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Test can find tiny tumor level in blood

MGH method gives new treatment tool

Email|Print|Single Page| Text size + By Stephen Smith
Globe Staff / July 3, 2008

Boston researchers have developed a test that can identify minute amounts of tumor cells floating in the blood of cancer patients, a discovery that could lead to better treatments with fewer side effects.

The technology, invented at Massachusetts General Hospital, uses a microchip scanner no bigger than a business card to analyze a patient's blood, hunting for stray cells shed by tumors. The device is so powerful that it can detect a single cancer cell among 1 billion healthy blood cells.

Once those cells are captured, their genetic fingerprints can help determine the most effective drug for a patient whose cancer has already begun spreading, and also show whether medication has lost its power. The technology is now being tried in patients whose cancer has already spread, but scientists hope in the fu ture the chip will be able to detect cancer's spread before secondary tumors have become established.

Although the device is not yet ready for widespread use, a report posted online yesterday by the New England Journal of Medicine showed that it successfully identified migrating cancer cells in lung cancer patients and spotted important genetic quirks in those cells.

Scientists not involved with the research said the innovation represents a significant improvement on existing cancer blood tests and predicted that it could revolutionize treatment, especially for lung cancer, which kills more Americans than any other cancer.

Mass. General's approach brings together two of the hottest fields in cancer research: the incredibly tiny devices of nanotechnology, and personalized medicine - tailoring treatments to individual patients.

"To me, as a scientist, this is huge," said Dr. Shakun Malik, director of the lung cancer program at Georgetown University's Lombardi Comprehensive Cancer Center in Washington, D.C. "To be able to just do a blood test, that opens a whole new, wide world."

For decades, physicians have relied on biopsies and medical snapshots such as CAT scans to track the progress of cancer, but both approaches carry significant limitations.

Doctors, for example, can conduct repeated biopsies, using a needle to extract chunks of a tumor. "But those biopsies are associated with significant risks, particularly if we're looking at a lung cancer buried deep in the lung," said Dr. Charles Rudin, a cancer specialist at Johns Hopkins University in Baltimore. "The risks can be bleeding, infection, collapse of the lung, shortness of breath."

And while high-tech scans can show whether a tumor is growing or shrinking, it can take a couple of months for that change to be evident on a scan. And an image cannot explain what is happening at a biological level, such as whether tumor cells are mutating. As a result, doctors try a hit-or-miss approach, leaving patients on treatments without always having a clear sense of how well those approaches will work.

"So we unfortunately have exposed those patients to drugs that have side effects, are costly, and have wasted the patient's time, and many of these patients don't have time," said Dr. Joan Schiller, deputy director of the cancer center at the University of Texas Southwestern Medical Center in Dallas. "They don't have time to try this, try that, try this, try that, hoping that you will eventually hit upon something."

The new research, underwritten by a $5 million federal grant and additional money from foundations, is an attempt to do for cancer what scientists had done for AIDS and other illnesses: develop an easy-to-use, highly sensitive treatment scorecard. If the number of cancer cells in the bloodstream falls, treatment is probably working. If they increase, it means the tumor is growing, and suggests the need for a new approach. The tiny device has 78,000 posts imbedded inside to trap cancer cells. Each of those posts is coated with a substance that acts like glue - glue designed to stick only to circulating tumor cells, known by the acronym CTC.

"It's like a pinball machine - the blood has to flow through all of these columns to get to the other side," said Dr. Daniel Haber, director of the Mass. General Hospital Cancer Center and senior author of the study. "All the normal blood cells flow right through, but the very, very rare cancer cells stick to the columns."

The technology, known as the CTC-chip, has been shown to accurately identify bloodstream cancer cells in patients with advanced cancer of the lung, prostate, pancreas, breast, or colon.

In the new study, researchers focused on non-small-cell lung cancer, the deadliest form of the disease. Overall, lung cancer kills more than 160,000 Americans annually, accounting for 29 percent of all cancer deaths.

The Mass. General team took blood from 27 lung cancer patients. In each, the chip technology accurately detected circulating tumor cells.

And then they looked for crucial genetic mutations that would suggest particular treatments. By confirming with biopsied tissue, the scientists found that their test detected all the important genetic features they had sought.

"Someday, we might pick our cancer drugs like we pick our antibiotics," said Dr. Roy Herbst, a lung cancer specialist at M.D. Anderson Cancer Center in Houston.

The Mass. General device can find more cancer cells than an existing technology and does so while the cells are alive, according to the Boston researchers and other scientists. By isolating living cells, doctors could ultimately grow copies for further testing.

Veridex LLC of New Jersey makes a cancer blood test used in patients with advanced breast, colon, or prostate cancer. A Veridex executive said while he was familiar with Mass. General's claims about the superiority of its test, he could not verify the assertion.

The Mass. General technology needs to be tested in larger groups of patients before it can be used routinely, and Haber said scientists need to speed up the device's ability to process samples - right now, it takes about eight hours to run a blood sample and analyze it.

Stephen Smith can be reached at stsmith@globe.com.

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