CTCs in CSF as liquid biopsy

Cancer cells can show up in spinal fluid even when the standard microscope test says the sample is negative, according to data presented at the American Association for Cancer Research meeting in San Diego this week. (aacr.org) The sample in question is cerebrospinal fluid, the liquid around the brain and spinal cord. In patients with suspected leptomeningeal metastasis — cancer spread to those linings — doctors usually look for malignant cells by cytology, a lab review of the fluid under a microscope. (aacrjournals.org) That test misses cases. A 2025 breast cancer meeting abstract reported conventional cytology sensitivity of about 50% on the first lumbar puncture and 85% on the second, which is one reason patients often need repeat procedures. (aacrjournals.org) Circulating tumor cells are whole cancer cells that break away from a tumor and travel in body fluids. In cerebrospinal fluid, they can act like a liquid biopsy — a way to sample disease biology without taking tissue from the brain or spinal lining. (aacrjournals.org) That idea is not new, but the AACR discussion lands as cerebrospinal-fluid testing is already moving beyond plasma in central nervous system disease. A 2025 Nature Medicine study of 584 patients with non-small cell lung cancer and central nervous system metastases found cerebrospinal-fluid circulating tumor DNA positivity was independently associated with shorter survival, and CSF-matched therapy was linked to better outcomes. (nature.com) The distinction matters because plasma often underperforms behind the blood-brain barrier. In a 2022 Clinical Cancer Research study of breast cancer leptomeningeal metastasis, cerebrospinal-fluid tumor DNA was detected in all 24 patients with confirmed disease, including patients with negative cytology, while plasma tumor DNA was mainly seen when cancer was also progressing outside the brain. (aacrjournals.org) The newer cell-based work points in the same direction. In a 2025 abstract on 15 cerebrospinal-fluid samples from nine patients with breast cancer leptomeningeal metastasis, investigators using a microwell-chip workflow found tumor cells in five samples that were inconclusive or negative by cytology; counts ranged from 5 to 10,000 cerebrospinal-fluid circulating tumor cells per mL. (aacrjournals.org) Earlier studies suggested these cells can do more than confirm disease. A 2017 Clinical Cancer Research paper in 21 patients with suspected leptomeningeal metastases from non-small cell lung cancer found CellSearch detected cerebrospinal-fluid circulating tumor cells in 20 patients, for 95.2% sensitivity, and sequencing of those cells matched the primary tumor in 17 of 19 cases. (aacrjournals.org) That raises a workflow question for hospitals: whether cerebrospinal fluid should be processed not only for cytology, but also for rare-cell capture, counting, and molecular profiling. The breast cancer microwell-chip study reported less than 5% cell loss on-chip and more than 95% single-cell isolation in testing, but it covered only 15 samples and was presented as an abstract rather than a peer-reviewed full trial. (aacrjournals.org) For now, the standard test has not changed. But the direction of travel is clear: in cancers that spread through the central nervous system, the fluid around the brain and spinal cord is becoming less a discard sample and more a direct readout of the disease itself. (aacrjournals.org)