Glioblastoma: treatment and outlook

Glioblastoma is a tumour that starts in the support cells of the brain (glial cells) and spreads into the healthy tissue around it ^{[1, 2]}. Doctors grade brain tumours from 1 to 4; "grade 4" means the tumour is fast-growing and aggressive, both under the microscope and in its genetic changes ^[1]. Read: What is cancer grade? Grade versus stage

Since 2021, brain tumours have been diagnosed from both the appearance of the cells and the genetic changes in the tumour. The name "glioblastoma" is used only for gliomas without a mutation in the IDH gene; if certain genetic changes are found, the tumour counts as a glioblastoma even when it looks slow-growing under the microscope ^{[1, 2]}. The disease is seen mostly in middle-aged and older people ^[11]. In most patients no clear cause is found; only occasionally do inherited family conditions or previous radiotherapy to the head play a part, and there is no known way to prevent it ^[2]. To read about mobile phones, see Do mobile phones cause cancer?

The symptoms depend on where the tumour is. Because glioblastoma grows quickly, symptoms usually appear or get worse only a few weeks before diagnosis ^[2]. Common symptoms ^[2]:

• a new seizure in adulthood
• weakness or numbness on one side of the body, or new difficulty speaking or seeing
• changes in memory, thinking, behaviour or personality
• headache and nausea caused by raised pressure inside the head

In the year before diagnosis, most patients have only vague symptoms such as tiredness or headache ^[2]. Most headaches have a simple cause; to find out which symptoms you should show a doctor promptly, read: What are the symptoms of a brain tumour?

The main way to find the tumour is an MRI scan of the brain with contrast dye ^[2]. The diagnosis is confirmed by examining tumour tissue removed during surgery or by a needle biopsy; genetic tests such as IDH and MGMT are done on the same sample ^[2]. Before surgery, steroid medicines may be given to reduce the swelling around the tumour and its symptoms ^[2].

In patients aged 65 or over, shorter radiotherapy (about 3 weeks) with temozolomide tablets helped people live longer than radiotherapy alone, without worsening quality of life; the benefit was greater in tumours with a switched-off MGMT gene ^[8]. If the patient is older or their general health does not allow intensive treatment, radiotherapy alone (when MGMT is not switched off), temozolomide tablets alone (when MGMT is switched off) or supportive care alone to keep the patient comfortable are all reasonable choices ^{[2, 9]}. It is best for this decision to be made by the patient, family and care team together, based on the patient's own wishes. A guide for families: A guide for family members and caregivers of people with cancer.

Glioblastoma is a serious illness. With today's treatments it usually does not go away completely, and it often comes back, even after full treatment ^{[2, 7]}. But treatment helps people live longer:

• In the main study, with surgery and radiotherapy plus temozolomide tablets, about 1 in 4 patients lived more than 2 years, more than twice as many as with radiotherapy alone ^[4].
• After 5 years, about 1 in 10 of those who had the tablets were alive; most of these people had more favourable circumstances ^[5].
• Patients whose tumour had a switched-off MGMT gene benefited most from the tablets and lived longer ^[6].
• Adding the electric-field device to the tablets also helped people live longer ^[7].

These figures come from large groups and cannot predict exactly what will happen to any one person. Younger age, better general health, removal of more of the tumour and a switched-off MGMT gene are linked with longer survival ^{[2, 5, 6]}. Read more: What do cancer survival rates and life expectancy really mean?

Some grade 4 tumours have a mutation in the IDH gene. These tumours used to be called "IDH-mutant glioblastoma", but they are now called "astrocytoma, IDH-mutant, grade 4", because biologically they are a different disease ^{[1, 2]}:

• They are usually seen in younger people; in one study, patients with the mutation were typically around 30 years old and patients without it around 60 ^[11].
• They have a better outlook: in the same study, patients with the mutation lived about twice as long ^[11].
• They are usually treated with radiotherapy and temozolomide tablets, as for glioblastoma or grade 3 astrocytoma ^[9].

Read more about IDH-mutant gliomas: Brain tumours: IDH-mutant gliomas.

Most often the tumour comes back in the same place as before ^[7]. The choice of treatment depends on the patient's condition, where the tumour has come back and the treatments given before ^[2]:

• Another operation is always considered; it helps most when all of the visible tumour can be removed ^[2].
• Lomustine tablets, another chemotherapy medicine, are one of the main treatments at this stage ^{[2, 10]}. Adding the medicine bevacizumab to lomustine held back tumour growth for a while but did not help people live longer ^[10].
• Temozolomide tablets again, or radiotherapy (if radiotherapy has not been given before) are also options ^[2].

At this stage, supportive and palliative care to control symptoms and keep the patient comfortable matters a great deal.

Researchers are studying new treatments such as immunotherapy, cancer-killing viruses and targeted medicines; these treatments are not yet part of standard care ^[12]. So far, in large studies, the immunotherapy medicine nivolumab has not helped people with glioblastoma live longer than usual treatment ^[2]. The new naming of tumours in 2021 helps similar patients to be studied together in trials ^[12]. If you are interested, ask your doctor whether there is a suitable clinical trial for you.