New diagnostic test aims for same-day detection of leptomeningeal disease

With time being of the essence for patients facing one of cancer's most dire complications, UCLA researchers are working to create a new test to detect cancer's spread to the central nervous system on the same day as the doctor's visit.

When cancer spreads from its primary site, such as the lungs or breast, to the brain or spine, there are well-established methods of treating it. However, when these metastases spread to the cerebrospinal fluid (CSF), a condition known as leptomeningeal disease (LMD), median survival drops to around four months with treatment. If untreated, median survival is measured in weeks.

In addition to its low survivability, LMD is also difficult to detect in a timely manner using existing testing procedures. Currently, it can take several weeks before doctors can confirm whether the cancer has spread to the cerebrospinal fluid and several more weeks after that to determine if a treatment has been effective.

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."

Dr. Won Kim, Neurosurgical Director of the Brain Metastasis Program and co-investigator of the study

As part of a two-year study funded by the National Institutes of Health, Kim and Daniel Kamei, professor of Bioengineering in the UCLA Samueli School of Engineering and principal investigator of the study, are now working to develop a new test that would allow for same-day detection of LMD and allow doctors to monitor the effectiveness of treatments such as chemotherapy in real time.

"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."

To accomplish this, Kamei and Kim are working to develop a diagnostic kit that includes sample processing and a specialized paper-assay test, similar to those used in at-home COVID and pregnancy tests. Their goal would be to allow doctors to draw cerebrospinal fluid from the patient and, after processing, apply it to the paper test at the site of care. The test would ideally not only confirm the presence of cancer cells in the cerebrospinal fluid that same day, but also give doctors a measure of the concentration of cancer cells.

With existing tests, the cerebrospinal fluid must be sent to a lab for processing, which can take one to two weeks for results, Kim said. Even worse, the first test typically only has a 50% detection rate, with subsequent tests needed to improve accuracy. Another limitation of these tests is they do not accurately measure disease burden, limiting their usefulness in deciding if a treatment is working or not.

"The real time monitoring of circulating tumor cells allows the doctor to quickly determine whether the treatment is working or not," Kamei said. "The doctor can then continue or change the treatment regimen based on how the concentration of cancer cells is changing. Obtaining this information in real time is critical given the poor survival rates."

In addition to reducing time, the test could also reduce the costs of testing for LMD given that the tests are paper-based and do not require lab-processing.

"The infrastructure is there to mass produce these types of paper-based diagnostics with low cost and high shelf life," Kamei said.

The $375,000, two-year NIH-funded study will include the development of two types of diagnostics and testing with purchased cancer cells and some 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."

The study is currently underway, with initial results expected in 2026.