In the UK about 1600 children a year are diagnosed with childhood cancer. Brain and Spinal tumours are the second most common type with over 300 children and their families receiving this devastating diagnosis every year. Over the past few decades the outcome for many forms of childhood cancer has improved dramatically, but this progress has not been seen with brain tumours, where in many cases the prognosis remains very poor and the treatment related morbidity very significant. In brain tumours, upfront surgical treatment is highly invasive, with potential devastating outcomes. This in many cases, is followed by intensive and toxic chemotherapy and radiotherapy, in an attempt to afford a cure, but at a very high cost. At this point in time, there are no alternatives!

Fig. 1   This gives a very clear visual summary of the incidence of Brain and Spinal Tumours in comparison to other childhood cancers.

Fig. 1 This gives a very clear visual summary of the incidence of Brain and Spinal Tumours in comparison to other childhood cancers.

Over the past twenty years funding and research into childhood cancers such as Leukaemia has brought about a significant change in prognosis for this disease, with 2 in 10 children surviving the disease in the 1970’s to over 8 in 10 children today going on to be long term survivors and living normal lives.

The outlook for survival from Brain and Spinal tumours is very much less favourable and the long term damage from current treatment is, in  many cases, devastating and it is for this reason, that Blue Skye Thinking has been set up to assist in funding research to help redressing this balance.

Current treatments such as chemotherapy and radiotherapy damage both cancer cells and normal tissue. In the brain and spinal cord, this can lead to devastating problems as nerve cells do not have the capacity of repair and renewal. In order to improve both the success of treatment and long term quality of life for childhood survivors of brain and spinal tumours, research is required to develop treatments that can be targeted to the cancer cells.

There are different types of brain tumours and they’re usually named after the type of cells they develop from. Brain tumours can be either benign (non-cancerous) or malignant (cancerous). Most primary brain tumours are benign.

Benign brain tumours 

These tumours are usually developmental/anatomical anomalies and remain in the part of the brain where they develop, and do not spread into other areas of the brain. Sometimes they may be difficult to surgically remove due to their location. These tumours may need treatment if they are causing damage to nearby critical structures or increased pressure in the brain.

Malignant primary brain tumours 

These tumours are rapidly increasing in size causing increased pressure within the brain and damage to surrounding areas by invasion and destruction of normal cells. Malignant tumours also have the potential to spread away from their primary site to other parts of the brain and spinal cord and very rarely outside the nervous system to other organs in the body.

The two main types that affect children are:


Gliomas develop from the supporting cells of the brain known as glial cells. They can be subdivided into two main types in children: astrocytomas and ependymomas. Doctors group them by how quickly they grow (known as the grade of the tumour) and how the cells look under a microscope.

Medulloblastomas (MdB)

These usually develop in the cerebellum, at the back of the brain. They may spread to other parts of the brain or into the spinal cord.

(MacMillan - Brain Tumours in Children)

Recent research into  medulloblastoma has started to allow scientists and doctors to understand more about the cells that cause this disease and this indicates that MdB can be broken down into 3 distinct areas, namely Atypical Teratoid Rhabdoid Tumours (ATRT), Medulloblastomas, and ETANTR (Embryonal Tumours with Abundant Neuropil and True Rosettes).

Fig. 2 Image shows a medulloblastoma tumour in a 4 yr old patient, growing between the brain stem and the cerebellum.

Fig. 2 Image shows a medulloblastoma tumour in a 4 yr old patient, growing between the brain stem and the cerebellum.

Research has also allowed classification of medulloblastoma into 4 different subtypes depending upon the  specific intracellular pathway that has become abnormal in the cancer cell. It may be that in years down the line these different pathways could be classified as 4 different types of brain tumour.

1.  WNT (Wingless) - classic histology, rarely metastatic, very good prognosis

2. SHH (Sonic Hedgehog) - desmoplastic/nodular, uncommonly metastatic, intermediate to good prognosis

3. G3 - classic histology, very frequently metastatic, poor prognosis

4. G4 - classic histology, frequently metastatic, intermediate prognosis

Currently treatment for medulloblastoma is based on the presence or absence of metastatic disease and is not based on subtype analysis. This information opens up the possibility for disease and treatment stratification and the development of drugs which specifically target the abnormal pathways thus offering a way of giving  more 'tumour-directed' therapy. This type of research is essential and offers the only way forward for a better outcome for children with medulloblastoma.

Medulloblastoma, although one of the commonest types of childhood brain cancer, is rare, with only about 70 cases identified in the UK per year, which translates into about 650 new cases across Europe. Research funding for work on this rare tumour is difficult to obtain as much of the national funding for childhood cancer is directed to the more common cancers such as leukaemia. The funding that has gone into leukaemia research over the last few decades has made a tremendous difference to survival and outcome, and funding is now needed to try to achieve the same progress in the field of medulloblastoma.

MdB patients are currently treated with the Milan Protocol, following the publication in 2008, of a paper indicating the efficacy of the trials. But, the treatment is generic for most patients, and the doses given to patients are highly toxic, leaving them weak and vulnerable to infection. Variation occurs where patients are younger than 3 years and as such they are considered too young to go through the devastating process of Radiotherapy.

Newcastle is one of the leading centres in the UK for research into diagnosis and treatment of Medulloblastoma. They are gathering tumour samples from centres across Europe in order to accumulate data to categorise the samples to aid the development of new, more effective treatment protocols.

The research work in Newcastle is very active and intense. They are targeting their work at the molecular abnormalities causing the tumours to develop, and looking for new targets for treatment. Tumour cells are broken down into their individual component parts within the lab (ie into the DNA/RNA and coding sequences that direct the cells function). They are then reconstructed and ‘played with’ in order to understand what has gone wrong at the most basic level, to lead to the cell becoming a cancer cell . This reveals clues as to how to target the cells with more effective treatment to stop them from dividing and multiplying, thereby pushing the cancer cell into cell death.

In the case of  some tumours such as ATRT, of the 30 000 genes within the DNA,  a single gene fault has been shown to be the main causing the tumour. This has made research for new drugs and therapy easier than for medulloblastoma where a number of gene faults are known to be involved in the disease process and therefore made the research much more complex. The research work into Medulloblastoma is exciting but very painstaking and exacting. It is however leading to real progress. Research funding is vital to fund more research posts and for the purchase of specialist equipment to enable this work to move forward at a faster pace. 

The work in Newcastle is  the real chalk face of research. Lab coats, gloves, glasses, lots of gadgets and machines, and millions of bits of data being transferred to computer screens. The team are dedicated to their work and are making a real difference to our understanding and treatment of medulloblastoma. What happens next, is the appropriate question.

When the research teams are confident that they have enough information, a new treatment is tested  in  a Phase 1 Trial, and then pass to a Phase 2 Trial and eventually it is available as standard treatment for all children in the UK and worldwide.

Children who are not cured by first line treatment, (i.e. those who relapse), are currently in a very precarious place with few, if any, curative treatment options. It is here, that Newcastle is once again doing invaluable research by initiating a sample collection of tumour cells from relapsed patients from across Europe. This is understandably difficult in that sample collection requires a surgical procedure.

Newcastle currently hold a bank of 30 samples from patients who have relapsed. A comparison is made of these samples, with those collected at the patients' original presentation, to identify any cell changes in relapse. This sort of knowledge and understanding has helped direct treatment and offered children the hope of entry into new clinical trials. It is also possible to collect post mortem samples, where parents have given consent, and these tissues, which Newcastle also holds, offers further opportunities for ground breaking research.

Research into rare cancer types requires cooperation between research centres. In the UK, Newcastle, The Royal Marsden, and  Great Ormond Street are working together to ensure that the latest research on tumour stratification is incorporated into a clinical trial. It has taken since 2005, when the WNT pathway was first identified to be able to bring this work into clinical practice. Translational research is lengthy and frustrating but tremendously important and collaborative working is an exciting model for future research.

Blue Skye Thinking hopes to raise money to contribute to Medulloblastoma and other Malignant Brain Tumour research work in the UK, in the belief that, as with other cancer types, increased research will lead to more effective and less damaging  treatment for children with this dreadful disease.

(In conversation with Northern Institute of Cancer Research)