Neuroblastoma is the most common extracranial solid tumor diagnosed in children. The disease is an embryonal malignancy of the sympathetic nervous system arising from pluripotent sympathetic cells.
In the United States – and most developed countries – the disease accounts for about 6% of all cancers in children. On average, each year there are about 800 new cases of neuroblastoma in the United States. According to the American Cancer Society, This number has remained about the same for many years.
Neurobastoma is generally diagnosed in children between 1 to 2 years of age. However, in rare cases, the disease is detected by ultrasound even before birth. Nearly 90% of cases are diagnosed by age 5 and is considered rare in patients over the age of 10 years.
A study by researchers at the Princess Máxima Center for Pediatric Oncology in The Netherlands, demonstrates that, over the last decades, both the survival rate and the incidence of neuroblastoma have increased. The researchers observed that the improved chance of survival as well as the increase in the number of patients, has been greatest in the high risk group of children older than 18 months, with a stage 4 neuroblastoma. Results of the study, funded by Stichting Kinderen Kankervrij (KiKa) and the Villa Joep foundation, were published the European Journal of Cancer.
The researchers looked at 593 newly diagnosed neuroblastoma cases, 45% of the pediatric patients was older than 18 months of age at diagnosis while 52% had stage 4 disease.
In the early nineties, only 6% of the children with high risk neuroblastoma survived five years following diagnosis.
In their analysis, the researchers noticed that the five year Overall Survival (OS) increased from 44 ± 5% to 61 ± 4% from 1990 to 2014 (p < .01) and from 19 ± 6% to 44 ± 6% (p < .01) for patients with stage 4 disease, bringing the average number of pediatric patients surviving neuroblastoma to 43%.
“The prognosis for the high risk has improved most significantly,” noted Michelle Tas, a Ph.D candidate at the Princess Máxima Center for Pediatric Oncology. Tas, and her colleague Ardine Reedijk, another Ph.D student, performed the study.
A multivariable analysis demonstrated that high-dose chemotherapy followed by autologous stem cell transplantation and anti-GD2-based immunotherapy (including dinutuximab beta originally discovered by Austria-based biotech company Apeiron Biologics and co-developed by EUSA Pharma; marketed as Qarziba®) were associated with the increased survival (HR 0.46, p < .01 and HR 0.37, p < .01, respectively).
Netherlands Cancer Registry
Based on data from The Netherlands Cancer Registry (NKR), which covers the nearly 17 million citizens of The Netherlands collected nationwide since 1990, the researchers concluded that besides improved prognosis, more children were diagnosed with neuroblastoma in the 10 year.
The NKR data showed that between 1990-1994, on average, twenty patients were diagnosed with neuroblastoma in The Netherlands per year. This increased to 26 patients between 2010-2014. The data also showed an increase in stage 4 diases, while the incidence of other stages remained stable.
“The increase is most prominent in the same high risk group of children above 18 months with a stage 4 neuroblastoma’, said Max M Van Noesel, MD, MSc, Ph.D., Head of the Department of Pediatric Oncology and Hematology at the Erasmus University/Erasmus Medical Center, in Rotterdam, The Netherlands and the study’s lead author.
The reason for the increase is unknown. Although the researchers included data related to novel diagnostic approaches and improved registration of malignancies, in their analysis, this did not explain the increase.
“This is very frustrating,” Tas said.
“It [may be] possible that [our] Western lifestyle or environmental factors contributed to the increased incidence, these have changed with time. However, we don’t have an indication which factors play a role,” she added.
However, the overall results show that while the there is an ‘unexplained’ increase in incidence of neuroblastoma, more patients survive the disease.
“[In the end…] more children survive this disease [as a ] result of many international investments of oncologists and researchers in researching new treatment methods and adjusting the treatment strategies,” Van Noesel concluded.
 Tas ML, Reedijk AMJ, Karim-Kos HE, et al. Neuroblastoma between 1990 and 2014 in the Netherlands: Increased incidence and improved survival of high-risk neuroblastoma [published online ahead of print, 2019 Nov 11]. Eur J Cancer. 2019;124:47–55. doi:10.1016/j.ejca.2019.09.025 [Pubmed][Article][Download Full Article]