Known as one of the most aggressive forms of cancer, glioblastoma multiforme, also known as GBM, is a cancer in the brain and affects around 250,000 individuals worldwide on an annual basis.

Naturally, many ask whether there are ways to prevent this form of cancer from attacking the individual. Dismally, the answer to this is not positive as it effectively cannot really be avoided. Having said this, research shows that there are circumstances that increase the risk of developing this type of cancer.

Among others, these include (a) previous exposure to radiation therapy/ionising radiation, (b) history of other forms of cancer, (c) being male and over the age of 50 and (d) having chromosomal abnormalities on certain chromosomes. Additionally, as in the case of many other forms of illnesses, it comes as no surprise that stress, in particular of a chronic nature, may be the cause of the promotion of glioma growth.

Pathogenesis of the disease

In this malignant, grade 4 tumour (a fast-growing and aggressive tumour), a large portion of cells are mutating and continually reproducing at any given time. They continue to divide uncontrollably, invading even the healthy cells. Nourishing these ‘bad’ cells is an ample and abnormal supply of blood. Moreover, they are capable of infiltrating and invading nearby spaces of the brain to even crossing the corpus callosum and entering the opposite brain hemisphere.

Initially, these tumours tend to be slow growing, however, they can rapidly and progressively become extremely aggressive. The presenting patient may be complaining of symptoms suggestive of a glioblastoma, such as headaches, blurred vision, seizures, changes in speech, personality and possibly mental function. The gold standard for imaging and detecting this type of tumour is MRI (magnetic resonance imaging). For this diagnosis, this modality would generally show a heterogenous mass in the white matter of the brain with surrounding oedema.

Current treatment options

Although the course of treatment may differ between individuals, currently, the standard treatment options for a newly diagnosed glioblastoma include the resection of the maximum amount of the tumour (unless inoperable) followed by concurrent chemoradiation. The chemotherapy (usually temozolomide) and radiotherapy usually take around six-and-a-half weeks. The latter aids in slowing down the growth of the residual tumour post-surgery and eliminating as much of the tumour as possible. Both are used in conjunction to increase the efficacy of treatment.

As expected, a more extensive surgical resection brings along a longer life expectancy, however, care is taken to avoid resecting too much of the normal tissue as this would, in turn, affect brain function and may also bring a change in the individual’s personality.

Palliative care may also be considered in these cases in order to improve the individual’s quality of life by enhancing their symptom management while also providing them with psychological support. Steroids and other medications may also be administered to reduce swelling, presenting symptoms such as nausea and, in some cases, seizures.

What makes cure so difficult?

First and foremost, it is practically impossible to resect the whole mass without causing any damage to normal brain tissue. In fact, in most cases, partial removal or debulking is performed in order to preserve brain tissue and reduce the risk of neurological damage. As a result of this, the entirety of the tumour is not removed. Additionally, despite surgical resection, the individual may still be burdened with the risk of recurrence.

A trial vaccine for patients suffering from aggressive brain cancers is currently in its third phase of trials

With its finger-like tentacles extending away from the primary mass, a glioblastoma can invade other parts of the brain, making it even more difficult to treat and, thus, cure. Furthermore, certain drugs that may block this tumour growth cannot be used due to the blood-brain barrier. This would prevent the drugs from entering the brain, rendering them ineffective.

Besides, the chemotherapy drug that does in fact cross the blood-brain barrier – temozolomide − may not be as promising for some patients. This is because many glioblastomas produce a protein known as MGMT which tends to limit the effects of temozolomide, rendering this treatment ineffective. Unfortunately, with glioblastoma being such an aggressive cancer, the aforementioned treatment might still be insufficient to be able to actually treat the tumour completely.

Dismally, certain patients, in particular the elderly, may be unable to tolerate the aggressive treatment and side effects chemotherapy and radiotherapy bring along with them, leaving their odds for a successful recovery to be even poorer.

Hope for the future

Clinical trials are ongoing, hoping to improve on the patients’ prognosis, which currently stands at merely up to 12-14 months, with a 40 per cent survival in the first year of diagnosis and only 10 per cent in five years.

Tumour-treating fields

In this treatment modality, alternating electric fields are delivered using 200kHz frequency via electrodes applied to the scalp. It is locoregional and would thus help in sparing normal tissue. Research has shown that this treatment arrests cell division and destroys tumour cells through various mechanisms.

Immunotherapy

A therapy which uses the body’s immune system to fight off cancer. In the US, trials are being performed with oncolytic viruses which are specially engineered viruses that preferentially infect and kill cancer cells, while also stimulating an immune response to eradicate any remaining tumour. This virus is directly injected into the tumour so as to overcome the issue of the blood-brain barrier.

Brain cancer vaccine

A trial vaccine for patients suffering from aggressive brain cancers is currently in its third phase of trials. This vaccine would aid the body’s immune system recognise and attack the cancer cells, prolonging life to these patients. It combines proteins from the patient’s tumour with their white blood cells  and, in a way, allows these white cells to recognise the tumour as something it needs to fight against and destroy. Thus, this vaccine is considered to be a form of immunotherapy.

Conclusion

Further development in research has proven to provide a deeper understanding on how glioblastoma develops, giving rise to further insight into opportunities to control and, hopefully, eradicate this deadly disease.

Amy Xuereb is a radiographer with a special interest in the field of oncology.