As part of their own planning, she and her laboratory colleagues have worked with clinicians to simplify the workflow when CSF samples will be used for cfDNA extraction. To simplify the collection, and to ensure that the preanalytical variables are managed properly, the laboratory asks for the sample to be sent in a dedicated tube with a stabilizing agent. “When they know they’re sending us samples for a cell-free DNA assay, be that the plasma or the CSF, they know they need to reach for the Streck tube. It’s very basic,” she says, “but helpful to make sure the right kind of tubes are available to them.”
As Dr. Bale watches the field unfold, what gaps would she like to see filled in the not-too-distant future?
The first item on her wish list is straightforward. “I’d like to see the CSF more widely used—getting more people to do this routinely and making the case for other laboratories to start it, and for more patients to be able to benefit from it. I’m optimistic that we can adopt the CSF to be an informative standard sample for our patients.”
Like any change in practice, that will likely come the way it always does, with more conversations and education, presentations and publications, as well as new therapies.
There’s also the need for technical advances: developing more sensitive assays as well as a greater variety of assays that can capitalize on cell-free DNA. Dr. Bale points to the emerging importance of DNA methylation profiling in the diagnosis of brain tumor patients, for example. And while certain methods can be quite destructive to the DNA, some groups are looking into technologies and platforms, such as a nanopore, that might circumvent the issue of low starting DNA.
And big picture, she says, “Obviously the circulating tumor DNA is just one component in the cerebrospinal fluid. So there is so much more to query there.” It’s the tip of the iceberg, if not the Tetons, so to speak. “I think all things are possible.” Any advances in using expression profiles for monitoring tumor responses and identifying appropriate therapies should extend to the cerebrospinal fluid, she says. “I hope that as these conversations are taking place, more people will see that the CSF is just as important a sample as the blood.”
Dr. Bale has already seen the impact that clinical implementation of CSF cfDNA sequencing has had on patient care at her institution.
And like seeing the Tetons, the impact has been considerable. “It’s striking,” she says. “And once you see it, you can’t unsee it.”
Karen Titus is CAP TODAY contributing editor and co-managing editor.