Neuroblastoma In Children Research Articles

Bone Marrow Sampling in Aplastic Anemia and Neuroblastoma in Children and Adolescents: A Retrospective Data from a Single Tertiary Care Centre in Eastern India

Bone Marrow Sampling in Aplastic Anemia and Neuroblastoma in Children and Adolescents: A Retrospective Data from a Single Tertiary Care Centre in Eastern India

Prognostic factors for intermediate- or high-risk neuroblastomas in children in China

BackgroundEvidence regarding the characteristics and prognosis of neuroblastoma (NBL) in China is limited. We aimed to investigate the characteristics and prognosis of intermediate- or high-risk NBL in children in China.MethodsWe included 147 patients with intermediate- or high-risk NBL evaluated from January 2006 to March 2015. The patients were aged 1 month to 15.5 years, 66% of them were boys, and 117 (79.6%) were diagnosed with high-risk NBL.ResultsAfter a median follow-up of 32.5 months, 80 (45.6%) patients survived, with a median survival time of 48 months (95% confidence interval [CI]: 36.41–59.59). High-risk patients (hazard ratio [HR]: 12.467; 95% CI: 11.029–12.951), partial response (PR) (HR: 1.200; 95% CI: 1.475–2.509) or progression disease (PD) (HR: 1.924; 95% CI: 1.623–3.012) after induction chemotherapy, and intracranial metastasis (HR: 3.057; 95% CI: 0.941–4.892) were independent risk factors for survival (p < 0.05) and postrelapse survival (p < 0.05). NBL relapse, male sex, and PR or PD after induction chemotherapy were risk factors for event-free survival (p < 0.05).ConclusionsIn addition to previously established independent risk factors, such as age, risk group, and relapse, efficacy of induction chemotherapy and intracranial metastasis play significant roles in the prognosis of NBL.

The Value of MRI-Based Radiomic Nomograms in Differential Diagnosis and Metastasis Prediction of Rhabdomyosarcoma and Neuroblastoma in Children

Background: Rhabdomyosarcoma (RMS) and Neuroblastoma (NB) are highly malignant soft tissue sarcoma with tendency to metastasize. Due to the similarities in clinical manifestations and imaging features between RMS and NB, they are often misdiagnosed, which resulted in improper treatment progression of the mass. On the other hand, the treatment paradigm for patients with metastasis RMS/NB and non-metastasis RMS/ NB is different.

Application of amide proton transfer imaging to pretreatment risk stratification of childhood neuroblastoma: comparison with neuron-specific enolase.

The diagnosis and treatment of childhood neuroblastoma (NB) varies with different risk groups, thus requiring accurate preoperative risk assessment. This study aimed to verify the feasibility of amide proton transfer (APT) imaging in risk stratification of abdominal NB in children, and compare it with the serum neuron-specific enolase (NSE). This prospective study enrolled 86 consecutive pediatric volunteers with suspected NB, and all subjects underwent abdominal APT imaging on a 3T magnetic resonance imaging scanner. A 4-pool Lorentzian fitting model was used to mitigate motion artifacts and separate the APT signal from the contaminating ones. The APT values were measured from tumor regions delineated by two experienced radiologists. The one-way analysis of variance, independent-sample t-test, Mann-Whitney U-test, and receiver operating characteristic analysis were performed to evaluate and compare the risk stratification performance of the APT value and serum NSE index-a routine biomarker of NB in clinics. Thirty-four cases (mean age, 38.6±32.4 months; 5 very-low-risk, 5 low-risk, 8 intermediate-risk and 16 high-risk ones) were included in the final analysis. The APT values were significantly higher in high-risk NB (5.80%±1.27%) than in the non-high-risk group (3.88%±1.01%) composed of the other three risk groups (P<0.001). However, there was no significant difference (P=0.18) in NSE levels between the high-risk (93.05±97.14 ng/mL) and non-high-risk groups (41.45±30.99 ng/mL). The associated area under the curve (AUC) of the APT parameter (AUC =0.89) in differentiating high-risk NB from non-high-risk NB was significantly higher (P=0.03) than that of NSE (AUC =0.64). As an emerging non-invasive magnetic resonance imaging technique, APT imaging has a promising prospect for distinguishing high-risk NB from non-high-risk NB in routine clinical applications.

Prevalence And Clinical Significance Of Sarcopenia During Treatment Of Abdominal Neuroblastoma In Children

Prevalence And Clinical Significance Of Sarcopenia During Treatment Of Abdominal Neuroblastoma In Children

Opsoclonus-myoclonus Syndrome with Neuroblastoma in Children and their Anaesthetic Management.

Opsoclonus-myoclonus syndrome (OMS) or the dancing eye syndrome, is a rare inflammatory neurological disorder often with paraneoplastic aetiology. It has an incidence of 1 in 1000,000 population worldwide. Opsoclonus-myoclonus syndrome is associated with 2-3% of patients having neuroblastoma. The authors present 5 cases of OMS in children who had neuroblastoma and underwent surgical resection. The median age was 26 (14-36) months. Male: female ratio was 1:1.5. All the patients had moderate to severe symptoms. Duration of symptoms at presentation varied from 3 days to one and half years. The possibility of OMS should be considered in all children presenting with probable neurological symptoms. Pharmacological therapy combined with surgery results in a good outcome. Balanced anaesthesia with the most commonly used drugs can be safely administered in the patients with opsoclonus-myoclonus syndrome. Key Words: Opsoclonus, Myoclonus, Neuroblastoma, Child, Anaesthesia.

Comparing safety and adequacy between surgical biopsy versus core needle biopsy in diagnosing neuroblastoma

BackgroundAdequate tissue biopsy is essential for diagnosis and risk stratification of neuroblastoma (NB). Historically, NB diagnosis has relied on tissue obtained via surgical biopsy. However, core needle biopsy may provide a safe and adequate method of obtaining tissue in pediatric patients. AimThe aim of this study is to compare the adequacy and safety between core needle biopsy and surgical biopsy for the diagnosis of NB in children at our institution. MethodsInstitutional approval was obtained. Medical records of patients diagnosed with NB from 2004 – 2019 were retrospectively reviewed. Patients had either core needle biopsy (CNB) or surgical biopsy (SB) including open/minimally invasive biopsy. Data included patient demographics, tumor location and size, sample adequacy for diagnosis and risk stratification, post-biopsy complications, length of hospital stay, and need for repeat biopsy. Statistical analysis was conducted using the Mann-Whitney U test or Student's t-test. ResultsThirty-eight patients were included; 53 biopsies were performed including 41 SB and 12 CNB. Patient and tumor characteristics were similar in both groups, as well as the biopsy adequacy for diagnosis and risk stratification. In all cases, there was no need for repeat biopsy. The CNB group demonstrated reduced length of stay (2 ± 0.4 days vs 5 ± 0.5 days; P < 0.0001) and fewer complications (8%) than the SB group (44%) (P = 0.038). ConclusionCore needle biopsy is an acceptable modality for diagnosis and risk stratification in the pediatric population. Advantages include decreased length of stay and fewer post-procedure complications.

Identification of Prognostic Genes in Neuroblastoma in Children by Weighted Gene Coexpression Network Analysis.

Background Neuroblastoma is a malignant neuroendocrine tumor from the sympathetic nervous system, the most common extracranial tumor in children. Identifying potential prognostic markers of neuroblastoma can provide clues for early diagnosis, recurrence, and treatment. Methods RNA sequence data and clinical features of 147 neuroblastomas were obtained from the TARGET (Therapeutically Applicable Research to Generate Effective Treatments project) database. Application weighted gene coexpression network analysis (WGCNA) was used to construct a free-scale gene coexpression network, to study the interrelationship between its potential modules and clinical features, and to identify hub genes in the module. We performed Lasso regression and Cox regression analyses to identify the three most important genes and develop a new prognostic model. Data from the GSE85047 cohort verified the predictive accuracy of the prognostic model. Results 14 coexpression modules were constructed using WGCNA. Brown coexpression modules were found to be significantly associated with disease survival status. Multivariate Cox analysis was performed on genes from univariate Cox regression and Lasso regression analyses using the Cox proportional hazards regression model. Finally, we constructed a three-gene prognostic model: risk score = (0.003812659∗CKB) + (−0.152376975∗expDST) + (0.032032815∗expDUT). The prognosis of samples in the high-risk group was significantly poorer than that of samples in the low-risk group (P=1.225e − 06). The risk model was also regarded as an independent predictor of prognosis (HR = 1.632; 95% CI = 1.391–1.934; P < 0.001). Conclusion Our study constructed a neuroblastoma coexpressing gene module and identified a prognostic potential risk model for prognosis in neuroblastoma.

The Evaluation of Short-Term Outcome of Neuroblastoma in Children by 18F-FDG PET/CT Imaging and Ultrasonography

Objective: By exploring and analyzing the evaluation of the short-term outcome of neuroblastoma (NB) in children by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging and ultrasonography, the detailed values of 18F-FDG PET/CT imaging and ultrasonography in diagnosing and treating NB in children were discussed. The effectiveness and superiority of the two evaluation methods were verified, providing a theoretical basis for clinical applications. Methods: Child patients with NB diagnosis were included as research objects. Except for child patients in the IVs stage, other included child patients received the same surgical therapeutic plan. The clinical materials included child patients were collected, such as 18F-FDG PET/CT results, ultrasonography results, and serum neuron specific enolase (NSE) results. The data information was input into the database and statistically analyzed by SPSS 22.0 software. The specificity as well as sensitivity of 18F-FDG PET/CT imaging, ultrasonography, and serum NSE in the clinical evaluation were comparatively analyzed. The detection rates of 8F-FDG PET/CT imaging, ultrasonography, as well as other diagnostic ways were comparatively analyzed. Results: Consequently, 10 patients had no recurrence or metastasis of NB; 2 patients had recurrence as well as metastasis of NB but survived, but the remaining 2 patients died eventually. Besides, in terms of specificity, the NSE detection was the lowest, while the specificity of 18F-FDG PET/CT and ultrasonography was the same, which was 100%. In addition, 18F-FDG PET/CT and NSE were found to be statistically significant (P &lt; 0.05). Conclusion: The research results showed that image of the 18F-FDG PET/CT and ultrasonography were useful to diagnosis and treat NB in children, which could effectively predict the survival periods of patients. In certain aspects, these two methods were better than other traditional diagnostic methods. However, traditional diagnostic methods also had certain advantages. In the future, the clinical diagnosis and treatment of NB should value the joint application of various diagnostic methods to foster the strengths and avoid the weaknesses. The research results have provided the direction and guidance for clinical diagnosis and treatment of NB in children.

Neuroblastoma in Children: Intraoperative Goal Directed Therapy, Intraoperative and Postoperative Outcomes

Neuroblastoma in Children: Intraoperative Goal Directed Therapy, Intraoperative and Postoperative Outcomes

Incidence and Prognostic Role of the Ocular Manifestations of Neuroblastoma in Children

To describe the ocular manifestations of neuroblastoma in a large cohort of children. Retrospective cohort study. The medical records of patients diagnosed with neuroblastoma between 1989 and 2017 at a tertiary care pediatric hospital were analyzed. The main outcome measurements were the incidence and prognostic role of ocular findings. There were 523 patients with neuroblastoma in the study cohort. Median age at diagnosis was 1.9 years, median follow-up was 4.0 years, and 57.2% were male. At last follow-up, 55.3% were in disease remission, 5.0% had stable disease, 28.1% were deceased, and 11.7% were on active or palliative treatment. A total of 86 patients (16.4%) had ocular manifestations of neuroblastoma, 58 at presentation and 29 during the disease course. The most common findings were orbital involvement in 37 (43.0%), opsoclonus in 20 (23.3%), and Horner syndrome in 24 (27.9%). In 16 patients (3.1%), there were only ocular findings at presentation, including 8 (1.5%) with orbital involvement, 7 (1.3%) with Horner syndrome, and 1 (0.2%) with orbital involvement and a cranial nerve palsy. On survival analysis, a favorable prognosis was associated with opsoclonus, female sex, and diagnosis before 12months of age, whereas a worse prognosis was associated with orbital involvement. In this cohort, approximately 1 in 6 patients with neuroblastoma had ocular manifestations, but only 3% presented with only ocular findings. Orbital involvement was common and associated with a poor prognosis, whereas opsoclonus, female sex, and younger age at diagnosis were associated with a favorable prognosis.

Treatment of relapse/progression of the disease in patients with neuroblastoma in the Republic of Belarus over a 20-year period: a cohort study

Introduction. Neuroblastoma (NB) — is a malignant tumor of sympathetic nervous system in children. In our country there are about 50 % of patients in high risk group, 50 % have a relapse or a progression of the disease which is the main reason for their death. The purpose of the study . Our aim was to characterize a relapse/progression of NB in children in the Republic of Belarus, the analysis of results of treatment of patients from 1997 till 2017. Materials and methods . From October, 1997 to December, 2017 in Republican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology 293 protocol and observed patients received 1st line therapy. Out of them 73 patients had a progression or a relapse of the disease. This group of patients was taken for the analysis. Results. 14-year overal survival of patients with a relapse/progression of the disease was 21 + 6 % (n = 73), event free survival 18 + 5 % (n = 53). Patients older than 12 months at the time of diagnosis were statistically significantly more likely to recur, with 4th stage disease and having N-MYC amplification, diploid karyotype in the tumor. Adverse relapse options for localization are about 65 % (generalized — 41 %, osteomedullary — 12.3 %, relapses with CNS damage — 12.3 %). The most curable variants of relapses are found in 35 % (n = 25) of cases. In patients from the group of favorable and intermediate prognosis, relapses in the zone of primary tumor localization were significantly more frequent (p < 0.0001), bone loss in the relapse of the disease was significantly less common (p < 0.0001). The best results with the use of standard therapies are relapse with the primary tumor zone and soft tissue relapse (by 5 year relapse-free survival — 25% and 36 % respectively). Treatment of osteomedullary and generalized relapses using the methods available to us is not effective (EFS is 0). Conclusion. Further detailed study of the biology of the tumor is necessary, in order to create for the therapy of the disease targeted drugs and other biologically based approaches, such various types of immunotherapy.

Neuroblastoma in Sudan: experience of a single institute.

Neuroblastoma (NBL) is the most common malignant solid extracranial tumour in children. It accounts for about 8%-10% of overall childhood malignancies in developed countries and only 1%-3% in developing countries. We aim to study the clinical presentation and outcome of NBL in children treated at the National Cancer Institute (NCI), University of Gezira, Wad Madani, Sudan. This is a retrospective, descriptive, hospital-based study, where patients' records were reviewed from the years 2004-2015. During this period, 38 paediatric patients were treated in the Paediatric Oncology Unit at the NCI, accounting for about 4% of the overall childhood malignancies. Of them, 24 (63%) were males and 14 (37%) were females with a ratio of 1.7: 1. The age at presentation ranged between 2 months and 7 years with a mean age at the presentation of 3 years. Twenty-nine (76%) of them were classified as high-risk disease, no one received high-dose chemotherapy, 33(87%) died and only 5 (13%) achieved complete remission. This study reflects the poor outcome of NBL among Sudanese children which can be explained by the late presentation of the patients, lack of the diagnostic modalities and lack of the sophisticated treatment modalities for high-risk NBL.

Paediatric Horner’s syndrome: is investigation for underlying malignancy always required?

ObjectiveHorner’s syndrome (HS) is characterised by a triad of ocular miosis, ptosis and anhidrosis. HS may be a subtle sign of occult pathology in otherwise asymptomatic children, neuroblastoma (NBL) being...

Dinutuximab in the Treatment of High-Risk Neuroblastoma in Children

Neuroblastoma is the most common extracranial tumor derived from neural crest cells in childhood, and treatment of high-risk neuroblastoma is a difficulty in oncology field. The discovery of new treatment strategies to treat pediatric patients with high-risk neuroblastoma is important. Dinutuximab (ch14.18; Unituxin), a chimeric human-mouse monoclonal antibody, is approved by Food and Drug Administration in 2015 to be used specifically in the treatment of high-risk neuroblastoma. It binds the disialoganglioside (GD2) antigen on the surface of neuroblastoma cells and induces lysis of GD2-expressed neuroblastoma cells via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. To enhance its activity, it is used with a combination of granulocyte-macrophage colony-stimulating factor, interleukin 2, and 13-cis-retinoic acid. In this review, we discuss the use of dinutuximab in the treatment of high-risk neuroblastoma.

Neuroblastoma in Children Under 12 Months in Singapore—15-Year Experience and Outcomes From KKH

Background: Expectant observation of small adrenal lesions has shown promising results in recent studies. We present our 15 years outcome of managing infant neuroblastoma. Methods: All patients with neuroblastoma below the age of 1 year treated at the largest pediatric hospital in Singapore between 1998 and 2012 were identified. Results: Twenty-two patients were included in our study. Six were antenatally diagnosed. Nineteen (86%) patients had surgical resection of the tumor. Eight (36%) patients received chemotherapy as part of their treatment. Six patients were observed three of which had large adrenal tumors. Median follow-up in our series was 2.6 years. The 5 year overall survival was 90%. There were no recurrences and there were 2 deaths in our series. Conclusion: Our series shows excellent outcomes of infant neuroblastoma at our center. Careful observation of large tumors may be an option to avoid the morbidity of surgery.

Cochlear Implantation for Profound Hearing Loss After Multimodal Treatment for Neuroblastoma in Children

ObjectivesNeuroblastoma (NBL) predominantly affects children under 5 years of age. Through multimodal therapy, including chemotherapy, radiotherapy, surgery, and peripheral blood stem cell transplantation, the survival rate in patients with NBL have improved while treatment-related complications have also increased. Treatment-related ototoxicity, mainly from cisplatin, can result in profound hearing loss requiring cochlear implantation (CI). We analyzed the effectiveness and hearing preservation of CI recipients who had treated with multimodal therapy due to NBL.MethodsPatients who received multimodal therapy for NBL and subsequent CIs were enrolled. A detailed review of the perioperative hearing test, speech evaluation, and posttreatment complications was conducted. Speech performance was analyzed using the category of auditory performance (CAP) score and the postoperative hearing preservation of low frequencies was also compared. Patients who were candidates for electro-acoustic stimulation (EAS) used an EAS electrode for low frequency hearing preservation.ResultsThree patients were identified and all patients showed improvement of speech performance after CI. The average of CAP score improved from 4.3 preoperatively to 5.8 at 1 year postoperatively. Two patients who were fitted with the Flex electrode showed complete hearing preservation and the preserved hearing was maintained over 1 year. The one remaining patient was given the standard CI-512 electrode and showed partial hearing preservation.ConclusionPatients with profound hearing loss resulting from NBL multimodal therapy can be good candidates for CI, especially for EAS. A soft surgical technique as well as a specifically designed electrode should be applied to this specific population during the CI operation in order to preserve residual hearing and achieve better outcomes.

Single nucleotide polymorphisms in vascular endothelial growth inhibitor and its association with development and metastasis of children's neuroblastoma

Objective To identify functional single nucleotide polymorphisms(SNPs) in the promoter region of vascular endothelial growth inhibitor(VEGI) gene and to explore the relationship between these SNPs and the development and metastasis of children's neuroblastoma. Methods A case-control study was performed using PCR-restriction fragment length polymorphism(PCR-RFLP) assay in 126 patients with neuroblastoma and 196 healthy children to detect the genotype-358 T>C, -638 A>G of VEGI promoter region.The association between SNPs of VEGI and neuroblastoma in children was analyzed by using Logistic regression model.Odds ratios(OR) and 95% confidence intervals(CI) were estimated by using Logistic regression. Results Two SNPs, VEGI-358T>C and -638A>G located upstream the translation start site were identified associating with Logistic regression analysis showed that subjects carrying the VEGI-358CC and-638GG genotype played an important role of tumor malignancy in children(Ⅱstage, OR=10.667, 95%CI 1.387-82.033, P=0.023; Ⅲstage, OR=5.333, 95%CI 0.968-29.393, P=0.055; Ⅳstage, OR=4.606, 95%CI 1.007-21.072, P=0.049). The VEGI -638GG genotype significantly increased the risk of tumor malignancy in children, and the result was the same as VEGI -358CC. Conclusions These findings indicate that functional genetic variants in VEGI -358T>C and -638A>G may play an important role in neuroblastoma progression in children.VEGI -358CC and -638GG carriers have higher risk of proliferation and metastasis of neuroblastoma. Key words: Neuroblastoma; Vascular endothelial growth inhibitor; Single nucleotide polymorphisms; Metastasis

Pharmacologic Management of High-Risk Neuroblastoma in Children

Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Children with high-risk disease have a 3-year event-free survival rate of only 20%. Chemotherapy is the mainstay of treatment in children with advanced neuroblastoma. The aim of this article was to review and critically evaluate the pharmacotherapy of neuroblastoma, using peer reviewed and review literature from 2000-11. All peer reviewed, published human subject studies of therapy for neuroblastoma in children were included. Animal model and in vitro studies were included only if they added to the understanding of the mechanism of a proposed or existing human neuroblastoma therapy. Current therapeutic options for neuroblastoma involve insufficient differentiation of normal from neoplastic tissue. Critically needed new approaches will increasingly exploit targeting of therapy for unique characteristics of the neuroblastoma cell. Pharmacotherapy for neuroblastoma still suffers from an inadequate therapeutic window. Enhancement of toxicity for tumor and safety for normal tissues will entail innovation in targeting neuroblastoma cells and rescuing or protecting normal tissue elements.

Abstract 3625: Novel phage-display derived peptides for tumor- and vasculature-targeted therapies in neuroblastoma

Abstract Disseminated neuroblastoma (NB) is refractory to most current therapeutic regimens. The therapeutic index of anticancer drugs is increased by liposome encapsulation and further improvements is obtained by coupling tumor-targeting ligands to the surface of the lipidic envelop. Phage display technology is a powerful tool in discovering novel ligands specific to receptors on the surface of tumor epithelial and endothelial cells. Therapeutic targeting to tumor blood vessels combines blood vessel destruction with the expected anti-tumor activities of the drug, resulting in increased efficacy and reduced toxicity. To find NB-specific targeting moieties, we established a protocol for the isolation of heterogeneous cell populations by tissue fractionation of primary tumors and metastases from two models of human NB (with tumor cells injected either intravenously, to mimic minimal residual disease, or orthotopically in the adrenal gland of mice, to reflect the growth of advanced NB in children with large adrenal gland tumors and small metastatic lesions) and from stage IV, stroma poor, NB-derived specimens immediately after surgical removal. Cells extracted from corresponding healthy organs from mice and patients were used both in a negative pre-selection step and as a negative control for specific phage enrichment. The NB cell suspensions were subjected to multi-step screenings with the phage-displayed peptide library CX7C (where C = cysteine and X = any aminoacid). We globally isolated 135 NB-binding peptides. Of these, 31 were selected for binding to the primary tumor mass, 16 to the metastatic mass, 63 to tumor endothelial cells, and 25 to endothelial cells of metastases. Several proteins presenting sequence homology with the discovered peptides have been identified by BLAST analysis and were evaluated for their expression in NB tumors, derived from both mouse xenogratfs and patient specimens. Specifically, 5 novel phage display derived-peptides showed specific binding on NB specimens and homing to tumor cells and tumor vasculature, 10 minutes and 24 hours after injection through the tail vein of NB-bearing mice. We are testing the new molecular, tumor- and vasculature-specific peptides for generating novel tumor-specific liposomal therapies against NB. The availability of novel ligands binding to additional tumor-associated antigens and to targets on both endothelial and perivascular tumor cells will allow to design more sophisticated liposomal targeted anticancer strategies that exhibit high levels of selective toxicity for the cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3625. doi:10.1158/1538-7445.AM2011-3625