In children with leukemia, cerebral venous sinus thrombosis (CVST) has a significant incidence and mortality rate, which may interfere with the chemotherapy process and lead to long-term neurological complications. However, large studies and population-based data on CVST in children are scarce. This study aims to characterize pediatric CVST associated with pegaspargase (PEG-ASP) and evaluate the significance of magnetic resonance venography (MRV) screening following induction remission in acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). We present a retrospective cohort of a total of 27 children with CSVT and ALL/LBL. The study covers a 4-year period for MRV screening following induction remission and an 8-year comparison period, involving 716 children treated at the Department of Hematology, Children's Hospital of Fudan University. The detection rate of CVST significantly increased after MRV screening (8.4% vs. 1.6%, p < 0.01). Over half (58%) of the CVST cases were asymptomatic. Male (84% vs. 52%, p = 0.008), immune subtype of T (37% vs. 10%, p = 0.001) and higher initial platelet counts (196.25 ± 140.67 vs. 112.49 ± 115.62, p = 0.02) patients were more likely to develop CVST. The common symptoms were headache (56%), seizures (31%), vomiting (13%), lethargy (13%), coma (6%), hallucinations (6%), and schizophrenia (6%). Symptomatic patients had a higher likelihood of transverse sinus involvement (75% vs. 9%, p = 0.006). Asymptomatic patients had shorter treatment durations (25.5 ± 16.7 weeks vs. 51.6 ± 25.8 weeks, p = 0.02) and fewer long-term complications (50% vs. 0%, p = 0.02). Thromboelastographic amplitude values at 30 minutes after maximum amplitude were significantly higher in symptomatic patients (49.4 ± 13.2 vs. 35.1 ± 8.3, p = 0.01). This study highlights a significant incidence of PEG-ASP-related CVST in children, with MRV screening revealing a notably higher detection rate than previously reported. Most cases were asymptomatic, which demonstrated better prognoses, emphasizing the importance of MRV for early CVST diagnosis after induction remission in ALL/LBL.

Wilms tumor (WT), which represents about 90% of kidney tumors in children, is the most prevalent type of renal tumor among children. In developed countries, advancements in treatments such as chemotherapy and radiotherapy have led to high survival rates. However, developing countries face significant challenges, including late-stage diagnosis, metastasis at presentation, and high rates of treatment abandonment.

This retrospective study included all patients diagnosed with WT at a tertiary hospital in Western China from 2007 to 2021. It involved the collection of sociodemographic and clinical details, including data on patients who abandoned treatment. Follow-up continued until July 2024.

This study consisted of 301 WT patients. Of the 259 who completed the treatment, the 5-year event-free survival (EFS) and overall survival (OS) rates were 77.9% and 81.2%. Of the 42 patients who abandoned treatment, 13 refused further care immediately after diagnosis and signed a refusal document, 16 discontinued treatments during preoperative neoadjuvant chemotherapy, and 13 failed to complete the prescribed chemotherapy or radiotherapy.

Survival rates for WT patients at our institution approach those reported in developed countries. Challenges include late-stage diagnosis, metastasis at initial presentation, and treatment abandonment. To address these issues, implementing pediatric screening is critical for early detection and timely intervention, particularly for families vulnerable to abandoning treatment. For high-risk cases, oncologists need develop targeted strategies to enhance clinical outcomes.

PDGFRA is crucial to tumorigenesis and frequently genomically altered in high-grade glioma (HGG). In a comprehensive dataset of pediatric HGG (n = 261), we detect PDGFRA mutations and/or amplifications in 15% of cases, suggesting PDGFRA as a therapeutic target. We reveal that the PDGFRA/KIT inhibitor avapritinib shows (1) selectivity for PDGFRA inhibition, (2) distinct patterns of subcellular effects, (3) in vitro and in vivo activity in patient-derived HGG models, and (4) effective blood-brain barrier penetration in mice and humans. Furthermore, we report preliminary clinical real-world experience using avapritinib in pediatric and young adult patients with predominantly recurrent/refractory PDGFRA-altered HGG (n = 8). Our early data demonstrate that avapritinib is well tolerated and results in radiographic response in 3/7 cases, suggesting a potential role for avapritinib in the treatment of HGG with specific PDGFRA alterations. Overall, these translational results underscore the therapeutic potential of PDGFRA inhibition with avapritinib in HGG.

Innovative surgical approaches are crucial in pediatric oncology to enhance treatment outcomes and minimize morbidity. Robotic-assisted surgery (RAS) has shown promise in both surgical precision and recovery in pediatric patients. This systematic review aims to address this gap by examining the current role and impact of RAS in managing pediatric genitourinary tumors, focusing on its feasibility, safety, and patient outcomes. This review was registered with PROSPERO (CRD42023464820). We included studies involving pediatric patients undergoing RAS for genitourinary tumors, focusing on outcomes like conversion rates, resection completeness, and complications. Studies were identified through searches in PubMed, EMBASE, and Scopus until October 2023. Study quality and bias were assessed using ROBINS-I for cohort studies and Joanna Briggs Institute tools for case reports and series. Of 2119 citations, 42 studies were included, comprising 29 case reports, five case series, and eight retrospective cohort studies. Robotic-assisted renal surgeries were most common, with favorable outcomes in terms of resection completeness and low recurrence rates. Adrenal, bladder, and retroperitoneal surgeries also showed promising results, although rare instances required conversion to open surgery. Collaborative efforts and perioperative aids like intraoperative ultrasound and three-dimensional modeling were crucial for success. This work is limited by the lack of large cohort studies and addressing the learning curve associated with these procedures. RAS shows promise in treating pediatric genitourinary tumors, offering precise resections and favorable outcomes, warranting further research and refinement.

Acute abdominal pain is a prevalent clinical symptom in pediatric patients, primarily attributed to pediatric acute abdomen. However, there are rare exceptional instances where neoplastic diseases may cause acute abdominal pain.

The present study encompasses a case of pediatric Burkitt lymphoma wherein acute abdominal pain manifested as the initial symptom, erroneously diagnosed as acute appendicitis.

The immunohistochemistry results of laparoscopic biopsy revealed Burkitt lymphoma, characterized by positive expression of CD20, CD79a, CD10, BCL-6, MUM1, and strong positive expression of CD38, c-myc, cyclinD1, and Ki-67 positive index >90%+.

The child underwent regular chemotherapy according to the SCCCG-BL/DLBCL-2017 regimen.

During the 13-month follow-up period, the patient's obtained complete remission by Positron emission tomography-computed tomography scan.

The objective of this study is to enhance the awareness of clinical pediatricians regarding cases of acute abdominal pain caused by lymphoma.

Despite the growing population of young cancer survivors of reproductive age, the risk of cancer in offspring born to female cancer survivors has yielded inconsistent results. Therefore, this study aimed to investigate the risk of cancer among the offspring of female cancer survivors by maternal age at delivery, maternal age at cancer diagnosis, maternal cancer type, and the time interval between cancer diagnosis and pregnancy. Using nationwide retrospective mother-child linked data from the Korean National Health Insurance Service, we included the first child (N = 8031) of female cancer survivors aged < 40 years after excluding thyroid cancer survivors and matched controls (N = 24,093) between 2005 and 2019. Subgroup analysis was performed according to maternal age at delivery, maternal age at cancer diagnosis, maternal cancer type, and the interval between cancer diagnosis and delivery. Among the offspring, 19 children of cancer survivors and 30 in the control group were diagnosed with cancer, with a mean age of 2.0 years at diagnosis. The most prevalent cancer type was leukemia (26.5%), followed by liver tumor (10.2%) and brain tumor (8.2%). The hazard ratio (HR) for cancer in the offspring of female cancer survivors was 1.91 (95% confidence interval (CI) = 1.07-3.38) demonstrating consistently high risk over the follow-up period. HRs for cancer risk in offspring were high across all subgroups despite the low statistical power. Our study indicated that offspring born to maternal cancer survivors had an increased risk of cancer.

Maternal hormonal contraception use has been associated with childhood leukemia risk. However, studies are few and often based on self-reported information.

Using registry data from Denmark, Norway, and Sweden, we identified 3,183,316 children (born 1996-2018) and followed them from birth until leukemia diagnosis, censoring (death, emigration, other cancer, 20th birthday) or study closure (December 31st, 2017, 2018 or 2020). We estimated hazard ratios (HRs) and 95 % confidence intervals (CIs) for childhood leukemia (any, lymphoid and non-lymphoid) associated with maternal recent use (≤ 3 months before or during pregnancy) or previous use (before recent use) of hormonal contraception overall and by type, compared to no use.

During 29,455,528 person-years, 1701 children developed leukemia (no use: 518, previous use: 974, recent use: 209). Maternal recent use of hormonal contraception was associated with an increased leukemia risk in children (HR 1.22, 95 % CI 1.04-1.44; incidence rate per 1,000,000 person-years [IR] 65), compared to no use (IR 53). The association was strongest for non-lymphoid leukemia (HR 1.69, 95 % CI 1.20-2.37) and mainly driven by the oral combined products, both for any leukemia (HR 1.29, 95 % CI 1.05-1.59) and non-lymphoid leukemia (HR 1.75, 95 % CI 1.17-2.62). Additionally, non-lymphoid leukemia was associated with recent use of the non-oral progestin-only products (HR 2.10, 95 % CI 1.28-3.44).

Although the absolute risk was low, maternal hormonal contraception use up to or during pregnancy was associated with an increased childhood leukemia risk, particularly non-lymphoid leukemia, and mainly driven by oral combined and non-oral progestin-only products.

Survivors of pediatric head and neck rhabdomyosarcoma (HNRMS) are at risk of developing endocrinopathies following local treatment, resulting from radiation damage to the pituitary gland, hypothalamus, or thyroid gland, often at a young age. Our aim was to determine the prevalence of endocrine dysfunction in long-term HNRMS survivors and compare the prevalence of anterior pituitary insufficiency (API) among different local treatment strategies: external beam radiation with photons, external beam radiation with protons, microscopically radical surgery combined with external irradiation, and macroscopic radical surgery combined with brachytherapy.

Head and neck rhabdomyosarcoma survivors treated between 1993 and 2017, with ≥2 years of follow-up, without recurrent disease or secondary malignancy were eligible for this study. The presence of any endocrine dysfunction was assessed cross-sectionally using Common Terminology Criteria of Adverse Events grading, anthropometrics, and biochemical testing. Retrospective chart review was added to this clinical assessment.

Ninety-six survivors with long follow-up time (median, 9 years) were included. Any endocrinopathy was present in 35% of survivors, with 88% having pituitary, 6% peripheral (thyroid), and 6% combined insufficiencies. None had gonadal insufficiency. Growth hormone deficiency was diagnosed in 31 (32%) survivors, with additional pituitary insufficiencies in 12 (39%). In 8%, central precocious puberty preceded API. None of the survivors given brachytherapy had API.

The prevalence of pituitary dysfunction in HNRMS survivors is high, emphasizing the importance of systematic endocrine assessment during follow-up, including pubertal development and growth. Efforts should be made to further reduce extraneous irradiation to endocrine organs to prevent dysfunction later in life.

Changes in bone age and tooth development are late side effects of cancer therapy and can be identified by imaging examination.

To evaluate the late effects of antineoplastic treatment on bone age and dental development in childhood cancer survivors.

This is a retrospective case-control study on paediatric cancer survivors of both sexes who underwent antineoplastic treatment with 5-15 years of survival. Carpal radiographs were assessed for bone age and growth curve, and panoramic radiographs were used to evaluate dental development and alterations. Carpal radiographs were analyzed using the Greulich and Pyle inspection method, and the Martins and Sakima method was used to analyze the growth curve. All tests were applied with a confidence level of 95%.

The study and control groups comprised 28 and 56 patients, respectively. There was no significant difference in bone age and growth curve between the study and control groups. Nonetheless, when sex was compared to chronological and bone ages, there was a significant difference in bone age (p = 0.019) and an underestimation in both groups and sexes in the Greulich and Pyle method. As to late dental effects, dental agenesia, microdontia, gyroversion, and unerupted teeth were found. Dental shape alterations mainly involve the root region.

Close multidisciplinary collaboration is necessary during the follow-up period of young patients who have survived cancer.

Retinoblastoma is the most common intraocular malignancy in childhood. Despite one-third of cases occurring in Africa, little is known of the outcomes on the continent. This study aims to explore survival and globe salvage outcomes and identify their risk factors across a large cohort of patients from the African continent.

A 3-year prospective, observational study was conducted. Kaplan-Meier survival analysis was used to investigate the risk of globe loss and death from retinoblastoma in Africa. Cox regression was used to identify risk factors associated with these outcomes.

A total of 958 patients from 41 African countries and 66 participating centres were enrolled in the study. The survival rate was 78.2% at 1 year and 66.2% at 3 years after diagnosis. Cox regression showed a higher risk of death with the most advanced clinical stage (cT4, HR=6.29 vs cT2, p<0.001). The risk of losing at least one eye after diagnosis was 50% within 4 months and 72.6% within 3 years. Higher risk of enucleation was associated with a higher clinical stage compared with cT1 (cT3, HR=4.11, p=0.001; cT4, HR=3.77, p=0.005).

Nearly one in every four children diagnosed with retinoblastoma in African participating centres succumb to retinoblastoma within 1 year. There is also high morbidity associated with the diagnosis as a large majority of patients require eye removal surgery. The outcome of disease in children with retinoblastoma in Africa is poor compared with other continents and requires prompt intervention by increasing efforts to improve survival and eye salvage outcomes.

Smell and taste changes are frequently reported bothersome treatment symptoms during treatment for childhood cancer and assumed to influence outcomes such as food intake. Since nutritional status of children with cancer is already vulnerable, any detrimental effects on food intake should be prevented. Therefore, understanding the exact relationship between chemosensory changes and dietary intake, eating behavior, and other domains such as health-related quality of life (HRQoL), is important for improving outcomes.

In this longitudinal study, we followed 87 childhood cancer patients treated for hematological, solid, or brain malignancies. Smell (odor threshold and odor identification) and taste function (total taste score) were objectively investigated using commercial Sniffin' Sticks and Taste Strips respectively, and by self-report. Dietary intake was measured using a 3-day food dairy. For nutritional status, BMI expressed as standard deviation scores was derived from medical records. Eating behavior and HRQoL were assessed by the Behavioral Pediatrics Feeding Assessment Scale (BPFAS) and PedsQL 4.0 Generic Core Scales, respectively. Measurements were taken approximately 6 weeks (T0), 3 months (T1), 6 months after starting chemotherapy (T2), and 3 months after termination of chemotherapy or maintenance phase for children with acute lymphoblastic leukemia (ALL) (T3). Dietary intake, eating behavior, nutritional status, and HRQoL were modelled over time using mixed model analysis. Associations between smell and taste (objective and self-report), as well as patient characteries were studied.

Energy intake significantly increased during the study period, with a higher age, BMI, and total taste scores associated to this increase. Boys had higher energy intake compared to girls. Eating behavior scores significantly declined, indicating less eating problems. Age, pre-diagnosis eating behavior, self-reported smell changes, and tube feeding were associated to eating behavior. BMI significantly increased, with a higher BMI at diagnosis to be related to a higher BMI during the study period. A lower BMI was found in children receiving tube feeding and self-reported taste changes. HRQoL improved during the study period, with lower HRQoL in children receiving tube feeding and self-reported taste changes.

Both objective and subjective measures of taste and smell influence dietary intake, eating behavior, nutritional status, and HRQoL. Individual dietary advice and coping strategies are warranted to prevent detrimental effects of chemosensory changes on food intake and clinical outcomes in children with cancer.

Ototoxicity is an adverse effect of childhood cancer treatment with a negative impact on speech-language development and quality of life. This study aimed to retrospectively assess ototoxicity monitoring in a national cohort of pediatric patients with solid tumors, examining the frequency and determinants associated with hearing loss (HL).

This retrospective cohort study included 305 patients treated between 2015 and 2020 at the Princess Máxima Center. Patients receiving platinum agents, head and neck radiotherapy, and/or ear-nose-throat surgery were analyzed. Electronic patient files provided demographic, clinical, and audiological data. HL was defined as Muenster ≥ 2b or SIOP ≥ 2 grade. Associations between clinical characteristics and HL occurrence were analyzed using logistic regression analysis.

Audiological monitoring was performed at baseline (62.6%), during treatment (79.0%), and at the end of treatment (82.1%). Post treatment, 51.2% and 36.5% experienced Muenster and SIOP-defined HL, respectively. Multivariable analyses revealed that age at diagnosis (OR 0.9, 95% CI 0.9-1.0), total cumulative dose cisplatin per 100 mg/m2 (OR 1.6, 95% CI 1.4-2.0), and vincristine treatment (OR 3.3, 95% CI 1.4-7.8) remained significantly associated with Muenster grade ≥ 2b HL. Age at diagnosis in years (OR 0.9, 95% CI 0.8-1.0), total cumulative dose cisplatin per 100 mg/m2 (OR 1.5, 95% CI 1.2-1.8), and male sex (OR 2.7, 95% CI 1.4-5.3) were associated with SIOP ≥ 2 HL.

This study shows that more than half of the children treated with ototoxic cancer therapies develop HL by the end of treatment. Therefore, audiological monitoring during and after treatment is essential. Improved insight into clinical determinants aids in identifying patients at high risk for HL, who may benefit from prevention strategies that are currently being implemented.

Neuroblastoma (NB) remains a challenging pediatric malignancy with limited treatment options, particularly for high-risk cases. Drug repurposing offers a convenient and cost-effective strategy for treating rare diseases like NB. Using existing drugs with known safety profiles accelerates the availability of new treatments, reduces development costs, and mitigates risks, offering hope for improved patient outcomes in challenging conditions.

This review provides an overview of the advances in approaches used to repurpose drugs for NB therapy. The authors discuss strategies employed in drug repurposing, including computational and experimental methods, and rational drug design, highlighting key examples of repurposed drugs with promising clinical results. Additionally, the authors examine the challenges and opportunities associated with drug repurposing in NB and discuss future directions and potential areas for further research.

The fact that only one new drug has been approved in the last 30 years for the treatment of neuroblastoma plus a significant proportion of high-risk NB patients that remain uncurable, evidences the need for new fast and cost-effective alternatives. Drug repurposing may accelerate the treatment development process while reducing expenses and risks. This approach can swiftly bring effective NB therapies to market, enhancing survival rates and patient quality of life.

Ganglioneuroblastoma is a rare peripheral neuroblastic tumor located anywhere in the sympathetic nervous system but rarely in the retropharyngeal space. Diagnosis can often be difficult based on imaging alone. We describe one case of a child presenting with snoring. The lesion was located in the rare retropharyngeal space, and its histology finally revealed ganglioneuroblastoma. Therefore, clinicians should be aware of pediatric patients with respiratory symptoms indicating cervical ganglioneuroblastoma. To make a definite diagnosis as soon as possible, a core needle biopsy or even immunohistochemistry may need to be performed before surgery.

Neuroblastoma is the most prevalent solid tumor in early childhood, with a 5-year overall survival rate of 40-60% in high-risk cases. Therefore, the identification of novel biomarkers for the diagnosis, prognosis, and therapy of neuroblastoma is crucial for improving the clinical outcomes of these patients. In this study, we conducted the whole-exome sequencing of 48 freshly frozen tumor samples obtained from the Biobank. Somatic variants were identified and selected using a bioinformatics analysis pipeline. The mutational signatures were determined using the Mutalisk online tool. Cancer driver genes and druggable mutations were predicted using the Cancer Genome Interpreter. The most common mutational signature was single base substitution 5. MUC4, MUC16, and FLG were identified as the most frequently mutated genes. Using the Cancer Genome Interpreter, we identified five recurrent cancer driver mutations spanning MUC16, MUC4, ALK, and CTNND1, with the latter being novel and containing a missense mutation, R439C. We also identified 11 putative actionable mutations including NF1 Q1798*, Q2616*, and S636X, ALK F1174L and R1275Q, SETD2 P10L and Q1829E, BRCA1 R612S, NOTCH1 D1670V, ATR S1372L, and FGFR1 N577K. Our findings provide a comprehensive overview of the novel information relevant to the underlying molecular pathogenesis and therapeutic targets of neuroblastoma.

Magnetic resonance imaging (MRI) has become an important diagnostic tool for paediatric patients. The association between dental restorations and MRI artefacts/distortions, however, is unclear.

To investigate the association between dental restorations and artefacts in head MRI in children.

This retrospective analysis included patients who underwent head MRI and dental examination at Ramathibodi Hospital from January 2015 to March 2021. From dental records and dental radiographs, a dentist reviewed the amount and type of restorative materials used. Two radiologists examined the MRI scans in five sequences for the presence of distortions and quantified the magnitude and grading of any artefacts.

Ninety-four patients aged 3-15 years were included. Twenty-four patients who received preformed metal crowns (PMCs) had MRI distortions. Subjects with no restorations or with tooth-coloured material or amalgam restorations or both did not exhibit distortions. The number of PMCs was related to the size of an artefact. Almost all distortions were confined to the oral cavity and maxillary sinus and did not affect the diagnostic brain area.

Among the commonly used dental restorative materials for children, only PMCs were associated with artefacts on head MRI scans.

Pediatric oncohematological patients frequently require PICU admission during their clinical history. The O-PEWS is a specific score developed to predict the need for PICU admission of oncohematological children. This study aimed at i) describing the trend of the O-PEWS in a cohort of patients hospitalized in the Pediatric Oncohematology ward and transferred to the PICU of Padua University Hospital, measured at different time-points in the 24 hours before PICU admission and to evaluate its association with mortality and presence of organ failure; ii) investigating the association between the recorded O-PEWS, and PIM3, number of organ failure and the need for ventilation, dialysis and inotropes.

This retrospective single-center study enrolled oncohematological children admitted to the PICU between 2017 and 2021. The O-PEWS, ranging between 0 and 15, was calculated on the available medical records and the TIPNet-Network database at 24 (T-24), 12 (T-12), 6 (T-6) and 0 (T0) hours before PICU admission.

RESULTS: 101 PICU admissions, related to 80 children, were registered. During the 24 hours prior to PICU admission, the O-PEWS progressively increased in all the patients. At T-24 the median O-PEWS was 3 (IQR 1-5), increasing to a median value of 6 (IQR 4-8) at T0. The O-PEWS was positively associated with mortality, organ failure and the need for ventilation at all the analyzed time-points and with the need for dialysis at T-6.

The O-PEWS appears as a useful tool for predicting early clinical deterioration in oncohematological patients and for anticipating the initiation of life-support treatments.

Results from studies investigating the association between maternal or child epilepsy, use of anticonvulsants in pregnancy, and childhood cancer are inconsistent and at times contradictory. Linking Danish national databases, we obtained epilepsy and childhood cancer diagnoses, and anticonvulsant use data. We estimated adjusted odds ratios of all or specific childhood cancers in relation to maternal or child epilepsy and anticonvulsant therapies using conditional logistic regression. Maternal epilepsy was positively associated with all childhood cancers in offspring, specifically, with acute lymphoblastic leukemia (Odds Ratio (OR) = 1.68, 95% Confidence Interval (CI) = 1.16, 2.43) and Wilms tumor (OR = 2.13, 95% CI = 0.97, 4.68). When considering maternal ever (lifetime) ingestion of anticonvulsants, a positive association was found with all cancers (OR = 1.14, 95% CI = 1.00, 1.30), and central nervous system tumors (CNS) (OR = 1.36, 95% CI = 1.04, 1.76) as well as neuroblastoma (OR = 1.76, 95% CI = 1.06, 2.90) among offspring. Maternal anticonvulsant use before or during the index pregnancy was related to CNS tumors in offspring (OR = 1.99, 95% CI = 0.99, 4.00).

The aim of the study was to compare conventional sintering with additive manufacturing techniques for β-TCP bioceramics, focusing on mechanical properties and biocompatibility. A "critical" bone defect requires surgical intervention beyond simple stabilization. Autologous bone grafting is the gold standard treatment for such defects, but it has its limitations. Alloplastic bone grafting with synthetic materials is becoming increasingly popular. The use of bone graft substitutes has increased significantly, and current research has focused on optimizing these substitutes, whereas this study compares two existing manufacturing techniques and the resulting β-TCP implants. The 3D printed β-TCP hybrid structure implant was fabricated from two components, a column structure and a freeze foam, which were sintered together. The conventionally fabricated ceramics were fabricated by casting. Both scaffolds were characterized for porosity, mechanical properties, and biocompatibility. The hybrid structure had an overall porosity of 74.4 ± 0.5%. The microporous β-TCP implants had a porosity of 43.5 ± 2.4%, while the macroporous β-TCP implants had a porosity of 61.81%. Mechanical testing revealed that the hybrid structure had a compressive strength of 10.4 ± 6 MPa, which was significantly lower than the microporous β-TCP implants with 32.9 ± 8.7 MPa. Biocompatibility evaluations showed a steady increase in cell proliferation over time for all the β-TCP implants, with minimal cytotoxicity. This study provides a valuable insight into the potential of additive manufacturing for β-TCP bioceramics in the treatment of bone defects.

Liquid biopsies are emerging as an alternative source for pediatric cancer biomarkers with potential applications during all stages of patient care, from diagnosis to long-term follow-up. While developments within this field are reported, these mainly focus on dedicated items such as a specific liquid biopsy matrix, analyte, and/or single tumor type. To the best of our knowledge, a comprehensive overview is lacking. Here, we review the current state of liquid biopsy research for the most common non-central nervous system pediatric solid tumors. These include neuroblastoma, renal tumors, germ cell tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcomas, and liver tumors. Within this selection, we discuss the most important or recent studies involving liquid biopsy-based biomarkers, anticipated clinical applications, and the current challenges for success. Furthermore, we provide an overview of liquid biopsy-based biomarker publication output for each tumor type based on a comprehensive literature search between 1989 and 2023. Per study identified, we list the relevant liquid biopsy-based biomarkers, matrices (e.g., peripheral blood, bone marrow, or cerebrospinal fluid), analytes (e.g., circulating cell-free and tumor DNA, microRNAs, and circulating tumor cells), methods (e.g., digital droplet PCR and next-generation sequencing), the involved pediatric patient cohort, and proposed applications. As such, we identified 344 unique publications. Taken together, while the liquid biopsy field in pediatric oncology is still behind adult oncology, potentially relevant publications have increased over the last decade. Importantly, steps towards clinical implementation are rapidly gaining ground, notably through validation of liquid biopsy-based biomarkers in pediatric clinical trials.

Despite significant progress in supportive care and advancements in chemotherapy treatments, cancer remains a leading cause of mortality in children. The objective of this study was to assess the potential correlation between various risk factors and the consequences of patients with pediatric cancer who were admitted to the pediatric intensive care unit (PICU).

The present investigation is a retrospective cohort study that examined children with cancer who were between the ages of 1 month and 17 years and had been admitted to the PICU. Demographic and clinical information of all patients, including such as the age, type of cancer, sex, BMI, history of specific disease, PICU admission time, disease condition on PICU admission, patient's status at PICU admission, and number of organ failures, were extracted from each patient file.

The number of pediatric oncology patients admitted to the PICU was 127. The highest mortality rate was observed among children with heart problems (75%), followed by CNS involvement (54.2%) and sepsis (42.9%). The study found that various factors had a significant effect on the outcomes of patients who were admitted to the PICU, including but not limited to the primary type of malignancy, disease status, indications for hospital admission, patient's condition, inpatients' length of stay (LOS), tumor type, and the extent of organ failure at the time of admission to the PICU.

Despite recent advancements in healthcare, the prognosis of patients admitted to the PICU in underdeveloped areas remains suboptimal in comparison to those in developed regions. Poor outcomes were found to be significantly associated with various factors, including the primary type of malignancy, disease status, the reason for admission to the PICU, patient's condition, LOS, tumor type, and the extent of organ failure, especially in cases involving hematological malignancies.

B-cell lymphoblastic lymphoma (B-LBL) is a subtype of non-Hodgkin lymphoma characterized by the proliferation of abnormal B-cell lymphoblasts in lymphoid tissues. Typical presentations include lymphadenopathy, mediastinal mass, and involvement of organs such as the liver and spleen, but extranodal sites can also be affected. A previously healthy 20-month-old male child presented to the pediatric surgery clinic with a two-month history of a painless, progressively enlarging mass on the scalp as well as postauricular mass consistent with an enlarged lymph node. Ultrasound of the mass near the vertex demonstrated a hypoechoic complex cystic lesion for which excision was indicated. Preoperatively, acute enlargement of the entire postauricular lymphatic chain was noted. Intraoperatively, the scalp mass was noted to be firm with calcified tissue and no identifiable cystic or infectious components. The mass and part of the overlying skin were excised. Pathologic evaluation was consistent with B-LBL. The patient was therefore referred to a pediatric oncologist for further evaluation and management. Bone marrow examination revealed greater than 25% blasts in the clot section, consistent with B-ALL. He was promptly initiated on induction therapy with maintenance chemotherapy to ensure continued remission. This case highlights the atypical presentation of B-cell lymphoblastic leukemia/lymphoma (B-ALL/LBL) as a scalp mass in a 20-month-old male. It underscores the importance of considering malignancy in the differential diagnosis of unusual masses. Prompt collaboration between pediatric surgeons and oncologists facilitates timely diagnosis and initiation of appropriate treatments for optimal outcomes.

This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL.

The study group included 2303 children receiving intensive chemotherapy for ALL. The group was divided into patients with at least one episode of AP and those who did not develop AP after treatment for ALL.

The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for the development of AP (OR = 1.05; 95%CI = 1.006-1.098; p = 0.03). The overall mortality associated with AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) in both subgroups were 0.84 vs. 0.86, log-rank p = 0.65 and 0.75 vs. 0.80, log-rank p = 0.12, respectively. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent treatment phases. Only one patient re-exposed to ASP (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p = 0.27 and 0.63 vs. 0.79, log-rank p = 0.09, respectively).

The incidence of AP in children with ALL is low and related to patients' age. The development of AP does not seem to influence p-DFS and p-EFS in children with ALL. Recurrence of AP after re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP does not improve either p-DFS or p-EFS in children with ALL.

International comparisons of cancer surveillance measures may provide insight into inequalities in registration practices, etiological factors, and treatment strategies. This study aimed to compare incidence, survival, and mortality of cancer in children and young adolescents between Belgium and the Netherlands. All children (0-14 years) and young adolescents (15-17 years) diagnosed with cancer between 2004 and 2015 were selected from the population-based cancer registries of Belgium (N = 4739) and the Netherlands (N = 7322). Differences in incidence and mortality were expressed as standardized rate ratios (SRR; BE/NL). Five-year observed survival was calculated using the Kaplan-Meier method. During 2004-2015, the overall cancer incidence among children and young adolescents was similar in both countries. Incidence of neuroblastoma was significantly higher in Belgian children (2010-2015: SRR = 1.3, 95% CI 1.0-1.6). Five-year survival of all malignant cancers was comparable in 2010-2015, exceeding 80% in both age groups. Remarkable differences in survival existed in children for malignant central nervous system (CNS) tumors in 2004-2009 (BE = 62%, NL = 45%), for acute myeloid leukemia (BE = 68%, NL = 78%) and rhabdomyosarcomas (BE = 60%, NL = 79%) in 2010-2015, and for neuroblastoma in both periods (2004-2009: BE = 76%, NL = 64%; 2010-2015: BE = 82%, NL = 64%). Overall cancer mortality in children decreased by approximately 3 percent-points annually in both countries, but was slightly lower in Belgium in 2004-2009 (SRR = 0.9, 95% CI 0.7-1.0). Despite differences for specific cancer types, overall cancer incidence, survival, and mortality were comparable between Dutch and Belgian children and young adolescents in 2010-2015. Variability in screening, diagnosis, and registration practices probably explains the observed differences in incidence and survival of neuroblastoma and malignant CNS tumors.

Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies -with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer).

The objective of this study was to construct a prognostic nomogram for ganglioneuroblastoma (GNB), as the prognosis of GNB is difficult to accurately predict before therapy.

The data were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients included in this study were randomly divided into a development group and a validation group at a ratio of 7:3. Univariate and multivariate Cox regression analyses were used to filter the variables. Receiver operating characteristic (ROC) curves and calibration curves were used to assess the nomogram. All patients were redivided into two groups based on their nomogram total points, and overall survival was compared.

A total of 1194 GNB patients were retrospectively included, with 835 and 359 patients in the development and validation groups, respectively. Five independent prognostic factors, including age, primary tumor site, SEER stage, surgery and chemotherapy, were screened out and included in the nomogram. The consistency index (C-index) of the Cox regression model was 0.862 and 0.827 in the development group and the validation group, respectively. The areas under the receiver operating characteristic (ROC) curve (AUC) showed that the nomogram had good accuracy in predicting 3-, 5- and 10-year overall survival for GNB patients. The calibration curves of the nomogram showed good agreement between the predicted outcomes and the actual observations. The Kaplan-Meier (KM) survival curves revealed that patients with nomogram scores below the median had a better prognosis.

Age, primary tumor site, SEER stage, surgery and chemotherapy may be independent prognostic factors for GNB. We constructed a nomogram based on the SEER database to predict the prognosis of GNB, but further optimization by adding more risk factors is needed for clinical application.

French Guiana is a French territory in South America. The exposome of persons living there is quite different from that in mainland France and the ethnic make-up of the population is also quite different. Poverty is also widespread with difficulties in accessing care magnified by the low medical-professional density. In this singular context, we aimed to measure the incidence of pediatric cancers and to compare it with other continents. We used French Guiana's certified cancer registry to study this between 2003 and 2017. Incidences were standardized using the world population with three strata: 0-4 years, 5-9 years, and 10-14 years. There were 164 solid tumors or hematologic malignancies diagnosed in children under the age of 15 (92 in boys and 72 in girls). Over the study period, the standardized incidence rate was 14.1 per 100,000 among children aged under 15 years. There was no significant trend during the study period. The three most common causes of cancer were leukemias-mostly lymphoblastic-CNS tumors, and sarcoma. The standardized incidence of pediatric cancers in French Guiana was similar to those in Western Europe and North America. As others have discovered, we found that males tended to be more likely to develop cancer, notably leukemia, CNS tumors, sarcoma, and retinoblastoma. As elsewhere, the predominant cancer types changed with age. Our initial assumption was that given the singular context of French Guiana, there may have been differences in pediatric cancer incidences. Here we showed that overall, contrary to our assumption and to trends in tropical countries, the incidence of pediatric cancers was in a range between Western Europe and North America with some apparent but non-significant differences in the main types of cancers observed in global statistics. Quality cancer registry data in this tropical region confirm the suspicion that lower incidences in tropical low- and middle-income countries are likely to result from incomplete diagnosis and data collection.

To describe the situation of childhood cancer survivors and their parents before and one year after a family-oriented rehabilitation program (FOR) and to identify factors influencing reintegration.

We included parents of children diagnosed with leukemia or central nervous system tumor. We assessed parental functioning using the functioning subscale of the Ulm Quality of Life Inventory for Parents (ULQIE) and children's school/kindergarten related quality of life (parental assessment, subscale KINDL-R). Descriptive analyses, group comparisons and multiple regression analyses on data of 285 parents of 174 children diagnosed with leukemia or central nervous system tumor.

Parents reported changes in their work situation (e.g., reduction of working hours) due to their child's diagnosis. Parental functioning increased significantly over time. Children's leukemia diagnosis and shorter time since the end of treatment were associated with higher functioning in parents one year after FOR. Parents reported difficulties in the child's work pace, concentration, stress resilience and empathy. The school/kindergarten-related quality of life (QoL) of the children was lower than in the general population. One year after FOR, most children reintegrated fully in school/kindergarten, partly with support (e.g., integration assistant). No significant predictors for children's reintegration were identified.

Parents and children experience major changes in their work/school/kindergarten life. One year after FOR most parents reported a reintegration of their children, however the children's school/kindergarten-related QoL remained below average compared to norm values. Even after rehabilitation families of childhood cancer survivors might benefit from psychosocial and practical support offers to support families with the reintegration into work/school/kindergarten.

to carry out a scoping review with the purpose of mapping the scientific evidence on the use of the neutropenic diet in neutropenic pediatric cancer patients.

The scoping review protocol was prepared in accordance with the PRISMA-ScR and the checklist before the literature search was performed. Articles on nutritional management in adults or on the treatment of other diseases, and articles that were not in Portuguese or English and published before the year 2000, were excluded. Data were extracted based on the Cochrane Consumer and Communication Review Group form.

Three hundred and forty scientific articles were identified, with the final sample of this review consisting of nine studies. Although the neutropenic diet has been part of the nutritional management of pediatric cancer patients for more than 20 years, there is still great variation in the criteria for indicating use and starting and discontinuing it, as well as in the nutritional composition of the diet. Furthermore, there is no consensus on the impact of using a neutropenic diet on different clinical and nutritional outcomes.

In the absence of guidelines that standardize the use of a neutropenic diet in pediatric patients with neutropenia, there are heterogeneous approaches reported in the literature, even within the same institution. The available literature presents an absence of evidence on the use, viability, and effectiveness of the neutropenic diet in oncological children with neutropenia. More studies are needed to identify the real impact of the neutropenic diet on clinical and nutritional outcomes.

Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional photon radiotherapy has made significant contributions to survival, but can be associated with long-term side effects. Proton beam radiotherapy (PBT) reduces the volume of irradiated tissue outside the tumour target volume which may potentially reduce toxicity. Our aim was to assess the effectiveness and safety of PBT and make recommendations for future research for this evolving treatment.

A systematic review assessing the effects of PBT for treating CNS tumours in children/young adults was undertaken using methods recommended by Cochrane and reported using PRISMA guidelines. Any study design was included where clinical and toxicity outcomes were reported. Searches were to May 2021, with a narrative synthesis employed.

Thirty-one case series studies involving 1731 patients from 10 PBT centres were included. Eleven studies involved children with medulloblastoma / primitive neuroectodermal tumours (n = 712), five ependymoma (n = 398), four atypical teratoid/rhabdoid tumour (n = 72), six craniopharyngioma (n = 272), three low-grade gliomas (n = 233), one germ cell tumours (n = 22) and one pineoblastoma (n = 22). Clinical outcomes were the most frequently reported with overall survival values ranging from 100 to 28% depending on the tumour type. Endocrine outcomes were the most frequently reported toxicity outcomes with quality of life the least reported.

This review highlights areas of uncertainty in this research area. A well-defined, well-funded research agenda is needed to best maximise the potential of PBT.

PROSPERO-CRD42016036802.

This is a retrospective cross-sectional study examining the association between unemployment, cancer type, treatment and total body fat percentage of childhood cancer survivors recruited at St. Anne's University Hospital in Brno, Czech Republic. A total of 55 survivors aged 18-49 who were in remission of cancer and fulfilled the criteria for body composition measurements by the BIA and completed questionnaires investigating their socioeconomic status, employment status, and history. There was a significant relationship between the employment status and central nervous system-directed treatment (c2(1) = 7.53, p = 0.006, Cramér's V = 0.38) and between the type of cancer and employment status (c2(3) = 7.83, p = 0.049, Cramér's V = 0.38), the highest unemployment rate was recorded for brain and spine survivors (72.7%) compared to survivors with other diagnosis (35.7%) (uLR(1) = 4.91, p = 0.027; OR = 4.80, 95% CI:1.10-20.86, p = 0.036); these survivors did not have a significantly different body fat percentage compared to survivors with other diagnoses (t(53) = 1.29, p = 0.202, Cohen's d = 0.41) Interestingly, the survivors reporting having a partner also had a significantly higher percentage of body fat (t(53) = 2.90, p = 0.005, Cohen's d = 0.81). A linear regression model was used to model the percentage of body fat in relation to a set of selected variables and the we observed a significant effect of sex (female vs male: b = 6.37, 95% CI: 1.82-10.93, p = 0.007), partnership status (yes vs no: b = 5.65, 95% CI: 0.67-10.62, p = 0.027) and category of diagnosis (Brain and spinal column tumors vs Other solid tumors: b = 12.40, 95% CI: 0.59-24.21, p = 0.040; Brain and spinal column tumors vs Lymphoma: b = 14.02, 95% CI: 2.06-25.97, p = 0.023). Employment status and risk of adiposity in childhood cancer survivors depends on the type of treatment and diagnosis group, which may significantly impact their lifestyle and overall quality of life after treatment. Trial registration: This study was registered on July 29, 2022, at ClinicalTrials.gov (NCT05481229).

This study is the first report regarding childhood cancer in the Faroe Islands and describes the incidence and survival of childhood cancer over the last 60 years in the Faroe Islands.

We included all Faroese children registered with a cancer diagnosis up to the age of 19 years in the Faroese Cancer Registry from 1960 to 2019 and in the Danish Childhood Cancer Registry from 1985 to 2019 in this study. We report the number of incident cancers classified according to the 12 main diagnostic groups in the International Classification of Childhood Cancer, third edition (ICCC-3), but due to small numbers some groups have been combined in the results shown. We report age-standardized incidence rates (world standard population) (ASIR). We also show all-cause survival by incidence stratified by 20-year periods.

There were 114 childhood cancers in the Faroe Islands from 1960 to 2019, corresponding to an ASIR of 13.0 per 100,000 person-years. The most common cancer groups in Faroese children were brain and spinal tumors, followed by leukemias and lymphomas. All-cause survival improved for children diagnosed over time, with a 5-year survival of 43.5% for those diagnosed from 1960 to 1979 and 85.6% for children diagnosed from 2000 to 2019.

Childhood cancer in the Faroes was slightly rarer than in most other high-income countries. Brain and spinal tumors were the most common cancer group in Faroese children. Survival for Faroese children with cancer has improved substantially in the study period.