Podcast: Which method of determining MGMT promoter methylation best predicts survival in people with glioblastoma treated with temozolomide?

In March 2021, the Cochrane Neuro-Oncology Group published a series of eight new systematic reviews on priority topics for the brain tumour community. These were selected from the most important unanswered questions identified by patients, the public and practitioners. In this podcast, Kathreena Kurian from the University of Bristol in the UK tells us about one of the reviews, which looked at the evidence on tests that might help to predict survival in patients who have received chemotherapy for glioblastoma.

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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 systematic reviews on priority topics for the brain tumour community. These were selected from the most important unanswered questions identified by patients, the public and practitioners. In this podcast, Kathreena Kurian from the University of Bristol in the UK tells us about one of the reviews, which looked at the evidence on tests that might help to predict survival in patients who have received chemotherapy for glioblastoma.

Kathreena: Glioblastoma is a very aggressive type of brain cancer and people with it are usually treated with surgical removal of the tumour followed by radiotherapy, chemotherapy, or both. The standard chemotherapy is a medicine called temozolomide. Some glioblastoma tumours have a particular modification in their genetic code, or DNA, and knowing whether a person has this modification is useful to predict how long the person may live after their diagnosis with cancer and how they may respond to temozolomide. This modification is known as 'methylation of the MGMT promoter region' and it can also affect the way that MGMT is made and modified. There are many ways to work out whether a tumour has this modification and we did this review to try to work out which method is best.
We identified 32 studies comparing different ways to measure whether the MGMT promoter region is methylated. The main three methods are called 'methylation‐specific polymerase chain reaction (PCR),' 'pyrosequencing' (both of which look directly at the MGMT promoter region) and 'immunohistochemistry' (which looks at MGMT protein expression). Methylation‐specific PCR and pyrosequencing can be carried out by targeting different parts of the tumour DNA, and pyrosequencing can be performed using different cut‐off thresholds to determine whether a tumour is methylated or unmethylated. 
Looking at the research done to date, we found that methylation‐specific PCR and pyrosequencing are better at predicting overall survival than immunohistochemistry. However, we did not identify very clear signals in terms of the best parts of the DNA to target or which are the best cut‐off thresholds. We also found some evidence that pyrosequencing may be better than methylation‐specific PCR at predicting overall survival, depending on the DNA targets and cut‐off thresholds used. Our review will also help clinicians interested in the most frequent DNA targets used in methylation‐specific PCR and pyrosequencing and the cut‐off thresholds used in pyrosequencing, although, as I mentioned, it is currently unclear which of these is best.

Monaz: For more details about how these tests might help in the treatment of patients with glioblastoma, you can read it online. It's available at Cochrane Library dot com, with a simple search for 'MGMT promoter glioblastoma'.

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