- Group 4: Patients receive 8 courses of initial chemotherapy. Patients under 12 months of age with stage 3, 4, or 4S disease who achieve a very good PR (VGPR) (> 90% reduction in the volume of the primary tumor and resolution of metastatic disease, with the exception of liver and skin metastases) to chemotherapy proceed to observation. Patients 12-18 months of age with stage 3 or 4 disease [age 365 to < 547 days at diagnosis, INSS stage 3, MYCN-NA, unfavorable histology, any ploidy and patients age 365 to < 547 days at diagnosis, INSS stage 4, MYCN-NA, favorable histology, DI > 1] who achieve a VGPR proceed to isotretinoin therapy. Patients who do not achieve a VGPR after 8 courses of initial chemotherapy +/- surgery will proceed to retrieval chemotherapy with cyclophosphamide/topotecan for 2-6 courses until a VGPR can be achieved with a combination of chemotherapy and surgery.