GLIOBLASTOMA

Glioblastoma (GBM) is a type of aggressive brain cancer that develops and spreads quickly, often causing pressure inside the brain. In Australia, roughly 1,900 people are diagnosed with brain cancer each year, with approximately 1,500 dying from the condition. Every year, around 6 or 7 people are impacted for every 100,000 people in Australia.

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It is unknown why some people get GBM, however it is critical to understand that GBM is not inherited and cannot be passed down to your offspring. There is no proof that GBM was caused by any dietary factors, activities, potential exposure, or anything you did.

GBM is classified into two categories.

• Primary (or de novo) GBM is the more common of the two forms, developing spontaneously within the brain (i.e., for no apparent reason) and accounting for 90% of cases observed in clinical practise. They carry the genetic designation of IDH wild-type tumours. There is a small male predominance (men are 1.3 times more likely to be affected), and affected persons are often older at the time of diagnosis (mean age around 60 years).

• Secondary GBM develops from slower developing tumours that become into aggressive tumours over time. They carry the genetic designation IDH mutant. These tumours are less common and affect younger individuals (mean age: 30-50 years), with no evident sex preference.

 

GBM has been proven in studies to be genetically heterogeneous (i.e., have different types of genetic information and expression). This means that the cells within the tumour are not all the same type and may express and behave differently. As a result, while some tumours respond well to traditional treatment, others continue to grow despite extensive surgery and therapy.

 

 

Natural History

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Predicting survival (prognosis) is at best an estimate and can be highly variable as this depends on your age, the genetic profile of the tumour, where it’s located, and how well you might respond to treatment. It is important to remember that statistics and averages cannot tell you what will happen to you specifically. This is why prognosis is often an ongoing process, revised at different stages in your journey.

The average survival time following diagnosis of GBM is 12 to 18 months. Only 1 in 4 patients survive more than one year, and only 1 in 20 patients survive more than 5 years.

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Factors that may affect your overall survival include:

1. Age – younger patients have better chance of survival

2. Genetic profile of the tumour – certain tumour subtypes respond better to chemotherapy and radiation treatment than others.

3. Your functional performance status – in general, if you remain fit and well during the course of your treatment, you are likely to do better and survive longer.

4. Extent of disease – tumour that are confined to one part of the brain behave better than those that are diffuse or are located in multiple locations in the brain.  

 

Tumour recurrence is unavoidable. In ninety percent of instances, recurrence occurs within two centimetres of the original tumour margin. Recurrence can occur between 4 and 14 months after initial diagnosis, either during or after initial therapy. Untreated recurrent GBM results in mortality within 2 to 7 months.

 

 

Treatment Options

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Since 2005, the gold standard (optimal) treatment for individuals with GBM has been surgery to remove as much of the tumour as feasible, followed by concomitant chemotherapy and radiation therapy after the surgical site has healed.

 

Surgery

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Surgery is generally required at the time of diagnosis for one or more of the following reasons:

1. To obtain tissue for formal laboratory diagnosis of the tumour

2. To relieve pressure inside the brain

3. To improve symptoms by removing the mass and reducing swelling inside the brain

4. To reduce tumour burden so that adjuvant radiotherapy and chemotherapy can be more effective

5. To provide additional tissue for research and clinical trial inclusion

 

Due to the infiltrative nature of the disease, total resection is challenging, and the ability to completely resect the tumour is primarily dependent on its location in the brain. If a brain tumour is located in a deep brain region or near a "essential" (eloquent) brain region, complete resection is less likely due to the greater risk of triggering a stroke during surgery.

A meta-analysis of 41,117 GBM patients revealed that the greater the amount of tumour removed during the initial operation, the higher the overall survival rate and the lower the risk of tumour recurrence. In general, it is acceptable to remove at least 70% of the tumour.

 

Concurrent chemoradiation therapy

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Chemotherapy and radiation therapy are used to inhibit the growth of any cancer cells that cannot be eliminated by surgery. The most common chemotherapy medicine is Temozolomide (TMZ), which prevents cancer cells from producing new DNA. Hence, if cancer cells cannot produce DNA, they cannot divide into new cancer cells, and the tumour cannot develop. It is believed that TMZ makes tumour cells more sensitive to radiation and is typically administered for a further six months after radiotherapy has concluded.

It is well recognised that radiation prolongs survival in GBM patients. Radiotherapy reduces the risk of death within 12 months by 19%, according to a meta-analysis of six randomised controlled trials.

 

 

 

Some useful references

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1. Michaelsen SR, Christensen IJ, Grunnet K, et al. Clinical variables serve as prognostic factors in a model for survival from glioblastoma multiforme: an observational study of a cohort of consecutive non-selected patients from a single institution. BMC Cancer. 2013;13(1):402.

2. van Linde ME, Brahm CG, de Witt Hamer PC, et al. Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis. Journal of Neuro-Oncology. 2017;135(1):183-192.

3. Bette S, Barz M, Huber T, et al. Retrospective analysis of radiological recurrence patterns in glioblastoma, their prognostic value and association to postoperative infarct volume. Scientific Reports. 2018;8(1):4561.

4. Park C-K, Kim JH, Nam D-H, et al. A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma. Neuro-oncology. 2013;15(8):1096-1101.

5. Tully PA, Gogos AJ, Love C, Liew D, Drummond KJ, Morokoff AP. Reoperation for recurrent glioblastoma and its association with survival benefit. Neurosurgery. 2016;79(5):678-689.

6. Lu VM, Jue TR, McDonald KL, Rovin RA. The survival effect of repeat surgery at glioblastoma recurrence and its trend: A systematic review and meta-analysis. World Neurosurgery. 2018; 115:453-459.