Malignant Tumors In Children Research Articles

Locally Advanced Childhood Nasopharyngeal Cancer: A Case Series

Nasopharyngeal carcinoma is a rare malignant tumor in childhood. To date, no consensus has been achieved concerning the recommendations for the management of childhood Nasopharyngeal carcinoma. Chemotherapy and radiotherapy are the main modalities in the management of nasopharyngeal carcinoma (NPC). Five cases (with an age range between 10 and 16 years), including one patient with stage III NPC and four patients with stage IV NPC, are reported in this study. All patients received four courses of induction chemotherapy followed by concurrent chemoradiation with cumulative irradiation, with a dose of 70 Gy in 33-37 fractions. Patients were treated with intensity modulated radiation therapy with simultaneous integrated boost technique using helical Tomotherapy. After two-year’s follow-up, four patients were achieved complete response, one patient showed residual disease in lymph nodes in the neck and bone metastases one year after the completion of treatment. Treatment side effects were well tolerated, there was no acute toxicity grade 3 or 4, and late toxicity consisted of chronic sinusitis, grade 1 xerostomia, and grade 1 skin fibrosis.

Existence and Distribution of the Microbiome in Tumour Tissues of Children with Hepatoblastoma

Cancer microbiota have recently been demonstrated in several cancer types. The microbiota enhances inflammation in the cancer microenvironment and affects the disease pathology by regulating tumourigenesis, cancer progression, and chemotherapy resistance. Hepatoblastoma (HB), the most common childhood malignant tumour, is a malignant embryonic tumour. However, the pathogenesis and molecular basis of HB remain poorly understood. In this study, to explore the existence and distribution of the microbiome in tumour tissues and adjacent non-tumour tissues of children with HB, we mainly performed 16S rDNA sequencing, and the results showed that the diversity and abundance of the microbiome in children with HB were significantly different between HB tumours and adjacent non-tumour tissues (p < 0.01). At the phylum level, the dominant microbiomes in the tumour tissues were Proteobacteria, Bacteroidetes, and Firmicutes. At the genus level, Ruminococcus was more abundant in HB tumours than in the adjacent non-tumour tissues. Simultaneously, the abundances of Bacteroides, Parabacteroides, Lachnospiracea-NK4A136, and Alistipes in HB tumours were lower than those in the adjacent non-tumour tissues. In addition, Romboutsia strongly correlated with alpha-fetoprotein, an important indicator of HB. Sphingomonas was abundant in primary HB tumours, whereas Oscillibacter and Pandoraea were abundant in metastatic HB tumours. However, whether these bacteria are associated with HB needs further evaluation. Therefore, we identified the microbiome that correlated with the occurrence and development of HB. Ruminococcus and Romboutsia were identified as potential bacterial markers of HB tumours. To conclude, we found that HB also contains cancer microbiota, and it is necessary to shed light on the microbiome characteristics of HB in the future.

Racial/ethnic disparities in all-cause and cause-specific death among children with malignant central nervous system tumours: a registry-based cohort retrospective analysis

It is generally recognized that there is unequal mortality in childhood central nervous system (CNS) malignancy in the United States (US), but little is known about the trends and contributors of racial/ethnic disparities in death. We assessed the trends of racial/ethnic disparities in all-cause and cause-specific death, and the contributions of tumour, treatment and socioeconomic factors to this disparity. This registry-based cohort study included children (aged ≤19 years) diagnosed with malignant CNS tumours, using data from the US population-based cancer registry in the Surveillance, Epidemiology, and End Results (SEER) Program. The clinical outcomes were all-cause and cause-specific death for each racial/ethnic group (White, Black, Hispanic, non-Hispanic Asian/Pacific Islander [API], and non-Hispanic American Indian/Alaska Native [AI/AN] children). We quantified absolute disparities using absolute rate difference in 5-year cumulative incidence of death. Cox proportion risk models were used to estimate the relative racial/ethnic disparities, and the contribution of factors to disparities in death. In this study, data from 14,510 children with malignant CNS tumours (mean [SD] age, 8.5 [5.7]; 7988 [55.1%] male) were analysed. Overall, the cumulative incidence of death from CNS tumours across four racial/ethnic groups decreased from 2001 to 2020. Black patients had the highest risk of death from all causes and CNS tumours between 2001 and 2020, with adjusted hazard ratios (HR) of 1.52 (1.38-1.68) and 1.47 (1.31-1.64), respectively. The absolute disparity in all-cause death between Hispanic and White patients increased slightly (from 8.2 percentage points [ppt] to 9.4ppt), and the relative disparity in death from CNS tumours increased from 1.33 (1.15-1.55) in 2001-2005 to 1.78 (1.44-2.20) in 2016-2020. The absolute disparities in death from CNS tumours between Black and White patients (from 11.8ppt to 4.3ppt) and between API and White patients (from 10.1ppt to 5.1ppt) decreased from 2001-2005 to 2011-2015. Race/ethnicity disparities in death from CNS tumours among childhood malignant CNS tumours had reduced from 2001 to 2020, and quantifying the contribution of factors to this disparity in death could provide a basis for decreasing mortality among racial/ethnic minority patients. Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program.

Vasoactive Intestinal Peptide-Producing Neuroblastic Tumors: A Rare Cause of Refractory Diarrhea.

Neuroblastic tumors are the most common malignant extracranial solid tumors of childhood. A small subgroup presents chronic incoercible diarrhea due to the tumor's production of vasoactive intestinal peptide (VIP). The hypothesis of an occult tumor is not always considered, which delays and impairs treatment. We aim to identify these patients' characteristics and help alert health professionals to the hypothesis of a neuroblastic tumor in children with chronic diarrhea refractory to the usual approach. We carried out an epidemiological study on all retrievable reports of neuroblastic tumors between 1975 and 2021 described in the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and Latin American & Caribbean Health Sciences Literature (LILACS) databases. Patient information was divided into categories, and we performed a descriptive analysis. We analyzed 96 cases; 83 (86.5%) cases had diarrhea prior to the diagnosis of the neoplasm, 49 (51%) were ganglioneuroblastomas, 69 (71.8%) were abdominal, and 59 of the 60 patients (98%) with reported acid-base disorders had hypokalemia. When serum VIP was reported, the majority of values varied between one and 20 times the upper reference limit. Seventy-two (75%) patients underwent complete tumor resection, and the overall survival rate was 70%. Serum VIP production by neuroblastic tumors is related to cell differentiation and better prognosis. Such children often require intensive hospital support to reverse the malnutrition and acid-base disorders related to this paraneoplastic syndrome. Its early diagnosis and treatment significantly change the prognosis and quality of life. We, therefore, suggest screening for neuroblastic tumors when health professionals encounter unmanageable chronic secretory diarrhea in children with no defined etiology in the usual investigations.

The value of radiomics features of the spleen as surrogates for differentiating subtypes of common pediatric lymphomas.

Lymphoma is a common malignant tumor in children. The pathologic subtyping of lymphoma is high complex, and the treatment options vary. The different pathologic subtypes of lymphomas have no significant differences on computed tomography (CT) images. As it is a hematologic disease, patients with lymphoma often show abnormalities in the spleen, and so the aim of this study was to construct a model for differentiating Burkitt lymphoma (BL) from lymphoblastic lymphoma through the extraction of radiomic features of the spleen from CT images. This could provide an efficient, noninvasive method that can differentiate the common pathological subtypes in patients with pediatric lymphoma. The clinical data and imaging data of 48 patients with lymphoblastic lymphoma and 61 patients with BL were retrospectively analyzed. The dataset was divided into a training set (n=76) and a test set (n=33) through complete randomization. Radiomics features of the spleen were separately extracted from CT images in the noncontrast enhanced, arterial, and venous phases. These phase-specific features were integrated to construct fusion models. Three classifiers, quadratic discriminant analysis (QDA), logistic regression (LR), and support vector machine (SVM), were employed to build the models. The fusion model exhibited superior performance compared to individual models. There was no significant difference between the fusion models constructed by QDA and LR in either the training set or the test set. Among the four fusion models constructed with the SVM classifier, SVM_4 emerged as the best performing model. The area under the curve, sensitivity, specificity, and F1-score of the SVM_4 model were 0.967 [95% confidence interval (CI): 0.935-0.998], 0.86, 0.97, and 0.913 in the training set, respectively, and 0.754 (95% CI: 0.584-0.924), 0.611, 0.867, and 0.71 in the test set, respectively. The radiomics features of the spleen demonstrated the capability to distinguish between the two most common lymphoma subtypes in pediatric patients. This noninvasive approach holds promise for efficient and accurate discrimination.

Factors influencing parental fatigue in children with retinoblastoma based on the unpleasant symptoms theory

Parents of children with retinoblastoma, the most common primary ocular malignant tumour in childhood, bear a heavy caregiving burden and are very susceptible to fatigue. However, little is known about their current status of fatigue and factors influencing fatigue; therefore,this study, based on the theory of unpleasant symptoms, and included 317 parents of children with retinoblastoma in China, whose general demographic data were collected, and on whom the fatigue severity scale (FSS), the generalized anxiety disorder (GAD-7) and 2-item patient health questionnaire (PHQ-2) were administered, from 9 March to 1 June 2020. The parents’ FSS score and fatigue incidence were 4.41 ± 1.14 and 67.19%, respectively. The fatigue level was positively correlated with anxiety, depression, education, times of hospitalisations, and treatment types (r = 0.125–0.468, P < 0.05) and negatively correlated with health status, sleep quality, economic status, and family economic situation (r = − 0.120 to − 0.322, P < 0.05). Parent’s anxiety level, being an only child and female sex of child influenced parents’ fatigue. Healthcare personnel need to focus their attention on this high-risk fatigue group and implement appropriate interventions to reduce their fatigue level, promote their physical and mental health, and facilitate better care for children.

Prognostic significance of migrasomes in neuroblastoma through machine learning and multi-omics

This study explores migrasomes' role in neuroblastoma, a common malignant tumor in children, and their potential impact on tumor formation. We analyzed neuroblastoma RNA-seq datasets from public databases, including GSE62564, GSE181559, target, and fwr144. Through data normalization and unsupervised classification using migrasome-specific molecular markers, Differentially Expressed Genes were identified, followed by functional enrichment analysis. Our novel migrasome-associated machine learning model, MigScore, was developed using ten algorithms and 101 combinations, validated on two single-cell datasets. This enabled immune infiltration assessment and drug compatibility prediction, highlighting the utility of MS275, a histone deacetylase inhibitor. Results showed a significant inverse relationship between MigScore and favorable clinical outcomes, elucidating the link between migrasome pathways and tumor immunogenicity. These findings suggest that migrasomes are crucial in neuroblastoma prognosis, leading to the possibility of personalized treatment strategies and improved outcomes.

Varied toxicity profile of intravitreal melphalan in two retinoblastoma eyes.

Retinoblastoma (RB) is the most common primary intraocular malignant tumor of childhood. Persistent or recurrent vitreous seeding is the most common reason for therapeutic failure in advanced RB. Intravitreal chemotherapy has emerged as an effective therapy for vitreous seeding in RB, with a generally acceptable safety profile. However, intravitreal chemotherapeutics, especially melphalan, can cause toxicity that may progress to total retinal atrophy. In this report, we present two cases with retinal melphalan toxicity that had varied clinical findings. One of the cases had extensive retinal atrophy that was demonstrated by hand-held spectral domain optical coherence tomography (HHSD-OCT), while the other had normal retinal anatomy on HHSD-OCT but markedly diminished retinal function on flash electroretinography.

Current situation and prospect of diagnosis and therapy of childhood acute leukemia in China

Acute leukemia is the most common hematopoietic stem cell malignant tumor in children, which ranks in the top one of the incidence of tumor in children, it is a major disease that affects the growth and survival of children. With the continuous improvement of medical diagnosis and treatment and the extensive development of immunotherapy, the survival rate and quality of life of children with acute leukemia have been significantly improved. In recent years, three cooperative groups of childhood leukemia have been established in China, and a series of high-level research results have been published. In the future, efforts should be made to promote the process of standardization and homogenization in the diagnosis and treatment of children's acute leukemia, explore the monitoring targets of sensitive residual diseases, and find the best treatment for refractory/recurrent cases. Speeding up the clinical research of new drugs will be an urgent problem and development direction in the field of acute leukemia diagnosis and treatment in children.

Multimodal imaging for the differential diagnosis and efficacy evaluation of intraocular retinoblastoma in children with selective ophthalmic artery infusion.

Retinoblastoma (RB) is the most common malignant tumor in children under the age of 3 years and is associated with a high disability and mortality rate. The aim of this study was, first, to evaluate the clinical efficacy of multimodal imaging in differentially diagnosing RB in children and in predicting the efficacy of selective ophthalmic artery infusion (SOAI) and, second, to identify the factors associated with this efficacy. This study retrospectively collected the data from 256 children with unilateral RB and intraocular involvement, including multimodal imaging magnetic resonance imaging (MRI), computed tomography (CT), and clinical characteristics. Among the cases, 33 with both CT and MRI data available were used to evaluate the diagnostic accuracy in distinguishing RB, with histopathological results serving as the gold standard. Additionally, a retrospective analysis was conducted on the MRI and clinical characteristics of 256 cases of unilateral RB with intraocular involvement before SOAI treatment. The predictive ability of imaging features and clinical characteristics for the treatment efficacy of children was analyzed, and the differences in globe salvage rates and visual preservation based on different tumor stages were evaluated. The diagnostic accuracy of CT imaging for RB was 96.96% while that of MRI was 84.84%, with both showing high consistency with the histopathological results. CT images demonstrated a posterior intraocular mass with a high-density appearance, with spots, patches, or clustered calcifications visible within the tumor. The CT values were mostly above 100 Hounsfield units (HU), and enhanced scanning showed varying degrees of enhancement in noncalcified masses. MRI showed low or moderate signal intensity on T1-weighted images and moderate-to-high signal intensity on T2-weighted images, with significant enhancement after contrast administration. Tumors with more calcifications showed long T1 and short T2 signals. Patients with better prognosis had a higher delta signal increase (ΔSI), a greater distance from the optic disc, smaller tumor diameter, absence of implantation nodules or smaller implantation range, endogenous growth pattern, smaller extent of retinal detachment, absence of clinical high-risk factors, no vitreous hemorrhage, no globe shrinkage, and smaller calcification volume. The distance between the tumor and optic disc, clinical high-risk factors, and tumor growth pattern were found to be independent factors associated with prognosis. The rate of successful globe salvage and visual acuity decreased with increasing tumor stage. CT and MRI are highly valuable for the comprehensive assessment of tumors in pediatric RB. MRI alone can complete a comprehensive assessment of patients with RB and thus allow for the reduction radiation dose in children. Calcification of the tumor is crucial for diagnosis, and imaging findings can serve to inform patient prognosis and treatment planning. The distance between the tumor and optic disc, clinical high-risk factors, and tumor growth pattern are closely related to the prognosis of children.

Factors Associated with Outcomes at 1 Year in Paediatric Post-nephrectomy Patients for Nephroblastoma at the University Teaching Hospital and Cancer Diseases Hospital in Lusaka, Zambia.

Nephroblastoma is the most common primary malignant renal tumour of childhood. The survival rates in high-income countries are approximately 90%. However, low-income countries have low survival rates of 20%-50%. This study assessed factors associated with treatment outcomes of children post-nephrectomy for nephroblastoma at the University Teaching Hospital and Cancer Diseases Hospital in Lusaka, Zambia. A retrospective observational cohort study was conducted, where all children diagnosed with unilateral Wilms tumour below the age of 16 years who had nephrectomy from July 2016 to June 2019 were enrolled. Sociodemographic, clinical characteristics and treatment outcomes were noted. All data were coded and stored in a tabular format using Microsoft Excel. Statistical software STATA version 13 was used for analysis. Thirty patients were enrolled. The male-to-female ratio was 1:1. The 1-year event-free survival was 46.7%. Treatment abandonment accounted for 36.6% of the participants. 16.7% of the patients had disease progression. No patient had a relapse or died during the 1-year follow-up period. 66.7% had advanced disease stages III and IV. Advancement in age (above 4.3 years), living in a rural environment more than 100 km away from Lusaka and advanced disease stage were all associated with a poor outcome. Factors associated with a poor outcome in this study were advanced age and late presentation.

MDB-64. NOVEL TRANSCRIPTS ASSOCIATE WITH SURVIVAL IN CHILDHOOD MEDULLOBLASTOMA

Abstract BACKGROUND Medulloblastoma is the commonest malignant brain tumour in childhood, with progression-free survival (PFS) &amp;lt;65% in high-risk disease. Novel biomarkers, independent of current clinicopathological risk factors, could enhance understanding of biology and support improved treatment approaches. METHODS Using high-depth RNA sequencing of 217 patients, we identified novel multi-exonic medulloblastoma transcripts using a de novo analysis. We evaluated these alongside known/curated gene transcripts, including correlative survival analysis for 170 patients (aged 3-16 years and treated with curative intent). Multivariable survival analyses of the overall cohort (n=145) and a MBGroup3/MBGroup4 (Group3/Group4)-specific subcohort (n=95) was undertaken to identify prognostic transcripts, adjusting for current risk criteria and correcting for multiple testing. RESULTS From 3,150 novel transcripts identified, expression of 217 varied significantly and were further assessed. One was prognostic for PFS independent of subgroup (located on chromosome 20) while three were independently prognostic within Group3/Group4 (located on chromosome 1, 4 and 21 respectively). Transcript presence was validated by qPCR. From &amp;gt;60,000 known transcripts identified, 9693 were assessed. Four were independently prognostic for PFS in the whole-cohort (MRPS12, SLC25A34, MLYCD and ROGD1). In Group3/Group4, the top upregulated canonical pathways associated with PFS were: polo-like kinase, cyclin/cell cycle regulation, BRCA1/ DNA damage response, and glutamate receptor signalling. MELK and NQO2 were among the top 10 transcripts most highly associated with Group3/Group4 PFS. The prognostic significance of six transcripts (MRPS12, MLYCD, MELK, CDK4, NQO2, ROGD1) was validated in an independent Group3/Group4 dataset (n=470) while ROGD1 was prognostic independent of subgroup. Immunohistochemical validation showed low CDK4 expression, low MLYCD expression and high CHK1 expression were independent prognosticators in Group3/Group4. CONCLUSION De novo transcripts represent a significant component of the medulloblastoma transcriptome, providing prognostic information, and enhancing biological understanding of Group3/Group4 disease. CHK1 and MELK represent promising validated candidates for further evaluation as prognostic biomarkers in Group3/Group4 medulloblastoma.

LMIC-01. SURVIVAL AND PROGNOSTIC FACTORS IN CHILDHOOD MEDULLOBLASTOMA SINGLE TERTIARY CENTER EXPERIENCE FROM KING FAHAD MEDICAL CITY KFMC SAUDI ARABIA

Abstract BACKGROUND Medulloblastoma (MB) is the most common childhood malignant brain tumor treated with intensive multimodalities therapy including Surgery, Craniospinal Radiation, and chemotherapy. Our study aims to document the clinical courses, prognostic factors, and survival outcomes in Saudi children above three years with Medulloblastoma treated in King Fahad Medical City KFMC. METHODS Retrospective analysis of MB patients diagnosed between January 2009 to January 2022 All patients received Risk-adapted Radiation therapy followed by maintenance chemotherapy,3 patients progressed and died after surgery and were excluded from analysis. RESULTS We identified 145 MB patients 65.5 % were male. median age at Diagnosis 7.00 years (range3-14 years), Age less than 5 years did not have a worse outcome in our cohort. Classic histology was predominant (80%), 42.1% of patients had metastatic disease at presentation; the Median time to start radiation therapy after surgery was 35 days. 51.7% were treated as High-Risk HR MB and Average Risk AR MB 48.3%. 65 cases having molecular testing for MB molecular subgroups. 6 patients 4.1% developed a second malignancy with a median time of 6 years post diagnosis. Multivariate survival analysis showed that progression-free survival was significantly reduced by the extent of surgical resection (P=0.021) and Metastatic MB at diagnosis(P=0.014). At Median follow-up of 7 years, Progression-free survival PFS and overall survival OS for the whole cohort were 72.4% and 71.7% respectively. PFS for AR MB and HR MB was 81.4% and 64.0% respectively. PFS analysis based on molecular subgroup: WNT subgroup 92.3%, SHH 69.2%, Group 4:57.7%:and group 3: 46.2%. CONCLUSIONS Our study is the largest analysis of childhood MB treatment outcomes in Saudi Arabia Defining the poor prognostic factor for these patients and will form the baseline for future pediatric Neuro-Oncology studies in KFMC, which may help to improve the outcome of childhood MB in Saudi Arabia.

System analysis based on Anoikis-related genes identifies MAPK1 as a novel therapy target for osteosarcoma with neoadjuvant chemotherapy

BackgroundOsteosarcoma (OS) is the most common bone malignant tumor in children, and its prognosis is often poor. Anoikis is a unique mode of cell death.However, the effects of Anoikis in OS remain unexplored.MethodDifferential analysis of Anoikis-related genes was performed based on the metastatic and non-metastatic groups. Then LASSO logistic regression and SVM-RFE algorithms were applied to screen out the characteristic genes. Later, Univariate and multivariate Cox regression was conducted to identify prognostic genes and further develop the Anoikis-based risk score. In addition, correlation analysis was performed to analyze the relationship between tumor microenvironment, drug sensitivity, and prognostic models.ResultsWe established novel Anoikis-related subgroups and developed a prognostic model based on three Anoikis-related genes (MAPK1, MYC, and EDIL3). The survival and ROC analysis results showed that the prognostic model was reliable. Besides, the results of single-cell sequencing analysis suggested that the three prognostic genes were closely related to immune cell infiltration. Subsequently, aberrant expression of two prognostic genes was identified in osteosarcoma cells. Nilotinib can promote the apoptosis of osteosarcoma cells and down-regulate the expression of MAPK1.ConclusionsWe developed a novel Anoikis-related risk score model, which can assist clinicians in evaluating the prognosis of osteosarcoma patients in clinical practice. Analysis of the tumor immune microenvironment and chemotherapeutic drug sensitivity can provide necessary insights into subsequent mechanisms. MAPK1 may be a valuable therapeutic target for neoadjuvant chemotherapy in osteosarcoma.

Posterior fossa primary intracranial extraosseous Ewing’s sarcoma: case report

BackgroundPrimary intracranial Ewing’s sarcoma (ES) is a type of primitive neuroectodermal tumour and is a rare malignant tumour in children and adolescents. The imaging features of ES overlap with other central nervous system embryonal tumours, making it difficult to pinpoint a specific diagnosis. We aim to explore the clinical, neuroimaging and differential diagnoses of this entity.Case presentationWe describe a 6-month-old infant who presented with complaints of enlarging the head size and poor feeding. Imaging revealed a contrast-enhancing large solid-cystic mass lesion with internal calcification, focal bone erosion and haemorrhage in the posterior fossa. Histopathological examinations, immunohistochemistry, and molecular analysis confirmed ES.ConclusionsThe confirmative diagnosis of primary intracranial ES requires histological examination, immunohistochemical analysis, and genetic detection, along with radiological findings. Surgical excision followed by combined radiotherapy and chemotherapy is the treatment of choice.

Molecular Biological Research on the Pathogenic Mechanism of Retinoblastoma.

Retinoblastoma (RB) is the most common intraocular malignant tumor in children, primarily attributed to the bi-allelic loss of the RB1 gene in the developing retina. Despite significant progress in understanding the basic pathogenesis of RB, comprehensively unravelling the intricate network of genetics and epigenetics underlying RB tumorigenesis remains a major challenge. Conventional clinical treatment options are limited, and despite the continuous identification of genetic loci associated with cancer pathogenesis, the development of targeted therapies lags behind. This review focuses on the reported genomic and epigenomic alterations in retinoblastoma, summarizing potential therapeutic targets for RB and providing insights for research into targeted therapies.

Long Non-Coding RNAs in Neuroblastoma: Pathogenesis, Biomarkers and Therapeutic Targets.

Neuroblastoma is the most common malignant extracranial solid tumor of childhood. Recent studies involving the application of advanced high-throughput "omics" techniques have revealed numerous genomic alterations, including aberrant coding-gene transcript levels and dysfunctional pathways, that drive the onset, growth, progression, and treatment resistance of neuroblastoma. Research conducted in the past decade has shown that long non-coding RNAs, once thought to be transcriptomic noise, play key roles in cancer development. With the recent and continuing increase in the amount of evidence for the underlying roles of long non-coding RNAs in neuroblastoma, the potential clinical implications of these RNAs cannot be ignored. In this review, we discuss their biological mechanisms of action in the context of the central driving mechanisms of neuroblastoma, focusing on potential contributions to the diagnosis, prognosis, and treatment of this disease. We also aim to provide a clear, integrated picture of future research opportunities.

FOXM1 and CHD4 expression is associated with chemoresistance in hepatoblastoma

Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although pre-operative cisplatin (CDDP)-based chemotherapy is often used in cases of HB, about 20％ of HB patients exhibit resistance to CDDP. Forkhead box protein M1 (FOXM1) and chromo-domain-helicase-DNA-binding protein 4 (CHD4) have been associated with CDDP resistance in various tumors. We here analyzed the immunohistochemical expression of FOXM1 and CHD4 in HB specimens of 33 patients (mean age: 20 months) post-chemotherapy. The differentiation of specimens was assessed using the digital pathology software QuPath®, and then the relation between the FOXM1 or CHD4 expression and the differentiation and various other clinicopathological parameters was investigated. The histological type was epithelial in 19 cases (57.6%) and mixed epithelial and mesenchymal in 14 cases (42.4%). Nine cases had only a fetal component, 1 case had only an embryonal component, 22 cases had both fetal and embryonal components, and 1 case had no viable tumor. Both the FOXM1 and CHD4 immunoexpressions were found significantly more frequently in the embryonal than fetal components (p<0.0001 and p<0.0001, respectively). Regarding chemotherapy efficacy, the alpha-fetoprotein (AFP) level after chemotherapy was correlated with both the imaging shrinkage rate (R=-0.52) and histological residual rate (the percentage of the viable tumors of HB after chemotherapy)(R=0.62). High FOXM1 score was correlated with a high-postoperative AFP value (p<0.01) and a low AFP attenuation rate (p<0.05), but the FOXM1 score was not correlated with the imaging shrinkage rate (p=0.4418) or histological residual rate (p=0.4418). High CHD4 score showed a nonsignificant trend toward correlation with high postoperative AFP value (p=0.0849) and was not significantly correlated with the other parameters. Collectively, our results showed that FOXM1 expression may be useful in evaluating the response to CDDP-based chemotherapeutic regimens. Accurate measurement of FOXM1 expression by our scoring system using QuPath® is important in cases with mixed HB components of various differentiation levels.

Ewing's Sarcoma of the Scapula in an Infant: About a Case

Ewing sarcoma (ES)/primary neuroectodermal tumor (PNET) is the second most common malignant bone tumor of childhood and adolescence. It can occur at central or peripheral sites, at skeletal or extraskeletal sites, and is more common at the femurs, ilium, and tibia. We report a rare case of Ewing's sarcoma of the scapula in a 2-year-old infant diagnosed with pain and swelling of the left shoulder. Histopathological confirmation of Ewing's sarcoma was possible following ultrasound-guided biopsy. Treatment consisted of initial chemotherapy, followed by surgical tumor resection after good initial response, followed by adjuvant therapy. The current post-treatment follow-up is 2 years without incident. This case is reported to highlight the rarity of localization and therapeutic modalities, particularly surgical.

Proton therapy in pediatric neuro-oncology. Potential advantages and the relationship between cost and results

The aim of study: to analyze the accumulated experience and try to identify those clinical situations in which the use of protons will be economically and clinically more effective than photon radiation therapy. Material and methods. The articles devoted to the study of the evaluation and comparison of the effectiveness of proton and photon radiation beams in the treatment of tumors of the central nervous system and published over the past 25 years were searched in the Medline, Embase and the Cochrane Library databases. Results. the analysis of available publications has shown that accelerated protons do not improve survival rates and disease-free rates in all forms of brain tumors compared with photon therapy. However, protons can significantly increase the level of dose distribution conformity and reduce the dose to critical structures (pituitary gland, cochlea, eye lenses, hypothalamus), thus reducing the risk of hearing and visual impairment as well as hormonal and cognitive disorders. All this is critically important for potentially curable malignant tumors, such as medulloblastoma and germinoma, for low malignant potential tumors (grade 1–2 glioma) or tumors with decreased metastatic potential, since proton therapy compared to photon therapy reduces the risk of late side effects that worsen the quality of life of cured children. Conclusion. central nervous system tumors are one of the most common solid malignant neoplasms in children. Radiation therapy (RT) is recognized as an important therapeutic component of treatment and is often used in strategies for multimodal therapy of tumors of the central nervous system in children. Proton radiation therapy is one of the attractive methods of radiotherapy with minimal dose distribution to normal tissues and a decrease in the absorbed dose. The precision of protons reduces the risk of long-term side effects associated with this type of treatment and the induction of secondary malignancies, which is of particular importance for the quality of life.