Multi-analyte test accurately identifies brain cancers using small cerebrospinal fluid

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A novel, multi-analyte test developed by researchers at the Johns Hopkins Kimmel Cancer Center, its Ludwig Center and the Johns Hopkins Department of Neurosurgery can accurately identify brain cancers using small samples of cerebrospinal fluid (CSF), offering a promising new tool to guide clinical decision-making.

The findings, supported by funding from the National Institutes of Health, were published Aug. 25 in Cancer Discovery and demonstrate that combining multiple biological markers, including tumor-derived DNA and immune cell signatures, is more effective for diagnosing central nervous system cancers than using any one marker alone.

"This study highlights how much more information we can gain when we evaluate several analytes together," says senior study author Chetan Bettegowda, M.D., Ph.D., Harvey Cushing Professor and Director of the Department of Neurosurgery at the Johns Hopkins University School of Medicine, director of the Reza Khatib Brain Tumor Research Center at Johns Hopkins, medical director of the Ludwig Center, and a senior author on the study. "The ability to detect cancers with high specificity and also gain insight into the immune environment of the brain could be an important advance in the care of patients with brain tumors."

To evaluate the potential of a multi-analyte approach, investigators analyzed 206 CSF samples, including samples from patients with high-grade gliomas, medulloblastomas, metastases and central nervous system lymphomas. Their test, called CSF-BAM (cerebrospinal fluid–B/T cell receptor, aneuploidy and mutation), measured chromosomal abnormalities, tumor-specific mutations, and T and B cell receptor sequences. In combination, these markers identified brain cancers with more than 80% sensitivity (ability to detect cancer) and 100% specificity (correctly identified those who were cancer-free) in the validation cohort. The 100% specificity means no false positives were recorded among individuals with noncancerous conditions.

The study also showed that the assay could distinguish between the immune cell populations present in cancer and noncancer cases, offering additional biological context that could be helpful in more-challenging clinical scenarios. Investigators say this ability to categorize T and B cell populations in the CSF provides insights into both disease presence and immune response.

Researchers say the test could be particularly useful for cases in which conventional imaging or cytology is inconclusive, or in situations when obtaining tissue for diagnosis is risky or not possible. The multi-analyte approach, they say, enables clinicians to better detect cancer and better understand the disease status, supporting a more tailored approach to patient care.

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