Current Clinical Trials

In North America, the Children’s Oncology Group (COG) is investigating a risk-based neuroblastoma treatment plan that assigns all patients to a low-, intermediate-, or high-risk group based on age, International Neuroblastoma Staging System (INSS) stage, and tumor biology (i.e., MYCN gene amplification, Shimada classification, and DNA ploidy) (COG-P9641). (Risk groups are defined in the table in the Stage Information section of this summary.)

Patients with low-risk neuroblastoma have a cure rate higher than 90%.[1-5] The following tumors are categorized as low risk (see table):

1. INSS stage 1 tumors in patients of any age. Stage 1 is defined as gross complete resection.
2. INSS stage 2A and 2B tumors in infants.
3. INSS stage 2A and 2B tumors in children older than 1 year and in whom the tumor demonstrates either favorable Shimada classification or nonamplification of MYCN.
4. INSS stage 4S tumors in infants younger than 1 year with all favorable biological features (i.e., MYCN not amplified, favorable Shimada classification, and hyperdiploid DNA).

Low-risk neuroblastomas are generally treated with surgical resection and observation or observation alone (COG-9641).

Stage 2 low-risk tumors are treated with chemotherapy only if less than 50% of the tumor has been resected. In the other low-risk patients, chemotherapy is recommended only for life-threatening or organ-threatening symptoms that cannot be relieved by safe surgical resection of the mass. Such symptoms include respiratory distress, renal or bowel ischemia, spinal cord compression, gastrointestinal or genitourinary obstruction, or coagulopathy (COG-9641). Chemotherapy is given for 6 to 24 weeks and consists of moderate doses of carboplatin, cyclophosphamide, doxorubicin, and etoposide. The cumulative dose of each agent is kept low to minimize permanent injury from the chemotherapy regimen (COG-9641). Radiation therapy is reserved for patients with symptomatic life-threatening or organ-threatening tumor that does not respond rapidly enough to chemotherapy.

Studies suggest that selected presumed neuroblastomas detected in infants by screening may be safely observed without surgical intervention and without pathologic diagnosis.[6,7] The COG is investigating systematic observation without diagnostic surgery for selected infants with presumed INSS stage 1 adrenal neuroblastoma detected by prenatal or perinatal ultrasound (COG-ANBL00P2).

The treatment of children with low-risk stage 4S disease is dependent on clinical presentation.[8,9] Children who are clinically stable with this special pattern of neuroblastoma may not require therapy. The development of complications, such as functional compromise from massive hepatomegaly, is an indication for intervention, especially in infants younger than 2 to 3 months.[8,10,11] In a study of 80 infants with 4S disease, those who were asymptomatic had 100% survival with supportive care only, and patients with symptoms had an 81% survival rate when they received low-dose chemotherapy.[10] Resection of primary tumor is not associated with improved outcome.[8-10]

The COG neuroblastoma treatment plan also defines the treatment for progression or recurrence of low-risk neuroblastoma. The treatment is dependent on the characteristics of the progression or recurrence. (Refer to the Recurrent Neuroblastoma section of this summary for more information.)

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with neuroblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Matthay KK, Perez C, Seeger RC, et al.: Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children's Cancer Group study. J Clin Oncol 16 (4): 1256-64, 1998.  [PUBMED Abstract]
   
   
2. Hayes FA, Green A, Hustu HO, et al.: Surgicopathologic staging of neuroblastoma: prognostic significance of regional lymph node metastases. J Pediatr 102 (1): 59-62, 1983.  [PUBMED Abstract]
   
   
3. Evans AR, Brand W, de Lorimier A, et al.: Results in children with local and regional neuroblastoma managed with and without vincristine, cyclophosphamide, and imidazolecarboxamide. A report from the Children's Cancer Study Group. Am J Clin Oncol 7 (1): 3-7, 1984.  [PUBMED Abstract]
   
   
4. Alvarado CS, London WB, Look AT, et al.: Natural history and biology of stage A neuroblastoma: a Pediatric Oncology Group Study. J Pediatr Hematol Oncol 22 (3): 197-205, 2000 May-Jun.  [PUBMED Abstract]
   
   
5. Perez CA, Matthay KK, Atkinson JB, et al.: Biologic variables in the outcome of stages I and II neuroblastoma treated with surgery as primary therapy: a children's cancer group study. J Clin Oncol 18 (1): 18-26, 2000.  [PUBMED Abstract]
   
   
6. Nishihira H, Toyoda Y, Tanaka Y, et al.: Natural course of neuroblastoma detected by mass screening: s 5-year prospective study at a single institution. J Clin Oncol 18 (16): 3012-7, 2000.  [PUBMED Abstract]
   
   
7. Holgersen LO, Subramanian S, Kirpekar M, et al.: Spontaneous resolution of antenatally diagnosed adrenal masses. J Pediatr Surg 31 (1): 153-5, 1996.  [PUBMED Abstract]
   
   
8. Guglielmi M, De Bernardi B, Rizzo A, et al.: Resection of primary tumor at diagnosis in stage IV-S neuroblastoma: does it affect the clinical course? J Clin Oncol 14 (5): 1537-44, 1996.  [PUBMED Abstract]
   
   
9. Katzenstein HM, Bowman LC, Brodeur GM, et al.: Prognostic significance of age, MYCN oncogene amplification, tumor cell ploidy, and histology in 110 infants with stage D(S) neuroblastoma: the pediatric oncology group experience--a pediatric oncology group study. J Clin Oncol 16 (6): 2007-17, 1998.  [PUBMED Abstract]
   
   
10. Nickerson HJ, Matthay KK, Seeger RC, et al.: Favorable biology and outcome of stage IV-S neuroblastoma with supportive care or minimal therapy: a Children's Cancer Group study. J Clin Oncol 18 (3): 477-86, 2000.  [PUBMED Abstract]
    
    
11. Hsu LL, Evans AE, D'Angio GJ: Hepatomegaly in neuroblastoma stage 4s: criteria for treatment of the vulnerable neonate. Med Pediatr Oncol 27 (6): 521-8, 1996.  [PUBMED Abstract]
    
    

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