The treatment section of this document is organized to correspond with the Children's Oncology Group (COG) risk-based schema for the treatment of neuroblastoma. This schema is based on three factors: patient age at diagnosis, certain biological characteristics of the patient's neuroblastoma tumor, and the stage of the tumor as defined by the International Neuroblastoma Staging System (INSS). The INSS has replaced the previously used Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) staging systems. The INSS is described below, and the COG risk-based treatment schema is described in Table 1 in this section.
A thorough evaluation for metastatic disease should be performed prior to therapy initiation. The following investigations are recommended:
- Bone marrow should be assessed by bilateral posterior iliac crest marrow aspirates and trephine (core) bone marrow biopsies to exclude bone marrow involvement. To be considered adequate, core biopsy specimens must contain at least 1 cm of marrow, excluding cartilage. Bone marrow sampling may not be necessary for tumors that are otherwise stage 1.
- Bone should be assessed by metaiodobenzylguanidine (MIBG) scan, which is applicable to all sites of disease, and by technetium 99 scan if the results of the MIBG scan are negative or unavailable. Plain radiographs of positive lesions are recommended.
- Palpable lymph nodes should be clinically examined and histologically confirmed if indicated for staging.
- The abdomen and liver should be assessed by computerized tomography (CT) scan and/or magnetic resonance imaging (MRI). Ultrasound is considered suboptimal for accurate 3D measurements. If extension of abdominal disease or pulmonary metastasis is suspected, the chest should be examined by CT scan.
- Lumbar puncture should be avoided as central nervous system (CNS) metastasis at diagnosis is rare, and lumbar puncture may be associated with an increased incidence of subsequent development of CNS metastasis.
- Paraspinal tumors may extend through neural foramina to compress the spinal cord. Therefore, MRI of the spine adjacent to any paraspinal tumor is recommended.
International Neuroblastoma Staging System
INSS combines certain features of the previously used POG and CCG systems [1,6] and has identified distinct prognostic groups.[1,6,7,8]
- Stage 1: Localized tumor with complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes negative for tumor microscopically (i.e., nodes attached to and removed with the primary tumor may be positive).
- Stage 2A: Localized tumor with incomplete gross excision; representative ipsilateral nonadherent lymph nodes negative for tumor microscopically.
- Stage 2B: Localized tumor with or without complete gross excision, with ipsilateral nonadherent lymph nodes positive for tumor. Enlarged contralateral lymph nodes must be negative microscopically.
- Stage 3: Unresectable unilateral tumor infiltrating across the midline, with or without regional lymph node involvement; or localized unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral extension by infiltration (unresectable) or by lymph node involvement. The midline is defined as the vertebral column. Tumors originating on one side and crossing the midline must infiltrate to or beyond the opposite side of the vertebral column.
- Stage 4: Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin, and/or other organs, except as defined for stage 4S.
- Stage 4S: Localized primary tumor, as defined for stage 1, 2A, or 2B, with dissemination limited to skin, liver, and/or bone marrow (limited to infants younger than 1 year). Marrow involvement should be minimal (i.e., <10% of total nucleated cells identified as malignant by bone biopsy or by bone marrow aspirate). More extensive bone marrow involvement would be considered stage 4 disease. The results of the MIBG scan, if performed, should be negative for disease in the bone marrow.