Doctors discover a simple method to predict the risk of brain tumour recurrence
The risk of a brain tumour recurring can be predicted more accurately by counting the number of immune cells in the tumour under a microscope. These are the findings from research conducted by LUMC, Erasmus MC and Heidelberg University.
Meningioma is the most common type of brain tumour. It does not develop in the brain tissue itself but on the inside of the meninges, the membranes that surround the brain. In most cases, a meningioma is benign. However, it can still cause symptoms, such as headaches and loss of bodily functions. Neurosurgeon Eelke Bos from Erasmus MC explains: ‘The tumour cells of a meningioma do not usually grow into surrounding tissue. That is why we often call it a benign tumour. However, as the tumour grows, it presses on the brain, causing symptoms such as headaches and loss of bodily functions. So there is nothing benign about these “benign” brain tumours.’
Treatment usually involves surgery, radiation therapy or a combination of both. Radiation can also lead to side effects that significantly affect daily life, including concentration problems, forgetfulness and fatigue. In addition, some meningiomas return over time, causing lasting uncertainty for many patients.
Difficult to predict
Doctors divide tumours into risk groups. For most tumours, this classification helps predict how severe the disease course will be and how likely the tumour is to return. In many cases, this prediction remains stable over time: patients in a low-risk group usually stay in that group. However, with meningiomas, things work differently. Even tumours classified as low-risk can still recur.
Niek Maas, a neuropathologist at LUMC and Erasmus MC, explains: ‘For the past ten years, we have been wondering whether we can reduce this uncertainty. At present, risk assessment often involves analysing the tumour’s DNA profile. This requires advanced and expensive techniques. We therefore wanted not only to improve risk assessment but also to explore whether this could be done in an affordable way, so it can be applied worldwide.’
The results of the research by Maas, Bos and their colleagues were recently published in Nature Genetics.
Unique collection in Heidelberg
This research required a large number of tumour samples. Although meningiomas are the most common type of brain tumour, they are still relatively rare. In the Netherlands, around 1,600 people are diagnosed with a meningioma each year, and only a small proportion of them undergo surgery. Through a collaboration with Professor Felix Sahm of Heidelberg University, the research team gained access to DNA profiles from the tumours of 4,500 patients. Maas completed part of his pathology training in Heidelberg and continues to work closely with Sahm on a daily basis.
‘Worldwide, patients with meningiomas undergo surgery after which the tumour’s DNA profile is analysed,’ Maas continues. ‘These profiles are sent to Heidelberg for a specialised calculation. Some patients have given permission for their data to be used for research. As a result, Heidelberg has built the largest collection of genetic data on meningiomas worldwide, which is a real treasure trove for research.’
DNA profile of tumours
The DNA profile of a tumour shows which genes are present and which genes are switched on or off. This information is used worldwide to classify tumours into risk groups. Thanks to the large dataset in Heidelberg, the researchers discovered that these classifications do not have clear boundaries in meningiomas. ‘We have shown that there are no strict divisions between the different risk groups,’ Maas explains. ‘The groups overlap. They are not separate categories but rather a sliding scale.’
‘With a simple and inexpensive technique that pathologists already use every day, it is now possible to make a better risk assessment, even in countries where advanced technologies are not available.’
Under the microscope
In addition to the DNA profiles, the researchers also examined the tumour tissue under the microscope. This yielded new insights. ‘The microscopic images taught us a great deal,’ says Maas. ‘It is not so much the tumour itself but rather the immune cells within the tumour that play an important role. Low-risk tumours contain more immune cells, and these cells are dormant. In high-risk tumours, we saw far fewer immune cells, and those that are present are active.’
The images also showed that a single tumour sample can contain areas with many immune cells as well as areas with very few, sometimes just millimetres apart. ‘This finding confirms that risk profiles overlap and are not clearly defined categories,’ Maas adds.
Simple and affordable solution
While the microscope revealed that risk can vary greatly within a single tumour, this finding also points to a practical solution. The risk of recurrence can be predicted more accurately by simply counting immune cells than by using the current microscopic assessment.
‘With a simple and inexpensive technique that pathologists already use every day, it’s now possible make a better risk assessment, even in countries where advanced technologies are not available,’ says Maas. It is not yet clear whether counting immune cells can replace the more expensive DNA tests in the Netherlands. ‘Further research is needed to compare the accuracy of these predictions. We will be working on this intensively in the coming years.’
Photo: Neuropathologist Niek Maas. Niek works at the LUMC and the Erasmus MC.