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An Alternative to Biopsy: Improved CTC Collection Method

The wearable CTC collection device.

Researchers at the University of Michigan have developed a prototype of a wearable device that can continuously collect circulating tumor cells (CTCs) directly from a patient's bloodstream. The investigators hope that this device, which has thus far proven successful in canine models, could ultimately be used as an alternative to biopsies.

Circulating tumor cells, which circulate through lymphatic channels and blood after they are shed from the primary tumor, are the basis for cancer metastases. Studies have shown that elevated CTC levels found in a single blood draw can indicate prognosis in early-stage breast and prostate cancers and in metastatic breast, colorectal, prostate, and lung cancers. In addition, analysis of CTCs could be used to predict the benefit of targeted therapies, to monitor the effects of ongoing drug treatment, and to gain further insight into the nature of metastases.

"CTC evaluation might be used for early detection of malignancy, if an assay with sufficient sensitivity and specificity could be developed," comment the authors of the study, published in Nature Communications.

The difficulty with using CTCs in an assay arises from the fact that they are quite rare. Even in the average patient with metastatic breast cancer, typically no more than 10 CTCs will be found in an entire 7.5-mL tube of whole blood.

Although many CTC capture devices have been developed to enrich and isolate CTCs from whole blood, these are limited to small blood volumes because of the safety issues involved in extracting large amounts of blood from a patient. For this reason, the devices only identify a small number of CTCs. To increase the volume of blood available for CTC isolation, researchers have proposed alternative sites of blood collection, such as the vessels draining primary cancers, which are accessed during surgery, but this method could not be used in routine diagnostic situations. Other proposed methods of CTC isolation that would not involve excessive blood draw also have limited general practicality.

The researchers at the University of Michigan have now found a solution to this problem in their design of a temporary indwelling, intravascular CTC isolation system. This system could be worn by a patient for several hours so that a relatively large volume of blood could pass through it, allowing for the collection of a much larger quantity of CTCs. In canine models, the capture device was capable of screening 1% to 2% of the entire blood of a dog's body over a two-hour period. It captured 3.5 times as many CTCs per milliliter of blood as that collected through serial blood draws.

"It's the difference between having a security camera that takes a snapshot of a door every five minutes or takes a video. If an intruder enters between the snapshots, you wouldn't know about it," commented Sunitha Nagrath, PhD, Associate Professor of Chemical Engineering at the University of Michigan and the lead developer of the device.

"Nobody wants to have a biopsy," remarked Daniel F. Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center and the paper's senior author. "If we could get enough cancer cells from the blood, we could use them to learn about the tumor biology and direct care for the patients. That's the excitement of why we're doing this."

For More Information

Kim TH, Wang Y, Oliver CR, et al (2019). A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells. Nat Commun, 10:1478. DOI:10.1038/s41467-019-09439-9

Image: Measuring approximately 2 x 2.75 x 1 inches, the wearable device has a cancer-cell-capturing chip mounted on top. The hole in the top left corner is where the patient's catheter is attached. Image credit: Tae Hyun Kim

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