OBJECTIVE: Cancer is a leading cause of global childhood mortality, affecting 400,000 children annually. While treatable with modern therapies, children living in low- and middle-income countries (LMICs) have limited access to care and lower survival rates. Hospital-based cancer registries (HBCRs) collect detailed patient information to critically evaluate and evolve care. The St. Jude Global Childhood Cancer Analytics Resource and Epidemiological Surveillance System (SJCARES) is a cloud-based HBCR network facilitating quality data collection of pediatric cancer. Wide variation in the success of implementation has warranted further research into the implementation approach, to create a sustainable and adaptable HBCR in LMICs.
METHODS: Seven of 89 sites using the SJCARES registry were selected, stratified by global region and stage of implementation. Semi-structured interviews were conducted with key groups (clinicians, administrators, data clerks) using an interview guide developed from the Consolidation Framework for Implementation Research (CFIR). Interviews were conducted via a video-telephone software program and transcribed by a transcription service. Transcripts were thematically coded using rapid qualitative analysis.
RESULTS: A total of 18 participants (11 clinicians, 4 administrators, 3 data clerks) were interviewed. Several barrier themes were identified, including: difficulty integrating the registry into existing workflow; lack of resources; lack of government or administrative support; and damaged, misplaced, or illegible medical records. Facilitator themes were identified, including: internal support for the registry; clear and extensive training; and dedicated support staff.
CONCLUSIONS: Interviewed participants identified key barriers and facilitators to the implementation of the SJCARES registry across multiple phases. We plan to use these results to develop targeted implementation strategies including a readiness assessment tool to help guide more successful implementation of the SJCARES registry and other HBCRs in LMICs.

The knowledge surrounding the application of immune checkpoint inhibitors (ICIs) in the treatment of pediatric cancers is continuously expanding and evolving. These therapies work by enhancing the body\'s natural immune response against tumors, which may have been suppressed by certain pathways. The effectiveness of ICIs in treating adult cancers has been widely acknowledged. However, the results of early phase I/II clinical trials that exclusively targeted the use of ICIs for treating different pediatric cancers have been underwhelming. The response rates to ICIs have generally been modest, except for cases of pediatric classic Hodgkin lymphoma. There seems to be a notable disparity in the immunogenicity of childhood cancers compared to adult cancers, potentially accounting for this phenomenon. On average, childhood cancers tend to have significantly fewer neoantigens. In recent times, there has been a renewed sense of optimism regarding the potential benefits of ICI therapies for specific groups of children with cancer. In initial research, individuals diagnosed with pediatric hypermutated and SMARCB1-deficient cancers have shown remarkable positive outcomes when treated with ICI therapies. This is likely due to the underlying biological factors that promote the expression of neoantigens and inflammation within the tumor. Ongoing trials are diligently assessing the effectiveness of ICIs for pediatric cancer patients in these specific subsets. This review aimed to analyze the safety and effectiveness of ICIs in pediatric patients with different types of highly advanced malignancies.

OBJECTIVE: Emerging evidence suggests a higher risk of human papillomavirus-associated subsequent malignant neoplasms (HPV-SMNs) in childhood cancer survivors. However, comprehensive population-based risk estimates for HPV-SMNs are lacking.
METHODS: We utilized longitudinal data obtained from the Surveillance, Epidemiology, and End Results program between 1975 and 2018 to establish a cohort comprising childhood cancer individuals who survived for at least 5 years. Standardized incidence ratio (SIR) with corresponding 95 % confidence interval (95 %CI) was used to evaluate the relative risk of HPV-SMNs. The competing risk regression model was performed to identify risk factors associated with HPV-SMNs.
RESULTS: A total of 35,397 childhood cancer survivors were included. Among them, 42 individuals subsequently developed HPV-SMNs (median time from primary cancer, 25 years). HPV-SMN anatomic sites included cervix (N=16), oropharynx (N=15), anus (N=5), vulva\\vagina (N=5), and penis (N=1). The 40-year cumulative incidence rate of HPV-SMNs was estimated to be 0.51 %. All survivors had a 10-fold increased risk of developing HPV-SMNs compared to individuals of similar age in the general population (SIR 10.1, 95 %CI 7.3-13.6). The competing risk regression model indicted that age at diagnosis and the type of primary malignancy could potentially influence the development of HPV-SMNs. Furthermore, multivariable Cox regression analysis confirmed that the presence of HPV-SMNs significantly increased the risk of mortality for survivors (hazard ratio 2.63, 95 %CI 1.68-4.14).
CONCLUSIONS: Childhood cancer survivors have a significantly elevated risk of developing HPV-SMNs, accompanied by poor survival outcomes. Encouraging HPV vaccination and robust surveillance protocols may improve long-term health outcomes in childhood cancer survivors.

BACKGROUND: Hepatoblastoma (HB) is the most common pediatric liver tumor, presenting significant therapeutic challenges due to its high rates of recurrence and metastasis. While Inosine Monophosphate Dehydrogenase 2(IMPDH2) has been associated with cancer progression, its specific role and clinical implications in HB have not been fully elucidated.
METHODS: This study utilized Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Tissue Microarray (TMA) for validation. Following this, IMPDH2 was suppressed, and a series of in vitro assays were conducted. Flow cytometry was employed to assess apoptosis and cell cycle arrest. Additionally, the study explored the synergistic therapeutic effects of mycophenolate mofetil (MMF) and doxorubicin (DOX) on HB cell lines.
RESULTS: The study identified a marked overexpression of IMPDH2 in HB tissues, which was strongly correlated with reduced Overall Survival (OS) and Event-Free Survival (EFS). IMPDH2 upregulation was also found to be associated with key clinical-pathological features, including pre-chemotherapy alpha-fetoprotein (AFP) levels, presence of preoperative metastasis, and the pre-treatment extent of tumor (PRETEXT) staging system. Knockdown of IMPDH2 significantly inhibited HB cell proliferation and tumorigenicity, inducing cell cycle arrest at the G0/G1 phase. Notably, the combination of MMF, identified as a specific IMPDH2 inhibitor, with DOX, substantially enhanced the therapeutic response.
CONCLUSIONS: The overexpression of IMPDH2 was closely linked to adverse outcomes in HB patients and appeared to accelerate cell cycle progression. These findings suggest that IMPDH2 may serve as a valuable prognostic indicator and a potential therapeutic target for HB.
CONCLUSIONS: The present study unveiled a significant overexpression of inosine monophosphate dehydrogenase 2 (IMPDH2) in hepatoblastoma (HB) tissues, particularly in association with metastasis and recurrence of the disease. The pronounced upregulation of IMPDH2 was found to be intimately correlated with adverse outcomes in HB patients. This overexpression appears to accelerate the progression of the cell cycle, suggesting that IMPDH2 may serve as a promising candidate for both a prognostic marker and a therapeutic target in the context of HB.

UNASSIGNED: Childhood and adolescent cancer represent a significant health burden in the United States. Current and precise epidemiological data are crucial to develop effective cancer control plans and ultimately reduce the burden of childhood and adolescent cancer.
UNASSIGNED: We analyzed data obtained from cancer registries in the National Cancer Institute\'s Surveillance, Epidemiology, and End Results Program. Age-standardized incidence and death rates, assessed using joinpoint analysis, were quantified as annual percentage changes (APC) and average percentage changes (AAPC).
UNASSIGNED: The overall cancer incidence rate in 2008-2018 was 187.9 per 1,000,000 persons. Cancer incidence rates demonstrated a sustained upward trend, with an APC of 0.8 from 1975 to 2018. Incidence rates during 2008-2018 remained stable among non-Hispanic Black children but increased among other racial and ethnic groups. Leukemias, central nervous system tumors, and lymphomas were the most common cancer groups for patients aged 0-19 years. Cancer death rates decreased among children [AAPC, -1.3 (95% CI, -1.5 to -1.1)] during 2009-2019, while were stable among adolescents during that period.
UNASSIGNED: In this study, we analyzed cancer incidence and mortality rates and trends in children aged 0-19 years in the United States. Our findings revealed an overall increase in cancer incidence rates among children and adolescents, accompanied by a decline in cancer mortality rates over time. These rates and trends varied by age, sex, and particularly race and ethnicity, highlighting the significance of comprehending and addressing disparities and ultimately reducing the disease burden of childhood and adolescent cancer.

OBJECTIVE: Pediatric cancer is a significant health concern in China, and evaluating the impact of cancer and its treatment on the well-being of young patients is essential for both clinical care and research purposes. This study aimed to psychometrically validate the Patient-reported Outcomes Measurement Information System Pediatric-25 Profile (PROMIS-Pediatric-25) among Chinese children with cancer.
METHODS: We enrolled a group of 114 children living with cancer between the ages of 8 and 17. Each participant completed questionnaires that covered sociodemographic and clinical information and the PROMIS-Pediatric-25. The floor and ceiling effect was examined. Cronbach\'s alpha and split-half coefficient were examined to determine the reliability. Factor structure was explored by factor analysis. Three assumptions of Rasch model-based item response theory (IRT) were assessed. Differential item functioning (DIF) was investigated concerning factors of gender, diagnosis, and treatment stage.
RESULTS: The floor or ceiling effects were detected for six domains. The reliability was found to be excellent. Furthermore, the factor structure of these six domains was validated. Our analysis confirmed that the assumptions required for IRT were met with acceptable unidimensionality, local independence, and good monotonicity. Additionally, we observed measurement equivalence, with outstanding levels of DIF across factors such as gender, diagnosis, and treatment stage.
CONCLUSIONS: PROMIS-Pediatric 25 is a highly reliable and valid instrument for evaluating key domains of health-related quality of life in Chinese pediatric cancer patients.
CONCLUSIONS: Nursing practice could engage the PROMIS-Pediatric 25 for accurate and quick children symptom and function assessment.

To evaluate the efficiency and long-term renal function of nephron sparing surgery (NSS) in unilateral WT patients compared with radical nephrectomy (RN). The review was performed following Cochrane Handbook guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched five databases (Pubmed, Embase, Scopus, Web of Science and Cochrane) for studies reporting the efficiency and late renal function of NSS and/or RN on February 10, 2023. Comparative studies were evaluated by Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) and RoB 2.0. Assessed outcomes included survival rate, relapse rate, eGFR, renal dysfunction and hypertension. 26 studies involving 10322 unilateral WT cases underwent RN and 657 unilateral WT cases underwent NSS were enrolled. Overall effect estimates demonstrated that NSS significantly increased eGFR at follow-up (SMD, 0.38; 95% CI 0.05-0.72; p = 0.025) compared to that at diagnosis, and RN did not significantly decrease eGFR at follow-up (SMD, - 0.33; 95% CI - 0.77-0.11; p = 0.142) compared to that at diagnosis. Moreover, no significant difference was found in outcomes of survivability (OR, 1.38; 95% CI 0.82-2.32; p = 0.226), recurrence (OR, 0.62; 95% CI 0.34-1.12; p = 0.114), eGFR at follow-up (SMD, 0.16; 95% CI - 0.36-0.69; p = 0.538), renal dysfunction (OR, 0.36; 95% CI 0.07-1.73; p = 0.200) and hypertension (OR, 0.17; 95% CI 0.03-1.10; p = 0.063). Current evidence suggests that NSS is safe and effective for unilateral WT patients, because it causes better renal function and similar oncological outcomes compared with RN. Future efforts to conduct more high-quality studies and explore sources of heterogeneity is recommended.

Acute lymphoblastic leukemia (ALL) is the most prevalent form of pediatric leukemia. The gut microbiome (GM) is crucial for proper nutrition, immunity, and biological conflict. Since the relationship between ALL and GM is bidirectional, ALL occurrence and treatment are closely related to GM destruction and the development of impaired immunity. Studies have discovered significant GM alterations in patients with ALL, including decreased diversity, that are likely directly caused by the development of ALL. Chemotherapy, antibiotic therapy, and hematopoietic stem cell transplantation (HSCT) are the mainstays of treatment for pediatric ALL. These approaches affect the composition, diversity, and abundance of intestinal microorganisms, which in turn affects therapeutic efficiency and can cause a variety of complications. Modulating the GM can aid the recovery of patients with ALL. This article discusses the various treatment modalities for pediatric ALL and their corresponding effects on the GM, as well as the changes in the GM that occur in children with ALL from diagnosis to treatment. Gaining a greater understanding of the link between ALL and the GM is expected to help improve treatment for pediatric ALL in the future.

UNASSIGNED: Anthracycline cardiotoxicity is a concern in survivors of childhood cancers. Recent evidence suggests that remote ischemic conditioning (RIC) may offer myocardial protection.
UNASSIGNED: This randomized sham-controlled single-blind study tested the hypothesis that RIC may reduce myocardial injury in pediatric cancer patients receiving anthracycline chemotherapy.
UNASSIGNED: We performed a phase 2 sham-controlled single-blind randomized controlled trial to determine the impact of RIC on myocardial injury in pediatric cancer patients receiving anthracycline-based chemotherapy. Patients were randomized to receive RIC (3 cycles of 5-minute inflation of a blood pressure cuff placed over 1 limb to 15 mm Hg above systolic pressure) or sham intervention. The intervention was applied within 60 minutes before initiation of the first dose and before up to 4 cycles of anthracycline therapy. The primary outcome was the plasma high-sensitivity cardiac troponin T (hs-cTnT) level. The secondary outcome measures included echocardiographic indexes of left ventricular systolic and diastolic function and the occurrence of cardiovascular events.
UNASSIGNED: A total of 68 children 10.9 ± 3.9 years of age were randomized to receive RIC (n = 34) or sham (n = 34) intervention. Plasma levels of hs-cTnT showed a progressive increase across time points in the RIC (P < 0.001) and sham (P < 0.001) groups. At each of the time points, there were no significant differences in hs-cTnT levels or LV tissue Doppler and strain parameters between the 2 groups (all P > 0.05). None of the patients developed heart failure or cardiac arrhythmias.
UNASSIGNED: RIC did not exhibit cardioprotective effects in childhood cancer patients receiving anthracycline-based chemotherapy. (Remote Ischaemic Preconditioning in Childhood Cancer [RIPC]; NCT03166813).

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) can be used in pediatric patients. This study assessed the safety and efficacy of PEG-rhG-CSF as a primary prophylactic drug against neutropenia after chemotherapy in pediatric patients with solid tumors or non-Hodgkin lymphoma (NHL).
This phase II study (between October 2020 and March 2022) enrolled pediatric patients with solid tumors or NHL treated with high-intensity chemotherapy and with grade ≥3 myelosuppression for at least 14 days during chemotherapy. Prophylactic PEG-rhG-CSF was given at 100 μg/kg body weight (maximum total dosage of 6 mg) once 24-48 h following chemotherapy for two cycles. The primary endpoint was the incidence of PEG-rhG-CSF-related adverse events (AEs). The key secondary endpoints were the rates of grade 3/4 neutropenia and febrile neutropenia (FN).
This study included 160 pediatric patients with a median age of 6.22 (0.29, 18.00) years. Fifty-eight patients (36.25%) were diagnosed with sarcoma. AEs potentially related to PEG-rhG-CSF included bone pain (n = 32), fatigue (n = 21), pain at the injection site (n = 21), and myalgia (n = 20). The rates of grade 3/4 neutropenia and FN during treatment were 57.28% and 29.45%, respectively.
PEG-rhG-CSF is well tolerated and effective in pediatric patients with solid tumors or NHL. These findings should be substantiated with further trials.
ClinicalTrials.gov identifier: NCT04547829.