Treatment of brain tumours

Fortunately the treatment of gliomas is common to all three subtypes and depends more on grade than whether the disease is an astrocytoma, ependymoma or oligodendroglioma.

 

The first and best therapy is a surgical debulking of as much tumour as possible, without causing irrevocable neurological damage. The problem of normal and critical surrounding functioning brain is the reason that complete resection of gliomas is impossible. Before taking the patient to theatre the surgeon may well wish the patient to have an initial period on potent steroid therapy. This serves to reduce the oedema (‘water-logging’) that surrounds every glioma (more so in higher grade tumours) and renders the patient in better neurological condition to undergo operation.

 

The extent of surgery will depend on the situation of the growth. For example, in the non-dominant frontal lobe (the right frontal lobe in right handed people), it is often safe to perform a major debulking operation, whereas in the middle of the dominant hemisphere such a radical debulking could render the patient paralysed down his dominant right side and to loose speech (aphasia).

Occasionally the surgeon will have a radical attempt to resect a known single brain metastasis, but will not risk much neurological damage to do so, as radiation therapy can take over where the surgery has stopped. Nevertheless, where the patient is in good clinical condition (i.e not about to succumb to cancer progression in the rest of the body) then the results of surgical removal of an ostensibly isolated brain metastasis followed by brain radiotherapy are better than radiotherapy alone.

Surgery is the therapy of choice for meningiomas and for pituitary tumours (the surgical access to the latter being often via the nasal cavity (the trans-sphenoidal route) with the intention of cure. Similarly surgery is the first therapy for craniopharyngiomas but cure without post-operative radiotherapy is less readily achieved.

 

Surgery is often (but not invariably vide infra) recommended for acoustic neuromas with the intention of complete removal and cure; hearing preservation microsurgical operations are now routine but still formidable posterior craniotomies.

 

Following surgery the need for other therapy is discussed. In most gliomas this is a routine course of post-operative radiotherapy carefully delivered in small daily doses (as this is the kindest way to deliver radiation to high dose without harming the normal nervous system) over a period of six weeks. Occasionally, low grade gliomas may be watched for a time before radiation therapy is recommended when the scan shows progression but for all high grade gliomas radiotherapy to high dosage is recommended unless the patients outlook is very poor.

 

The outlook (prognosis) in gliomas is predictable to some extent. Younger patient in good clinical condition (i.e no severe neurological damage due to the tumour) and lower grade tumours do well; conversely elderly patients presenting with high grade tumours and marked neurological deficit due to their disease do badly. Indeed, almost all grade 4 (glioblastoma multiforme) patients are dead by two years and the elderly high grade ones well before this time point. These facts temper the routine administration of radiotherapy to all patients given that it has at most a growth delaying effect in grade 4 patients and only cures a small fraction of grade 3 patients.

 

In younger patient of all grades the effects of radiotherapy are more pronounced and there is a definite group of grade 3 patients who are long term survivors and an increasing proportion of the low grade patients.

In older patients with higher grade tumours the decision for post-operative radiotherapy is taken in conjunction with the patient/family. Following radiotherapy, the patients loose some/a lot of hair and feel tired towards the end of the course.

Following the complete excision of a meningioma, there is no need for other therapy and the patient is cured in most cases. However, in 5% of cases the disease is malignant when looked at down the microscope (a subgroup of meningioma patients with a very poor outlook) and in other patients with benign meningiomas, but the position of which prevents complete removal, post-operative radiotherapy is advised. Radiotherapy is also advised for recurrent disease that cannot be wholly removed. The usual course of radiotherapy is a fractionated course over six weeks, as for gliomas.

However, for the incompletely resected benign growths of small size the modern focal radiation therapy method of stereotactic radiosurgery (the radio’surgery’ being a nickname as the technique is one of radiation therapy only) may be a good substitute for the conventionally fractionated course over six weeks.

 

In stereotactic radiosurgery, the patient is immobilised in a frame which encircles the head as does an equator encircle the globe (the head in this case). The patient then has a scan and this allows three dimensional co-ordinates – longitudes and latitudes continuing the former analogy or x,y,z co-ordinates in stereotactic language – to be obtained and for the x or gamma ray beams to then be concentrated on the growth.

 

Such is the concentration of dose on the target region and the speed of dose ‘fall-off’ at the edge of the targeted tumour that it is possible to deliver obliteratively high single radiation doses to the tumour without over-irradiating the surrounding normal brain. The technique of stereotactic radiation therapy is becoming an increasingly important tool in the neuro-oncologist’s armamentarium.

The post-operative therapy of pituitary adenomas is individualised but certain general principles apply. Where the surgeon has radically resected the growth and there are no aggressive features (such as invasion into the sphenoid sinus for example) then the doctor may choose to watch and wait, scanning with MR at six to twelve monthly intervals.

 

Where there are aggressive features or evidence incomplete resection, or residual serum testing abnormalities in hormones (for the secreting tumours) then post-operative radiotherapy is advised and reduces the recurrence rate. Without radiotherapy, up to 40% of operated adenomas of the pituitary recur by ten years and so a policy of post-operative radiotherapy is essential. Similarly, the recurrence rate of craniopharyngioma following surgery alone is high; the achievement of complete resection is difficult in this disease because it has a sticky capsule that is difficult to strip from the very delicate indeed, underlying structures such as the hypothalamus. The addition of post-operative radiotherapy reduces the recurrence rate and is almost always recommended.

 

Acoustic neuromas may respond well to stereotactic radiosurgery and this has become a popular alternative to the operative approach in recent years with excellent control rates and hearing preservation rates comparable with the very best surgical series. It is not possible for very large tumours (say over 3 cm diameter) but for smaller growths it is the main alternative to surgery.

Chemotherapy has a limited place in the treatment of most brain tumours. Following surgical debulking and radiotherapy, the two most powerful therapies have been given and the addition of chemotherapy may help somewhat but it is not as strong as radiotherapy. If the traditional drugs that are active against gliomas are: nitrosoureas (BCNU,CCNU and Methyl-CCNU), procarbazine and vincristine.

 

Recently a drug called temozolamide has been shown to be active in high grade gliomas and occasionally platinum analogues. It is common to deliver a course of these drugs either after the radiotherapy course or at the time of relapse to try to prolong life in patients whose general condition warrants such an attempt.