Blood Source May Explain Low Numbers of Circulating Tumor Cells in Liquid Biopsies

The mystery of unexpectedly low numbers of circulating tumor cells (CTCs) in a liquid biopsy may be explained by whether the blood is drawn from a vein or an artery. This finding was published in EBioMedicine (2015; doi:10.1016/j.ebiom.2015.09.019).

As the field of liquid biopsies for tracking disease progression and therapeutic response heats up, many doctors are looking for ways to apply this approach to their patients. Currently, assays for CTCs, one type of liquid biopsy, are approved for diagnostic purposes in metastatic breast, colorectal, and prostate cancers. In these diseases, the presence of CTCs in the peripheral blood is associated with decreased progression-free survival and decreased overall survival.

The major challenge for liquid biopsy technology is that the number of CTCs found in the blood of patients with aggressive disease is not always as high as expected. Now, researchers at Thomas Jefferson University in Philadelphia, Pennsylvania, have shown that the low numbers could be explained simply by from where the blood is drawn: a vein or an artery. The researchers are investigating uveal melanoma, a type of melanoma that originates in the eye.

In breast cancer, a high number of CTCs (more than five cells in 7.5 ml of blood collected from the veins) indicates aggressive metastatic disease, or disease that has stopped responding to treatment.

"If we can validate this approach for uveal melanoma, we hope to be able to catch cancer before it develops into metastatic disease," said lead investigator Takami Sato, MD, the K. Hasumi Professor of Medical Oncology at Thomas Jefferson University.

"The work by Dr. Mizue Terai [PhD] and others at Jefferson gives us hope that CTC might be useful for uveal melanoma patients as well. On the other hand, our research raised a concern that venous blood specimens, which are tested as the standard practice for CTC measurement, might not be the best source for CTC detection."

Circulating tumor cells are larger than other blood cells and have different characteristics from normal blood cells. Therefore, CTCs can be detected in blood samples with modern technology. Most commonly, blood samples are obtained from a patient's vein, and the blood cells have already passed through an intricate sieve of narrow capillaries throughout the body before draining to the veins.

Indeed, when Terai and colleagues compared blood samples taken from the veins of patients with uveal melanoma with blood samples collected from arteries, they saw a much higher number of CTCs in arterial blood than in venous blood. In fact, all of the patients with uveal melanoma patients who had multiple liver metastases had CTCs present in their arterial blood, but only 53% of blood sampled from the veins of those same patients had CTCs.

Although collecting blood from an artery is more technically difficult than collecting from a vein, this and other research suggests that checking arterial blood may be a more accurate way of assessing the number of CTCs, and therefore assessing metastatic disease.

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