Doctors often prescribe radiation therapy combined with surgery to treat a brain tumor called a meningioma that begins in the protective membranes surrounding the brain. But the side effects of radiation can be serious, including memory loss and cognitive decline. It is therefore important to know which patients really need it.
Now, researchers at UC San Francisco and Northwestern Medicine, in collaboration with 10 other medical centers, have found a highly accurate way to predict the best treatment for patients based on gene expression patterns – which genes are turned on and off – in their tumors.
Screening tumors using this new approach could change treatment for nearly one in three people with meningioma, the most common form of brain tumor diagnosed in 42,000 Americans each year. Unlike other brain tumors, meningiomas occur most often in female, black, and older patients.
In an article published on November 9, 2023 in Natural medicinethe team concluded that only 1 in 5 patients with low-grade tumors (the least likely to grow back) might need radiation therapy, while about 2 in 5 patients with higher-grade tumors might be better off lotis without radiotherapy, based on the results of the new study. gene expression assay.
“There has been a lot of controversy in the field about who should receive radiation therapy and who should not,” said David Raleigh, MD, PhD, a radiation oncologist at the UCSF Brain Tumor Center and author principal of the study. with Stephen Magill, MD, PhD, assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine. “Our biomarker eliminates the guessing game and shows us which patients are likely to benefit from radiotherapy and which may experience toxicity and possibly no benefit from radiotherapy.”
From microscopes to molecules
Because meningiomas grow slowly, a patient may be unaware of their tumor until they begin to experience neurological symptoms like numbness, vision loss, or personality changes. There is no pharmaceutical treatment, so doctors use surgery to remove the tumor and radiotherapy to stop it from growing back. Doctors treat these tumors based on World Health Organization guidelines, which classify them based on their severity.
Pathologists currently classify meningiomas by examining them under a microscope for features that indicate whether they can grow back, a system that is very good but not perfect. Patients with grade 1 tumors generally do not receive radiation therapy if their tumors can be completely removed during surgery. However, in approximately 20% of cases, tumors recur. People with grade 2 and 3 tumors, which are much more aggressive and more likely to grow back after surgery, are often treated with radiation therapy after surgery. It’s unclear how many of these patients, especially those with grade 2 tumors, actually need radiation therapy.
Raleigh, along with Magill and lead author William Chen, MD, decided to examine the classification of tumors by which of their genes are turned on and off, thus offering clues about how aggressive they are.
“Gene expression tests like this, which analyze a small number of genes at a time, are widely available for breast, prostate and some other cancers, and they have proven to be a very accurate alternative and inexpensive to other types of tests,” Chen says.
How to turn guesses into answers
Raleigh and Chen and their multidisciplinary team suspected that gene expression could more accurately identify patients who would benefit from radiation therapy. Using samples from 1,856 meningioma patients at 12 medical centers in the United States, Europe and Hong Kong, the Raleigh team developed a set of 34 genes whose gene expression patterns had the potential to predict tumor recurrence.
A fifth of grade 1 tumors — the same number that grow back after surgery — expressed the patterns that the Raleigh team said could predict tumor regrowth. This fraction of patients can benefit from radiotherapy. The researchers also found that two-fifths of patients with grade 2 and 3 tumors did not have recurrence, which could also be predicted by tumor gene expression.
“When to proceed with additional surgery, radiation therapy, or just observe a small residual meningioma is not always clear,” Magill said. “This test adds information that can allow us to tailor our surgical and radiological approach to provide the best outcomes for each patient and maximize both quality and quantity of life.”
The team’s next step is to test this approach in two clinical trials currently under development.
Funding: This study was supported by grants from the NIH (P50 CA097257, P50 CA221747, U01 CA180868, U10 CA180822, R01 CA262311, F32 CA213944, F30 CA246808, T32 GM007618) and philanthropy. For a full list of funders, please see the study.
