Doctors discover a simple method to predict the risk of brain tumor recurrence
Onderzoek image: LUMC
The risk of recurrence of a brain tumor can be predicted more accurately by counting the number of immune cells in the tumor 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 tumor. 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 tumor cells of a meningioma usually do not grow into surrounding tissue. That is why we often call it a benign tumor. However, as the tumor grows, it presses on the brain and causes symptoms such as headaches and loss of bodily functions. So, there is nothing benign about these ‘benign’ brain tumors.’
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, which causes lasting uncertainty for many patients.
Difficult to predict
Doctors divide tumors into risk groups. For most tumors, this classification helps predict how severe the disease course will be and how likely the tumor 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 tumors classified as low-risk can still recur.
Niek Maas, neuropathologist at LUMC and Erasmus MC, explains: ‘For the past ten years, we have been asking ourselves whether we can reduce this uncertainty. At present, risk assessment often involves analyzing the tumor’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 the scientific journal Nature Genetics.
Unique collection in Heidelberg
This research required a large number of tumor samples. Although meningiomas are the most common type of brain tumor, 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 tumors of 4,500 patients. Maas completed part of his pathology training in Heidelberg and continues to work closely with Sahm on a daily basis.
Maas continues: ‘Worldwide, patients with meningiomas undergo surgery after which the tumor’s DNA profile is analyzed. These profiles are sent to Heidelberg for a specialized 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 true treasure trove for research.’
Tumor DNA profiles
The DNA profile of a tumor shows which genes are present and which genes are switched on or off. This information is used worldwide to classify tumors into risk groups. Thanks to the large dataset in Heidelberg, the researchers discovered that these classifications do not have clear boundaries in meningiomas. Maas explains: ‘We have shown that there are no strict divisions between the different risk groups. The groups overlap. They are not separate categories, but rather a sliding scale.’
‘By using 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 tumor tissue under the microscope. This yielded new insights. Maas continues: ‘The microscopic images taught us a great deal. It is not so much the tumor itself, but mainly the immune cells within the tumor that play an important role. Low-risk tumors contain more immune cells, and these cells are dormant. In high-risk tumors, we saw far fewer immune cells, and those that are present are active.’
The images also showed that a single tumor sample can contain areas with many immune cells as well as areas with very few, sometimes just a few millimeters apart. Maas adds: ‘This finding confirms that risk profiles overlap and are not clearly defined categories.’
A simple and affordable solution
While the microscope revealed that risk can vary greatly within a single tumor, this finding also points to a practical solution. The risk of recurrence can be predicted more accurately by simply counting immune cells than by the current microscopic assessment.
Maas explains: ‘By using 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.’ 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 is working both at the LUMC and the Erasmus MC.