Treatment of High-Risk Neuroblastoma

Children with high-risk neuroblastoma is the most challenging group to treat. Current treatment strategy for this group consists of 3 treatment blocks:

  1. induction: chemotherapy and primary tumour resection;
  2. consolidation: high-dose chemotherapy with autologous stem-cell rescue and external-beam radiotherapy [XRT];
  3. 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.
Reference:

Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, Nakagawara A, Berthold F, Schleiermacher G, Park JR, Valteau-Couanet D, Pearson AD, Cohn SL. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.J Clin Oncol. 2015 Sep 20;33(27):3008-17.

 

 

What is the risk group classification system?

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:

  1. Very low risk (A, B, C)
  2. Low risk (D, E, F)
  3. Intermediate risk (G, H, I, J)
  4. 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.

* The epigenome is made up of chemical compounds and proteins that can attach to DNA and direct such actions as turning genes on or off, controlling the production of proteins in particular cells

References:

Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, Nakagawara A, Berthold F, Schleiermacher G, Park JR, Valteau-Couanet D, Pearson AD, Cohn SL. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.J Clin Oncol. 2015 Sep 20;33(27):3008-17.

What is neuroblastoma?

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:

 

The types of treatment used for neuroblastoma can include:

Children who survive have a high chance of developing long term side effects as a result of the treatment that saved their lives

More details about neuroblastoma can be found here:

American Cancer Society

Cancer Research UK

What is cancer?

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.

This video ‘Cancer: from a healthy cell to a cancer cell’ nicely explains this transformation.

This video ‘How does cancer spread through the body?’ gives a perspective on the ways cancer cells travel in the body.

September is Childhood Cancer Awareness Month

September is Childhood Cancer Awareness Month!
Facts about childhood cancer

Please watch this video created by St. Baldrick’s Foundation | The Childhood Cancer Ripple Effect

References:
Gatta G, Botta L, Rossi S, Aareleid T, Bielska-Lasota M, Clavel J, et al. Childhood cancer survival in Europe 1999-2007: Results of EUROCARE-5-a population-based study. Lancet Oncol. 2014;15(1):35–47.
Ward E, Desantis C, Robbins A, Kohler B, Jemal A. Childhood and Adolescent Cancer Statistics, 2014. Ca Cancer J Clin. 2014;64(2):83–103.
Dolgin MJ, Jay SM. Childhood cancer. 1989;327–40.
Miller RW, Young Jr. JL, Novakovic B. Childhood cancer. Cancer [Internet]. 1995;75(1 Suppl):395–405.
Raab CP, Gartner JC. Diagnosis of Childhood Cancer. Primary Care – Clinics in Office Practice. 2009. p. 671–84.
Howlader N, Noone A, Krapcho M, Garshell J, Miller D, Altekruse S, et al. SEER Cancer Statistics Review, 1975-2011 [Internet]. National Cancer Institute. 2014.
Ries L a. G, Smith M a., Gurney JG, Linet M, Tamra T, Young JL, et al. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. NIH Pub No 99-4649. 1999;179 pp
Warren KE. Diffuse intrinsic pontine glioma: poised for progress. Front Oncol [Internet]. 2012;2(December):205.
Lackner H, Benesch M, Schagerl S, Kerbl R, Schwinger W, Urban C. Prospective evaluation of late effects after childhood cancer therapy with a follow-up over 9 years. Eur J Pediatr. 2000;159(10):750–8.

 

SIOPEN Meeting 2017

The dates for the SIOPEN AGM and Neuroblastoma Research Symposium were announced. This meeting will be hosted by the German So­cie­ty for Pa­ed­ia­tric On­co­lo­gy and Hae­ma­to­lo­gy and will take place @ Langenbeck Virchow Haus, Berlin, Germany on October 25-27, 2017.

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
  • To identify leaders for specific topics

Scientific Topics/Plenary Sessions

  1. Molecular Risk Stratification
  2. Liquid Biopsies
  3. Tumor Heterogeneity+Tumor Microenvironment
  4.  New Preclinical Models: PDX, GEMM, zebrafish
  5. New Immunotherapy Approaches
  6. New Drug Targets/Early Clinical Trials
  7. Neuroblastoma Pathogenesis/Genetics
  8. Targeting MYC
  9. Targeting ALK
  10. Targeting RAS/MAPK
  11. SIOPEN HR-NBL2 Clinical Trial Strategy
  12. Update ongoing SIOPEN trials: HR-NBL-1, LINES, VERITAS, OMS
  13. Update SIOPEN Bioportal
  14. Concept Biology+Relapse Umbrella Trial

August is a very quiet month

It is very quiet in the lab this month. No troubleshooting, no more long working hours, endless repetition of experiments, smiles and upsets… Almost all students completed their projects, submitted their works for grading and graduated. The last student is finishing at the end of August.

Time to focus on the collected data, reading literature, writing papers and new grants.

http://www.ifunny.com/pictures/its-rather-interesting-phenomenon-every-time-i/

Research Summer School in Action

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.

Congratulations to Dr.John Nolan!

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.

7th OLCHC RESEARCH & AUDIT DAY

 

7th OLCHC RESEARCH & AUDIT DAY Programme can be downloaded here Final Programme – OLCHC 2017