Researchers at UMC Utrecht have developed a method to diagnose a rare form of brain cancer faster and more safely. In some cases, this allows doctors to replace a brain surgery-based diagnosis with a lumbar puncture. As a result, patients can start the appropriate treatment sooner and may avoid an invasive operation with a risk of complications.
The method focuses on primary central nervous system lymphoma (PCNSL), a rare form of lymphoma that is diagnosed in approximately 120 people in the Netherlands each year. Rapid diagnosis is essential for this type of cancer, as it is treated differently from most brain tumors: with chemotherapy rather than surgical removal.
Currently, doctors often diagnose the disease using a brain biopsy, in which a small piece of tissue is removed during brain surgery and examined. This procedure carries risks. Four to eight percent of patients experience serious complications, such as infection or intracranial bleeding.
Neurologist Tom Snijders and PhD candidate Sjo van Rooij are therefore working to improve diagnosis using a lumbar puncture. In this procedure, doctors collect a small amount of cerebrospinal fluid.
“With this method, we used to be able to diagnose brain lymphoma in only one out of ten patients,” says Van Rooij. “Thanks to this research, that has now increased to about half of the patients.” For this group, a brain biopsy may no longer be necessary.
For the diagnosis, the researchers used a combination of known biomarkers characteristic of this type of cancer. These include a mutation in cell-free DNA, DNA fragments from tumor cells in the cerebrospinal fluid, and cytokines, which are signaling molecules of the immune system.
By combining these markers, the researchers were able to diagnose brain lymphoma with certainty in about half of the patients.
“We are the first to validate that this combination works reliably in patients suspected of having brain lymphoma,” says Van Rooij. “In addition, we tested our method before the diagnosis was known,” adds Snijders. “This makes it more representative of real clinical practice.”
The new method not only reduces the number of high-risk biopsies but also enables faster treatment. “This is particularly important for brain lymphoma,” says Snijders. “For most brain tumors, we can only slow down the disease, but with the right treatment, sixty to seventy percent of patients with brain lymphoma can be cured.”
On average, patients receive a lumbar puncture six days after the first symptoms, whereas a biopsy often takes more than two weeks. This time gain can help prevent permanent brain damage.
The method also offers practical advantages. Unlike a brain biopsy, a lumbar puncture can be performed in hospitals without a neurosurgeon. This means patients can more often be diagnosed in a local hospital, reducing the burden on them.
The researchers are continuing to improve the method. “Not all brain lymphomas have the same profile, and lymphomas with different biomarker combinations cannot yet be diagnosed using this approach,” says Snijders. For some patients, a biopsy will therefore still be necessary for the time being. By adding additional mutations in cell-free DNA to the analysis, the researchers hope to make the test more broadly applicable in the future.
For widespread implementation, technical integration is also required. Not all hospitals have access to the necessary equipment, and a standardized approach is essential. “This requires close collaboration between neuro-oncology centers in the Netherlands,” says Van Rooij. “We are already working with several centers to make this test available in clinical practice as soon as possible.”
This study was conducted in close collaboration with neurologist Peter Wessels and St. Antonius Hospital, with support from the Annie van Koeverden Foundation. Radboudumc, Amsterdam UMC and Erasmus MC also contributed to the study. This multi-centre collaboration enabled the researchers to develop and evaluate the method in clinical practice.
