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Saudi Medical Journal Aug 2001Due to the poor results achieved on combination chemotherapy and the unproven cost-effectiveness value of myeloablative therapy, the question has been raised; should...
OBJECTIVE
Due to the poor results achieved on combination chemotherapy and the unproven cost-effectiveness value of myeloablative therapy, the question has been raised; should patients with stage IV neuroblastoma be actively treated? The aim of the current study is to analyze retrospectively treatment results of 43 children with neuroblastoma with special stress on the rate and duration of remission in children with disseminated neuroblastoma.
METHODS
Treatment of children with neuroblastoma consisted of surgical removal of the tumor, if possible, followed by chemotherapy for unresectable residual tumor including metastases. Second look surgery was performed to resect residual masses rendered resectable on chemotherapy in the absence of distal metastases. The chemotherapy protocol used in the current study consisted of alternating combination chemotherapy regimens containing, Cyclophosphamide, Vincristine and Doxorubicin, alternating with Cis-platinum and Etoposide.
RESULTS
The male to female ratio was 2:1 with a median age of 2.1 years. The abdomen was the primary site of involvement encountered in 32 patients (74%). According to the childrens cancer study group (CCSG) staging system, only 6 patients (14%) had localized tumors (stages I and II). Two patients (5%) were found to have stage IV. Stage III was documented in 5 patients (12%). The majority of patients (70%) had disseminated disease at presentation. The bone marrow was the most common site of metastatic deposit, encountered in 23 patients out of the 30 with stage IV disease (77%). Out of the 12 evaluable non-stage IV patients, only one patient (8%) showed treatment failure. Assessment of response by the end of the 6th month from the date of diagnosis revealed that out of the 27 evaluable patients with stage IV, 4 patients achieved complete remission, 7 patients achieved very good partial remission, 8 patients achieved partial remission and 4 patients achieved mixed response. Three patients showed progressive disease on chemotherapy. Twenty-one patients (78%) were symptom-free and were conducting normal life. Assessment of response to treatment by the end of the 12th month from diagnosis revealed that 6 patients (2 complete remissions, 1 very good partial response, 3 partial responses) were maintaining their remission. Out of the 19 patients showing complete or partial remission at early assessment, 4 patients maintained their remission for more than 18 months. Two (one was in complete remission and the other was in partial response) of them progressed in areas of previous involvement after 20 and 21 months. The other 2 patients (one was in complete remission and the other was in partial response) showed disease progression in areas not previously affected by disease at presentation after 23 and 42 months.
CONCLUSION
Results of treatment by multiagent chemotherapy regimens used in the current study show that children with neuroblastoma, even those with advanced stages, should receive the benefit of intensive multimodal therapy, even those with partial response to initial therapy. These patients may experience reasonable symptom-free and sometimes, disease-free survival.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Doxorubicin; Etoposide; Female; Humans; Infant; Male; Neoplasm Staging; Neuroblastoma; Retrospective Studies; Second-Look Surgery; Survival Rate; Treatment Outcome; Vincristine
PubMed: 11573111
DOI: No ID Found -
European Journal of Cancer (Oxford,... Aug 1997The neuroblastic tumours, derived from primordial neural crest cells which ultimately populate the sympathetic ganglia, adrenal medulla and other sites, (Brodeur GM and... (Review)
Review
The neuroblastic tumours, derived from primordial neural crest cells which ultimately populate the sympathetic ganglia, adrenal medulla and other sites, (Brodeur GM and Castleberry RP. Neuroblastoma. In Pizzo PA, Poplack DG, eds, Principles and Practice of Pediatric Oncology. Philadelphia, J. B. Lippincott Co., 1997, 761-797) are an enigmatic group of neoplasms which have the highest rate of spontaneous regression of all human malignant neoplasms yet one of the poorest outcomes when occurring as disseminated disease in children. Significant advances in understanding and predicting the natural history of neuroblastoma have resulted from translational studies coupling tumour biology and clinical features to form prognostic strata and allowing more accurate routeing of patients to risk-related management. While this strategy has clarified the management for lower risk tumours, little improvement in survival for higher risk disease has been realised. Ironically, this latter patient subset, for which the most innovative therapeutic strategies are needed, is also the one from which the least tumour biology is gleaned owing to inadequate tissue sampling. This update will summarise the evolving biology of neuroblastoma and its relationship to current risk-related therapy and future management strategies. Throughout this report, prognostic grouping by age will be infants (< 1 year) versus children (> or = 1 year) since the change of risk according to age seems most distinct at this cut-off point.
Topics: Adolescent; Adult; Child; Child, Preschool; Forecasting; Genes, myc; Humans; Infant; Infant, Newborn; Neoplasm Staging; Neuroblastoma; Prognosis; Risk Factors
PubMed: 9337686
DOI: 10.1016/s0959-8049(97)00308-0 -
Indian Journal of Pediatrics 1998The neuroblastic tumours originate from primordial neural crest cells that normally develop into sympathetic nervous system, including the adrenal medulla. Neuroblastoma... (Review)
Review
The neuroblastic tumours originate from primordial neural crest cells that normally develop into sympathetic nervous system, including the adrenal medulla. Neuroblastoma is the most intriguing pediatric neoplasm displaying diverse clinical and biologic characteristics and natural history. It has the highest rate of spontaneous regression of all human cancers, yet exhibits extremely malignant behaviour in older children with regional and disseminated disease. In the last 30 years, only a nominal improvement has occurred in the outlook of older children with metastatic disease at diagnosis. Tremendous gains in understanding of the biology of neuroblastoma in recent years have led to development of risk-related therapy based on age, stage and biological characteristics of neuroblastoma.
Topics: Adolescent; Adult; Biomarkers, Tumor; Child; Child, Preschool; Combined Modality Therapy; Female; Humans; Infant; Male; Neoplasm Staging; Neuroblastoma; Prognosis; Survival Rate
PubMed: 10773924
DOI: 10.1007/BF02731044 -
International Journal of Molecular... Jul 2023High-risk neuroblastoma remains a profound clinical challenge that requires eradication of neuroblastoma cells from a variety of organ sites, including bone marrow,...
High-risk neuroblastoma remains a profound clinical challenge that requires eradication of neuroblastoma cells from a variety of organ sites, including bone marrow, liver, and CNS, to achieve a cure. While preclinical modeling is a powerful tool for the development of novel cancer therapies, the lack of widely available models of metastatic neuroblastoma represents a significant barrier to the development of effective treatment strategies. To address this need, we report a novel luciferase-expressing derivative of the widely used Th-MYCN mouse. While our model recapitulates the non-metastatic neuroblastoma development seen in the parental transgenic strain, transplantation of primary tumor cells from disease-bearing mice enables longitudinal monitoring of neuroblastoma growth at distinct sites in immune-deficient or immune-competent recipients. The transplanted tumors retain GD2 expression through many rounds of serial transplantation and are sensitive to GD2-targeted immune therapy. With more diverse tissue localization than is seen with human cell line-derived xenografts, this novel model for high-risk neuroblastoma could contribute to the optimization of immune-based treatments for this deadly disease.
Topics: Mice; Humans; Animals; N-Myc Proto-Oncogene Protein; Mice, Transgenic; Neuroblastoma; Adaptation, Physiological; Acclimatization
PubMed: 37569447
DOI: 10.3390/ijms241512071 -
Current Medicinal Chemistry Feb 2018Neuroblastoma is the most common extracranial solid tumor in infancy. The majority of children have a disseminated disease at diagnosis with bone marrow as the most... (Review)
Review
BACKGROUND
Neuroblastoma is the most common extracranial solid tumor in infancy. The majority of children have a disseminated disease at diagnosis with bone marrow as the most common site of metastasis. Although several prognostic factors have been defined (i.e. age, stage, histology, recurrent genetic anomalies), the identification of non-invasive biomarkers for disease follow-up and therapy monitoring is indeed still a clinical need. Aberrant regulation of microRNAs (miRNAs) expression has been implicated in several malignancies.
OBJECTIVES
In this mini-review, we describe the recent findings about miRNAs in neuroblastoma, both in the tumor and circulation, with particular focus on those involved in tumor progression and drug resistance. Furthermore, we will discuss the use of specific miRNAs as potential therapeutic tools in this tumor.
RESULTS
Several miRNAs have been identified to be down- or up-regulated in primary tumors and have been associated with MYCN amplification, differentiation, dissemination and chemoresistance. Little evidence is available in the literature about circulating miRNAs which are of particular interest as potential biomarkers for liquid biopsy.
CONCLUSION
Identification of body-fluid markers for non-invasive diagnosis, risk stratification, treatment monitoring and tumor follow-up, is gaining growing interest, especially in the pediatric field. miRNAs are suitable candidates as biomarkers in neuroblastoma but further investigations are needed to expand knowledge regarding their role in this malignancy to design specific approaches of miRNAs-mediated therapies.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Drug Resistance, Neoplasm; Humans; Liquid Biopsy; MicroRNAs; Neuroblastoma
PubMed: 28971761
DOI: 10.2174/0929867324666171003120335 -
Australian Veterinary Journal Apr 2017A 4-year-old neutered male Rhodesian Ridgeback dog with right-sided Horner's syndrome, bilateral laryngeal paralysis, neck pain and bilateral hindlimb ataxia was...
CASE REPORT
A 4-year-old neutered male Rhodesian Ridgeback dog with right-sided Horner's syndrome, bilateral laryngeal paralysis, neck pain and bilateral hindlimb ataxia was euthanased following deterioration of its neurological status. Necropsy examination revealed an off-white retropharyngeal neoplastic mass (100 × 30 × 30 mm) attached to the base of the skull on the right side and macroscopic nodular metastases in the spleen and three vertebral bodies (C6, C7 and T6), including a nodule attached to the dura at C7. Histological evidence of neuroblastic tumour was detected in these macroscopic lesions, a regional lymph node, bone marrow of a femur and all 15 vertebral bodies (C1-T8) examined, including the three with macroscopic metastases, and in the lumens of small blood vessels in the lungs and liver. Ganglion cell differentiation was detected only in the primary retropharyngeal mass, one splenic nodule and the C7 dural nodule. Neoplastic cells were immunoreactive to neurofilament protein (ganglion cells only), vimentin and synaptophysin, and were negative for S100 protein, GFAP, CD3 and Pax5.
CONCLUSION
The diagnosis was disseminated peripheral neuroblastoma, differentiating subtype (International Neuroblastoma Pathology Classification), with likely primary involvement of the right cranial cervical ganglion. This appears to be the first report of neuroblastoma in a dog with widespread occult haematogenous metastasis to bone marrow.
Topics: Animals; Ataxia; Bone Marrow Neoplasms; Bone Neoplasms; Dog Diseases; Dogs; Horner Syndrome; Male; Neuroblastoma; Peripheral Nervous System Neoplasms; Splenic Neoplasms; Vocal Cord Paralysis
PubMed: 28346666
DOI: 10.1111/avj.12565 -
Journal of Pediatric Surgery Dec 1991Recurrence in neuroblastoma more than 5 years after diagnosis is extremely rare. One case of neuroblastoma recurring 10 years after complete remission from disseminated... (Review)
Review
Recurrence in neuroblastoma more than 5 years after diagnosis is extremely rare. One case of neuroblastoma recurring 10 years after complete remission from disseminated neuroblastoma at the 5th month of life is reported. Twelve additional cases in the literature are reviewed. Despite the apparent rarity of this event, it should be considered that the patients with disseminated neuroblastoma induced to complete remission without definitive treatment have a potential for late recurrence and should be followed over long periods of time, especially during puberty.
Topics: Child, Preschool; Female; Humans; Neoplasm Recurrence, Local; Neuroblastoma; Retroperitoneal Neoplasms; Time Factors
PubMed: 1765927
DOI: 10.1016/0022-3468(91)91053-2 -
The Journal of Pediatrics Aug 1983We performed coagulation studies in 16 patients with advanced neuroblastoma. Four of these patients had major hemorrhagic or thromboembolic complications. Abnormal...
We performed coagulation studies in 16 patients with advanced neuroblastoma. Four of these patients had major hemorrhagic or thromboembolic complications. Abnormal coagulation screening tests were seen in all patients with active metastatic disease. We also measured plasma fibrinopeptide A, a sensitive measure of intravascular thrombin generation. Increased concentrations of fibrinopeptide A were found in each patient studied with active metastatic disease. Coagulopathy is a frequent finding in metastatic neuroblastoma and may cause severe morbidity. Laboratory studies suggesting either hyper- or hypocoagulability are frequent findings.
Topics: Blood Coagulation Factors; Child, Preschool; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Infant; Male; Neuroblastoma; Partial Thromboplastin Time; Prothrombin Time
PubMed: 6875712
DOI: 10.1016/s0022-3476(83)80348-5 -
Cancer Medicine Jan 2023Neuroblastoma is the most common extracranial solid tumor in children, accounting for 10% to 20% of deaths of pediatric malignancies. Due to the poor prognosis and... (Review)
Review
Neuroblastoma is the most common extracranial solid tumor in children, accounting for 10% to 20% of deaths of pediatric malignancies. Due to the poor prognosis and significant biological heterogeneity of neuroblastoma, it is essential to develop personalized therapeutics and monitor treatment response. Circulating tumor cells (CTCs), as one of the important analytes for liquid biopsy, could facilitate response assessment and outcome prediction for patients in a non-invasive way. Several methods and platforms have been used for the enrichment and detection of CTCs. The enumeration of CTCs counts and evaluation of tumor-specific mRNA transcript levels could provide prognostic information at diagnosis, during or after chemotherapy, and during the process of disease progression. So far, studies into neuroblastoma CTCs are only in the preliminary stages. The quality-controlled large prospective cohort studies are needed to evaluate the clinical significance and statistical rigor of CTC detection methods. Moreover, there remains a lot to be explored and investigated in genotyping characterization of neuroblastoma (NB) CTCs and construction of in-vitro or in-vivo functional models. CTCs and circulating tumor DNA (ctDNA) analysis will be complementary in understanding tumor heterogeneity and evolution over the course of therapy for patients with NB in the future.
Topics: Child; Humans; Neoplastic Cells, Circulating; Prospective Studies; Prognosis; Neuroblastoma; Circulating Tumor DNA; Biomarkers, Tumor
PubMed: 35632981
DOI: 10.1002/cam4.4893 -
Radiographics : a Review Publication of... Sep 1989Neuroblastoma is a common tumor in childhood. It arises in the adrenal gland or in various extraadrenal primary sites of the sympathetic chain. Clinically, it may... (Review)
Review
Neuroblastoma is a common tumor in childhood. It arises in the adrenal gland or in various extraadrenal primary sites of the sympathetic chain. Clinically, it may present as an abdominal mass or as disseminated metastatic disease. We studied 52 patients with neuroblastoma, and the typical and unusual radiographic features of the disease are presented.
Topics: Adrenal Gland Neoplasms; Bone Neoplasms; Brain Neoplasms; Child; Diagnostic Imaging; Humans; Neuroblastoma; Thoracic Neoplasms
PubMed: 2678295
DOI: 10.1148/radiographics.9.5.2678295