Children with high-risk neuroblastoma is the most challenging group to treat. Current treatment strategy for this group consists of 3 treatment blocks:
induction: chemotherapy and primary tumour resection;
consolidation: high-dose chemotherapy with autologous stem-cell rescue and external-beam radiotherapy [XRT];
post-consolidation: anti–ganglioside 2 immunotherapy with cytokines and cis-retinoic acid.
Adopted from: Pinto NR et al JCO 2015, 33, 3008-3017.
Up to 50% of children that do respond experience disease recurrence with tumour resistant to multiple drugs and more aggressive behaviour that all too frequently results in death.
For the majority of children who do survive cancer, the battle is never over. Over 60% of long‐term childhood cancer survivors have a chronic illness as a consequence of the treatment; over 25% have a severe or life‐ threatening illness.
To be able to guide the treatment of neuroblastoma patients, doctors have developed a number of classification systems. Although sharing common features, they slightly vary by medical center, country and continents making direct comparisons of treatment results difficult. Doctors and scientists are trying to consolidate all systems in one in order to evaluate treatments in the past, currently ongoing and in the future.
Scientists have suggested a newer risk group classification system, the International Neuroblastoma Risk Group (INRG) classification that would incorporate the best knowledge gained and recent advancements in the disease imaging and neuroblastoma molecular diagnostics. This system is based on imaging criteria using the image-defined risk factors (IDRFs) and the prognostic factors such as:
The child’s age
Tumour histology (the tumour appearance under the microscope)
The presence or absence of MYCN gene amplification
Certain changes in chromosome 11 (known as an 11q aberration)
DNA ploidy (the total number of chromosomes in the tumour cells)
The table is adapted from Pinto NR J Clin Oncol. 2015
Using these factors the INRG classification put children into 16 different pre-treatment groups (lettered A through R). Each of these pretreatment groups is within 1 of 4 overall risk groups:
Very low risk (A, B, C)
Low risk (D, E, F)
Intermediate risk (G, H, I, J)
High risk (K, N, O, P, Q, R)
This system has not yet become common across all medical centers, but it is being researched in new treatment protocols.
Doctors and scientists are planning to improve the INRG classification system by incorporating other molecular diagnostics data such as profiles of the neuroblastoma genome (DNA), transcriptome (RNA), and epigenome* in order to make precise prognostication even better.
Neuroblastoma is a childhood cancer. The word neuroblastoma consists of two words neuro and blastoma.The term neuro refers to nerves, blastoma – to a cancer of immature cells.
It starts in some types of nerve cells during embryo development.transforming immature nerve cells into cancerous cells. This type of cancer occurs most often in infants and young children mostly under the age of 5 years old.
Neuroblastoma cells
Neuroblastomas behave very differently:
Cells can grow and spread quickly,
Cells can grow slowly
Cells can die for no reason, so a tumour goes away on its own.
Cancer is an umbrella term that covers a group of diseases sharing the common features but diseases vary by site of origin, tissue type, race, sex, and age. One of the main features is an uncontrollable growth of cells. These cells are capable of spreading to other parts of the body. This process is also known as invasion and metastasis.
Though cancer in kids is not the same as in adults, childhood cancer cells behave in the same way. They grow uncontrollably and can travel to new destinations in the body.
Mission
To increase the understanding of neuroblastoma pathogenesis,
progression and treatment failure and to improve survival
and quality of life for children with neuroblastoma.
Main Objectives
To consolidate a platform for global collaboration
To establish networks of multidisciplinary caregivers
To develop new trial protocols
To develop standards for radiotherapy and surgery
To develop SOPs for biomaterial collection, handling and storage
To develop SOPs for application of major research technologies
It is always a pleasure to host undergraduate students during summer months. Two students joined the RCSI Research Summer School (RSS) Programme. Both are working on the NCRC funded project to understand mechanisms that drive neuroblastoma pathogenesis. None of them had a prior lab experience, but nothing is impossible under John’s supervision.
A full concentration on every single step of the research.
My PhD student John Nolan together with other 41 candidates graduated at the RCSI’s 2017 June Conferring ceremony which took place in the College Hall of 123 St. Stephen’s Green.
He continues his research in neuroblastoma as a Postdoctoral researcher on the project funded by the National Children’s Research Centre. I am glad to be able to keep expertise and young talents in our team.
The research is a long-term investment. It is always built up on the work of the predecessors. Keep research running is crucial to make the dreams come true. Dreams for better treatment options and quality of life.
Thank you to everyone involved in raising funds for CMRF!
It is fantastic to see so knowledgeable and enthusiastic young researchers in my research group. This year, the team is multinational with the Irish students mixing with Belgian and Malaysian. All together they are cracking the code of neuroblastoma microenvironment and tumour cells communication through understanding main differences between conventional cancer cell models and tumours.
The big research plan of the entire team consists of more smaller and focused projects to be completed within 10-12 weeks. All projects are unrestricted, they are driven by the intellectual curiosity of these students. This way is full of ups and downs, frustrations and encouragements when techniques do not work or reagents do not come in as expected. Some cancer concepts can also work differently in the given settings. Simple questions are bringing more challenges than expected. But at the end of the road is the best reward – contribution to the conceptual advancement of neuroblastoma microenvironment.
The Neuroblastoma Research Dream Team 2017: Dr. John Nolan, NCRC funded researcher, RCSI, Joe O’Brien, TCD MSc student, Ciara Gallagher, DIT undergraduate student, Jessica Tate, RCSI Medical student, Larissa Deneweth, Erasmus student, Ghent, Ying Jie Tan, TCD MSc student.
