Management Of Neuroblastoma Research Articles

Current Management of Neuroblastoma

Neuroblastoma is one of the more common pediatric cancers. Although there have undoubtedly been major advances in therapy over recent decades, there is still room for significant improvements in outcome to be made. Neuroblastoma is a disease with a variable outlook, encompassing a spectrum-from patients with disease which may undergo spontaneous regression, through those who may be cured with limited treatment, to others whose disease is refractory even to the most aggressive management strategies. Great progress has been made toward understanding the basic biology of the disease, which allows reliable allocation of individual patients to good, intermediate, or poor prognostic groups and aids selection of appropriate therapeutic approaches. Unfortunately, attempts to improve the outcome of patients with adverse prognostic factors have been less effective. This paper reviews the clinical and biological features of neuroblastoma which determine outcome, and outlines current management policies. Some experimental approaches involving translational research which seek to exploit the unique biology of neuroblastoma are discussed. Although currently unproven, such new treatments are undergoing clinical evaluation and may yet offer new hope for patients with this enigmatic disease.

2190 Experience with hyperfractionated radiotherapy (HFRT) in the curative management of neuroblastoma (NB)

2190 Experience with hyperfractionated radiotherapy (HFRT) in the curative management of neuroblastoma (NB)

280The current management of neuroblastoma (NBL) the role of radiation therapy (RT)

280The current management of neuroblastoma (NBL) the role of radiation therapy (RT)

Radioiodinated metaiodobenzylguanidine in neuroblastoma: influence of high dose on tumour site detection.

For more than a decade radioiodinated metaiodobenzylguanidine (mIBG) has been commonly used for neuroblastoma imaging. The accuracy of this scintigraphic method in detecting both primary and secondary tumour sites is crucial when evaluating the extent of disease. The aim of our study was to assess the impact of high-activity mIBG scintigraphy on neuroblastoma staging. Eighteen scans (TS) were obtained in 15 children after a therapeutic dose of iodine-131 mIBG and compared to diagnostic mIBG scans (DS) (in eight cases with 131I-mIBG and in ten cases with 123I-mIBG). The superiority of TS over DS was confirmed by the overall results: a total of 220 lesions were disclosed with TS and 171 with DS. However, in only one case did the TS findings, namely skeletal involvement not evidenced on corresponding DS, have an impact on clinical staging. In contrast, neither TS nor DS detected proven bone involvement in four patients. The dose-related sensitivity of mIBG scintigraphy in detecting neuroblastoma tumour sites was confirmed. The ultimate impact of high-dose scans on neuroblastoma management, however, seems limited.

Effects of CPT‐11 (a unique DNA topoisomerase I inhibitor) on a highly malignant xeno‐transplanted neuroblastoma

Although many advances have been made in the management of neuroblastoma, the prognosis of patients with advanced neuroblastoma remains poor, and constant efforts are being made to search for newer effective drugs. CPT-11 is a newly developed derivative of camptothecin and shows a unique anti-tumor activity by inhibiting DNA topoisomerase I. In this study the effects of CPT-11 on a human neuroblastoma xenograft, TNB9, were investigated according to the standard Battelle Columbus Laboratories protocol. TNB9 is one of the most malignant strains of neuroblastoma, showing a homogeneously staining resion (HSR) on chromosome 20 and 80-fold amplification of the N-myc gene. This study disclosed that CPT-11 was highly effective against TNB9. Maximum inhibition rate (IR) was 72.5% at a standard dose and 52.8% even at half the dose. No nude mouse used in this study lost weight after an administration of CPT-11. Plasma pharmacokinetics of CPT-11 administered in this experimental model were compared to that in clinical patients. Our data suggested that CPT-11 might be a promising new drug in the treatment of high-risk neuroblastoma patients and encouraged us to employ CPT-11 in the protocol of the Study Group of Japan.

Clinical and biologic features in the prognosis and treatment of neuroblastoma.

Recent advances in the management of neuroblastoma have their basis in an increasing understanding of the biologic diversity that typifies these tumors. Current therapy is defined by risk of disease progression or relapse and has become best delineated in lower-stage disease and in infants. Older children with disseminated disease continue to exhibit very poor overall outlook, despite recent advances in dose-intensive chemotherapy. This review updates the clinical and biologic features of neuroblastoma that have a significant impact on prognosis and therapeutic design and discusses recent trends and controversies in the treatment of specific subsets of patients.

Mass screening may not actually aid the management of neuroblastoma in children

Mass screening may not actually aid the management of neuroblastoma in children

Neuroblastoma, retinoblastoma, and brain tumors in children

Considerable progress has been made recently in the biologic understanding and the clinical management of pediatric tumors of the peripheral and central nervous system. Here we review important representative studies published primarily in the past 2 years regarding neuroblastoma, retinoblastoma, and brain tumors in children. Highlights include 1) the importance of tumor DNA content, N-myc amplification, and chromosome 1 deletion in predicting outcome of patients with neuroblastoma; 2) the impact of mass screening for neuroblastoma in Japan and elsewhere; 3) improvements in the clinical management of neuroblastoma, retinoblastoma, and brain tumors; and 4) neurologic sequelae of these tumors and their treatment.

Clinical utility of fine needle aspiration in the diagnosis and management of neuroblastoma

Clinical utility of fine needle aspiration in the diagnosis and management of neuroblastoma

RETROSPECTIVE ANALYSIS OF SURVIVAL IN NEUROBLASTOMA

A retrospective clinical analysis was carried out on 39 patients with neuroblastoma treated from 1960 to June, 1988. Survival rate was analyzed according to stage, primary site, histology and age. Two-year survival was as follows : stage I, II and IVS, 100% ; stage III, 53% ; stage IVB, 40% : and stage IVA, 0 %. For all stages, patients younger than 1 year of age survived longer than those older than 1 year of age (p <0.05). However, prognosis for stage IV (stage IV S is not included) was poor regardless of age. The primary site and histology were not important with respect to prognosis. For advanced neuroblastoma (stage III and IV) the survival rate tends to be improved after 1984, but is not significant. From these results it is concluded that management of neuroblastoma should be altered to minimize therapeutic strategy in stage I, II, III (patients younger than 1 year of age) and IVS, and to improve survival in stage III (patients older than 1 year of age) and IV.

Clinical utility of fine needle aspiration in the diagnosis and management of neuroblastoma

Eleven fine needle aspiration (FNA) biopsies were performed in five children with neuroblastoma, including one patient with peripheral neuroectodermal tumor of the thoracopulmonary region (Askin tumor). Cytologic features in conjunction with immunocytochemistry and electron microscopy on the aspirated material enabled us to make a primary diagnosis in four of the five patients and diagnose local recurrence and metastatic disease in three patients. There were no false-positive or false-negative cytologic diagnoses; therefore, diagnostic accuracy was 100%. FNA is an extremely useful technique for the primary diagnosis and management of neuroblastoma and excludes other small cell malignancies of children. The results of this study and literature review demonstrate that FNA cytology coupled with ancillary techniques of immunocytochemistry and electron microscopy is a rapid, safe, minimally invasive procedure which can aid in the diagnosis and management of patients with neuroblastoma without resorting to more aggressive diagnostic procedures in selective cases.

Urinary catecholamines and their metabolites in management of neuroblastoma.

Measurements of urinary total catecholamines expressed as dopamine (TC) and their metabolites, total metadrenalines (TM) and 3-methoxy-4-hydroxy mandelic acid (HMMA) were made on 24-h urine collections from 56 previously untreated children with neuroblastoma. All results were expressed as a ratio to the creatinine excretion and were compared with "smoothed" age-related reference ranges derived from results in 704 children with other illnesses. Urinary catecholamines/metabolites excretion was elevated in 55 of the 56 patients, the exception being a baby with opsomyoclonus. TC was raised in 47, HMMA in 41, and TM in 37. Eleven patients had elevations of one parameter (TC in 10, HMMA in 1), 15 had 2 elevated levels, and 29 had elevations of all three. The TM level was the least contributory, as in no patient was it the only parameter elevated. Serial measurements were performed in 40 children, and the results correlated closely with the clinical progress of the disease and in some children permitted early detection of recurrence.

Radiation therapy in the management of neuroblastoma: The Duke University medical center experience 1967–1984

We have evaluated the role of radiotherapy in providing local control of primary tumors and to palliate metastases from neuroblastoma (NB). Fifty-five children with histologically verified NB were evaluated and treated from 1967 to 1984. In univariate analysis, the actuarial survival of eight children with thoracic primaries (85%) was significantly better than the survival of 39 children with intra-abdominal primaries (35%, p = 0.0287). The survival of 28 children less than or equal to 18 months of age at diagnoses was 73%, whereas 27 children older than 18 months had a survival probability of 10% ( p = 0.0001). The survival by Evans stage was: I 100% (2 patients), II 85% (7), III 60% (13), IV 4% (27) and IV-S 100% (6). According to the Pediatric Oncology Group (POG) staging system, the survival was: A 100% (3), B 66% (9), C 66% (9), D 23% (34). A multivariable analysis indicated that the Evans staging system was a more powerful indicator of prognosis than the POG system. The analysis also indicated that Evans stage and patient age were independent determinants of survival. The primary tumor site did not add significant prognostic information beyond these two factors. Children with Stage I disease were treated with surgery alone. Most children with Stages II and III disease were treated with surgery, irradiation, and Cyclophosphamide or Cyclophosphamide plus Vincristine. All seven patients with Stage 11 disease received post-operative irradiation to the primary tumor and were locally controlled with doses of 4.8 to 26.5 Gy. Eleven of the 13 patients with Stage III disease were irradiated post-operatively. Seven of these 11 patients were locally controlled with doses of 12 to 48.4 Gy. The four Stage III patients with in-field recurrences were older children with large radiotherapy fields and/or low doses administered. The Radiation Therapy Oncology Group pain score system was used to evaluate response of painful bony metastases to irradiation. A response was observed in 65% of the sites irradiated. A response was observed at 67% of the soft tissue metastases irradiated. Hepatomegaly causing respiratory embarrassment or inferior vena cava obstruction was treated with irradiation in seven patients. All patients responded with doses ranging from 5 to 24.4 Gy. Five of the 17 children who survived for more than 5 years following treatment had significant scoliosis or kyphosis secondary to vertebral body abnormalities in irradiated bones. All five children were irradiated at a young age with megavoltage equipment. Three of the five were irradiated to the full width of the vertebral body. We conclude that (a) the experience at Duke confirms previous reports that young age and early Evans stage are favorable prognostic signs in NB. (b) Stage III disease was not uniformly controlled locally by irradiation. It is not clear if this was caused by low doses or tumor biology (failures occurring in older children). (c) Post-operative wide-field irradiation and chemotherapy were used in almost all node positive (POG C) and node negative (POG B) patients. Survival in Stages B and C were equivalent. The lack of influence of nodal involvement on survival in irradiated patients is discussed.

Neuroblastoma. Evaluation of the treatment of 90 children.

NEUROBLASTOMA is the most commonly encountered soft tissue malignancy in childhood. At the Columbus Children's Hospital, 92 cases have been recorded during the past 21 years. We have studied these variously managed patients retrospectively and, in doing so, we have attempted to answer several questions regarding the treatment of this disease. What length of tumor free survival is necessary before a patient may be considered cured? Has chemotherapy, particularly with cyclophosphamide (Cytoxan), prolonged survival or increased the cure rate? Do repeated operations improve curability for persistent or recurrent tumor? What is the contribution of irradiation treatment to curability rate? Finally, what should be the projected method of management of children with neuroblastoma over the next few years? There have been four eras in the management of neuroblastoma. The first or do nothing era in the early 1920's took advantage of the fact that this particular malignant tumor may spontaneously regress