In the fight against cancer, timely diagnosis is critical, particularly when the disease metastasizes to the central nervous system. One of the most severe complications of such metastasis is leptomeningeal disease (LMD), which occurs when cancer cells invade the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord. Now, the University of California, Los Angeles (UCLA) researchers are working to significantly shorten the diagnostic turnaround time for LMD via research that aims to develop a rapid, paper-based test to detect cancer cells in CSF the same day patients visit their doctor.
Currently, the detection of LMD is both long and not very accurate. Existing testing methods can require sending CSF samples to laboratories for processing, which can take one to two weeks before results are returned. Additionally, the initial tests have a detection rate of only about 50%, often necessitating further testing to improve accuracy. Further, the long diagnostic and monitoring time also means it can be several weeks before doctors can determine if treatments are being effective.
This form of metastatic disease already has a low four-month median survival when treated and untreated LMD survival drops to mere weeks.
“You can’t wait a month or two to establish a diagnosis or see if treatment is working. That is critical time that we do not have,” said study co-investigator Won Kim, MD, neurosurgical director of the brain metastasis program at UCLA Health.
Joining Kim as a co-investigator is Daniel Kamei, PhD, a professor of bioengineering at UCLA, who has previously developed a test to detecting CFS leaks. The two are now working to develop a paper-based point-of-care test that would allow for the analysis of CSF and return results the same day. This kit would allow doctors to extract CSF from patients and apply it directly to a paper-based test. As they envision it, the test kit will include sample processing and a paper-assay that is similar to home pregnancy tests and at-home COVID tests.
“The infrastructure is there to mass produce these types of paper-based diagnostics with low cost and high shelf life,” Kamei noted.
But the team has a couple of hurdles to clear to accomplish this.
“One of the challenges is being able to detect very low concentrations of cancer cells in cerebrospinal fluid with a paper-based test,” Kamei said. “Another challenge is being able to determine concentrations of cancer cells since these types of tests generally provide only yes or no answers. Such yes or no answers are all you need to detect for COVID and pregnancy, but for this application, you need to determine if the concentration of cancer cells is decreasing with a particular treatment regimen.”
The UCLA work is funded by a two-year, $375,000 grant from the National Institutes of Health. Initial phases will involve developing two different assays, then testing them with purchased cancer cells, followed by trials with patient samples.
“If the technologies work with cancer cells, then we’ll start testing with cerebrospinal fluid samples from patients,” Kim said. “If we’re able to validate this in our human patients for the initial testing phase, we would like to move towards a multicenter clinical trial.”
