So the rationale is simply that spinal fluid is, in most cases, in closer proximity to the tumor, direct contact with the tumor in many cases. And so you may get higher levels of tumor-derived DNA in the spinal fluid than you would in the systemic circulation. And in fact, there’s been numerous studies over the years that have proven that on average, the amount of tumor-derived DNA or ctDNA is higher in the spinal fluid compared to plasma in patients with brain cancer such as glioblastoma...
So the rationale is simply that spinal fluid is, in most cases, in closer proximity to the tumor, direct contact with the tumor in many cases. And so you may get higher levels of tumor-derived DNA in the spinal fluid than you would in the systemic circulation. And in fact, there’s been numerous studies over the years that have proven that on average, the amount of tumor-derived DNA or ctDNA is higher in the spinal fluid compared to plasma in patients with brain cancer such as glioblastoma. So that’s the rationale. Now, in terms of what’s been done, you know, there have been a good number of clinical studies now, both retrospective and prospective, that have alluded to the potential utility of performing liquid biopsy on the spinal fluid in patients with gliomas and certainly other types of primary brain tumors that include medulloblastoma and a few others. And if you look at these studies, about 50% of the time, that seems to be the typical number, you will find at least one tumor somatic mutation. So a variant that’s present from the tumor’s DNA in the spinal fluid. And so that number of 50% tends to hold up across numerous different studies, particularly in patients with glioma. And so if your patient is in that 50% where you can detect a mutation in the spinal fluid, it could be helpful for that patient. And it sometimes could lead to identification of something useful for therapy, or it may just be used as a way to detect tumor versus no tumor. You can imagine if you have positive ctDNA in the spinal fluid, probably there is some, you know, tumor activity that’s going on. So now, what is generally lacking is, you know, a larger study, prospective larger clinical study to really prove how use of CSF liquid biopsy, again, in patients with glioblastoma, for example, how that would actually impact clinical management and whether or not it’s something we should be doing on a routine basis for our patients. That remains unknown until such studies are done. I will say that there are a couple of recent papers that suggest with the right assay, the right technology, you can have pretty high sensitivity now for detection of tumor-derived DNA in the spinal fluid of patients with brain cancer. And so I think we are moving closer and closer towards this being implemented in routine practice.
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