eMedicine Specialties > Urology > Cancer, Wilms Tumor and Neuroblastoma

Neuroblastoma: Follow-up

Author: Byron D Joyner, MD, Associate Professor, Department of Urology, University of Washington School of Medicine; Consulting Staff, Program Director, Department of Surgery, Division of Pediatric Urology, Children's Hospital and Regional Medical Center
Coauthor(s): Natalya Lopushnyan, Yale University School of Medicine
Contributor Information and Disclosures

Updated: Dec 4, 2007

Outcome and Prognosis

For more than 40 years, the age at diagnosis and the stage have been the dominant independent variables used as prognosticators in children with neuroblastoma. In 1984, Shimada classified neuroblastoma, relating its histopathologic features to its clinical behavior.10 To this end, Shimada divided neuroblastoma into favorable and unfavorable categories, depending on the degree of neuroblast differentiation, Schwannian stromal content, mitosis-karyorrhexis index, and age at diagnosis. In 1999, the Shimada classification was modified to the International Neuroblastoma Pathology Classification system.

Because of the various approaches to risk stratification, efforts have been made in the last 2 years to develop a consensus approach that will allow comparison of patients around the world. In 2005, a large group of patients from Europe, Japan, the United States, Canada, and Australia diagnosed with neuroblastoma between 1974 and 2002 was reviewed in an effort to develop an International Neuroblastoma Risk Group (INRG). Consensus was reached to consider age (dichotomies around 18 mo), stage assessed before treatment, and N-myc status in the risk-group schema. Once the final statistical analyses are available, the specific criteria will be included in the final INRG report.

The COG recently developed a process called the Neuroblastoma Risk Stratification System (NRSS), which is used for treatment stratification. Like the Shimada Index, this new system is based on clinical and biological factors that are predictive of outcome. The NRSS is different in that it is based on the INRG system and is used for treatment-stratification purposes. Patients are assigned to low-, intermediate-, or high-risk categories based on age at diagnosis, INSS stage, histopathology, N-myc amplification status, and DNA index.

However, certain biological variables that affect the prognosis of children with neuroblastoma have been identified. Specific examples include aneuploidy of tumor DNA and N-myc oncogene amplification. N-myc amplification occurs in 20% of primary neuroblastoma tumors and is associated with a subset of neuroblastomas that have high metastatic potential and, consequently, a poor prognosis. N-myc is thought to contribute to the aggressive behavior of neuroblastoma. However, the precise role of N-myc in nonamplified tumors is unknown.

Hyperdiploid tumor DNA is associated with a favorable prognosis. N-myc amplification is associated with a poor prognosis in children older than 1 year but not in children younger than 1 year. The N-myc amplification is linked to the deletion of chromosome arm 1p and a gain of the long arm of chromosome 17. In neuroblastoma, consistent areas of chromosomal loss of heterozygosity (LOH) include chromosome bands 1p36, 11q23, and 14Q23qter. In 2000, Maris et al reported from the Children's Cancer Group (CCG) that 1p deletion independently predicted a lower event-free survival but not overall survival. The clinical relevance of 14q LOH is unclear at this time.

Allelic loss of 11q is present in 35-45% of primary tumors. Notably, this aberration is rarely seen in tumors with N-myc amplification yet remains highly associated with other high-risk features.

Other variables carry varying degrees of prognostication. These include the site of the primary tumor, serum ferritin levels, NSE, and nutritional status.

Future and Controversies

Neuroblastoma continues to be one of the most frustrating childhood tumors to manage. Although the tumor has been studied extensively and great efforts have been extended to secure appropriate therapy and achieve a cure, little has altered the prognosis in affected children over the past 20 years.

In vitro cultures demonstrate that neuroblastoma is radiosensitive, but results from clinical trials have been inconsistent and inconclusive. As a primary treatment modality, radiation therapy can be used in regional lymph node metastases with sequential cyclophosphamide therapy, in infants with stage-4 disease who have Pepper syndrome (to control respiratory compromise), and in TBI combined with ABMT.

Further consensus data are needed to provide more definitive information regarding risk stratification, treatment, and prognosis in patients with neuroblastoma.

 


More on Neuroblastoma

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References
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Further Reading

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Keywords

neuroblastoma, great mimicker, the great mimicker, intra-abdominal malignancy, extracranial solid tumor, Ewing sarcoma, non-Hodgkin lymphoma, neuroectodermal tumors, undifferentiated soft tissue sarcoma, rhabdomyosarcoma, glioma, sympathetic ganglia, ganglioneuroma, sympathoblastoma, ganglioneuroma, neurocristopathy, ganglioneuroblastoma, metastatic neuroblastoma, localized neuroblastoma, disseminated neuroblastoma, stage 4S neuroblastoma, Pepper syndrome, “blueberry muffin” babies, “blueberry muffin” baby, Hutchinson syndrome, Kerner-Morrison syndrome, Wilms tumor, congenital mesoblastic nephroma, primitive neuroblasts, neuropil, Homer-Wright pseudorosettes, Opsoclonus-myoclonus syndrome

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Contributor Information and Disclosures

Author

Byron D Joyner, MD, Associate Professor, Department of Urology, University of Washington School of Medicine; Consulting Staff, Program Director, Department of Surgery, Division of Pediatric Urology, Children's Hospital and Regional Medical Center
Byron D Joyner, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Urological Association, Association of Military Surgeons of the US, Massachusetts Medical Society, Society of University Urologists, Society of Urology Chairpersons and Program Directors, and Washington State Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Natalya Lopushnyan, Yale University School of Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting

Chief Editor

Allen R Wyler, MD, Former Medical Director, Northstar Neuroscience, Inc
Allen R Wyler, MD is a member of the following medical societies: American Academy of Neurological and Orthopaedic Surgeons, American Association of Neurological Surgeons, and Society of Neurological Surgeons
Disclosure: Nothing to disclose.

 
 
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