Neuro-Oncology

What I have tried to do in this section is to provide general information about brain tumours and their management as well as outlining my own experience in this field. As will become obvious there is no consensus regarding the management of many brain tumours so much depends on the philosophy of the clinicians involved. I hope my own philosophy about this will become apparent.

Neuro-oncology is the field of brain tumour treatment. The diagnosis of a brain tumour is always serious from a patient’s view. Whatever the type of tumour the diagnosis of a brain tumour will have life changing effects on a patient and their families. The field includes the management of entirely benign tumours to some extremely malignant tumours, some of which require surgery while others do not. The devil in this subject is in the detail which makes writing meaningful general comments about brain tumours and their management extremely difficult. They are not common tumours, so people’s experience of them is usually not great. If a patient or their family or indeed their GP does know of other people who have a brain tumour, the chances are that it will be different from the tumour that they have been diagnosed as having. Even two tumours with the same name may behave completely differently in different people and require completely different treatment.

Every first year medical student should be able to classify tumour into: benign, malignant, primary or secondary. They should be able to tell you that benign tumours are those that grow slowly without invading or destroying tissue locally and which do not spread around the body, while malignant tumours do the opposite. They do invade locally and they do spread around the body i.e. they metastasise. Brain tumours are further classified by their tissue of origin, either from the brain itself, the gliomas, or from the tissues surrounding the brain, meningiomas, acoustic neuromas, pituitary tumours etc. In simple terms tumours arising from the tissues surrounding the brain concur with the medical student classification outlined above. However the situation regarding primary brain tumours is more complex and often leads to confusion, worry and uncertainty amongst patients, their families and their doctors!

Primary brain tumours arise from the support cells of the brain, the glial cells. They are therefore called gliomas or are named after the cells from which they arise, astrocytomas, oligodendrogliomas or ependymomas. Some of these tumours behave in an entirely benign fashion while others behave very aggressively. The thing that distinguishes one type from another is their rate of growth. They all infiltrate (invade) into normal brain and even the most malignant do not metastasise (except in the rarest circumstances). The simple definitions of benign / malignant cannot therefore be applied to brain tumours. We talk about low grade (grade 2), intermediate grade (grade 3) and high grade tumours (grade 4) to determine the rate of growth of a tumour and therefore its degree of malignancy. (There is a grade 1 tumour which is entirely benign but this only occurs in children) The situation is further complicated by the fact a low grade tumour may remain so for many years but then ‘change its spots’ and become more malignant. It used to be thought that all gliomas eventually did this which led to the traditional definition of all these tumours being classified as malignant This might still be considered to be the case by some clinicians. However the modern view is that this is not the case and that some low grade tumours do behave in an entirely benign fashion. (This is particularly the case amongst the population of patients that have chronic epilepsy). However this does produce a great deal of uncertainty and worry for patients who have been diagnosed as having a low grade glioma and who have been told about the likelihood of it behaving benignly, who then read in a text book or indeed on the internet that their tumour is actually classified as malignant.

While there is uncertainty in the profession about the classification of brain tumours, there is certainly no consensus about how best to treat these tumours. Do you operate or don’t you? If so, what do you aim to achieve with surgery, just a biopsy for tissue diagnosis, a partial or more radical resection? When do you offer adjuvant therapy such as radiotherapy or chemotherapy? What is the role of newer therapies such as stereotactic radiosurgery? Do alternative therapies have a role? How a neurologist, neurosurgeon or oncologist approaches these questions depends a great deal on their experience and personal philosophy. What we are only just accepting as a profession is that the patient has a say in all this! There is probably no area of cancer care where a patient centered approach is more important or where an environment of ‘fully informed consent’ more difficult to achieve.

This is an outline of my experience and my philosophy. My first informative experience of the management of glioma patients was as a registrar in Liverpool in the early 1980’s. At that time neurologists were extremely conservative about the management of glioma patients especially those presenting with epilepsy. It was the norm not to scan patients unless there was a focal element to their seizures. The only type of scan available was a CT scan which in those days was not good quality. Patients presenting with progressive neurological deficit, cognitive impairment or symptoms of raised intracranial pressure were scanned more regularly and referred for surgery.

Worldwide the conventional neurosurgical approach was to do a craniotomy remove some of the tumour, then offer patients radiotherapy, as treatment for high grade tumours and as prevention in low grade tumours. This was the time when all gliomas were thought to be malignant. The results of this approach were pretty awful. Median survival times, i.e. the time within which 50% of patients died was 9 months with treatment and no more than 2 months without. It was recognized that patients with low grade tumours did better with median survivals of two years or so.

Liverpool proved to be a unique working environment in which to study the management of gliomas for two reasons. Firstly there was only one CT scanner in the whole region serving a population of 3.5 million. All patients with a scan diagnosis of a glioma were therefore managed at one hospital, the neurological center at Walton. Secondly everyone in the neuroscience department, surgeons, neurologists and oncologists took a very conservative approach to gliomas. Routinely the most aggressive surgery done was a biopsy, while radiotherapy was only offered to patients of in a good neurological state. This gave me the opportunity to study a unique database consisting of a complete cohort of glioma patients.

The results produced were very controversial at the time. Firstly there was no apparent difference in outcome between those patients treated by surgeons and those treated by neurologists – uniformly bad, except obviously the incidence of surgical complications. Secondly the median survival of patients undergoing a biopsy followed by radiotherapy was just the same as published series of patients undergoing the conventional craniotomy and internal decompression. Thirdly it was possible using multivariate analysis statistical techniques to demonstrate that what really influenced outcome in glioma patients was not the treatment they received but to certain presenting features that were associated with better survival, namely young age, presentation with epilepsy and good neurological condition at presentation. The philosophy in the department at the time was that there was no point in ‘wasting’ scarce neurosurgical resources on glioma patients when these resources were better spent on the treatment of other tumours such as meningiomas.

This situation influenced me in two fundamental ways. Firstly my studies did demonstrate a benefit from decompressive surgery and this was that the long term use of steroids in patients who had their tumours decompressed was considerably less than in those patients who had just had a biopsy. This had a considerable effect on the quality of a patient’s life. Secondly I was made aware that all conventional adjuvant therapy for gliomas was never going to be curative because it was not selective. In other words, the damage done to the normal brain always limited its use and therefore its effectiveness.

I spent a year in the mid 1980’s studying a form of laser treatment for brain tumours, namely photodynamic therapy which I hoped be able to produce selective tumour cell death. This we were able to demonstrate in the lab (perhaps for the first time) but the depth within the brain to which the selective photodynamic effect could be produced was only a few millimeters which was not enough to be clinically significant so I never developed the technique clinically although it was used in Australia for a while. I therefore left Liverpool with the conviction that thorough surgical decompression did have a role in glioma management after all.

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Following my senior registrar years in Manchester, I was appointed as neurosurgical consultant in Bristol in 1991. My specific remit was to develop stereotaxy in the department in addition to taking a role in the neuro-oncology program. I was fortunate to be joining an enlightened neuro-oncology team led by my surgical colleague, Brian Cummins and his neuro-oncology colleague Gill Bullimore. They were both ahead of their time in recognizing the need for multidisciplinary team working, setting up multidisciplinary clinics as early as the late 1980’s. In Bristol at the time the surgeons took as radical approach to gliomas as they could within the limitations of the technology available to them. Reoperating on recurrent tumours was recognized as useful palliative treatment in selected cases. In general the system was much more supportive to patients than what I had been used to in the north.

Two developments in the last decade have improved our ability to resect intrinsic brain tumours, image guidance and improvements in anesthesia that have allowed us to operate under local anesthetic. Where it is appropriate it is now possible to remove the radiological extent of a tumour even in some cases where the tumour is arising from eloquent cortex (i.e. areas of the brain known to have important function as opposed to silent cortex that apparently we can do without!) Developing image guided surgery and local anaesthetic techniques have been one of my major activities as a consultant, allowing me to take an aggressive approach to the surgery of gliomas where appropriate. So although, in general, I have a very conservative approach to surgery including tumour surgery where radical surgery is indicated I am fortunate to have the tools to do this as safely as possible.

My prime indications for surgery for brain tumours and those of the clinicians with whom I work, are:

 

• to establish a tissue diagnosis,

   

• to reverse or prevent symptoms from a tumour,

   

• to reverse or prevent life threatening problems from a tumour and where possible to cure patients.

Some tumours do not require immediate surgery although all need to be watched carefully with regular follow up and scanning. A common group of patients in this category are patients that present with an epileptic seizure out of the blue who have a lesion on an MRI scan that looks abnormal but not sinister and who is symptom free on anticonvulsant drugs. It is perfectly reasonable to follow patients like this up with regular scans. If, however, a patient presents with progressive symptoms, the commonest being neurological deficit like a stroke, progressive mental deterioration or symptoms of raised pressure inside the head i.e. headache, then surgery to remove some or all of a tumour is usually required. Sometimes I will just biopsy a tumour in order to plan further treatment. This is particularly important where the mainstay of treatment might be therapy other than surgery e.g. cerebral lymphoma. Otherwise I will offer surgical resection of the tumour.

It is not appropriate to opt for radical resection of all tumours as in many instances partial resection is all that is required in terms of establishing a tissue diagnosis, treating the presenting symptoms and preventing problems in the future. In these cases I want to avoid the extra risk associated with radical tumour resection where this is not in a patient’s interest. However radical resection is beneficial I would expect to be able to offer patients this service in an appropriate timescale with the resources to treat them safely. (This may sound like an obvious statement but this is not a foregone conclusion in the modern NHS) The definition of who requires radical surgery and who does not is too complex to define in a general article like this and needs to be discussed on an individual case basis. I would expect that this is discussed thoroughly with all my patients, all the options for treatment presented and a consensus reached as to the best way forward for each individual patient. However this more holistic, patient centered approach is not easy to achieve in the conveyor belt, target driven environment in which we now work.

There is no consensus as to the best management of a patient with a radiological diagnosis of a low grade tumour who is clinically well. Early surgery serves to establish a tissue diagnosis and remove the bulk of a tumour. However there is no evidence that this prolongs survival in the long term or is better management than the conservative approach of monitoring the progress of a tumour with regular scanning. The primary indication for surgery in this situation is often patient choice. There are as many patients who prefer to know what is going on and who wish to get on with their lives knowing that the bulk of their tumour has been removed as there are those who prefer to avoid surgery if at all possible. In the past clinicians took a paternalistic approach and decided for their patients. In broad terms a neurologist would decide against surgery whereas a surgeon would offer surgery. The modern approach is to recognize that the doctor is the servant of the patient and that our role is make sure that our patients are fully informed of the situation regarding their condition and to support them in the approach to their condition that they wish to take.

If it is decided to operate in this situation then every effort must be made to do so safely. For tumours arising in cortex that might control speech or movement the most sophisticated way of assessing a patient’s function during surgery is to monitor it directly i.e. do the operation under local anaesthetic. With modern anaesthetic techniques this is more straightforward than it sounds. This is the technique developed in our department with Dr John Carter, Consultant Anaesthetist.

The set up is more elaborate than for a procedure under general anaesthesia. First of all we do not give any premedication as we require the patient to be fully awake during the procedure. We take great care to position the patient carefully, usually on their side so that their airway is protected for the portion of the operation that they are asleep. The only pain sensitive part of the head is the skin so local anaesthetic is applied liberally to the places where the points of the head fixator penetrates the skin to hold the skull and to the incision site itself. Image guidance is always used so that a minimally invasive approach can be taken. We use ‘see through’ drapes so that we can watch the patient carefully throughout the procedure.

Once the patient is positioned, the head fixed, the image guidance set up and the incision site prepared, draped and anaesthetized, the patient is put to sleep using short acting anaesthetic agents. This is to allow the ‘carpentry’ to de done – the skull is opened with a high speed drill / saw system. This part of the procedure is not painful but it is a little noisy so I prefer patients not to be awake for this.

When the tumour has been exposed and I have orientated myself fully using the image guidance, the patient is the woken up, a process that takes about ten minutes. When they are fully awake I then proceed to resect the tumour, testing the patient’s speech and movement continually. When the resection is complete the patient is put back to sleep and the wound closed. If at any stage things become uncomfortable or the patient becomes concerned it is a very simple process to put them straight to sleep and proceed under general anaesthetic.