Pediatric Tumors Research Articles

IN VIVO APPLICATION OF LOCAL DRUG DELIVERY SYSTEMS AGAINST MEDULLOBLASTOMA GROUP 3 AND ATYPICAL/TERATOID/RHABOID TUMOURS

Abstract AIMS Local drug delivery systems (LDDSs) applied during neurosurgery offer a means of overcoming poor blood brain barrier (BBB) permeability and have been extensively investigated for the treatment of adult gliomas, but to the best of our knowledge, not for the treatment of paediatric cerebellar tumours. Here we report the applicability of an LDDS against medulloblastoma group 3 (MB3) and atypical teratoid/rhaboid tumours (AT/RT), both of which are associated with poor prognoses. METHOD We prepared and characterised an injectable and biodegradable poly(ethyleneglycol)-poly(caprolactone)- poly(ethyleneglycol) (PECE) hydrogel, which has been investigated with an array of therapeutic agents against numerous cancer types. Here, we loaded the PECE hydrogel with chemotherapeutics previously identified as being effective against primary MB3 and AT/RT in vitro, but which do not cross the BBB in vivo, namely CHIR99021, ribavirin and PG545. Biocompatibility and cytotoxicity of drug loaded hydrogels was assessed in vitro. LDDSs safety and efficacy was evaluated using patient derived MB3 and AT/RT intracranial xenograft surgical resection models. RESULTS The hydrogel was both biocompatible and effected cytotoxicity following drug release. In vivo efficacy experiments against MB3 indicated a comparable median survival in treatment arms receiving radiotherapy or CHIR99021 and PG545 loaded LDDS. However, combined radiotherapy and LDDS conferred a significant survival enhancement, including long-term survivors. Against AT/RT, the median survival of arms receiving radiotherapy was comparable to that of the CHIR99021 and ribavirin loaded LDDS, with long-term survivors observed only in the latter arm. CONCLUSION The application of LDDSs against cerebellar brain tumours offers a promising novel therapeutic alternative. For MB3, the combination of radiotherapy and a LDDS significantly enhances survival compared to radiotherapy alone. For AT/RT, the comparable survival of the LDDS and radiotherapy alone is encouraging and indicates the possibility of circumventing radiation-induced adverse effects for young children impacted by this disease.

Unusual Presentation: Nephroblastoma/Wilms tumor in an Adult – A Case Report

Abstract Introduction/Objective Nephroblastoma/Wilms tumor is a common renal tumor primarily observed in children, and its occurrence in adults is exceedingly rare. This rarity contributes to the diagnostic challenges encountered in adults. Here, we present a case of a 32-year-old male diagnosed with biphasic nephroblastoma/Wilms tumor in the kidney, with liver and lung metastases. Methods/Case Report A 32-year-old male, without significant past medical history, presented with the chief complaint of abdominal pain for 2-3 weeks. Imaging studies revealed a substantial 17.5 cm kidney lesion accompanied by numerous lung and liver lesions. A liver biopsy indicated a small blue cell tumor, morphologically and immunophenotypically, (positive WT1) resembling nephroblastoma, with a strong suspicion of metastasis. Subsequent kidney biopsy confirmed a small blue cell malignant tumor demonstrating biphasic features, including blastema and epithelial components forming tubular structures similar to the liver biopsy, predominantly showing the blastemal component. The renal tumor biopsy supported the diagnosis of nephroblastoma. Despite chemotherapy, the patient passed away two months after the initial liver tumor biopsy. Results (if a Case Study enter NA) NA Conclusion Diagnosing nephroblastoma in adults poses significant challenges, particularly when initial presentations involve metastases. The occurrence of pediatric tumors in adulthood, though rare, should be considered in the diagnostic process after exhausting other possibilities. It is also important to note that the clinical presentation of pediatric tumors in adults may deviate from typical patterns. While Wilm’s tumor commonly presents as a painless, palpable abdominal mass in pediatric cases, adults may exhibit abdominal pain as the predominant symptom, as present in our case.

Complex structural variation is prevalent and highly pathogenic in pediatric solid tumors

In pediatric cancer, structural variants (SVs) and copy-number alterations contribute to cancer initiation as well as progression, thereby aiding diagnosis and treatment stratification. Although suggested to be of importance, the prevalence and biological relevance of complex genomic rearrangements (CGRs) across pediatric solid tumors is largely unexplored. In a cohort of 120 primary tumors, we systematically characterized patterns of extrachromosomal DNA, chromoplexy, and chromothripsis across five pediatric solid cancer types. CGRs were identified in 56 tumors (47%), and in 42 of these tumors, CGRs affect cancer driver genes or result in unfavorable chromosomal alterations. This demonstrates that CGRs are prevalent and pathogenic in pediatric solid tumors and suggests that selection likely contributes to the structural variation landscape. Moreover, carrying CGRs is associated with more adverse clinical events. Our study highlights the potential for CGRs to be incorporated in risk stratification or exploited for targeted treatments.

Blood transfusion in pediatric intracranial tumor surgery

BackgroundPediatric central nervous system tumors are the most common solid tumors in children and leading cause of cancer-related morbidity and mortality. Various factors may influence the practice of blood transfusion during this tumor diagnosis. The primary aim of this study was to determine the factors that may influence intraoperative blood transfusion in pediatric patients undergoing surgery for intracranial tumors and to predict patients who may require blood transfusion.MethodsA retrospective study was performed in all pediatric patients younger than 15 years who underwent craniotomy for brain tumor removal from January 2018 to December 2023 in our institution. Preoperative, intraoperative and postoperative data were collected from medical and store anesthesia records. The predictors of intraoperative blood transfusion were determined using multivariate logistic regression.ResultsA total of 138 patients were enrolled in the study, of whom 62 (44.9%) required intraoperative blood transfusion. In multivariate regression analysis age < 4 years and operating time > 490 min were determined as independent variables in terms of need for intraoperative blood transfusion. It was determined that the need for transfusion was higher in patient who were operated on urgently and patients with comorbidities (p = 0.023, p = 0.005).ConclusionIn conclusion, the findings obtained in this study suggest that age and surgical duration are independent risk factors for intraoperative blood transfusion in pediatric patients undergoing surgery for intracranial tumors. Particularly, in younger patients and prolonged surgeries, closer monitoring and awareness may enhance early detection, leading to the prevention of complications.

Spinal diffuse midline glioma: An unusual case presentation

Primary spinal cord neoplasms are rare, accounting for 1% of paediatric central nervous system tumours. The majority of which are low-grade gliomas (LGG). A teenage male presented with rapidly progressive lower limb paralysis. He subsequently underwent a near-total resection of an intramedullary thoracic tumour. Although the initial histopathology report suggested a LGG, closer review of the morphology and immunohistochemical staining revealed a diffusely infiltrating high-grade astrocytoma. Methylation profiling later confirmed a H3K27M-mutated spinal DMG. He underwent spinal radiation to the tumour bed soon after surgery but succumbed to his disease 8 days after completing radiation, and 3 months after presentation.Conclusion: Spinal DMGs are rare, can lead to diagnostic challenges and have a poor prognosis.

Developing CAR T-Cell Therapies for Pediatric Solid Tumors.

Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies, inducing notable and durable clinical responses. However, for solid tumors, including but not limited to pediatric tumors, several peculiar biological features posed substantial challenges for achieving comparable results. Despite sound pre-clinical evidence of the ability of CAR T cells to eradicate solid malignancies, their activity remains suboptimal when facing the in vivo complexity of solid tumors, characterized by antigen heterogeneity, scarce T-cell infiltration, and an immunosuppressive microenvironment. Neuroblastoma was amongst the first tumors to be evaluated as a potential candidate for GD2-targeting CAR T cells, which recently documented promising results in high-risk, heavily pre-treated patients. Moreover, innovative engineering strategies for generating more potent and persistent CAR T cells suggest the possibility to reproduce, and potentially improve, these promising results on a larger scale. In the next years, harnessing the full therapeutic potential of CAR T cells and other immunotherapeutic strategies may open new possibilities for effectively treating the most aggressive forms of pediatric tumors.

Myeloid sarcomas with CBFA2T3 : GLIS2 fusion: clinicopathologic characterization of 4 cases mimicking small round cell tumors.

Acute myeloid leukemia with CBFA2T3::GLIS2 fusion can initially present as extramedullary lesions (myeloid sarcoma), leading to a misdiagnosis of nonhematologic pediatric solid tumors. We characterized the clinicopathologic features of 4 cases of CBFA2T3::GLIS2 fusion-positive myeloid sarcoma in pediatric patients where the sarcoma presented either without leukemic involvement (isolated myeloid sarcoma; 3/4 [75%]) or had concurrent leukemic disease (1/4 [25%]). All cases mimicked nonhematopoietic tumors at morphologic and immunophenotypic levels, so the initial evaluation did not raise suspicion for acute myeloid leukemia/myeloid sarcoma. After extensive workup, however, including molecular studies, the diagnosis of myeloid sarcoma with CBFA2T3::GLIS2 fusion was rendered. This study highlights the need for a high suspicion index of GLIS2-rearranged myeloid sarcoma in the differential diagnosis of pediatric small round cell tumors in tissue biopsies and the application of adequate workup to avoid misdiagnosing this entity.

8120 Effective Management of Neonatal Hypercalcemia in Congenital Mesoblastic Nephroma: A Case Report on the Use of Calcitonin

Abstract Disclosure: C.S. Galvez: None. K. Rifai: None. C. Moorthy: None. S. Chheda: None. M. Zerah: None. Introduction: Pediatric patients with hypercalcemia of malignancy are typically treated with hyperhydration, loop diuretics and bisphosphonates. Calcitonin, a peptide functionally antagonizes the effects of PTH. Calcitonin has limited pharmacokinetic data in neonates, especially those with Congenital Mesoblastic Nephroma (CMN), making treatment challenging with unclear safety and efficacy parameters. We present the fourth published case describing the use of calcitonin for likely PTH-rP-mediated severe hypercalcemia in a neonate with CMN. Clinical Case: A 15-day-old late preterm male, presented with lethargy, poor feeds, severe failure to thrive and a large abdominal mass. The mother is a G4P4, with good prenatal care. On admission, the patient was hypertensive (138/84 mmHg) and appeared dehydrated. Physical examination revealed a firm mass in the right abdomen crossing the midline. Serum calcium levels were 13.5 mg/dL (normal 9.0-10.9 mg/dL), with an ionized calcium 1.71 mmol/L (normal 1.15 and 1.30 mmol/L). Abdominal ultrasound showed a large, 9.1 x 8 cm dominant solid right renal mass, most likely CMN, with left-sided medullary nephrocalcinosis. Cardiac Echo and EKG were within normal limits. The patient received hydration, nicardipine (titrated to decrease blood pressure by 10-15 mmHg per day) and furosemide at 1 mg/kg/day IV q6h. Due to the persistence of hypercalcemia after 24 hours of treatment (14.7 mg/dL serum calcium with ionize of 1.81 mmol/L), the patient received one dose of calcitonin (4 units/kg subcutaneously), resulting in a decrease in serum calcium to 11.5 mg/dL in 4 hours. The patient underwent a successful radical right uretero-nephrectomy, with post-surgery improvement of neurological, cardiovascular and electrolyte status. Unfortunately, PTH-rP sample was insufficient. Pathology reported CMN of the cellular type. CMN is a rare tumor with low malignant potential, representing approximately 3% of all pediatric renal tumors. It is the most common renal neoplasm diagnosed in the first 6 months of life. The most common symptom is an abdominal mass (76%), with hypertension (19%). Hypercalcemia was reported in only 4% which can be secondary to paraneoplastic secretion of PTH or PTH-rP. Conclusion: This case represents the fourth instance of calcitonin use in a neonate with CMN to manage persistent hypercalcemia. Subcutaneous administration of calcitonin at 4 units/kg proved effective with a short onset of action (within 2 hours) and duration of 6 to 8 hours, making it a viable alternative to bisphosphonates (action around 48 hours and duration of 7 to 14 days). Calcitonin's advantages include less significant side effects and a faster resolution of complications like "Hungry bone Syndrome." The flexibility of repeated dosing every 6 hours, with the option to increase the dose, if necessary, adds to its clinical utility. Presentation: 6/3/2024

Characterization of aberrant splicing in pediatric central nervous system tumors reveals CLK1 as a candidate oncogenic dependency.

Pediatric brain cancer is the leading cause of disease-related mortality in children, and many aggressive tumors still lack effective treatment strategies. We characterized aberrant alternative splicing across pediatric brain tumors, identifying pediatric high-grade gliomas (HGGs) among the most heterogeneous. Annotating these events with UniProt, we identified 11,940 splice events in 5,368 genes leading to potential protein function changes. We discovered CDC-like kinase 1 (CLK1) is aberrantly spliced to include exon 4, resulting in a gain of two phosphorylation sites and subsequent activation. Inhibition of CLK1 with Cirtuvivint significantly decreased both cell viability and proliferation in the pediatric HGG KNS-42 cell line. Morpholino-mediated depletion of CLK1 exon 4 splicing reduced RNA expression, protein abundance, and cell viability with concurrent differential expression of 78 cancer genes and differential splicing at functional sites in 193 cancer genes. Our findings highlight a dependency of pediatric HGGs on CLK1 and represent a promising therapeutic strategy.

Comparison of human pluripotent stem cell differentiation protocols to generate neuroblastoma tumors

Neuroblastoma is the most common pediatric extracranial solid tumor and is derived from trunk neural crest cells (tNCC) and its progenitor sympathoadrenal (SA) cells. While human pluripotent stem cell (PSC) models of neuroblastoma have been described, the PSC were differentiated using protocols that made neural crest cells, but not specifically the trunk subtype. Here, we compared four recent protocols to differentiate pluripotent stem cells (PSC) toward SA cells and examined their efficiency at generating SA cells along with earlier cell states (neuromesodermal progenitors [NMP], tNCC), as well as generating MYCN-driven tumors. Interestingly, the protocols that created cells with the highest level of NMP markers did not produce cells with the highest tNCC or SA cell markers. We identified a protocol that consistently produced cells with the highest level of SA markers using two PSC lines of different genders. This protocol also generated tumors with the highest level of PHOX2B, a marker of neuroblastoma. Transcriptionally, however, each protocol generates tumors that resemble neuroblastoma. Two of the protocols repeatedly produced adrenergic neuroblastoma whereas the other two protocols were ambiguous. Thus, we identified a protocol that reliably generates adrenergic neuroblastoma.

Small Molecule Compound DHPA Screened by Computer-Aided Drug Design and Molecular Dynamics Simulation Inhibits Neuroblastoma Cell Proliferation by Targeting TrkB.

Neuroblastoma (NB) is a rare and malignant pediatric solid tumor. Due to its heterogeneity, it poses significant challenges for treatment, resulting in a high mortality rate. This study aimed to identify new therapeutic drugs by modeling the TrkB receptor from PDB 4AT5 and conducting virtual screening of compounds from the YaTCM database (containing 47,696 compounds derived from 6220 Traditional Chinese Medicines). The screening utilized the E-pharmacophore approach to select compounds with potential binding affinity to TrkB. The binding abilities of these compounds were tested through molecular dynamics simulations, stretch dynamics simulations, and US simulations. Among the top 11 optimized hit compounds, DHPA and 3″-demethylhexahydrocurcumin are prominent. Further simulations reveal that they form stable receptor-ligand binary complexes with TrkB. In subsequent in vitro cell experiments, 3″-demethylhexahydrocurcumin is eliminated due to its high IC50 for killing NB cells. Low concentrations of DHPA can significantly kill NB cells. Additionally, DHPA can inhibit the expression of TrkB, the activation of TrkB's downstream signaling pathways, and affect the thermal stability of TrkB protein and its response to streptase protease degradation. DHPA may be a potential TrkB inhibitor.

OTHR-01 HISTOLOGICAL TYPES OF BRAIN TUMORS DIAGNOSED AT THE KENYATTA NATIONAL HOSPITAL BETWEEN 2016 AND 2019: A RETROSPECTIVE STUDY

Abstract OBJECTIVE To determine the histological types of brain tumors (BTs) diagnosed at the Kenyatta National Hospital (KNH), Nairobi, Kenya. METHODS This retrospective study retrieved patient-archived records at KNH for the period 2016–2019. The histological types of brain tumors were assessed according to age, sex, and the WHO classification for CNS tumors. RESULTS During the study period, brain tumors appeared to increase gradually; however, there was a decline in 2018. During the study period, 345 brain tumor records were retrieved. Data on age were missing 33 records; hence, 312 records were included for age analyses. The mean age for the pediatrics and adults was 9 (± 5 SD) and 45 (± 14 SD) years, respectively. 88 (28.2%) and 224 (71.8%) tumors were diagnosed among pediatrics and adults, respectively. Overall, two peaks were observed in patients aged 5–15 years and 40–45 years. Gliomas, 43 (48.9%) and medulloblastomas, 21 (23.9%) were the most common tumors in pediatrics, whereas meningiomas, 107 (47.8%) and gliomas, 70 (31.3%) were the most common tumors in adults. Most pediatric and adult tumors were benign with 50 (56.8%) and 157 (70.1%) cases, respectively. Low-grade gliomas and medulloblastoma were the commonest benign and malignant tumors among pediatrics, with 31 (62%) and 21 (55.3%) cases, respectively. Conversely, meningiomas and high-grade gliomas were the most common benign and malignant tumors in adults, with 106 (67.5%) and 44 (65.7%) cases, respectively. CONCLUSION This study highlights the existing burden of brain tumors in Kenya and data from KNH may be representative of the national burden of BTs. This study lays a foundation for subsequent clinical and epidemiological studies and emphasizes the need to adopt existing reporting standards to help realize a complete picture of the burden of brain tumors in Kenya.

PADV-01 CHALLENGES OF NEURO-ONCOLOGY CARE IN ZIMBABWE

Abstract Due to the advent of covid 19 coupled with the socio-economic crisis in Zimbabwe, this has resulted in numerous challenges in terms of health care access and resultant diagnostic and treatment barriers for neuro-oncology cases. A retrospective analysis of the burden of neuro-oncology cases which have been seen at a single center in Zimbabwe over the past 5 years and the resultant diagnostic and treatment barriers that have incurred. METHODS An audit of brain tumor cases was done through the analysis of Outpatient department records, Neurosurgery Admission records, and Neurosurgery theatre records at Sally Mugabe Central hospital. RESULTS Total number of cases recorded for the period were 71. Meningiomas 11 (15,5%), Posterior fossa tumors 12 (17%), Gliomas 6 (0.08%), Craniopharyngiomas 6(0.08%), Metastasis 5(0.07%), Pituitary tumors 4(0.06%), choroid plexus papilloma 3(0.04%), Lymphoma 2(0.03%), Pineal region tumor 1(0.01%). 21(30%) tumors were unclassified. Posterior fossa tumors were most common in the pediatric population less than 10years of age. Meningiomas had a female to male ratio of 1.75: 1. 9 (12%) patients were operated on during the same period mostly pediatric tumors. CONCLUSION There is a great deal of institutional as well as patient related factors affecting the diagnosing and treatment of neuro-oncology care in Zimbabwe. This includes lack of operating time, inadequate intensive care facilities, a general unavailability of medical imaging services, delay in pathological reporting, unavailability and costly adjuvant treatment. This is leading to late diagnosis and suboptimal treatment of the various tumors. Although brain tumors are rare, they are not uncommon and there is thus need to improve service delivery to ensure early diagnosis and treatment to have good outcomes.

Pediatric soft tissue tumors : Tumors of uncertain origin

Soft tissue tumors of childhood are an extremely heterogeneous group of tumors that require precise diagnosis for therapy. In this article, selected tumors of uncertain origin that exhibit characteristic histological, immunophenotypical, and molecular features are addressed. Angiomatoid fibrous histiocytoma, alveolar soft part sarcoma, extrarenal rhabdoid tumor, synovial sarcoma, and desmoplastic small round cell tumor differ in their pathology, their clinical behavior, and prognosis.

Local Sustained Dinutuximab Delivery and Release From Methacrylated Chondroitin Sulfate.

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. High-risk NB is a subset of the disease that has poor prognosis and requires multimodal treatment regimens, with a 50% rate of recurrence despite intervention. There is a need for improved treatment strategies to reduce high-risk patient mortality. Dinutuximab is an anti-GD2 antibody ideal for targeting GD2 expressing NB cells, but binding of the antibody to peripheral nerve fibers leads to severe pain during systemic administration. Intratumoral delivery of the anti-GD2 antibody would allow for increased local antibody concentration, without increasing systemic toxicity. Chondroitin Sulfate (CS) is a biocompatible glycosaminoglycan that can be methacrylated to form CSMA, a photocrosslinkable hydrogel that can be loaded with therapeutic agents. The methacrylation reaction time can be varied to achieve different degrees of substitution, resulting in different release and degradation profiles. In this work, 4 and 24 h reacted CSMA was used to create hydrogels at 10% and 20% CSMA. Sustained in vitro release of dinutuximab from these formulations was observed over a 24-day period, and 4 h reacted 10% CSMA hydrogels had the highest overall dinutuximab release over time. An orthotropic mouse model was used to evaluate in vivo response to dinutuximab loaded 4 h methacrylated 10% CSMA hydrogels as compared to bolus tail vein injections. Tumor growth was monitored, and there was a statistically significant increase in the days to reach specific tumor size for tumors treated with intratumoral dinutuximab-loaded hydrogel compared to those treated with dinutuximab solution through tail vein injection. This supports the concept that locally delivering dinutuximab within the hydrogel formulation slowed tumor growth. The CSMA hydrogel-only treatment slowed tumor growth as well, an interesting effect that may indicate interactions between the CSMA and cell adhesion molecules in the tumor microenvironment. These findings demonstrate a potential avenue for local sustained delivery of dinutuximab for improved anti-tumoral response in high-risk NB.

Individual- and community-level correlates of pediatric central nervous system tumor disparities in the US.

The aim of this study was, through comprehensive, multilevel models of social determinants of health (SDoH) factors, including the Yost Index socioeconomic status (SES) score, to determine whether community- or individual-level SDoH factors quantifiably influence pediatric CNS tumor disparities more in care and prognosis across the US. The authors performed a retrospective cohort study assessing specialized Surveillance, Epidemiology, and End Results data of pediatric patients (≤ 19 years old) with nonmalignant and malignant tumors of the CNS from 2010 to 2018. A census-level Yost Index SES score and rurality/urbanicity measures were incorporated with individual characteristics of age, sex, and race/ethnicity. Chi-square analyses for clinical and demographic descriptions, multivariate Cox proportional hazards logistic regressions for survival, and multivariate logistic regressions for resection, radiation treatment, treatment delay, and advanced staging on preliminary presentation were performed. Across 18,236 patients, age-adjusted analyses showed substantially increased mortality risk among 6 of 11 subtypes (highest hazard ratio [HR] 1.91, 95% CI 1.59-2.28, p < 0.001 for glioma NOS), decreased odds of first-line therapy among 7 of 18 subtypes (lowest OR 0.36, 95% CI 0.11-0.97, p = 0.043 for resection of choroid plexus papilloma), increased odds of treatment delay among 6 of 11 subtypes (highest OR 2.47, 95% CI 1.01-6.49, p = 0.047 for germinoma), increased odds of advanced staging on preliminary presentation among 3 of 10 malignant subtypes (highest OR 2.56, 95% CI 1.27-5.52, p = 0.008 for malignant ependymomas), and increased odds of receipt of radiation therapy among 3 of 10 malignant subtypes (highest OR 2.30, 95% CI 1.87-2.84, p < 0.001) observed across many disease subtypes contributed by certain individual- and community-level SDoH factors. Through comprehensive analyses combining individual- and community-level SDoH factors, this study identified detrimental interrelated SDoH associations with poorer care and prognosis of pediatric patients with CNS tumors, delineating how both levels differentially contribute to observed disparities across different subtypes.

Approaches to the Diagnosis and Management of Paediatric Ovarian Tumours and Oncological Outcomes in a Single-centre Study. Evidence in Support Of IPSO Reccomendations

BackgroundApproaches to paediatric ovarian tumours vary. Cross-sectional imaging is reliable but not always performed. Laparoscopic tumourectomy, although popular, is not recommended by International Paediatric Surgical Oncology Society (IPSO); tumour spillage remains the main concern. We aimed to investigate the reliability of preoperative evaluation and identify perioperative factors associated with adverse outcomes. MethodsSingle-centre retrospective study (2015–2022) of clinical presentation, preoperative investigation, operative approaches and oncological outcomes in all females <18 years treated for ovarian tumours. Logistic regression was used to identify predictors of malignancy and of second disease events. Data are presented as median (IQR) or rates. ResultsSixty girls aged 12.5 (10–15) years with follow-up of 51 (30.5–76.3) months were included. Incidence of malignant and low malignant potential tumours was 19/60 (32%). Tumour size and consistency proved predictive of malignancy. Clinical assessement, tumour markers and cross-sectional imaging combined showed 75% sensitivity, 100% specificity and 7% misclassified malignancy rate. Second disease events (11/60, 18%) were associated with misclassified malignancy (2/11 vs. 1/49, p = 0.04) and positive margins (4/11 vs. 5/49, p = 0.02). Ovarian-sparing surgery did not influence second events (5/11 vs. 28/49, p = 0.48). There was no significant association between second events and laparoscopic tumourectomy (3/11 vs. 20/49, p = 0.40); spillage rate was however more frequent with laparoscopy (5/11 vs. 2/32, p = 0.008). ConclusionMisclassified malignancy, noted in 7% of patients undergoing optimal work-up, adversely impacted outcomes, highlighting the importance of oncological principles in both oophorectomy and ovarian-sparing surgery. Malignancy incidence and misclassification can be underestimated when tumours with malignant behaviour potential, such as immature teratomas and borderline tumours, are grouped as benign. There was no direct association between operative approaches and second events. Laparoscopy, however, failed to maintain oncological principles more frequently than open surgery and hence risks upstaging of paediatric ovarian pathology. Level of evidenceIII.

Robotic Surgery in Paediatric Oncology: Expanding Boundaries and Defining Relevant Indications

This article reviews the establishment and progress of the Multidisciplinary Paediatric Robotic Program in a high-volume paediatric surgery department at Hôpital Necker-Enfants Malades, Paris, France. A major foundational principle of the program was to establish a safe and secure environment for patients and staff, both pre-operatively, intra-operatively and post-operatively. This founding principle when applied systematically has allowed increasing confidence across the program and service. The robotic platform allows for precision surgery when approaching tumours, with freedom of movement adapted to meticulous vascular and organ dissection. Surgical feasibility is based on tumour characteristics, pre-operative imaging, with a focus on vascular and organ involvement, considering goals of surgery and surgical experience. Case complexity has been gradually increased (where appropriate) through an iterative process. The future of surgery is robotic, and even more so image-guided surgery, and this synergy has been instrumental when approaching tumour surgery in children. The current principles that guide application of robot-assisted surgery in paediatric tumours are presented. With this blueprint, excellent oncological outcomes can be achieved while utilising a minimally invasive approach in children with selected endocrine, neuroblastic and renal tumours.

DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres.

DNA methylation profiling, recently endorsed by the World Health Organisation (WHO) as a pivotal diagnostic tool for brain tumours, most commonly relies on bead arrays. Despite its widespread use, limited data exist on the technical reproducibility and potential cross-institutional differences. The LOGGIC Core BioClinical Data Bank registry conducted a prospective laboratory comparison trial with 12 international laboratories to enhance diagnostic accuracy for paediatric low-grade gliomas, focusing on technical aspects of DNA methylation data generation and profile interpretation under clinical real-time conditions. Four representative low-grade gliomas of distinct histologies were centrally selected, and DNA extraction was performed. Participating laboratories received a DNA aliquot and performed the DNA methylation-based classification and result interpretation without knowledge of tumour histology. Additionally, participants were required to interpret the copy number profile derived from DNA methylation data and conduct DNA sequencing of the BRAF hotspot p.V600 due to its relevance for low-grade gliomas. Results had to be returned within 30 days. High technical reproducibility was observed, with a median pairwise correlation of 0.99 (range 0.94-0.99) between coordinating laboratory and participants. DNA methylation-based tumour classification and copy number profile interpretation were consistent across all centres, and BRAF mutation status was accurately reported for all cases. Eleven out of 12 centres successfully reported their analysis within the 30-day timeframe. Our study demonstrates remarkable concordance in DNA methylation profiling and profile interpretation across 12 international centres. These findings underscore the potential contribution of DNA methylation analysis to the harmonisation of brain tumour diagnostics.

TCF3::BEND2 in paediatric supratentorial tumour with carcinoma-like epithelial features classifying as MN1-altered astroblastoma by DNA methylation profiling.

TCF3::BEND2 in paediatric supratentorial tumour with carcinoma-like epithelial features classifying as MN1-altered astroblastoma by DNA methylation profiling.