Podcast: Long-term effects of radiotherapy for glioma treatment on brain functioning

In March 2021, the Cochrane Neuro-Oncology Group published a series of eight new complex systematic reviews on priority topics for the brain tumour community. These were selected from the most important unanswered questions identified by people in this area using James Lind Alliance Priority Setting Partnership methods, which bring together patients and the public with practitioners. In this podcast, one of the Group’s consumer representatives, Helen Bulbeck, talks with author Robin Grant, a consultant neurologist involved in the Edinburgh Centre for Neuro-Oncology in the UK about the review of the long-term neurocognitive and other side effects of using radiotherapy as a treatment for glioma.

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Monaz: Hello, I'm Monaz Mehta, editor in the Cochrane Editorial and Methods department. In March 2021, the Cochrane Neuro-Oncology Group published a series of eight new complex systematic reviews on priority topics for the brain tumour community. These were selected from the most important unanswered questions identified by people in this area using James Lind Alliance Priority Setting Partnership methods, which bring together patients and the public with practitioners. In this podcast, one of the Group's consumer representatives, Helen Bulbeck, talks with author Robin Grant, a consultant neurologist involved in the Edinburgh Centre for Neuro-Oncology in the UK about the review of the long-term neurocognitive and other side effects of using radiotherapy as a treatment for glioma.

Helen: Hello Robin, could you begin with one or two sentences about the neurocognitive side effects of radiotherapy. What are they and who gets them? 

Robin: Hello Helen. Radiotherapy can cause changes in the white and grey matter in the brain, around the area of treatment. These usually start a year or two after the radiotherapy, getting slowly worse as years go by. They cause slowing of speed of thought, multitasking and poor memory. The frequency and severity relate to how the radiotherapy is given and, the older the patient is, the sooner they tend to start. 

Helen: So, why is it important to have a review of this area?

Robin: We need to bring all the evidence together so that we can discuss this with patients and work with them to make the best decision for their treatment. For example, gliomas with low aggressive potential, called WHO grade 2 or grade 3, are associated with long-term survival, with most patients presenting with seizures but being otherwise well. Because grade 2 glioma grow very slowly, this means there is a balance between treating the tumour early with radiotherapy and chemotherapy or just monitoring it, treating any seizures and then treating the tumour at a later date. This is a reasonable approach because there is no evidence that early treatment influences overall survival for patients with this type of glioma. However, radiotherapy with or without chemotherapy does improve progression free survival, and so we need to know more about the side effects to reach a balanced decision. 

Helen: I guess that's where your systematic review comes in. What did you do for it?

Robin: Our over-arching aim was to evaluate the long‐term neurocognitive and other side effects of radiotherapy versus no radiotherapy; radiotherapy versus chemotherapy; radiotherapy with chemotherapy versus radiotherapy alone, and different types and doses of radiotherapy in young people and adults with cerebral glioma.
We looked at randomised and non‐randomised trials  and controlled before‐and‐after studies where neurocognitive outcomes were assessed two or more years after the patient's treatment.

Helen: Did you find the evidence you needed and what does it tell us?

Robin: We found nine randomised trials involving over 2,400 people: 7 trials were in people with grade 2 glioma and two were in people with grade 3 disease. Because of the nature of brain cancer, many people did not complete their follow-up assessments in the trials and final data were available for only a minority of people, but some conclusions can be drawn.
For instance, we can say that early radiotherapy for lower grade gliomas with a good prognosis may increase the risk of neurocognitive side effects five and more years after treatment. One study showed that, after 12 years, cognitive impairment was almost twice as common in the group given radiotherapy early but another study showed no significant difference at 5 years. There were no differences between low dose and higher dose radiotherapy by 2-5 years; but focal radiotherapy seemed less likely than conventional radiotherapy to cause neuro-cognitive problems at 5 years.
Turning to the combination of radiotherapy and chemotherapy: radiotherapy followed by chemotherapy did not show differences compared with radiotherapy alone between 2-5 years, but perhaps more time is required before this side effect becomes more apparent and severe.

Helen: What about the benefits of radiotherapy and chemotherapy for these lower grade tumours?

Robin: We didn't look at this in our review but there are ongoing trials looking at whether there are survival benefits from early treatment in cases with certain molecular markers. However, we do know that where there is persisting or recurrent tumour in grade 2 glioma, chemo-radiation is better at extending survival than radiotherapy alone.

Helen: Overall, what's your take-home message?

Robin: There's still a lot of uncertainty about the best time to use radiotherapy without chemotherapy in these lower grade gliomas. Our hope is that the new treatments will extend survival, but the worry is that they will be accompanied with more serious neuro-cognitive side effects in those people who survive beyond 5 years. We need high quality randomised trials to resolve this and neurocognitive assessment should be an integral part of long‐term follow‐up in trials involving radiotherapy for lower‐grade gliomas. Such trials should also assess other potential long‐term effects and evaluate costs and cost effectiveness.

Helen: Thanks Robin. If people would like to read the review, how can they get hold of it?

Robin: Thanks Helen. It's available online from Cochrane Library dot com. If people type 'neurocognitive side effects and glioma' in the search box, they'll see it near the top of the list.

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