocial Assessment Tool [adapted from PAT 3.1], with five subscales included in the data analysis (Social Support, Child Problems, Family Problems, Stress Reactions, and Family Beliefs). The Family Belief subscale was adjusted specifically to address the unique objectives and research questions of the current study. Results: Significant correlations were found between children's psychological problems (e.g., getting upset about medical procedures, hyperactivity, excessive use of electronic devices, etc.) and parental stress reactions after diagnosis and with self-reported symptoms of anxiety and depression. The associations were statistically significant, even after controlling for sociodemographic and medical factors such as diagnosis. The relationship between children's problems and parental stress reactions was partly mediated by Family Beliefs about illness. The most informative beliefs associated with parental stress symptoms and the family's psychosocial risk level were identified, and significant results were found according to the main component of beliefs (catastrophic vs. optimistic) that explained 42% of the variance in the Family Beliefs subscale. Implication: Understanding the habitual responses to stress and identifying the thinking patterns of parents that lead to distorted views and maladaptive coping are essential for customizing personalized interventions to enhance treatment compliance. The Latvian version of PAT is a useful psychosocial screening measure in pediatric oncology settings. [ABSTRACT FROM AUTHOR]

Neuroblastoma is the most common extracranial solid tumor in children, and a leading cause of childhood cancer deaths. All neuroblastomas arise from neural crest-derived sympathetic neuronal progenitors, but numerous mutations, the most common of which is MYCN amplification, give rise to these lesions. Epigenetic aberrations also play a role in oncogenesis and tumor progression. To better understand biologic diversity of neuroblastomas, we performed joint single-nucleus ATAC sequencing and single-nucleus RNA sequencing on six neuroblastoma cell lines, three of which are MYCN amplified. After standard filtering for high-quality nuclei, we obtained chromatin accessibility and transcript abundance data from 41,733 neuroblastoma tumor cells. Preliminary analysis reveals significant diversity in chromatin landscape and gene expression across neuroblastoma cell lines. This dataset is a valuable resource for studying the transcriptional and epigenetic mechanisms of this deadly childhood disease. [ABSTRACT FROM AUTHOR]

Introduction: Ependymoma is the third most frequent central malignant nervous system tumor in the pediatric age group. There is scarce data in the literature on survival of these patients, especially in upper and lower middle-income countries. We aimed to describe the clinical and demographic characteristics, treatment, and outcome of pediatric patients with ependymoma admitted to a public cancer hospital. Methods: Retrospective analysis of medical records of patients with ependymoma, admitted to the Pediatric Oncology department (0-20 years) during the period of 2000-2022. Data on patient, disease characteristics, and treatment were analyzed. Overall survival (OS) was calculated using the Kaplan-Meier method. Results: Seventy-two patients were evaluated; median age at diagnosis was 6.5 years (range: 1-20), 63% were male, 54% of the tumors were in the posterior fossa (PF-EPN), 45% were classified as WHO grade 3, and 68% were operated on in other institutions before referral. Regarding treatment, 72% underwent radiotherapy and 33% of patients underwent chemotherapy. Almost 70% percent of the patients had relapses. The median follow-up time was 5.2 years (Range: 0,1-21,4). The OS in 5 years was 67%. Totally resected tumors had OS in 5 years of 88% (p: 0.028). Conclusion: The results achieved in this series show a survival gap between UMIC and HIC. Relapses occurred mainly in the first ten years and then reached a plateau, with the majority of patients experiencing endocrinological and neurological sequelae. [ABSTRACT FROM AUTHOR]

The 3D genome prediction in cancer is crucial for uncovering the impact of structural variations (SVs) on tumorigenesis, especially when they are present in noncoding regions. We present InfoHiC, a systemic framework for predicting the 3D cancer genome directly from whole-genome sequencing (WGS). InfoHiC utilizes contig-specific copy number encoding on the SV contig assembly, and performs a contig-to-total Hi-C conversion for the cancer Hi-C prediction from multiple SV contigs. We showed that InfoHiC can predict 3D genome folding from all types of SVs using breast cancer cell line data. We applied it to WGS data of patients with breast cancer and pediatric patients with medulloblastoma, and identified neo topologically associating domains. For breast cancer, we discovered super-enhancer hijacking events associated with oncogenic overexpression and poor survival outcomes. For medulloblastoma, we found SVs in noncoding regions that caused super-enhancer hijacking events of medulloblastoma driver genes (GFI1, GFI1B, and PRDM6). In addition, we provide trained models for cancer Hi-C prediction from WGS at https://github.com/dmcb-gist/InfoHiC, uncovering the impacts of SVs in cancer patients and revealing novel therapeutic targets. Synopsis: InfoHiC is developed for cancer 3D genome prediction enabling to find neo-TADs and neo-loops starting from whole genome sequencing reads. InfoHiC is trained from available cancer Hi-C data and predicts Hi-C matrices for patients with cancer, which eliminates the burden of high Hi-C sequencing costs. InfoHiC takes whole genome sequencing reads in contrast to other Hi-C prediction tools requiring pre-defined sequences, enabling Hi-C prediction from cancer genomes where users cannot define sequence inputs easily. It analyzes all structural variation types including those found in non-coding regions, and predicts the impact on cancer development in the 3D genome context. It can lead to personalized medication by discovering neo-TADs and neo-loops in patients where common coding driver mutations or copy number changes are not found. InfoHiC is developed for cancer 3D genome prediction enabling to find neo-TADs and neo-loops starting from whole genome sequencing reads. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Design Methods Results Conclusions Impact Reporting Method Patient or Public Contribution To explore the mediating roles of family resources (at the individual [parental self‐efficacy], family [family resilience] and social level [social support]) and parental problem‐solving skills in the association between family functioning and family adaptation in families of children with cancer.A cross‐sectional study.This study recruited 318 parents of children with cancer from three tertiary hospitals in mainland China. Self‐report questionnaires were used to collect data on key variables, including family functioning, parental self‐efficacy, family resilience, social support, parental problem‐solving skills and family adaptation. Data analyses were carried out using descriptive analysis, univariate analysis, Pearson correlation analysis, hierarchical linear regression and bootstrapping.Family functioning was significantly and positively correlated with family adaptation. Family resources (parental self‐efficacy at the individual level, family resilience at the family level or social support at the social level) and parental problem‐solving skills both independently mediated the relationship between family functioning and family adaptation. Additionally, family resources at all three levels mediated the relationship through their effects on cumulatively parental problem‐solving skills, constructing a chain mediating model.The study underscores the significance of family functioning, family resources at the individual, family and social levels and parental problem‐solving skills in promoting adaptation in families of children with cancer. It highlights the need for family‐centred interventions targeted at these factors to improve family adaptation.This study extended related theories and previous studies to confirm the mediating role of family resources and parental problem‐solving skills, both independently and sequentially. Moreover, parental problem‐solving skills were confirmed as key elements that can be incorporated into future interventions, suggesting that problem‐solving skills training may serve as a highly promising program for families of children with cancer.This study was reported according to the STROBE checklist.No Patient or Public Contribution. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is the most common solid extracranial neoplasm found in children and is derived from primitive sympathoadrenal neural precursor. The disease accounts for 15% of all cancer deaths in children. The mortality rate is high in patients presenting with a metastatic tumour even with extensive treatments. This signifies the need for further research towards the development of new additional therapies that can combat not only tumour growth but metastasis, especially amongst the high-risk groups. During metastasis, primary tumour cells become migratory and travel towards a capillary within the tumour. They then degrade the matrix surrounding the pericytes and endothelial cells traversing the endothelial barrier twice to establish a secondary. This led to the hypothesis that modulation of the endothelial cell junctional stability could have an influence on tumour metastasis. To test this hypothesis, agents that modulate endothelial permeability on NB cell line migration and invasion were assessed in vitro in a tissue culture model. The cAMP agonist and its antagonists were found to have no obvious effect on both SK-N-BE2C and SK-N-AS migration, invasion and proliferation. Next, NB cells were cocultured with HDMEC cells and live cell imaging was used to assess the effect of an Epac agonist on trans-endothelial cell migration of NB cells. Epac1 agonist remarkably reduced the trans-endothelial migration of both SK-N-BE2C and SK-N-AS cells. These results demonstrate that an Epac1 agonist may perhaps serve as an adjuvant to currently existing therapies for the high-risk NB patients. [ABSTRACT FROM AUTHOR]

Introduction: Optimal outcomes during childhood cancer treatment require effective management of toxicities, often called supportive care. A lack of agreement on what comprises supportive care limits the development and provision of comprehensive guidance (for this work, we have defined supportive care as any disease‐ or treatment‐related condition experienced by children with cancer, excluding psychosocial conditions, palliative care, survivorship, or procedural topics). To address this gap, we conducted a consensus‐building exercise among global experts to define and prioritize topics for supportive care. Methods: Two rounds of brainstorming and prioritization exercises were conducted. A multidisciplinary panel nominated by professional societies and cooperative groups was formed to ensure geographic and resource representation using snowball sampling. An internal expert panel generated an initial list of supportive care topics. In round one, the multidisciplinary panel reviewed the initial list and recommended additional topics, followed by prioritization in round two using a seven‐point Likert scale. Results were summarized using descriptive statistics. Results: The multidisciplinary panel consisted of 57 members representing 32 countries. The initial list included 46 topics; 161 additional topics were suggested. After removing duplicates and out‐of‐scope additions, the final list contained 62 topics. Febrile neutropenia, sepsis, bloodstream infections, and pain were ranked highest priority. Mortality, morbidity, and frequency of the event were identified as the most important factors influencing prioritization. Conclusion: Through a multidisciplinary and globally representative process, we identified core supportive care topics and factors influencing their prioritization for childhood cancer. Outputs from this work will inform efforts to generate resource‐adapted recommendations for a global audience. This supports ongoing WHO CureAll work to develop a health systems‐level policy brief of supportive care requirements in the management of children with cancer. [ABSTRACT FROM AUTHOR]

Cancer predisposition syndromes (CPS) are a group of genetic disorders that increase the risk of various cancers. Identifying CPS has a significant impact on the treatment plan, screening and follow-up strategy, and genetic counseling of the family. However, in children, it goes underdiagnosed in most clinical setups, especially in low- and middle-income (LMIC) countries. In the present study, we screened 60 pediatric oncology patients for a possible CPS based on pre-defined selection criteria. Six patients met the criteria, three of whom had hematological malignancy, while the remaining three had sarcoma. Whole exome sequencing was performed in the selected patients to confirm the diagnosis. Germline mutation in CPS-related genes was discovered in five of six cases, including novel mutations discovered in two. An adverse outcome was observed in all five patients with underlying cancer predisposition syndrome, with three having relapsed and two having progressive disease. Our study reflects a prevalence of 10% underlying CPS in a limited cohort of patient based on the phenotype-genotype approach in our cohort. Using pre-defined clinical selection criteria, screening can be directed to a high-risk patient cohort with high-pick up rate for CPS. The selection criteria could be utilized in any LMIC-based clinical setup for pediatric cancer patients who may benefit from modification of treatment as well as genetic counseling. [ABSTRACT FROM AUTHOR]

Today, a majority of children diagnosed with cancer are expected to grow up and live—hopefully until old age. Still, knowledge of the lived experience of childhood cancer survivors is sparse. In pursuit of knowledge expansion, by combining my intersecting roles as an academic, educational counselor, and childhood cancer survivor, I approach my personal illness narrative. By means of evocative autoethnography, I write intentionally vulnerably about my experiences and make them available for consideration. I explore my narrative through archives, artifacts, memories of the past, and conversations evoked in the present. I re-visit the cultural landscape of a southern Norwegian girl growing up in the 00s with cancer. Through this, my illness narrative presents as positioned, tangled, and interwoven with a developmental trajectory. Specific educational experiences seem to linger, and many are related to being absent from or re-entering school after the onset of illness. To grasp the intersecting and conflicting experiences of being very ill while also young, I suggest Erik Erikson's moratorium as a key concept. To complement Arthur Frank's illness narratives of restitution, chaos, and quest, I establish the moratorium narrative. As a fresh resource, the moratorium narrative underlines the need to make sensitive our academic community's gaze on illness trajectories unfolding in formative phases and illness narratives defined by growing up. By providing a point of recognition that prompts elaboration, this could also provide the young and very ill with a much-needed narrative space of opportunity, of which more narratives are invited and insisted upon. [ABSTRACT FROM AUTHOR]

Childhood cancers are life-threatening diseases that affect the whole family. During the treatment moral situations might arise. Research on how parents perceive moral challenges in childhood cancer care is sparse. The aim was to explore parents' main concern, and how they deal with their main concern, when facing moral challenges in childhood cancer care. Data collection included focus group interviews with parents. The data analysis was carried out according to a classical theory and revealed the core category "Sheltering in chaos". The strategies to handle the main concern included "To bring the child through a life-saving trajectory" by "Balancing control" and "Deliberating of suffering. The consequences included feelings of being "Torn between roles". "Familiarity" emerged as a facilitating factor to handle moral challenges. The results indicate that parents are torn between different roles, and that the care experience is improved through familiarity with the healthcare professionals. The following findings may inspire new ways of offering moral support to families in childhood cancer care. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. ALL originates from precursor lymphocytes that acquire multiple genomic changes over time, including chromosomal rearrangements and point mutations. While a large variety of genomic defects was identified and characterized in ALL over the past 30 years, it was only in recent years that the clonal heterogeneity was recognized. Thanks to the latest advancements in single-cell sequencing techniques, which have evolved from the analysis of a few hundred cells to the analysis of thousands of cells simultaneously, the study of tumor heterogeneity now becomes possible. Different modalities can be explored at the single-cell level: DNA, RNA, epigenetic modifications, and intracellular and cell surface proteins. In this review, we describe these techniques and highlight their advantages and limitations in the study of ALL biology. Moreover, multiomics technologies and the incorporation of the spatial dimension can provide insight into intercellular communication. We describe how the different single-cell sequencing technologies help to unravel the molecular complexity of ALL, shedding light on its development, its heterogeneity, its interaction with the leukemia microenvironment and possible relapse mechanisms. [ABSTRACT FROM AUTHOR]

Although survivors of childhood cancer are at an increased risk, little is known about the prevalence of chronic pain, associated interference, and daily pain experiences. Survivors (N 5 233; mean age 5 40.8 years, range 22-64 years; mean time since diagnosis 5 32.7 years) from the Childhood Cancer Survivor Study completed pain and psychosocial measures. Survivors with chronic pain completed 2-week, daily measures assessing pain and psychological symptoms using mHealth-based ecological momentary assessment. Multivariable-modified Poisson and linear regression models estimated prevalence ratio estimates (PR) and mean effects with 95% confidence intervals (CI) for associations of key risk factors with chronic pain and pain interference, respectively. Multilevel mixed models examined outcomes of daily pain and pain interference with prior day symptoms. Ninety-six survivors (41%) reported chronic pain, of whom 23 (24%) had severe interference. Chronic pain was associated with previous intravenous methotrexate treatment (PR 5 1.6, 95% CI 1.1-2.3), respiratory (PR 5 1.8, 95% CI 1.2-2.5), gastrointestinal (PR 5 1.6, 95% CI 11.0-2.3), and neurological (PR 5 1.5, 95% CI 1.0-2.1) chronic health conditions, unemployment (PR 5 1.4, 95% CI 1.0-1.9) and clinically significant depression and anxiety (PR 5 2.9, 95% CI 2.0-4.2), as well as a diagnosis of childhood Ewing sarcoma or osteosarcoma (PR 5 1.9, 95% CI 1.0-3.5). Higher pain interference was associated with cardiovascular and neurological conditions, unemployment and clinical levels of depression and/or anxiety, and fear of cancer recurrence. For male, but not female survivors, low sleep quality, elevated anxiety, and elevated depression predicted high pain intensity and interference the next day. A substantial proportion of childhood cancer survivors experience chronic pain and significant associated interference. Chronic pain should be routinely evaluated, and interventions are needed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Early life exposure to cisplatin induces TRPV1 and nociceptor sensitisation. • Cisplatin alters the developmental trajectory of nociceptors to be TrkA dependent. • Cisplatin induced survivorship pain is dependent upon TrkA signalling. Cisplatin-based chemotherapy is a common treatment for paediatric cancer. Unfortunately, cisplatin treatment causes neuropathic pain, a highly prevalent adverse health related complication in adult childhood cancer survivors. Due to minimal understanding of this condition, there are currently no condition tailored analgesics available. Here we investigated an alteration in nociceptor maturation that results in neuronal sensitisation and manifestation of cisplatin induced survivorship pain in a TrkA dependent manner. Cisplatin was administered (i.p. 0.1 mg/kg Postnatal day 14 and 16) to neonatal male and female Wistar rats and nociceptive behavioural assays were performed. In vitro studies utilised isolated neonatal dorsal root ganglia sensory neurons treated with cisplatin (5 μg/ml) to elucidate impact upon nociceptor activation and neurite growth, in combination with TrkA inhibition (GW441756 10 nM and 100 nM). Cisplatin treated male and female neonatal Wistar rats developed a delayed but lasting mechanical and heat hypersensitivity. Cisplatin administration led to increased TrkA expression in dorsal root ganglia sensory neurons. Nerve growth factor (NGF) induced TrkA activation led to sensory neuritogenesis and nociceptor sensitisation, which could be prevented through pharmacological TrkA inhibition (GW441756 either s.c. 100 nM or i.p. 2 mg/kg). Administration of TrkA antagonist suppressed cisplatin induced TRPV1 mediated nociceptor sensitisation and prevented cisplatin induced neuropathic pain. These studies provide greater understanding of the underlying mechanisms that cause cisplatin induced childhood cancer survivorship pain and allowing identification of potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of pediatric cancer related deaths. Targeting neuroblastoma with immunotherapies has proven challenging due to a paucity of immune cells in the tumor microenvironment and the release of immunosuppressive cytokines by neuroblastoma tumor cells. We hypothesized that combining an oncolytic Herpes Simplex Virus (oHSV) with natural killer (NK) cells might overcome these barriers and incite tumor cell death. Methods: We utilized MYCN amplified and non-amplified neuroblastoma cell lines, the IL-12 expressing oHSV, M002, and the human NK cell line, NK-92 MI. We assessed the cytotoxicity of NK cells against neuroblastoma with and without M002 infection, the effects of M002 on NK cell priming, and the impact of M002 and priming on the migratory capacity and CD107a expression of NK cells. To test clinical applicability, we then investigated the effects of M002 and NK cells on neuroblastoma in vivo. Results: NK cells were more attracted to neuroblastoma cells that were infected with M002. There was an increase in neuroblastoma cell death with the combination treatment of M002 and NK cells both in vitro and in vivo. Priming the NK cells enhanced their cytotoxicity, migratory capacity and CD107a expression. Conclusions: To the best of our knowledge, these investigations are the first to demonstrate the effects of an oncolytic virus combined with self-maintaining NK cells in neuroblastoma and the priming effect of neuroblastoma on NK cells. The current studies provide a deeper understanding of the relation between NK cells and neuroblastoma and these data suggest that oHSV increases NK cell cytotoxicity towards neuroblastoma. [ABSTRACT FROM AUTHOR]

Objective The way in which parental posttraumatic stress symptoms (PTSS) unfold in the first year after a cancer diagnosis in their child is poorly understood. The aims of this study were to identify parental PTSS trajectories and to examine couple-related predictors (dyadic coping and we-disease appraisals), sociodemographic predictors (education and sex), and medical predictors (child's physical impairment) of trajectory membership. Method A 1-year prospective study was conducted, and 157 parents of children newly diagnosed with cancer were assessed. PTSS was measured with the Posttraumatic Diagnostic Scale for DSM-5 (PDS-5) at 3–6 weeks (T1), 6 months (T2), and 12 months (T3) after the diagnosis. The trajectories were identified with Latent Class Growth Analysis, the predictors were explored with binomial logistic regression. Results Two distinct trajectories were found. The majority of parents (86.0%) followed a low PTSS trajectory, characterized by initially low scores that slightly decreased over 12 months. In contrast, 14.0% of parents displayed a stable, high PTSS trajectory. A high trajectory of child's physical impairment and low scores in parental dyadic coping were significantly associated with the likelihood of a high parental PTSS trajectory. Conclusions The findings provide new insights into the critical period of the first year after a child's cancer diagnosis. While most parents display a resilient, low PTSS trajectory, a minority consistently experience high PTSS levels. Child's physical impairment and dyadic coping should be considered as predictors for early identification of vulnerable parents. Incorporating dyadic coping in parental support following a childhood cancer diagnosis could be beneficial for parental mental health. [ABSTRACT FROM AUTHOR]

Introduction: Childhood cancers as a group affect around 1 in 500 children but each individual diagnosis is a rare disease. While research largely focuses on improving cure rates, the management of side effects of treatment are high priority for clinicians, families and children and young people. Areas covered: The prevention and efficient management of infectious complications, oral mucositis, nausea and vomiting and graft-vs-host disease illustrated with examples of implementation research, translation of engineering to care, advances in statistical methodologies, and traditional bench-to-patient development. The reviews draw from existing systematic reviews and well conducted clinical practice guidelines. Expert opinion: The four areas are driven from patient and family priorities. Some of the problems outlined are ready for proven interventions, others require us to develop new technologies. Advancement needs us to make the best use of new methods of applied health research and clinical trial methodologies. Some of the greatest challenges may be those we're not fully aware of, as new therapies move from their use in adult oncological practice into children. This will need us to continue our collaborative, multi-professional, multi-disciplinary and eclectic approach. [ABSTRACT FROM AUTHOR]

Acute Lymphoblastic Leukemia (ALL) is one of the most common cancers among children under the age of 15. An increasing awareness to detect early leukemia can be avoided preventable deaths from leukemia. Accurate leukemia cells image classification plays a crucial role in reducing health risks by enabling early diagnosis, which helps in mitigating the severity of the disease through timely and targeted treatment The detection of Acute Lymphoblastic Leukemia incurs significant costs in terms of time. We have developed an alternative method, A Modified EfficientNetV2-S to detect Acute Lymphoblastic Leukemia quickly, accurately, and affordably. We proposed a new architecture called Hybrid Kernel on EfficientNetV2-S. Our architecture integrates three convolutions with different kernels: regular convolution, dilated convolution, and depth-wise convolution. Three convolutions work together in one layer to provide detailed information about the object. The Network Encapsulation method uses convolution results to find object features from an image based on different locations and directions and provide combined convoluted information. We update the weight to customize the Networks Encapsulation feature map results iteratively. We continuously repeat this operation until the updated weight difference falls below the specified threshold. The approach we suggested is unique because it uses several kernels for convolutions to help capture various feature variations. We have evaluated our new architecture using the C-NMC-2019 dataset at three learning and epoch pairs: {0.001;5}, {0.0001;10}, and {0.00001;15}. We used 12,528 images to assess the reliability of our proposed new architecture. The results showed that the best accuracy, precision, recall, and F1-Score were 97.44%, 97.35%, 98.88%, and 97.48%, respectively. Our proposed method performance outperformed VGG19, Xception, RestNet50, and EfficientNetB0. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to analyze the clinicopathological characteristics and survival outcomes of tongue cancer in the pediatric population, a topic with limited existing data, using a population‐based cohort. Methods: Pediatric patients diagnosed with tongue cancer from 1975 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Survival rates were assessed using Kaplan–Meier analysis. Univariate survival analysis was conducted with the log‐rank test, while multivariate analysis involved Cox proportional‐hazards regression to identify factors influencing overall survival (OS). A predictive nomogram was developed based on Cox regression findings. Results: In total, 97 pediatric patients with tongue cancer were identified, with a median age at diagnosis of 15 years (range: 1–19 years). Tumors were classified as squamous cell carcinoma (45.4%), rhabdomyosarcoma (RMS) (13.4%), and others (41.2%). Of the patients, squamous cell carcinoma was more common in older children, whereas rhabdomyosarcoma was more common in younger children. The Cox proportional hazard regression revealed that histology and surgery were significant independent predictors of overall survival. The chance of death increased with no surgery. Moreover, patients with squamous cell carcinoma or rhabdomyosarcoma have a poorer survival percentage than patients with other subtypes. Conclusions: Tongue cancer in children is rare and associated with poor survival outcomes. This study highlights the significance of tumor histology and surgical intervention in determining overall survival, offering valuable insights for clinical decision‐making in pediatric tongue cancer. [ABSTRACT FROM AUTHOR]

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with germline pathogenic/likely pathogenic variants in TP53. Genotype-phenotype correlations are progressively being characterized in LFS with certain TP53 variants associated with attenuated penetrance and phenotypes. We report on a family harboring a TP53 p.R181H variant presenting with a restricted cancer phenotype in adulthood. The proband was a female with breast cancer at the age of 71 years who had three first degree relatives also diagnosed with breast cancer after the age of 40 years (mother, two sisters). Of the nine individuals harboring the variant (6 genetically confirmed, 3 obligate heterozygous), six have not developed malignancies at this time (age range: 36–42). No childhood-onset cancers were reported in this family. A concomitant literature review identified 51 additional individuals harboring the p.R181H variant in TP53, presenting a tumor phenotype dominated by breast cancer. Rare occurrences of other adult-onset cancers (prostate, colorectal and thyroid) and only few childhood onset cancer were documented. These observations are consistent with functional analysis showing that p.R181H retains partial p53 function and suggesting possible reduced cancer penetrance, particularly in the pediatric setting. [ABSTRACT FROM AUTHOR]

Constitutional Mismatch Repair Deficiency (CMMRD) is a rare childhood cancer predisposition syndrome, caused by biallelic pathogenic germline variants in the mismatch repair genes. Diagnosis and management of this syndrome is challenging, especially in low-resource settings. This study describes a patient diagnosed with colorectal cancer and grade 3 astrocytoma at the age of 11 and 12 respectively. Immunohistochemistry analysis showed a loss of MSH2 and MSH6 protein expression in CRC tissues of the patient. We identified by Targeted Exome Sequencing a homozygous pathogenic germline variant in exon 9 of the MSH6 gene (c.3991 C > T; p.Ala1268Glyfs*6). Genetic investigation of the family showed that the father was heterozygous for the identified pathogenic variant while the brother was wild type for this variant. Our study highlights the importance of a correct and timely diagnosis of CMMRD which can have implications for treatment. It also underlines the imperative need to enhance awareness, diagnostic standards, and surveillance that are crucial for patients and their families. [ABSTRACT FROM AUTHOR]

Background: Adaptation of evidence-based interventions (EBIs) often occurs when implemented in new local contexts and settings. It is unclear, however, during which phase of implementation adaptations are most frequently made and how these changes may impact the fidelity, effectiveness, and sustainability of the EBI. Pediatric Early Warning Systems (PEWS) are EBIs for early identification of deterioration in hospitalized children with cancer. This study evaluates adaptations of PEWS made among resource-variable pediatric oncology hospitals in Latin America implementing and sustaining PEWS. Methods: We conducted a cross-sectional survey among pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), a collaborative to implement PEWS. Adaptations to PEWS were assessed via 3 multiple choice and 1 free text question administered as part of a larger study of PEWS sustainability. Descriptive statistics quantitatively described what, when, and why adaptations were made. Qualitative analysis of free text responses applied the Framework for Reporting Adaptations and Modifications Expanded (FRAME) to describe respondent perspectives on PEWS adaptations. Results: We analyzed 2,094 responses from 58 pediatric oncology centers across 19 countries in Latin America. Participants were predominantly female (82.5%), consisting of nurses (57.4%) and physicians (38.2%) who were PEWS implementation leaders (22.1%) or clinical staff (69.1%). Respondents described multiple PEWS adaptations across all implementation phases, with most occurring during the planning and piloting of EBIs. Adaptations included changes to PEWS content (algorithm, scoring tool, terminology, and use frequency) and context (personnel delivering or population). Respondents felt adaptations streamlined monitoring, enhanced effectiveness, improved workflow, increased comprehension, and addressed local resource limitations. Qualitative analysis indicated that most adaptations were categorized as fidelity consistent and planned; fidelity inconsistent adaptations were unplanned responses to unanticipated challenges. Conclusion: Adaptations made to PEWS across implementation phases demonstrate how EBIs are adapted to fit dynamic, real-world clinical settings. This research advances implementation science by highlighting EBI adaptation as a potential strategy to promote widespread implementation and sustainability in hospitals of all resource levels. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Childhood cancer therapy may cause subfertility. This study correlated cancer therapy exposures with testicular volumes from puberty to adulthood, spermatogenesis, and paternity outcomes in adulthood.The study population comprised 255 male childhood cancer survivors (CCS) (survival ≥5 years, diagnosed in 1964–2000 at the Helsinki Children's Hospital) whose testicular volume was measured at ages 12 years (n = 38), 14 years (n = 57), 16 years (n = 63), 18 years (n = 105), and in adulthood (n = 43; median age, 27 years). Testicular volumes were converted to age‐specific z scores. In addition, 92 CCS provided semen sample in adulthood (median age, 25.2 years); and paternity was evaluated through national register data (mean age at assessment, 37.6 years; n = 252).Compared with age‐specific reference values, CCS generally exhibited low testicular volume z scores at ages 12–18 years. Testicular volume z scores in CCS treated exclusively with chemotherapy returned to the reference range in adulthood. In contrast, patients exposed to testicular radiation ≥1 gray (Gy) (median dose, 12 Gy) showed no late recovery in testicular size. Testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥12 g/m2 were identified as risk factors for azoospermia in adulthood. Patients exposed to testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥4 g/m2 had lower paternity rates.Testicular volume growth after prolonged follow‐up suggests a potential late recovery of spermatogenesis in CCS treated exclusively with chemotherapy. However, alkylating agents increased the risk of having prolonged azoospermia and nonpaternity. High‐dose testicular radiation causes long‐term depletion of spermatogonia and was the strongest risk factor for azoospermia and nonpaternity. [ABSTRACT FROM AUTHOR]

Background: Child cancer impacts the entire family. However, those who identify as mothers may be most negatively affected due to the societal expectations placed upon them in primary caregiving. This study was conducted with the aim of exploring the lived experiences of mothers of children with cancer and their adaptation to their child's illness. Methods: This study employed a qualitative and hermeneutic approach using Heideggerian phenomenology as a philosophical framework. Our sampling strategy was purposive. Mothers (n = 14) of children diagnosed with cancer participated in face-to-face semi-structured interviews. The seven-steps of critical hermeneutic analysis were used to summarize and interpret findings. Results: Analysis revealed that participants' adaptation to their child's illness occurs through comprehensive support and the utilization of empowering beliefs. The theme of comprehensive support included sub-themes of seeking informational support, seeking psychological support, and seeking social support. The theme of utilizing empowering beliefs encompassed sub-themes of resilience against cultural misconceptions and reliance on spiritual beliefs. Furthermore, one constitutive pattern 'mothers' efforts to overcome difficult twists and turns in living with children with cancer' was identified.This related to participants' striving to navigate the twists and turns of life's hardships. Conclusions: Relationships and social context are vital and important features of this phenomena. Employing a team approach to provide comprehensive support to mothers of children with cancer involving physicians, nurses, and psychologists can be supportive in their adaptation to their child's cancer. Additionally, reductions in cultural taboos surrounding cancer could facilitate improved adaptation to childhood cancer for these mothers. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Paediatric cancers are rare, and most children requiring radiation therapy receive external beam radiation (EBRT). Although EBRT may offer organ preservation compared to surgery, it can be associated with significant late effects. Image‐guided brachytherapy is a highly specialised technique offering both organ preservation and dose conformity to minimise late toxicity.This is a retrospective mono‐institutional review of paediatric brachytherapy in one of the largest paediatric centres in Australia. Outcomes and toxicities are presented as well as brachytherapy versus proton plan comparison in four patients.A total of 14 patients were treated with adjuvant brachytherapy between 2012 and 2022. The predominant histology was rhabdomyosarcoma, and all patients had pelvic tumours. High‐dose rate (HDR) brachytherapy was given for 13 patients with one patient receiving low‐dose rate (LDR) brachytherapy. Only one grade three late toxicity was reported and two patients developed metastatic disease within one year of completion of treatment. The brachytherapy plan was superior to protons in two of four patients and equivocal in one patient.This is the first Australian publication of a paediatric brachytherapy series from a single institution. This retrospective series demonstrates the feasibility and safety of brachytherapy in paediatric pelvic tumours. The initial work presented here demonstrates the value of a comprehensive radiation plan review in selecting the optimal modality for an individual paediatric patient. [ABSTRACT FROM AUTHOR]

Background: Pediatric pancreatic tumors, especially with duodenal invasion, are exceptionally rare and a strategy for their treatment has not been established. A pancreaticoduodenectomy is often the desired treatment, but may be over-invasive for solid pseudopapillary neoplasm (SPN). This study reports an innovative surgical approach for SPN with duodenal invasion using pancreatic enucleation and endoscopically guided partial duodenectomy. Case presentation: An 11-year-old girl complained of malaise and presented with severe anemia; imaging revealed a tumor of undetermined origin, involving the pancreatic head and descending duodenum. Intraoperative findings showed tumor adherence to the pancreatic head and endoscopy revealed invasion of the duodenum. The tumor was enucleated from the pancreatic head, and partial duodenectomy was performed under endoscopically guided direct visualization. Pathology confirmed SPN with duodenal invasion, and no residual tumor. Although a Grade B pancreatic fistula occurred postoperatively, it was managed conservatively. At the 15-month follow-up, no signs of tumor recurrence, duodenal stenosis, or pancreatic dysfunction were evident. Conclusions: Given the good prognosis of SPN, we believe that enucleation from the pancreatic head combined with an endoscopically guided partial duodenectomy could be a useful and less invasive alternative to pancreaticoduodenectomy for cases with duodenal invasion. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is one of the most lethal childhood cancers due to its propensity to become treatment resistant. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicate these two contrasting scenarios and show branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment. Neuroblastoma (NB) is a frequent childhood cancer that often becomes resistant to therapy. Here, the authors perform spatiotemporal genomic profiling of NBs before and after chemotherapy and find an evolutionary process characteristic of NBs growing resistant after first responding to treatment. [ABSTRACT FROM AUTHOR]

H3K27M diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPG), exhibit cellular heterogeneity comprising less-differentiated oligodendrocyte precursors (OPC)-like stem cells and more differentiated astrocyte (AC)-like cells. Here, we establish in vitro models that recapitulate DMG-OPC-like and AC-like phenotypes and perform transcriptomics, metabolomics, and bioenergetic profiling to identify metabolic programs in the different cellular states. We then define strategies to target metabolic vulnerabilities within specific tumor populations. We show that AC-like cells exhibit a mesenchymal phenotype and are sensitized to ferroptotic cell death. In contrast, OPC-like cells upregulate cholesterol biosynthesis, have diminished mitochondrial oxidative phosphorylation (OXPHOS), and are accordingly more sensitive to statins and OXPHOS inhibitors. Additionally, statins and OXPHOS inhibitors show efficacy and extend survival in preclinical orthotopic models established with stem-like H3K27M DMG cells. Together, this study demonstrates that cellular subtypes within DMGs harbor distinct metabolic vulnerabilities that can be uniquely and selectively targeted for therapeutic gain. Pediatric brain cancers are lethal malignancies driven by less-differentiated stem-like cells. Here the authors show that these cells exhibit distinct mitochondrial metabolism programs with targetable vulnerabilities. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors face high risks of adverse late health effects. Long‐term follow‐up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high‐quality long‐term follow‐up care, we explored expected barriers and facilitators for establishing this follow‐up care among healthcare providers from four European clinics. Methods: A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi‐structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political. Results: Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long‐term follow‐up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long‐term follow‐up care results to convince hospital managers. Conclusion: This study identified several factors for successful implementation of long‐term follow‐up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors. [ABSTRACT FROM AUTHOR]

Background: Subsequent short‐latency leukemias are well‐described among survivors of childhood cancer. However, late (5–14.9 years from diagnosis, LL) and very late (≥15 years from diagnosis, VLL) subsequent leukemias have not been well studied. We assessed risk factors, prevalence, and outcomes for LL and VLL in the Childhood Cancer Survivor Study cohort. Methods: Subsequent leukemias, among 25,656 five‐year survivors, were self‐reported and confirmed by pathology review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, and relative risks (RR) were estimated using Cox regression for exposures. Results: Seventy‐seven survivors developed subsequent leukemia, 49 survivors with LL (median time from diagnosis 7.8 years, range 5.0–14.5 years) and 28 with VLL (median time from diagnosis 25.4 years, range 15.9–42.8 years), with a cumulative incidence of 0.23% (95% CI 0.18%–0.30%) 20 years from diagnosis for all subsequent leukemias. The most common leukemia subtypes were acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. Compared to the general population, survivors were at increased risk, for developing LL (SIR 9.3, 95% CI 7.0–12.1) and VLL (SIR 5.9, 95% CI 3.9–8.4). In multivariable relative risk analyses, cumulative epipodophyllotoxin dose >4000 mg/m2 was associated with increased risk for LL and VLL (RR 4.5, 95% CI 2.0–9.9). Conclusions: In this large series of late subsequent leukemias, survivors of childhood cancer are at increased risk, with no evidence of plateau over time. We observed most risk among survivors who received high cumulative doses of epipodophyllotoxins. Ongoing consideration for this late effect should continue beyond 10 years. [ABSTRACT FROM AUTHOR]

Background: The KDM1A histone demethylase regulates the cellular balance between proliferation and differentiation, and is often deregulated in human cancers including the childhood tumor neuroblastoma. We previously showed that KDM1A is strongly expressed in undifferentiated neuroblastomas and correlates with poor patient prognosis, suggesting a possible clinical benefit from targeting KDM1A. Methods: Here, we tested the efficacy of NCL-1, a small molecule specifically inhibiting KDM1A in preclinical models for neuroblastoma. Results: NCL-1 mimicked the effects of siRNA-mediated KDM1A knockdown and effectively inhibited KDM1A activity in four neuroblastoma cell lines and a patient-representative cell model. KDM1A inhibition shifted the aggressive tumor cell phenotypes towards less aggressive phenotypes. The proliferation and cell viability was reduced, accompanied by the induction of markers of neuronal differentiation. Interventional NCL-1 treatment of nude mice harboring established neuroblastoma xenograft tumors reduced tumor growth and inhibited cell proliferation. Reduced vessel density and defects in blood vessel construction also resulted, and NCL-1 inhibited the growth and tube formation of HUVEC-C cells in vitro. Conclusions: Inhibiting KDM1A could attack aggressive neuroblastomas two-fold, by re-directing tumor cells toward a less aggressive, slower-growing phenotype and by preventing or reducing the vascular support of large tumors. [ABSTRACT FROM AUTHOR]

Background: Identifying and recognizing environmental risk factors for childhood cancer is crucial to prevent it. Medical guild are the first contact to monitor children's health. Therefore, courses about the contribution of chemical toxins in the environment and health outcomes such as cancer should be included in their professional training. This study aimed to evaluate the perceptions and attitudes of a medical guild and undergraduate students in health sciences about the contribution of the environment to childhood cancer. Methods: A pilot study was conducted, an online survey including thirteen questions was shared among medical guild members and undergraduate students in health sciences. Frequencies, percentages, and chi-square homogeneity tests were calculated to compare groups. Results: Genetic factors ranked as the first possible cause of childhood cancer (88.2% medical guild and 97.7% undergraduate students). However, 70.6% of medical guild and 64.6% of undergraduate students reported that they have ever suspected that childhood cancer could be related to the environmental conditions in which children live. More than 95% of the participants reported that they would find it useful to have more knowledge about environmental risks and cancer. When data were analyzed by profession (medical guild) and academic year (undergraduate students), no significant differences were observed. Nonetheless, comparisons by academic discipline between undergraduate students, showed that a higher percentage of medicine and environmental sciences and health (over 98%) reported environmental exposure as risk factors associated with childhood cancer compared to 75% from physiotherapy, (p = 0.001). Conclusions: In this study, the environmental contribution to childhood cancer is not clear among the medical guild and undergraduate students. They should be trained on the topic of cancer and the environment. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Many childhood cancer survivors are at risk for cardiovascular disease and stroke. The North American Children's Oncology Group long‐term follow‐up guidelines recommend carotid ultrasound in cancer survivors 10 years after neck radiation therapy (RT) ≥40 Gy. The use of carotid ultrasound in this population has not been described.Survivors of childhood cancer diagnosed 1970‐1999 (N = 8693) and siblings (N = 1989) enrolled in the Childhood Cancer Survivor Study were asked if they had ever had a carotid ultrasound. Prevalence of carotid ultrasound was evaluated. Prevalence ratios (PR) and 95% confidence intervals (CIs) were evaluated in multivariate Poisson regression models.Among participants with no reported cardiovascular condition, prevalence of carotid ultrasound among survivors with RT ≥40 Gy to the neck (N = 172) was 29.7% (95% CI, 22.5–36.8), significantly higher than those with <40 Gy (prevalence 10.7%; 95% CI, 9.9%–11.4%). Siblings without a cardiovascular condition (N = 1621) had the lowest prevalence of carotid ultrasound (4.7%; 95% CI, 3.6%–5.7%). In a multivariable models among survivors with no reported cardiovascular condition and RT ≥40 Gy to the neck, those who were over age 50 (vs. 18–49) at follow‐up (PR = 1.82; 95% CI, 1.09–3.05), with a history of seeing a cancer specialist in the last 2 years (PR = 2.58; 95% CI, 1.53–4.33), or having a colonoscopy (PR = 2.02; 95% CI, 1.17–3.48) or echocardiogram (PR = 6.42; 95% CI, 1.54–26.85) were more likely to have had a carotid ultrasound.Many survivors do not undergo carotid ultrasound despite meeting existing guidelines. Health care delivery features such as having seen a cancer specialist or having other testing are relevant. [ABSTRACT FROM AUTHOR]

Purpose: Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS). Methods: We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals. Results: The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5–31.2 and RHR = 5.1, 95%CI 4.4–5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7–13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7–3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3–4.7) compared to those who did not receive radiotherapy. Conclusions: Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals. [ABSTRACT FROM AUTHOR]

Neurotrophic receptor tyrosine kinases (TrkA, TrkB, TrkC), despite their homology, contribute to the clinical heterogeneity of the childhood cancer neuroblastoma. TrkA expression is associated with low-stage disease and is often seen with spontaneous tumour regression. Conversely, TrkB is present in unfavourable neuroblastomas that often harbour amplification of the MYCN oncogene. The role of TrkC is less clearly defined, although some studies suggest its association with a favourable outcome. Understanding the differences in activity of Trk receptors that drive divergent clinical phenotypes as well as the influence of MYCN amplification on downstream Trk receptor signalling remains poorly understood. Here, we present a comprehensive label-free mass spectrometry-based total proteomics and phosphoproteomics dataset (432 raw files with FragPipe search outputs; available on PRIDE with accession number PXD054441) where we identified and quantified 4,907 proteins, 16,744 phosphosites and 5,084 phosphoproteins, derived from NGF/BDNF/NT-3 treated TrkA/B/C-overexpressing neuroblastoma cells with differential MYCN status. Analysing our dataset offers valuable insights into TrkA/B/C receptor signalling in neuroblastoma and its modulation by MYCN status; and holds potential for advancing therapeutic strategies in this challenging childhood cancer. [ABSTRACT FROM AUTHOR]

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 wildtype 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. [ABSTRACT FROM AUTHOR]

AbstractTemporal 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. [ABSTRACT FROM AUTHOR]

Objective: This report details the experience of a patient who developed a second primary glioblastoma (GB), offering insights into the treatment process and reviewing relevant literature. Case presentation: A male patient, who was diagnosed with medulloblastoma at age 9, received treatment with cobalt-60 craniospinal irradiation (CSI) (36 Gy/20 fractions) and a tumor bed boost (total of 56 Gy). After 32 years, at age 41, an MRI revealed a space-occupying mass in the left cerebellar hemisphere. Surgical resection was performed, and postoperative pathology confirmed a diagnosis of radiation-induced glioblastoma (RIGB). Given the history of irradiation and the current tolerability of brainstem doses, proton beam therapy (PBT) combined with Temozolomide (75 mg/m2) was chosen. The treatment plan included 60 Gy on the gross tumor bed and 54 Gy on the clinical target volume, delivered in 30 fractions. The patient underwent regular follow-up and achieved a complete response. Clinical discussion: For childhood cancer survivors, the development of a second primary tumor significantly impacts prognosis. RIGB is a rare form of secondary tumor with distinct molecular characteristics compared to primary GB and recurrent secondary GB. Molecular markers such as IDH and MGMT status can help differentiate between primary GB, recurrent secondary GB, and radiation-induced secondary GB in patients with a history of prior radiation therapy. Surgical resection remains a primary treatment option, while PBT is preferred for postoperative treatment due to its superior protection of normal tissues and the ability to deliver high-dose irradiation. Conclusion: RIGB is a rare second primary tumor that requires strategic molecular profiling and individualized management. Proton beam therapy provides effective high-dose irradiation in the postoperative phase and is the preferred treatment option for such cases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neuroblastoma is a devastating disease accounting for ~15% of all childhood cancer deaths. Collagen content and fiber association within the tumor stroma influence tumor progression and metastasis. High expression levels of collagen receptor kinase, Discoidin domain receptor II (DDR2), are associated with the poor survival of neuroblastoma patients. Additionally, cancer cells generate and sustain mechanical forces within their environment as a part of their normal physiology. Despite this, evidence regarding whether collagen-activated DDR2 signaling dysregulates these migration forces is still elusive. To address these questions, a novel shRNA DDR2 knockdown neuroblastoma cell line (SH-SY5Y) was engineered to evaluate the consequence of DDR2 on cellular mechanics. Atomic force microscopy (AFM) and traction force microscopy (TFM) were utilized to unveil the biophysical altercations. DDR2 downregulation was found to significantly reduce proliferation, cell stiffness, and cellular elongation. Additionally, DDR2-downregulated cells had decreased traction forces when plated on collagen-coated elastic substrates. Together, these results highlight the important role that DDR2 has in reducing migration mechanics in neuroblastoma and suggest DDR2 may be a promising novel target for future therapies. [ABSTRACT FROM AUTHOR]

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging childhood cancer to treat, with limited therapeutic options and high relapse rates. This study explores deamidated triosephosphate isomerase (dTPI) as a novel therapeutic target. We hypothesized that selectively inhibiting dTPI could reduce T-ALL cell viability without affecting normal T lymphocytes. Computational modeling and recombinant enzyme assays revealed that disulfiram (DS) and curcumin (CU) selectively bind and inhibit dTPI activity without affecting the non-deamidated enzyme. At the cellular level, treatment with DS and CU significantly reduced Jurkat T-ALL cell viability and endogenous TPI enzymatic activity, with no effect on normal T lymphocytes, whereas the combination of sodium dichloroacetate (DCA) with DS or CU showed synergistic effects. Furthermore, we demonstrated that dTPI was present and accumulated only in Jurkat cells, confirming our hypothesis. Finally, flow cytometry confirmed apoptosis in Jurkat cells after treatment with DS and CU or their combination with DCA. These findings strongly suggest that targeting dTPI represents a promising and selective target for T-ALL therapy. [ABSTRACT FROM AUTHOR]

Objective: This study examines the association between psychosocial risk and protective factors and a wide range of psychosocial outcomes including emotional, social, cognitive, and physical domains in childhood cancer survivors (CCS). Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)‐LATER cohort (diagnosed 1963–2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed questionnaires on psychosocial risk and protective factors (Benefit and Burden Scale, Illness Cognition Questionnaire, Rosenberg Self‐Esteem Scale, and Impact of Cancer Scale), and psychosocial outcomes (Hospital Anxiety and Depression Scale, Self‐Rating Scale for Post‐Traumatic Stress Disorder, TNO‐AZL Questionnaire for Adult Health‐Related Quality of Life, and Short Form‐36). Associations were assessed with regression analysis, adjusting for attained age, sex, number of health conditions, and time since diagnosis, while correcting for multiple testing (p < 0.004). Results: A total of 1382 CCS participated, all diagnosed ≥ 15 years ago. The mean age of participating CCS was 36 years, and 51% were female. Perceived benefit and burden, acceptance, and helplessness, self‐esteem and social support were associated with the psychosocial outcomes. In the models including all psychosocial factors, most associations with psychosocial outcomes were seen for self‐esteem (10×), and perceived burden (9×). Self‐esteem (all β ≤ 0.47) and perceived burden (all β ≤ 0.38) demonstrated strongest associations of medium/large size. Conclusions: Perceptions of childhood cancer, illness cognitions, self‐esteem, and social support play a role in explaining psychosocial functioning in CCS, outweighing the influence of socio‐demographic and medical variables. Addressing negative perceptions and reducing feelings of helplessness, while promoting acceptance, self‐esteem, and social support, could provide intervention targets for CCS who encounter psychosocial challenges. [ABSTRACT FROM AUTHOR]

Backgroud: Cancer‐related cognitive impairment is one of the common complications in children with cancer, but our understanding of their experience with cognitive deficits remains limited. From the perspective of parents, this study aimed to explore the distress and demands faced by children with cancer‐related cognitive impairment, to provide references for developing targeted intervention strategies for cancer children. Methods: We used a purposeful sampling method to conduct semi‐structured interviews with the parents of 18 children with cancer‐related cognitive impairment. The transcripts were analyzed using Colaizzi's method. Results: Three categories and 11 subcategories were obtained from the data analysis, including diverse levels of cognitive impairment in children (speech communication difficulties, impaired executive function, attention deficit, and intellectual disability), persistent negative emotions (anxiety and worry, complaints and resentment, negative avoidance and positive experiences after psychological adjustment), multiple needs (need for disease information, need for professional management, and an urgent need for more external support). Conclusion: Parents of children with cancer‐related cognitive impairment face a significant psychological burden, coupled with confusion and numerous inquiries regarding the symptoms and management of their children's cognitive impairment. It is imperative for medical professionals to strengthen the dissemination of information related to cancer‐associated cognitive impairments, while promptly recognizing and intervening in related symptoms. Rational allocation of resources, establishment of targeted support systems, and enhancement of social acceptance may be the key points that policymakers could consider. These efforts hold immense significance, as they play a pivotal role in elevating cognitive capabilities and enhancing the overall quality of life for children with cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Gangliosides are glycosphingolipids composed of a sialylated glycan head group and a ceramide backbone. These anionic lipids form lipid rafts and play crucial roles in regulating various proteins involved in signal transduction, adhesion, and cell–cell recognition. Neuroblastoma, a pediatric cancer of the sympathetic nervous system, is treated with intensive chemotherapy, radiation, and an antibody targeting the GD2 ganglioside. Gangliosides are critical in neuroblastoma development and serve as therapeutic targets, making it essential to establish a reliable, rapid, and cost-effective method for profiling gangliosides, particularly one capable of isomeric separation of intact species. In this study, liquid chromatography–mass spectrometry (LC-MS) was optimized using standard gangliosides, followed by the optimization of sphingolipid extraction methods from cell lines by comparing Folch and absolute methanol extraction techniques. Percent recovery and the number of identified sphingolipids were used to evaluate the analytical merits of these methods. A standard gangliosides calibration curve demonstrated excellent linearity (R2 = 0.9961–0.9975). The ZIC-HILIC column provided the best separation of ganglioside GD1 isomers with a 25 min runtime. GD1a elutes before GD1b on the ZIC-HILIC column. Absolute methanol yielded better percent recovery (96 ± 7) and identified 121 different sphingolipids, the highest number between the two extraction methods. The optimized method was applied to profile gangliosides in neuroblastoma (COG-N-683), pancreatic cancer (PSN1), breast cancer (MDA-MB-231BR), and brain tumor (CRL-1620) cell lines. The ganglioside profile of the neuroblastoma cell line COG-N-683 showed an inverse relationship between GD1 and GD2. Ceramide, Hex1Cer, GM1, and GM3 were highly abundant in CRL-1620, PSN1, and MDA-MB-231BR, respectively. These results suggest that our method provides a sensitive, reliable, and high-throughput workflow for ganglioside profiling across different cell types. [ABSTRACT FROM AUTHOR]