Revolutionizing the search for circulating tumor cells

In the Seattle Cancer Care Alliance's hemapathology lab, Dr. Daniel Sabath looks like a kid on Christmas morning as he talks about his department's new wonder machine: a cell-counting instrument called CellTracks, the first of its kind in the Pacific Northwest. The technology stands ready to improve cancer diagnostics and therapeutic approaches.

CellTracks performs a test, CellSearch, which identifies and counts circulating tumor cells in a blood sample to predict disease progression and survival in patients with metastatic breast cancer earlier than the current standard of care.

Cancer metastasis occurs when cells shed from the primary tumor, enter the bloodstream, and begin to grow in distant locations in the body. The ability to identify, count and characterize these circulating tumor cells holds significant clinical promise for better understanding the biological mechanisms of cancer development. Additionally, analyzing circulating tumor cells may improve diagnostic techniques and help with the development of new therapies.

Detects one cell among billions

Despite this potential, circulating tumor-cell analysis has been hindered by a lack of automated technology to do sensitive testing in a standardized, objective manner. That's where the CellTracks machine comes in. It's the first semi-automated system approved by the Food and Drug Administration to detect the cells and allow for more rapid observation of the cells as early as the first cycle of treatment. That helps evaluate disease progression and inform treatment decisions more quickly.

"With the CellSearch test, oncologists can clearly and consistently monitor the number of circulating tumor cells present in a patient's blood," said Sabath, an affiliate member of the SCCA faculty and head of the University of Washington's hematology division in the Laboratory Medicine department. The presence of five or more circulating tumor cells in a blood sample is associated with lower odds of progression-free survival and decreased overall survival.

According to the American Cancer Society, breast cancer claims approximately 40,000 lives each year, the vast majority of which are a result of recurrent metastatic disease. Although there are many treatment options for metastatic breast cancer, oncologists often have to wait several months before they can determine if a specific treatment is beneficial to the patient. The new test helps physicians predict treatment effectiveness early through its ability to locate one circulating tumor cell in the 40 billion cells contained in about a teaspoon-sized sample of blood — an achievement no other currently available clinical diagnostic test can accomplish.

Early findings show that the CellSearch test is as good or better than traditional radiography in looking for disease progression, and it's a less expensive method, too.

In addition to measuring circulating tumor cells, Sabath and colleagues are using the CellTracks machine to provide key data for SCCA breast-cancer clinical trials, with more studies on the horizon.

One study, proposed by Dr. Julie Garrison, the SCCA's breast cancer clinical-research manager, and oncologists Drs. Hannah Linden and Jennifer Specht, seeks to measure how many circulating endothelial cells breast-cancer patients have. The machine uses magnetic particles that have antibodies against endothelial cells, the cells that line the blood vessels. The particles stick to the endothelial cells and are retrieved. Then, using fluorescent antibodies, CellTracks employs a laser to look for cells that glow and counts those.

"Some studies show there is a correlation between the presence of circulating endothelial cells in the blood and the effectiveness of chemotherapy," Sabath said. "So from a research standpoint, the breast-cancer docs are almost more interested in looking at these circulating endothelial cells than just looking at circulating cancer cells."

Though not yet approved for use beyond breast cancer, Sabath sees the reward in being an early adopter of the technology and its potential. "Our lab already does a lot of work with more rare blood cancers. It's nice to be able to apply some of our very sensitive techniques that we're already good at with blood cancers to diseases that are more common, like breast cancer," he said. "It should work for prostate, colon and lung cancers as well. We're very eager for collaborations."

"In the short run, it's more of a research instrument, but in the long term, there may be a clinical shift in the way doctors routinely follow their breast-cancer patients. If CellTracks makes a difference in terms of therapy, I think it will prove very, very useful."