Neuroblastoma is the most common and most deadly solid tumour that occurs in children outside of the brain (1-5). Overall, it is the most common tumour diagnosed in the first year of life (6).
Approximately 50-70 new cases of neuroblastoma are diagnosed every year in Canada and in about 50-70% of these cases the disease has already metastasized at the time it is found. This is the highest rate of metastasis for all paediatric cancers (7).
Neuroblastoma accounts for about 15% of childhood cancer mortality (2,3). “Tumour groups that have disappointing survival rates include metastatic solid tumours such as Ewing’s sarcoma, rhabdomyosarcoma, osteosarcoma, and neuroblastoma” (7, p. 63).
“High-risk patients with evidence of metastasis, however, have an overall survival (OS) rate of less than 40%, despite intensive multimodality treatment” (3, p. 431). This survival rate has “shown only modest improvement, despite dramatic escalations in the intensity of therapy provided” (6).
Approximately 50-60% of high-risk neuroblastoma patients will have a relapse. There is no cure for relapsed neuroblastoma (6).
Immunotherapy is showing great promise for high-risk neuroblastoma and involves activating the body’s own immune system to kill cancer cells. In a recent trial, two-year survival rates increased by 20% for those children who had the ch14.18 immunotherapy therapy (8). Immunotherapy is now a new standard in the treatment of high-risk neuroblastoma.
“Treatment of older children with widely disseminated neuroblastoma (M or stage 4) remains one of the greatest challenges for paediatric oncologists” (2, p. 2111).
“Neuroblastoma has the highest rate of spontaneous regression observed in human cancers” (9, p. 209).
Patients who are classified within the low-risk category of the disease have an overall survival probability of 85-92% (2, p. 2111).
As few as 10 neuroblastoma tumour-initiating cells transplanted into an immune compromised mouse can form tumours which are both aggressive and metastatic (1,5).
“It is rare in adults and more than 96% of patients diagnosed with neuroblastoma are less than 10 years of age” (4, p. 555).
Neuroblastoma is one of the most expensive cancers to treat. The treatment regime for high-risk neuroblastoma includes multiple rounds of chemotherapy, surgery, high-dose chemotherapy with stem cell transplant, radiation, and immunotherapy. Patients must go through all these modalities, typically experience a wide-array of complications, and are monitored for years after completion of treatment (10, p. 2215).
Childhood Cancer in Canada
“Every year in Canada, cancer is diagnosed in about 850 children (143 per million in 2004) between birth and 14 years of age” (11, p. 422).
“The rate of death from childhood cancer has decreased substantially but is still about 135 deaths each year (24.6 per million in 2004)” (11, p. 422).
Out of all of the cancers diagnosed in Canada in a year, childhood cancers account for a little over half of one percent (7).
“Survivors of childhood cancer are at substantial risk for health problems, including late sequelae of cancer treatment and chronic psychological and cognitive impairments. The latter can hinder both their psychosocial adjustment after treatment and their health and well-being over the long term” (11, p. 422).
“Little is known about the cause of childhood cancers…Opportunities to prevent cancer in children are therefore limited. This is especially so because screening tests are lacking for most childhood cancers” (11, p. 422).
“Five-year survival rates for childhood cancers have improved considerably in Canada, from 71% in the late 1980s4 to 82% in the early 2000s” (11, p. 422).
“Childhood cancer is still rare, but the number of years survivors potentially have ahead of them mean their impact on the economy and society is equivalent to that of the much more numerous breast-cancer survivors, said David Malkin, medical director of the Pediatric Oncology Group of Ontario (POGO). While 60-65% of child patients survived cancer a generation ago, the rate is now 80-85%, he said” (12).
“Improving survival in childhood cancer (now at 82%), places increasing need for long term follow-up of late effects” (7, p. 2). “An estimated two-thirds of survivors have at least one chronic or late-occurring effect from their cancer therapy, while up to one-third have a major, serious or life threatening complication. Endocrine and metabolic complications are the most prevalent late effects among childhood cancer survivors, followed by sensory problems, neurocognitive impairment, cardiopulmonary dysfunction, gastrointestinal disorders and secondary malignant neoplasms. Survivors are also found to be at an increased risk of early death up to 25 years after diagnosis, owing mainly to a relapse of the primary cancer in the early years following the completion of therapy”. (7, p. 63)
“Definitive diagnosis and treatment for children with cancer is available at one of 17 specialized pediatric cancer centres in Canada” (7).
“Cancers in children differ from those occurring in adults in both their site of origin and their behaviour. The majority of cancers in adults are carcinomas which start in the glands or tissues that line organs such as the breast, lung, prostate or colon. In children, carcinomas are very rare. Tumours in children have short latency periods, often grow rapidly and are aggressive, invasive and frequently spread to other parts of the body” (7, p. 61).
Hansford, L.M., McKee, A.E., Zhang, L., George, R.E., Gerstle, J.T., Thorner, P.S., Smith, K.M., Look, A.T., Yeger, H., Miller, F.D., Irwin, M.S., Thiele, C.J., Kaplan, D.R. (2007). Neuroblastoma cells isolated from bone marrow metastases contain a naturally enriched tumor-initiating cell. Cancer Research. Dec 1;67(23):11234-43.
Maris, J.M. (2007). Neuroblastoma. The Lancet, 369, 2106-2120.
Mueller, S. and Matthay, K. (2009). Neuroblastom: Biology and Staging. Current Oncology Reports. Vol 11, Num 6, 431-438.
Chang, H., and Hsu, W. (2010). Neuroblastoma – A Model Disease for Childhood Cancer. Journal of the Formosan Medical Association. 109 (8), 555-557.
Smith, K. M., Datti, A., Fujitani, M., Grinshtein, N., Zhang, L., Morozova, O., Blakely, K. M., Rotenberg, S. A., Hansford, L. M., Miller, F. D., Yeger, H., Irwin, M. S., Moffat, J., Marra, M. A., Baruchel, S., Wrana, J. L., and Kaplan, D. R. (2010). Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens. EMBO Molecular Medicine.
Maris, J. M. (2010). Recent advances in neuroblastoma. The New England Journal of Medicine, 362, 2202-2211.
Canadian Cancer Society. (2008). Canadian Cancer Statistics 2008.
Yu, A.L. (2010). Progress in Treatment of High-Risk Neuroblastoma with Immunotherapy. American Society of Clinical Oncology, pps. 408-411.
Brodeur, G.M. (2003) Neuroblastoma: Biological Insights Into a Clinical Enigma. Nature Reviews. Vol 3, 203-216.
Kushner, B.H. and Cheung, N-K. (2005). Neuroblastoma—From Genetic Profiles to Clinical Challenge. New England Journal of Medicine, 353, 2215-2217.
Ellison, L.F., De, P., Mery, L.S., and Grundy, P.E. (2009). Canadian Cancer Statistics at a Glance: Cancer in Children. CMAJ. 180 (4), 422-424.
Tom Blackwell. (2011). For Children with Cancer, Surviving is Just the Start. National Post (online). http://news.nationalpost.com/2011/09/16/for-children-with-cancer-surviving-is-just-the-start/