Treatment for patients categorized as low risk (refer to Table 1 in the Stage Information section of this summary) may be surgery alone, but surgery may be combined with chemotherapy in some cases. Chemotherapy is reserved for patients who are symptomatic, such as from spinal cord compression or, in stage 4S, respiratory compromise secondary to hepatic infiltration. The chemotherapy consists of carboplatin, cyclophosphamide, doxorubicin, and etoposide. The cumulative dose of each agent is kept low to minimize permanent injury from the chemotherapy regimen (COG-P9641, COG-ANBL00B1, and COG-ANBL0531).
Observation without surgery for localized, suspected adrenal neuroblastoma in infants
Studies suggest that selected presumed neuroblastomas detected in infants by screening or incidental ultrasound may safely be observed without obtaining a definitive histologic diagnosis and without surgical intervention, thus avoiding potential complications of surgery in the newborn.[3,4,5] The experience with tumors detected by mass urinary catecholamine metabolite screening in Japan appears to be applicable to tumors detected by prenatal or perinatal ultrasound in the United States. The COG is investigating systematic observation without surgery for infants with presumed small Evans stage I adrenal neuroblastoma detected by prenatal or perinatal ultrasound.
Patients categorized as intermediate risk (refer to Table 1 in the Stage Information section of this summary) have been successfully treated with surgery and 12 to 24 weeks of the same chemotherapy regimen described above (COG-A3961). As a rule, patients whose tumors have unfavorable biology receive twice as many cycles of chemotherapy as those with favorable biology.
Whether initial chemotherapy is indicated for all intermediate-risk infants with localized neuroblastoma is controversial. In a German clinical trial of infants with stages 2A, 2B, and stage 3 disease and MYCN-nonamplified tumors that were not readily resectable with low-risk surgery, children were treated with chemotherapy only if symptoms developed or if tumor progression occurred, 82 of 93 infants avoided any chemotherapy and 34 avoided further surgery. This was due, in part, to spontaneous tumor regression. Overall survival was 99%. In North America, the standard practice is to treat infants with unresectable stages 2A, 2B, and stage 3 neuroblastoma with chemotherapy at diagnosis.
In contrast, patients categorized as high risk (refer to Table 1 of the Stage Information section of the summary) are generally treated with dose-intensive multiagent chemotherapy consisting of very high doses of the drugs listed above but often also including ifosfamide and high-dose cisplatin. After a response to chemotherapy, resection of the primary tumor should be attempted, followed by myeloablative chemotherapy and autologous stem cell transplantation. Radiation of residual tumor and original sites of metastases is often performed before, during, or after myeloablative therapy. After recovery, patients are treated with oral 13-cis -retinoic acid for 6 months. Both myeloablative therapy and retinoic acid improve outcome in patients categorized as high risk.[6,7]; [Level of evidence: 1iiA] Compared to retinoic acid alone, chimeric anti-GD2 antibody ch14.18 combined with granulocyte macrophage-colony stimulating factor and interleukin-2 and given in concert with retinoic acid improves event-free survival for high-risk neuroblastoma patients in remission after stem cell transplant.