Standard Treatment Options

In North America, the Children's Oncology Group (COG) investigated a risk-based neuroblastoma treatment plan that assigned 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, International Neuroblastoma Pathology Classification [INPC] system, and DNA index). The low-risk group was observed without further treatment in most cases. Chemotherapy was given for four cycles (12 weeks) to treat patients with life- or organ-threatening neuroblastoma. (Risk Groups are defined in Table 1 in the Stage Information section of this summary.)

Patients with low-risk neuroblastoma have a cure rate higher than 90%.[1,2,3,4,5]

Studies suggest that selected presumed neuroblastomas detected in infants by screening may be safely observed without surgical intervention and without pathologic diagnosis.[6,7] A COG trial investigating systematic observation without diagnostic surgery for selected infants with presumed INSS stage 1 adrenal neuroblastoma detected by prenatal or perinatal ultrasound (COG-ANBL00P2) has met its patient accrual goals. Analysis of the trial is pending. There is some controversy whether additional surgical resection should be attempted in infants with localized MYCN-nonamplified tumors after biopsy or partial resection. A German clinical trial observed a group of these patients and some infants did not require further intervention, in part due to spontaneous regression.[8]

The treatment of children with low-risk stage 4S disease is dependent on clinical presentation.[9,10] 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.[9,11,12] 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.[11] Resection of primary tumor is not associated with improved outcome.[9,10,11] In 45 patients with 4S neuroblastoma diagnosed in the first month of life, 16 patients developed dyspnea caused by massive liver enlargement; half of them did not survive.[13]

Treatment Options Under Clinical Evaluation

The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• COG-ANBL0531 (therapeutic trial) and COG-ANBL00B1 (biology study required for entry onto COG-ANBL0531): (Trials described together) A new risk group classification system has been developed for the current COG study (see Table 2 in the Treatment of Low-Risk Neuroblastoma section of the summary). Patients previously classified as low risk are now in treatment Group 1 or Group 2. The following tumors are classified as risk and treatment Group 1 (see Table 2). They are treated with surgery followed by observation. Chemotherapy is recommended only for life-threatening or organ-threatening symptoms that cannot be relieved by safe surgical resection of the mass. Life-threatening or organ-threatening symptoms include respiratory distress, renal or bowel ischemia, spinal cord compression, gastrointestinal or genitourinary obstruction, and coagulopathy.
  • Some patients categorized as low risk on previous studies were treated with up to four cycles of intermediate risk chemotherapy and are classified as risk and treatment Group 2 in the current study. They are treated with surgery followed by two cycles of chemotherapy, and if needed additional cycles of chemotherapy until partial response is obtained. If the tumor has 1p or 11q loss of heterozygosity (LOH) or the LOH studies are not performed, the patient will be in treatment Group 3 and receive four cycles of chemotherapy:
  • Chemotherapy is given for two cycles (6 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, as used in prior COG trials (COG-P9641 and COG-A3961). Radiation therapy is reserved for patients with symptomatic life-threatening or organ-threatening tumor that does not respond rapidly enough to chemotherapy and/or surgery.