Malignant Pediatric Tumor Research Articles

Myc 9aaTAD activation domain binds to mediator of transcription with superior high affinity.

The overexpression of MYC genes is frequently found in many human cancers, including adult and pediatric malignant brain tumors. Targeting MYC genes continues to be challenging due to their undruggable nature. Using our prediction algorithm, the nine-amino-acid activation domain (9aaTAD) has been identified in all four Yamanaka factors, including c-Myc. The predicted activation function was experimentally demonstrated for all these short peptides in transactivation assay. We generated a set of c-Myc constructs (1-108, 69-108 and 98-108) in the N-terminal regions and tested their ability to initiate transcription in one hybrid assay. The presence and absence of 9aaTAD (region 100-108) in the constructs strongly correlated with their activation functions (5-, 3- and 67-times respectively). Surprisingly, we observed co-activation function of the myc region 69-103, called here acetyl-TAD, previously described by Faiola et al. (Mol Cell Biol 25:10220-10234, 2005) and characterized in this study as a new domain collaborating with the 9aaTAD. We discovered strong interactions on a nanomolar scale between the Myc-9aaTAD activation domains and the KIX domain of CBP coactivator. We showed conservation of the 9aaTADs in the MYC family. In summary for the c-Myc oncogene, the acetyl-TAD and the 9aaTAD domains jointly mediated activation function. The c-Myc protein is largely intrinsically disordered and therefore difficult to target with small-molecule inhibitors. For the c-Myc driven tumors, the strong c-Myc interaction with the KIX domain represents a promising druggable target.

CNSC-41. DABRAFENIB AND TRAMETINIB AS A PROMISING TREATMENT OPTION FOR PEDIATRIC POPULATION WITH LOW-GRADE GLIOMAS THAT HAVE BRAF V600E MUTATION:A BREAKTHROUGH IN THE FIELD OF NEURO- ONCOLOGY

Abstract Two-thirds of all pediatric malignant central nervous tumors, including high-grade (glioblastoma, anaplastic astrocytoma) and low-grade (ganglioglioma, pilocytic astrocytoma) carcinomas, are gliomas. Low-grade glioma(LGG) exhibits genetic alterations caused by the BRAF kinase mutation, such as replacing glutamic acid (E) in place of valine (V) at the 600 positions, known as the V600E point mutation. Pediatric low-grade gliomas (PLGGs) also comprise around one-third of juvenile brain tumors and are the most frequent central nervous system tumors. Patients were randomized 2:1 to dabrafenib plus trametinib (D+T) or carboplatin plus vincristine (C+V). Where possible, complete surgical removal is the mainstay of treatment for progressing or symptomatic PLGG.Radiation therapy has historically been used to treat PLGG in both up-front and salvage scenarios. To delay or avoid the necessity for radiation therapy in young children with advancing or incompletely resected PLGG, chemotherapy was created in 1980. On March 16, 2023, the Food and Drug Administration approved the use of trametinib (Mekinist, Novartis) with dabrafenib (Tafinlar, Novartis) in pediatric patients suffering from low-grade glioma (LGG) who require systemic therapy and are at least one year old. Nevertheless, early-stage clinical trials have produced encouraging results that may revolutionize the treatment of LGG in the near future.

Characterisation of Paediatric Neuroblastic Tumours by Quantitative Structural and Diffusion-Weighted MRI

Purpose: To determine the diagnostic accuracy of quantitative diffusion-weighted (DW) MRI apparent diffusion coefficient (ADC) and tumour volumes to differentiate between malignant (neuroblastoma (NB)) and benign types of neuroblastic tumours (ganglioneuroma (GN) and ganglioneuroblastoma (GNB)) using different region-of-interest (ROI) sizes. Materials and Methods: This single-centre retrospective study included malignant and benign paediatric neuroblastic tumours that had undergone DW MRI at diagnosis. The outcome was diagnostic accuracy of the tumour volume from structural and ADC DW MRI, in comparison to histopathology (reference standard). Results: Data from 40 patients (NB, n = 24; GNB, n = 6; GN, n = 10), 18 (45%) females and 22 (55%) males, with a median age at diagnosis of 21 months (NB), 64 months (GNB), and 133 months (GN), respectively, ranging from 0 to 193 months, were evaluated. The area under the receiver operating characteristic (AUROC) curve for ADC for discriminating between neuroblastic tumours’ histopathology for a small ROI was 0.86 (95% CI: 0.75–0.98), and for a large ROI, 0.83 (95% CI: 0.71–0.96). An ADC cut-off value of 1.06 × 10−3 mm2/s was able to distinguish malignant from benign tumours with 83% (68–98%) sensitivity and 75% (95% CI: 54–98%) specificity. Tumour volume was not indicative of malignant vs. benign tumour diagnosis. Conclusions: In this study, both small and large ROIs used to derive ADC DW MRI metrics demonstrated high accuracy to differentiate malignant from benign neuroblastic tumours, with the ADC AUROC for the averaged multiple small ROIs being slightly greater than that of large ROIs, but with overlapping 95% CIs. This should be taken into consideration for standardisation of ROI-related data analysis by international initiatives.

Tumor ablation in children.

Tumor ablation represents an increasingly important topic in pediatric interventional radiology. Many ablative techniques are well known and established in the adult population, and the adoption of these techniques in the pediatric field is increasing. Image-guided tumor ablation represents a wide category of interventional radiology procedures that can be applied to both benign and malignant pediatric solid tumors. Tumor ablation, either alone or in combination with locoregional therapy, can have curative, debulking, or palliative effects on a wide variety of histological tumor types.

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.

CNS Embryonal Tumor with PLAGL Amplification, a New Tumor Type in Children and Adolescents: Insights from a Comprehensive MRI Analysis.

CNS embryonal tumor with PLAGL1/PLAGL2 amplification (ET, PLAGL) is a newly identified, highly malignant pediatric tumor. Systematic MRI descriptions of ET, PLAGL are currently lacking. MRI data from 19 treatment-naïve patients with confirmed ET, PLAGL were analyzed. Evaluation focused on anatomical involvement, tumor localization, MRI signal characteristics, DWI behavior, and the presence of necrosis and hemorrhage. Descriptive statistics (median, interquartile range, percentage) were assessed. Ten patients had PLAGL1 and nine PLAGL2 amplifications. The solid components of the tumors were often multinodular with heterogeneous enhancement (mild to intermediate in 47% and intermediate to strong in 47% of cases). Non-solid components included cysts in 47% and necrosis in 84% of the cases. The tumors showed heterogeneous T2WI hyper-and isointensity (74%), relatively little diffusion restriction (ADC values < contralateral normal-appearing WM in 36% of cases with available DWI), and tendencies towards hemorrhage/calcification (42%). No reliable distinction was found between PLAGL1-and PLAGL2-amplified tumors or compared to other embryonal CNS tumors. The study contributes to understanding the imaging characteristics of ET, PLAGL. It underscores the need for collaboration in studying rare pediatric tumors and advocates for the use of harmonized imaging protocols for better characterization. ATRT= atypical teratoid/rhabdoid tumor; ETMR= embryonal tumor with multilayered rosettes; ET, PLAGL= CNS embryonal tumor with PLAGL amplification; EVD= external ventricular drain; IQR: interquartile range; PLAGL1= pleomorphic adenoma gene-like 1; PLAGL2= pleomorphic adenoma gene-like 2; WHO= World Health Organization.

Investigating the molecular mechanisms of Fuzheng Yiliu Shenji prescription in SH-SY5Y neuroblastoma cells.

Neuroblastoma is the most common extracranial solid tumor in childhood. Fuzheng Yiliu Shenji Prescription (FYSP) has shown potential in treating malignant pediatric tumors in clinical settings. This study aims to explore the molecular mechanisms behind its effects, specifically in the context of neuroblastoma cell lines. To elucidate the active compounds in FYSP and their mechanisms of action in inhibiting neuroblastoma cell viability, inducing apoptosis, and affecting the cell cycle in SH-SY5Y cells through network pharmacology and empirical validation. We identified the major compounds in FYSP and their predicted targets, constructing a protein-protein interaction (PPI) network and performing GO and KEGG pathway analyses. The effects of FYSP were empirically validated through assays on cell viability, cell cycle, apoptosis, and protein expression in SH-SY5Y cells. The study identified 172 active chemical components in FYSP, with 188 common targets related to neuroblastoma. Network analysis highlighted the PI3K-Akt pathway as a significant target. Experimental validation in SH-SY5Y cells confirmed that FYSP could inhibit cell viability, induce G2/M cell cycle arrest, and promote apoptosis through modulation of the PI3K-Akt pathway, specifically upregulating caspase-3 and downregulating Bcl-2/Bax expression. The study elucidates the molecular basis of FYSP's effects on neuroblastoma cells in vitro, demonstrating its ability to modulate key pathways involved in cell cycle and apoptosis. While these findings suggest a potential therapeutic role for FYSP, they are limited to in vitro observations, and further research, including in vivo studies, is necessary to explore its clinical applicability.

Cytokine profile of cerebrospinal fluid in pediatric patients with metastatic medulloblastoma

BackgroundMedulloblastoma (MB) is a malignant pediatric central nervous system tumor that is prone to leptomeningeal metastasis. Currently, apart from magnetic resonance imaging and cerebrospinal fluid (CSF) cytology, there are no reliable biomarkers for MB progression. Cytokines are key proteins in signaling pathways in the tumor microenvironment and are closely related to tumor recurrence and progression. This study aimed to investigate the CSF cytokine profile in pediatric patients with MB to identify biomarkers of tumor progression and metastasis. MethodsIn total, 10 patients were recruited for this study. Five patients had nonmetastatic MB and five had metastatic MB. A cytokine antibody array was used to detect the expression of 120 cytokines in the CSF, and differentially expressed cytokines were screened by integrated bioinformatics analysis. ResultsTwenty-seven cytokines were upregulated in patients with MB compared to control individuals. Of these, eight were upregulated by >1.5-fold (CCL2, BMP-4, beta-NGF, FGF-7, IL-12p40, eotaxin-2, M-CSF, and NT-4). Twelve cytokines were differentially expressed between patients with metastatic MB and nonmetastatic (nine cytokines were upregulated and three were downregulated). Among them, NAP-2, MIP-1α, MIP-1β, IGFBP-1, IGFBP-2 and IGFBP-3 were upregulated by more than two-fold. Gene Ontology analysis revealed that the upregulated cytokines were enriched mainly in “epithelial cell proliferation” and “chemotaxis,” and the Kyoto Encyclopedia of Genes and Genomes analysis indicated the enrichment of the “MAPK,” “PI3K-Akt,” and “Ras” signaling pathways. ConclusionsThe present study investigated cytokine profiles in the CSF of pediatric patients with MB. Our results suggest that these differentially expressed cytokines may serve as novel markers for detecting MB, especially for assessing the risk of progression and metastasis.

MicroRNA-32-5p inhibits metastasis by directly targeting VPS4B and increases sensitivity to dihydroartemisinin in neuroblastoma

Abstract Background Neuroblastoma (NB) is a malignant pediatric tumor requiring new therapies. Accumulating evidence has confirmed that microRNAs play critical roles in NB metastasis. Dihydroartemisinin (DHA) is capable of inhibiting the growth of NB cells. The primary objective of the current investigation was to characterize a newly discovered microRNA, miR-32-5p, in terms of the functional role, underlying mechanism of action, and potential synergistic therapeutic impact in the context of NB metastasis. Materials and methods Real-time quantitative polymerase chain reaction and Western blotting were employed to assess the expression levels of miR-32-5p and its target, vacuolar protein sorting 4B (VPS4B). Furthermore, Transwell assay was utilized to evaluate in vitro cell migration and invasion, whereas a metastasis xenograft model was established in nude mice via caudal vein injections. Results Gene Expression Omnibus database and real-time quantitative polymerase chain reaction analysis showed that miR-32-5p was downregulated in human NB samples and NB cell lines, in comparison with the normal tissue and cell lines. Inhibiting miR-32-5p induced the migration and invasion of NB cells, whereas overexpression of miR-32-5p prevented the migration and invasion in NB cell lines. Furthermore, VPS4B was identified as the direct target of miR-32-5p and the miR-32-5p reduction associated with NB metastasis upregulated the expression of VPS4B. Conversely, overexpression of VPS4B reversed the suppressive effects of miR-32-5p on NB cells. Moreover, miR-32-5p increased the sensitivity to DHA both in NB cells and in the metastasis xenograft model of nude mice. Conclusions The downregulation of miR-32-5p in NB regulates NB metastasis by targeting VPS4B. Moreover, miR-32-5b can improve the sensitivity of DHA in the xenograft mouse model. Our findings have important implications for the combined application of miR-32-5p and DHA in the treatment of NB.

Imaging-Guided Metabolic Radiosensitization of Pediatric Rhabdoid Tumors.

Tumor hypoxia leads to increased resistance to radiation therapy (RT), resulting in markedly worse clinical outcomes in the treatment and management of pediatric malignant rhabdoid tumors (MRT). To alleviate hypoxia in MRT, we repurposed an FDA approved, mitochondrial oxidative phosphorylation (OXPHOS) inhibitor, Atovaquone (AVO), to inhibit oxygen consumption and thereby enhance the sensitivity of tumor cells to low dose RT in MRT by hypoxia alleviation. Additionally, to better understand the tumor response induced by AVO and optimize the combination with RT, we employed an emerging, noninvasive imaging modality, known as multispectral optoacoustic tomography (MSOT), to monitor and evaluate real-time dynamic changes in tumor hypoxia and vascular perfusion. Oxygen-Enhanced (OE)-MSOT could measure the change of tumor oxygenation in the MRT xenograft models after AVO and RT treatments, indicating its potential as a response biomarker. OE-MSOT showed that treating MRT mouse models with AVO resulted in a transient increase in oxygen saturation (ΔsO 2 ) in tumors when the mice were subjected to oxygen challenge, while RT or saline treated groups produced no change. In AVO+RT combination groups, the tumors showed an increase in ΔsO 2 after AVO administration followed by a significant decrease after RT, that correlated with a strong anti-tumor response, demarcated by complete regression of tumors, with no relapse on long-term monitoring. These observations were histologically validated. In MRT models of acquired AVO resistance, combination therapy failed to alleviate tumoral hypoxia and elicit any therapeutic benefit. Together, our data highlights the utility of repurposing anti-malarial AVO as an anticancer adjuvant for enabling low dose RT for pediatric patients.

Expansion of tumor-infiltrating and marrow-infiltrating lymphocytes from pediatric malignant solid tumors

The expansion of tumor-infiltrating lymphocytes (TIL) for adoptive cellular therapy is under investigation in many solid tumors of adulthood. Marrow-infiltrating lymphocytes (MIL) have demonstrated antitumor reactivity preclinically. Successful expansion of TIL/MIL has not been reported across pediatric solid tumor histologies. The objective of this study was to demonstrate successful expansion of TIL from pediatric solid tumors for translation in an adoptive cell therapy (ACT) treatment strategy. A prospective study of TIL/MIL expansion was performed on solid tumors of pediatric patients undergoing standard-of-care procedures. TIL/MIL expansions were performed in the presence of high-dose interleukin 2. To demonstrate a full-scale expansion to clinically-relevant cell doses for TIL therapy, initial TIL culture was followed by a rapid expansion protocol for select patients. Expanded specimens were analyzed for phenotype by flow cytometry and for anti-tumor reactivity by the interferon-gamma release assay. Eighteen tumor samples were obtained. Initial TIL cultures were successfully generated from 14/18 samples (77.7%). A median of 5.52 × 107 (range: 2.5 × 106-3.23 × 108) cells were produced from initial cultures, with 46.9% expressing a CD3 phenotype (46.9%). Eight samples underwent rapid expansion, demonstrating a median 458-fold expansion and a CD3 phenotype of 98%. Initial MIL cultures were successfully generated from five samples, with a predominantly CD3 phenotype (45.2%). Sufficient tumor tissue was only available for seven TIL samples to be tested for reactivity; none demonstrated responsiveness to autologous tumor. TIL and MIL expansion from pediatric solid tumors was successful, including the full-scale expansion process. This data supports translation to an ACT-TIL treatment strategy in the pediatric population and thus a Phase I trial of ACT-TIL in pediatric high-risk solid tumors is planned.

PL3 CendR peptide shows specific uptake in cultured Y79 retinoblastoma cells with nucleolar accumulation

Retinoblastoma is the most common pediatric intraocular malignant tumor affecting 1:15 000–1:20 000 live births. Even though the survival rate in developed countries is over 90 %, more efficient treatment options are needed for better vision salvage and reduction of the adverse effects. Therefore, we investigated fluorescein-labeled PL3 peptide targeting properties towards the Y79 retinoblastoma cell line in vitro. Through the application of cellular imaging and flow cytometry techniques, the PL3 peptide exhibited a rapid and specific internalization within Y79 cells, with subsequent translocation to the cell nuclei, showcasing notable accumulation in the nucleoli. This phenomenon was not present in other investigated cell lines and was not observable with similarly charged and length control peptide. However, the exact mechanism behind this Y79 cell line-specific nuclear and nucleolar targeting pattern remains elusive. In the future, this targeting process could facilitate specific treatment modalities of retinoblastoma with PL3 peptide-coupled drug delivery technologies.

Outcome of Reconstruction with Irradiated Tumour Bone in Paediatric Malignant Bone Tumours

Outcome of Reconstruction with Irradiated Tumour Bone in Paediatric Malignant Bone Tumours

Surgical management of liver tumors.

Two percent of pediatric malignancies arise primarily in the liver; roughly 60% of these cancers are hepatoblastoma (HB). Despite the rarity of these cases, international collaborative efforts have led to the consistent histological classification and staging systems, which facilitate ongoing clinical trials. Other primary liver malignancies seen in children include hepatocellular carcinoma (HCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), undifferentiated embryonal sarcoma of the liver (UESL), and hepatocellular neoplasm not otherwise specified (HCN-NOS). This review describes principles of surgical management of malignant pediatric primary liver tumors, within the context of comprehensive multidisciplinary care.

ONC206 targeting ClpP induces mitochondrial dysfunction and protective autophagy in hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family, has shown promising therapeutic potential and a good safety profile in both malignant pediatric central nervous system tumors (diffuse midline glioma [DMG]) and hematologic malignancies. ONC206 is a more potent analog of ONC201. However, the ONC206 potential and mechanism of action in HCC remain to be elucidated. We found that ONC206 hindered HCC growth by suppressing cell proliferation and inducing apoptosis. Moreover, ONC206 induced cytoprotective autophagy, and blocking autophagy enhanced the proapoptotic effect of ONC206. Additionally, ONC206 induced mitochondrial swelling, reduced the mitochondrial membrane potential (MMP), and led to the accumulation of mitochondrial ROS in HCC cells, ultimately resulting in mitochondrial dysfunction. The HCC patient samples exhibited notably elevated levels of caseinolytic protease proteolytic subunit (ClpP), which serves as a mediator of ONC206-induced mitochondrial dysfunction and the activation of protective autophagy. knockdown of ClpP reversed the cytotoxic effects of ONC206 on HCC cells. In summary, our results provide the first insight into the mechanism by which ONC206 exerts its anti-HCC effects and induces protective autophagy in HCC cells through ClpP.

The clinical application and laboratory management of molecular genetic diagnosis in children's hospital

AbstractBackgroundMolecular diagnostic technology is the foundation of precision medicine, which has the advantages of good specificity, high sensitivity, strong targeting, rapiddiagnosis, etc. It has a wide range of applications in the field of pediatrics. However, molecular diagnostic technology is characterized by complicated experimental operation, high difficulty in data analysis and interpretation, in consistent standards among laboratories, and difficult standardization of technical processes. Enhancing the application value of molecular diagnostic technology in pediatrics and promoting the high‐quality development of the discipline requires careful consideration by relevant management and professionals.MethodsThis study firstly outlines the development history of molecular diagnostic technology. Then, it analyzes the application of molecular diagnostic technology in the field of pediatrics. Finally, it explores the countermeasures for the management of molecular diagnostic laboratories.ResultsThis study highlights the importance of molecular diagnostic technology in providing information and decision‐making basis for disease prevention, prediction,diagnosis, treatment and regression. It has a wide range of applications in the molecular diagnosis of pediatric hereditary diseases, malignant tumors and infectious diseases. In addition, the countermeasures for the management of molecular diagnostic laboratories are proposed from the five aspects of laboratory, personnel team construction, standardized management,multidisciplinary cross‐discipline, research and translation, safety managementand ethical supervision, and management upgrading and modernization.ConclusionsMolecular diagnostic technology, as the basis of precision medicine, has become one of the important frontier fields in the development of contemporary pediatric medicine. Enhanced laboratory capacity in molecular diagnostic techniques can improve outcomes in the prevention, prediction, diagnosis, treatment, prognosis and research of pediatricdiseases, and lay the groundwork for child healthcare.

Evaluation of surgical strategies and long-term outcomes in pediatric hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the second most common pediatric malignant liver tumor after hepatoblastoma, represents 1% of all pediatric tumors. A retrospective study was conducted on children with HCC treated at our center from March 2002 to October 2022, excluding those with inadequate follow-up or records. Demographic data, initial complaints, alpha-fetoprotein (AFP) values, underlying disease, size and histopathological features of the masses, chemotherapy, and long-term outcomes were analyzed. Fifteen patients (8 boys, 7 girls) with a mean age of 11.4 ± 4.1years (0.8-16.4years) were analyzed. The majority presented with abdominal pain, with a median AFP of 3.9ng/mL. Hepatitis B cirrhosis in one patient (6.6%) and metabolic disease (tyrosinemia type 1) in two patients (13.3%) were the underlying diseases. Histopathological diagnoses were fibrolamellar HCC (n:8; 53.3%), HCC (n:6; 40%). Four of the 15 patients underwent liver transplantation, and 9 underwent surgical resection. Due to late diagnosis, two patients were considered inoperable (13.3%). The survival rate for the four patients who underwent liver transplantation was found to be 75%. Surgical treatment of various variants of HCC can be safely performed in experienced centers with a multidisciplinary approach, and outcomes are better than in adults.

Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in Children With Germ Cell Tumor After Chemotherapy.

18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a diagnostic tool widely used in adult oncology and some pediatric oncological settings. There are no established recommendations for the use of this imaging modality in pediatric malignant germ cell tumors (mGCT), however. Our aim is to evaluate the role of 18F-FDG PET/CT in the restaging of mGCT after chemotherapy in children and adolescents. We retrospectively reviewed patients with mGCT treated in Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers who underwent 18F-FDG PET/CT between 2011 and 2021. Seventeen patients (median age 13y) were included in the study. In 14 patients, 18F-FDG PET/CT was performed at diagnosis; 12 showed pathologic uptake. The 2 18F-FDG PET/CT negative cases were histologically defined as yolk sac tumor (YST) and mixed (chorioncarcinoma, YST). Nine of the 12 patients who had pathologic 18F-FDG PET/CT at diagnosis repeated the examination after neoadjuvant chemotherapy, before, second look surgery. In 5 cases, no pathologic uptake was evident. Histology showed necrosis alone in 4 cases and necrosis and mature teratoma in 1. In 3 of the 6 cases with pathologic uptake (2 of 6 patients did not perform the examination at diagnosis), histology showed persistence of malignant component, whereas in the remaining 3 cases, necrosis and mature teratoma were present. In our review of a series of children with mGCT, 18F-FDG PET/CT after neoadjuvant chemotherapy showed 1 of 5 false negatives and was unable to discriminate between residual malignant component and mature teratoma.

The importance of basic and translational research in caring for children with malignant solid tumors in Latin America.

Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

Scoliosis After Resection of Primary Pediatric Chest Wall Tumors

BackgroundScoliosis is one of the long-term consequences of surgical resection of pediatric chest wall tumors. This study aimed to identify the risk factors associated with scoliosis development following the resection of chest wall tumors. MethodsRetrospective cohort study of 64 children who underwent resection of malignant chest wall tumors from 2009 to 2022. Univariate and multivariate analyses were used to investigate factors associated with scoliosis development. ResultsThe median age at the time of surgery was 7 years (range, 3–21), with 33 (51.6%) patients undergoing surgery before the age of 10 years. The most common histology was Ewing sarcoma (n = 57). A median of 3 (range, 1–5) contiguous ribs were resected. A total of 34 (53.1%) patients had anterior CWTs and 30 (46.9%) had posterior CWTs. Concomitant partial lung and diaphragmatic resection were performed in 12 patients (lung, n = 7; diaphragm, n = 5). Scoliosis convex towards the resection side developed in 21 (32.8%). The primary risk factors for scoliosis were resecting 3 or more ribs (OR 6.44) and resection of the posterior rib segment (OR 5.49). Patients with a tumor resection below 10 years old were not associated with a higher risk of scoliosis. ConclusionsScoliosis following resection of a primary malignant pediatric chest wall tumor is associated with resection involving three or more ribs and resection of the posterior rib sector. Type of StudyRetrospective observational. Level of EvidenceIV.