Neuroblastoma is a cancer derived from the sympathetic nervous system and can be found anywhere in the body, but most commonly in the adrenal glands above the kidneys. Spontaneous regression to benign lesions (ganglioneuroma) is more common in neuroblastoma than in any other known human malignancy, particularly in the first year of life, where most infants with neuroblastoma experience complete regression with minimal therapy. However, older patients frequently have widespread disease (metastatic) that grows relentlessly despite even the most intensive multimodality therapy including stem cell transplantation. Recent advances in understanding the biology of neuroblastomas have allowed classification into low (40%), intermediate (25%), and high risk groups (35%), that permit risk adjusted therapy from observation alone in some cases to aggressive multi-modality therapy for high-risk disease.
Incidence of neuroblastoma
Neuroblastoma is the 4th most common childhood cancer behind acute leukaemias, brain tumours and lymphomas respectively and accounts for 8-10% of all cancers in children. The yearly incidence of neuroblastoma is 1-2 cases per 100,000 children aged <15 years and inWestern Australia 4-6 cases are diagnosed annually. In the first year of life, it is the most common childhood cancer and accounts for 50% of cases. The average age at diagnosis is 22 months and 80% of the cases present in the first 5 years of life and 95% by 10 years of age.
Clinical presentation
The location of the primary tumour at diagnosis is varied and changes with age. Most primary tumours occur within the abdomen (60%) and present with painful swollen abdomens. Infants have more chest and neck primary tumours however. Neuroblastoma spreads via the lymphatic channels and the blood and when present almost always involves bone marrow and bones (stage 4 neuroblastoma). Previously rarer metastatic sites such as the lung or brain are becoming more common and are present in up to 5% of cases. Several unique clinical presentations associated with neuroblastoma have been identified and include the dancing eyes and limbs syndrome (Opsomyoclonus Ataxia Syndrome), intractable diarrhoea and spinal cord compression leading to lower limb paralysis due to invasion of the neuroblastoma into the spinal canal.
Prognosis
The factors which predict outcome (prognostic factors) have been identified and include several clinical and molecular aspects of the disease to include age at presentation, extent of disease (stage), the pathology of the neuroblastoma (favourable vs unfavourable) and the number of copies of the MycN gene within the tumour cell. Based on these factors, low and intermediate risk neuroblastoma can be identified (stage 1 and 2 and selected stage 3, age <18 months, favourable histology and MycN copy number less than 10) which has over 90-95% cure rate with surgery alone or with additional minimal chemotherapy and high risk neuroblastoma (stage 4; age >18 months; unfavourable histology and MycN copy number >10) which, with aggressive multi-modality therapy, has a cure rate of only 35%.
Future treatments
Future directions include more accurate identification of low and intermediate risk neuroblastoma and reduction of therapy for these cases which have over 90% probability of cure with current management and improving the very guarded outcome for the high risk patient who, despite maximally aggressive chemotherapeutic approaches involving blood stem cell transplantation, suffer disease progression in two-thirds of the cases. Specifically, ongoing research into targeted therapy aimed at eradicating minimal residual disease after the stem cell transplant for high risk neuroblastoma is being undertaken via clinical trials. These therapies include targeted radiotherapy using radioactive MIBG (a substance taken up by neuroblastoma cells), tumour specific monoclonal antibodies (proteins) which attach to the neuroblastoma cell leading to cell death and agents (cis-Retinoic acid, Fenretinide) which promote the maturation of the neuroblastoma cells to a benign condition.