Kevin O’Neill is Consultant Neuro-surgeon at Charing Cross Hospital, Imperial College, London and Chairman of BTRC. On a personal note, Kevin has impacted on the lives of many people with brain tumours; they all say that he is much more than just a surgeon, he has become a friend.
Here is Kevin’s Story…
“The problem starts with the patient, the solution must end with the patient too.”
I started my medical career with the aim of becoming a brain surgeon and like many surgeons I had a great desire to be involved in work that would have an impact for good on people’s lives. Very soon after entering the specialty I became aware that there were certain areas of brain surgery where we had not made much advance if any for several decades. Brain cancer was one such area and probably the most devastating as survival time from diagnosis was so short despite our best endeavours.
With this frustrating position it was not surprising that many doctors would adopt a nihilistic view of brain tumours – in that there was nothing that could be done for these people. This I found equally frustrating and defeatist and realised these patients needed more options if they were to have anything of a brighter future. I decided that I would take up the challenge to research into and try to improve this situation.
I am a great believer in the power of positive thinking. Imparting hope and positivity is such powerful medicine. This has to be balanced by reality but gaining the confidence and understanding of your patients can impact quite significantly on their outcome.
Brain tumours are devastating. They cause the greatest reduction of expected life years than any other cancer and are on the increase particularly in the younger age groups. It was clear that something needed to be done but where were we to start. Part of the problem was that despite their poor prognosis and increasing incidence they are still relatively rare in comparison to the likes of breast and lung cancers. As such there is a lack of awareness and a lack of funding given for brain tumour research.
We aimed to tackle this by forming the Brain Tumour Research Campaign and creating the momentum for change and to fill the gaps missing for a successful programme of research and for the subsequent development of better treatments.
Up until very recently there were very few treatments on the table for those who had brain tumours. There was not much more available to them than surgery followed by radiotherapy and possibly some chemotherapy for those with malignant gliomas. For all but 2-3% of patients this was a death sentence.
Whatever treatment was provided in the past was always aimed at the dividing tumour cell mass. This would start with surgery which would often leave much of the tumour behind as it would be difficult to identify and discern from normal brain combined with the view that performing radical surgery may create neurological disability but not make a difference to survival. The evidence for the role of surgery is still not fully clear again because of the lack of good research. It is becoming apparent that refined optimal resection, that is removing as much as possible without injuring any functioning normal brain, is the way forward. This is an area we are working on by correlating intra-operative imaging such as 3D ultrasound and other visualisation techniques to identify tumour in relation to brain and make surgery much more effective and safer.
Radiotherapy might kill the large part of the dividing tumour, and chemotherapy could augment this but we would always be missing a resistant population of cells that prevent a cure.
Some of these would be within the dividing cell mass itself and just not be susceptible to the treatments as the tumour is made up of cells that can be very different from one another in their make-up. Some could be stem-like cells that are laying dormant not dividing and therefore resistant to the treatments but with the potential to form new tumour cells once the ‘storm’ of treatment is over like reinforcements being called up. Some will be cells that are resistant because they are not dividing but moving or migrating into the surrounding brain invading new areas of the brain to set up further sites of tumour.
There are therefore several areas to be researched into and work is already being done but not translating into treatments and a lot of research was happening in a vacuum but being confounded by a lack of national awareness, drive and collaboration.
We had to start locally and set up a driving body in the form of the Brain Tumour Research Campaign. The lack of funding available meant that the first task was to raise money to seed fund some important basic initiatives that would form the foundation of a good research programme.
Firstly was setting up a database of tumour cases and their important details regarding the tumour type and treatments received, to provide an idea of the extent of the problem and how we were dealing with it.
Secondly the establishment of a brain tumour tissue bank that would allow us to store and study the actual substance of the problem with our experiments and analyses right down to the molecular level. It also provides a vital resource for any group involved in brain tumour research to access this important material.
Thirdly we funded, equipped and manned a laboratory to study the molecular aspects of these brain tumours to find vulnerabilities and test new treatments.
Lastly we aimed to strengthen the links between the surgeon and oncologists in the clinical setting and the pathologist and scientist in the laboratory in a way that research is supported across the board. This is really the unique attribute that this charity has with really excellent and motivated people involved who provide the recipe for success. These include Dr Federico Roncaroli, Dr Nel Syed, Dr Karolina Janczar, Dr Tim Crook, Dr Catherine Brock, Dr Mark Glaser, Dr Adam Waldman, Dr Peter Schmidt, Dr Jon Bowen to name but a few.
Our aim for the BTRC thereafter was to create translational research that moves results from the laboratory to the clinic as soon as possible to help save lives as time is a luxury brain tumour patients do not have. Working with very little funding this was going to be difficult so we adopted a specific strategy.
We knew that we needed to look at things in a different way. Research groups can get so focused that they cease to see the wood for the trees. We decided to take a step back to see what was not being looked at to determine what was being missed.
At the same time we surveilled what was happening on the cutting edge in other better funded areas of cancer research to determine whether their results may be applicable to brain tumours. Utilising the premise that drugs or treatments may exist somewhere but their benefit was not being recognised or tapped. We have since tested these principles on brain tumours in our laboratory and found much in common.
A lot of scientists were looking at changes in genetic material within tumours to determine what was going on but very few were looking at the changes downstream in the expression of those genes that relates more to the cellular environment than changes in the genes themselves. This type of study is called epigenetics which is where we are also focused.
We began to explore within the patient with MR imaging and spectroscopic techniques and directly within the living tumour at surgery with microdialysis probes to determine what biochemicals existed in these tumours and what metabolites they were producing. After excising them at surgery we cultured them immediately in the laboratory so that we could explore what metabolic pathways were over expressed or deficient.
We have found some new pathways that could explain how these tumours overcome the brains immune response. In addition we know that the tumours create a relatively hostile environment for themselves and coping strategies are needed including switching on the growth of new blood vessels to sustain them and a dependency on the host for certain nutrients essential for growth and survival.
We have now discovered how to exploit at least one of these. We have found that at least 30% of primary tumours are dependent on a certain nutrient to survive and following radiotherapy this may increase to 70% or more. We have a non-toxic drug which can block this pathway and kill the tumour cells without any effect on normal cells and hope to bring this to trial later this year.
We think that this exemplifies the BTRC very well in that within one year of setting up the lab we have a potential new treatment to trial. We hope we have several more in the pipeline including several refinements to imaging and surgical technology.