Treatment of neuroblastoma is based on surgical staging and biologic features (Table 158-1). Complete surgical excision is the initial treatment of choice for localized neuroblastoma. Children with favorable biology who undergo a gross total resection require no further therapy. In patients with advanced disease, combination chemotherapy usually is given after confirmation of the diagnosis. The most commonly used agents are vincristine, cyclophosphamide, doxorubicin, cisplatin, and etoposide. Delayed resection of the primary tumor is undertaken after numerous courses of chemotherapy. Radiation therapy often is administered to the primary tumor bed and areas of metastatic disease. High-dose chemotherapy with autologous stem cell rescue has improved the outcome for patients with high-risk neuroblastoma. Survival has also improved with the addition of cis-retinoic acid (isotretinoin) and anti-GD2 monoclonal antibody therapy after maximal reduction of tumor burden with chemotherapy, surgery, and radiation therapy.
Spinal cord compression from neuroblastoma may cause an irreversible neurologic deficit and is an oncologic emergency. Children with the opsomyoclonus syndrome may suffer from developmental delay or mental retardation. The aggressive chemotherapy and radiation therapies currently used to treat high-risk neuroblastoma may result in complications such as ototoxicity, nephrotoxicity, growth problems, and second malignancies.
The prognosis for survival is affected by age at diagnosis, stage, primary site, presence or absence of metastasis, cytogenetics, DNA ploidy, MYCN status, and histopathology. Currently children with neuroblastoma can be divided into three groups: low, average, and high risk. Unfavorable biologic factors include lack of cell differentiation, amplification (>10 copies/cell) of the MYCN oncogene, lack of hyperdiploidy, and mutations of chromosome 1p, 11q, or 6p22. Patients with favorable biology tend to be younger and often have localized disease. Patients under 1 year of age generally have a better prognosis than older patients. Older patients with stage 4 disease most commonly have unfavorable biology, and more than 50% will relapse due to drug-resistant residual disease. Although neuroblastoma represents only 8% of cases of childhood cancer, it is responsible for 15% of cancer deaths in children.
Table 158-1 Proposed Children’s Oncology Group Neuroblastoma Risk Stratification Schema, by Stage STAGE AGE MYCN PLOIDY HISTOLOGY OTHER RISK GROUP 1 Low 2A/2B Not amplified >50% resection Low
From Maris JM, Hogarty MD, Bagatell R, et al: Neuroblastoma, Lancet 369:2106–2120, 2007. DI, DNA index.
Wilms tumor is thought to arise from primitive, metanephric blastema, the precursor of a normal kidney. Nephrogenic rests are foci of embryonal cells that may be rarely (<1%) found in normal infant kidneys and are commonly (25% to 40%) found in Wilms tumor-bearing kidneys. They may be perilobar, intralobar, or both, and are widely considered to be precursors to Wilms tumors. Although the cause of Wilms tumor is unknown, children with certain congenital anomalies or genetic conditions are at increased risk of developing the disease.
Multiple Wilms tumor or WT genes have been identified. The WT1 gene at chromosomal band 11p13 is important in a minority of tumors, and other genes at 11p15, 16q, and 1p are also involved. The identification of several genes involved in the etiology or progression of Wilms tumor and the loss of heterozygosity (LOH) in normal tissues of some patients demonstrate that the genetic predisposition to Wilms tumor is heterogeneous.