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Brain tumours kill more children and adults under the age of 40 than any other cancer

Society of Neuro-Oncology Annual Meeting 2016 – Part 2

by Elise O'Kelly

The new WHO brain tumour classification continued to be a key theme on the second day of the Society for Neuro-oncology meeting. There were further reports on research which aims to exploit the differences between tumour types, based on a combination of pathology and genetics, to try to direct targeted therapy. This will be more effective than the relatively non-specific drugs which are available at the moment.

In particular, a number of immunotherapy clinical trials are underway, although none of these have yet shown any clinical benefit. This is likely to be associated with the lack of specificity of the drugs in combination with the choice of the factors which have been identified on the tumour cells.

The ones used to date have been demonstrated to be relatively insensitive to the actions of the drugs. However, there is evidence that this approach may work, but needs to be developed further.

Another question to be addressed is whether the drugs will be most effective on either new or recurrent tumours and whether they should be administered in combination with other therapies.

The role of the blood-brain barrier was highlighted in a number of presentations, as this will prevent a lot of drugs from entering the brain. However, a number of researchers, including Geoff Pilkington at our Portsmouth Centre of Excellence, are experimenting with approaches which will place drugs within specific carriers to allow them to enter the brain.

One study reported how this approach can be used to actually inject genes into the brain as this could be a particularly effective therapy. Further research is now ongoing to determine whether this could have any clinical implications.

An additional approach would be to use immune cells which are present in the blood which could potentially be reprogrammed to allow them to enter the brain and to be directed to tumour cells. This could provide a very valuable new type of therapy, as it uses the body’s own immune system but reprograms it to recognise tumour cells as “foreign”, and therefore kill them.

Gene mutations play a role in the development of some brain tumour types and finding out how this happens can provide valuable information about which drugs may be more appropriate for the treatment of specific tumour types.

While there has been a significant investment in research to understand individual genes, another area of research is termed epigenetics. This does not focus on individual genetic mutations but rather on factors which may impact on the function of a large number of genes which together may cause the cells to form tumours. This is likely to be a key driver for tumour formation. Prof Silvia Marino at our QMUL Centre of Research Excellence is also carrying out research in this area.

Finally, there was a discussion on how we should assess whether a new treatment is successful. The current assessment scores are progression-free survival (PFS) – the time from therapy to relapse – and overall survival (OS), which is the time from therapy to death. These are complemented by brain scanning where the presence and size of the tumour can be identified.

However, as the treatments under development may significantly extend the survival time following treatment, new methods by which to assess the effectiveness of therapies need to be developed.

The RANO (Response Assessment for Neuro-oncology) group has been working to develop guidelines which will be much more sensitive in assessing clinical changes following treatments. This includes a combination of an assessment of scans with a detailed clinical assessment.

A scoring system has been developed in order that there is a uniformity between trials. However, of particular importance is the assessment of “patient-reported outcomes”. The patient is the person undergoing treatment and it is vital that they be provide their views in order that a decision on treatment and its success is a partnership between them and the doctor.

Dr Kieran Breen – Director of Research

Read Part 1 here