The treatment of malignant brain tumours has remained static for many years. The results have, up until recently, been poor and unchanged over a couple of decades.
Recently, improvements in surgery but predominantly improvements in radiotherapy and chemotherapy, have allowed better success with many brain tumours. In particular, Gamma Knife radiosurgery and other stereotactic radiosurgical methods, improved chemotherapy (e.g, Temozolomide) and improved imaging (notably MRI and PET scanning) have all improved the subject of neuro-oncology.
This article on brain tumours treatment is written by Dr Nick Plowman, MD, Senior Clinical Oncologist to St. Bartholomew’s Hospital and The Hospital for Sick Children, Great Ormond Street, London.
How it is diagnosed
Tumours of the brain and spine have traditionally been difficult to diagnose and treat. For brain tumours, patients usually present with symptoms of raised intracranial pressure (e.g. headache), neurological signs (e.g. weakness of a limb, visual symptoms) or epilepsy.
Diagnosis is suggested by the appearance of an intracerebral mass on MRI scan. If there are multiple masses, the possibility of the brain problem being metastatic (i.e. spread) from a primary cancer outside the brain (lung cancer and breast cancer being the commonest two) must be considered.
Where there is no obvious primary cancer outside the brain, then surgical debulking (removal of tumour tissue) at craniotomy (surgical opening of the skull to gain access to intracranial structures) is considered for most primary brain tumours unless they are critically placed (e.g. brainstem). Surgery may not be appropriate if the diagnosis can be definitely made by other means (e.g. a functioning pituitary tumour or a pineal germ cell tumour can be definitely identified by the measurement of the raised hormone secretory product of the tumour and the appearance of a discrete tumour on MRI in the pituitary and pineal regions respectively). In these two cases, surgery may not then be needed in that medical therapies may be curative without recourse to surgery.
However, the commonest primary brain tumour, the glioma, is firmly diagnosed and primarily managed by open craniotomy and debulking where it is safe to do so. The specimen tissue is sent for histology which confirms the diagnosis and grades the tumour (the high grade – most aggressive pattern of growth - glioblastoma multiforme being the most common type). In addition, more specific molecular and genetic testing of the tumours is now becoming more prevalent in helping to unravel the likely behaviour of the tumour in the future and this may impact on subsequent management. Modern surgical methods may allow the surgeon to achieve the optimum removal of tumour tissue, but usually the surgeon is limited as it is not safe to take ‘wide margins of safety’ around a brain tumour as any margin of safety would be normal vital brain.
Post-operative management of high-grade gliomas comprises a six-week course of radiotherapy involving attendance at hospital for 5 days a week for that period. X-ray beams are directed on the tumour with a margin of safety – the small daily radiation doses being better tolerated by the surrounding normal brain (which inevitably receives a high radiation dose in the immediate environs of the tumour).
The addition of a tablet chemotherapy agent (temozolomide) to the radiotherapy has improved the outlook for patients with this potentially dangerous tumour type in recent years. Overall, such treatment is well tolerated.
Low-grade glioma patients may move straight to post-operative radiotherapy (usually not chemotherapy - although a case can be argued for this in one type of tumour, the oligodendroglioma). It is not always necessary to proceed to radiotherapy immediately. It does not necessarily prejudice the long-term survival chance to employ ‘watchful waiting’ (which implies an MRI scan every six months or so) and employing radiotherapy only if the scan shows tumour progression.
The same principles apply to spinal gliomas, although it is usually more difficult to achieve good debulking of a spinal glioma as the surrounding tissue is so vital.
Benign (non-cancerous) tumours include meningiomas and pituitary adenomas. Surgical therapy is usually curative for typical meningiomas. Any residual core tissue that is difficult to remove can be definitively eliminated by focal radiation therapy – radiosurgery (Gamma Knife or X-knife options being the most common forms). Prolactinoma pituitary adenomas shrink well on dopamine agonist therapy, whilst surgery, radiosurgery (usually Gamma Knife) or conventional radiotherapy all have roles in the management of most others.
Acoustic neuromas are a further form of benign tumour and these in particular can be successfully treated by radiosurgery. A recent group of patients treated at our unit using the Gamma Knife clearly demonstrate the advantages of removing these tumours by this less invasive procedure than conventional surgery. In addition, these patients are more likely to retain their hearing, hearing loss being a risk of conventional surgical techniques. Radiosurgery has eclipsed surgery for most acoustic neuromas in recent years and is undoubtedly the most important for curative treatment of brain arteriovenous malformations (AVM). Our team at St. Bartholomew’s Hospital introduced radiosurgery to London in 1989 and has both Gamma Knife and X-knife options available for therapy. The exact treatment method chosen is based on each individual patient’s situation.
The use of radiosurgery for cerebral metastases has to be considered alongside the possibility of conventional surgery and radiotherapy. Conventional open surgery may be the initial therapy of choice for a patient suffering a lot of intracranial pressure caused by a large metastatic tumour on the surface of the brain. Such surgery decompresses the problem and radiotherapy then follows. Radiosurgery may be useful for deep single metastases where conventional radiotherapy has failed or is not perceived to be likely to eliminate the problem. Once again, the decision on the most appropriate treatment option is based on the individual’s problems.
Medical treatment can be highly effective too. Chemotherapy can cure primary brain germ cell tumours and lymphomas, backed up by good radiotherapy. Gliomas respond to temozolomide and nitrosourea based chemotherapy regimens; others are being trialled. Dopamine agonists shrink prolactinomas and reduce growth hormone secretion in acromegaly.
Our long experience with tumours of the brain and spinal cord, and the expert surgeons and histopathologists, who form an integral part of the team, all have helped improve the outlook for patients with brain and spine tumours considerably in the last decade.