Groundbreaking new brain cancer test has an 80% accuracy rate with no false positives

For decades, diagnosis of brain cancer has been medicine's most difficult and hazardous challenge. Simple imaging such as MRI scans may reveal a suspicious-looking lesion, but the only sure way to prove cancer has been through brain biopsy. The procedure involves cutting into delicate tissue and poses tremendous risks.

Now, scientists have developed a groundbreaking test that could reduce the need for, or eliminate entirely, such intrusive methods.

Scientists at Johns Hopkins Medicine have created a test called CSF-BAM, or cerebrospinal fluid–B/T cell receptor, aneuploidy and mutation. The test is designed to analyze tiny samples of cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord.

A biopsy entails removing tissue samples, while drawing samples of CSF is much less invasive, usually involving a lumbar puncture. By sampling genetic and immune system clues directly from the fluid, the test can diagnose brain cancer with unheralded accuracy.

The approach is more than looking for a single signal. Instead, it looks for many biological signs. These are mutations in DNA that have arisen from the tumor, alteration of the number of chromosomes known as aneuploidy, and patterns of receptors of immune cells such as T cells and B cells. Together, this collection of markers paints a detailed picture of what happens in the brain.

The CSF-BAM test was used on more than 200 fluid samples, including patients who had high-grade gliomas, medulloblastomas, metastatic cancer, and central nervous system lymphoma.

In examples involving the most aggressive varieties, the test scored a sensitivity rate of greater than 80%. That means in more than four out of five cases, it correctly identified the cancer. No less noteworthy, it scored 100% specificity, meaning that not a single cancer-free patient was falsely diagnosed with the disease.

Those results make CSF-BAM different from other strategies. Traditional cytology, in which cells within the liquid are examined under a microscope by pathologists, may not catch small or subtle differences at times. Alone, imaging is also not reliable since benign lesions can mimic tumors, at least sometimes. A test combining a number of lines of evidence offers a safer and more accurate method of guiding medical decisions.

The benefits of CSF-BAM extend beyond the detection of cancer. The test also reveals an understanding of how the immune system responds to disease within the brain.

By following the patterns of receptors from T and B cells in the CSF, researchers are able to distinguish between cancer and noncancer with even greater precision. Such immune signatures are the essence of context. Not only do they inform us as to whether or not there is cancer, but also how the defense system of the brain is reacting.

"This study shows how much more we can know by examining multiple analytes as a group," said Dr. Chetan Bettegowda, a senior author. "The potential for finding cancers with high specificity and learning about the immune status of the brain could be an important advance in the management of patients with brain tumors."

The immune profile can also help researchers discover why certain cancers progress more quickly than others, or why some individuals respond better to therapy. Over time, such knowledge could be used to develop new treatments designed to stimulate the body's own anti-tumor immunity.

Brain biopsies remain a dangerous but standard step in the diagnostic process. Surgeons must navigate around sensitive parts of the brain, risking infection, bleeding, or neurological damage. In others, lesions are located in areas too dangerous to try at all. For those patients, doubt may remain for months.

"Most brain lesion patients undergo very invasive diagnosis to diagnose cancer," says Dr. Christopher Douville, a second senior author. "A device like this would let us make better decisions on who really needs a biopsy and who doesn't." This shift may not only save medical risk but also yield faster answers to desperate patients and families.

One of CSF-BAM's more important discoveries is that none of the markers is individually robust. A cancer type can have a mutation in one but not in another. There is aneuploidy in cancer, but also in noncancerous illnesses. Even in the immune response, responses are deceptive when viewed in isolation. By layering these three types of evidence on top of each other, the test disqualifies false positives and yields a better result.

Researchers emphasize that the method's power is in this multi-analyte strategy. Statistically, sensitivity is a measure of how well a test identifies true positives, and specificity is a measure of how well it resists false positives. That more than 80% sensitivity is combined with perfect specificity implies an excellent balance—detecting most cancer yet never falsely labeling a healthy patient.

While CSF-BAM is not yet proven, researchers are optimistic that it will be used in clinics. It would be especially helpful when standard imaging is uncertain or cytology is unable to detect cancer cells in the fluid. It also can be employed to monitor patients post-treatment to see an early sign of relapse or resistance to treatment.

One day, this test may allow oncologists to personalize treatment even more. If oncologists understand not only whether or not a tumor is present, but also what particular genetic mutations and immune system reactions are in place, treatment can be specifically targeted to an individual's biology.

National Institutes of Health grants supported the development of this test.

For patients and families in the frightening reality of brain cancer, every new tool matters. The current process typically entails waiting, doubt, and risks related to surgery. A diagnostic that is capable of offering clean-cut answers from a simple fluid sample offers a safer exit.

The scientists note that additional research is needed before CSF-BAM becomes available on a large scale. There will be clinical trials which will test its consistency in larger and more diverse groups of patients. However, the initial findings are promising, and the advantages are clear.

As Dr. Bettegowda describes it, combining genetic and immune signals provides a better snapshot of what is happening in the brain. It says more to doctors than yes or no. It is a guide to assist them in making decisions, avoid risks, and pave the way for more personalized treatment. For an intricate and lethal disease like brain cancer, that is no small improvement.

Research findings are available online in the journal Cancer Discovery.

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