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Researchers at Massachusetts General Hospital (MGH) are testing a non-surgical technique that may help doctors monitor how well non-small cell lung cancer patients are responding to treatment. Using a device known as a CTC-chip to analyze circulating tumor cells from patients' blood samples, the scientists were able to identify whether patients had genetic mutations that would make them less likely to respond to certain therapies.

The research, published online in the New England Journal of Medicine, is still in the early stages. However, if future studies confirm it works, the technique could offer lung cancer patients a non-invasive, safe way to monitor their disease and find out which treatments will work. Currently, in order to get that type of information, patients would have to undergo dangerous, invasive procedures to sample tissues and cells.

Scientists will need to replicate the current findings in larger studies before the chip is used widely. Only 27 patients participated in the pilot study.

"The CTC-chip opens up a whole new field of studying tumors in real time," says Daniel Haber, MD, director of the MGH Cancer Center and lead author of the study. "When the device is ready for larger clinical trials, it should give us new options of measuring treatment response, defining prognostic and predictive measures, and studying the biology of blood-borne metastasis, which is the primary method by which cancer spreads and becomes lethal."

Tracking Tumor Cells

The researchers tested blood samples of 27 patients, 23 of whom had a cell-surface protein mutation known as the epidermal growth factor receptor (EGFR) mutation. Using the CTC-chip, the researchers were able to identify the mutation from the circulating blood tumor cells 92% of the time.

They also found the chip could detect changes over time. Research has shown that tumors with the EGFR mutation are more likely to respond to a class of drugs known as tyrosine kinase inhibitors, or TKIs; Tarceva (erlotinib) and Iressa (gefitinib) are 2 TKIs used against lung cancer. However, the patient's tumors eventually come back. Using the CTC-chip, the researchers found out why: it appears that the tumor cell's genetic makeup evolved over the course of treatment.

"Biopsy samples taken at the time of diagnosis can never tell us about changes emerging during therapy or genotypic differences that may occur in different sites of the original tumor, but the CTC-chip offers the promise of noninvasive continuous monitoring," said Haber.

This information could one day help doctors see when a patient was becoming resistant to treatment so that new therapies could be tried earlier. However, the researchers acknowledge they still have work to do to make this technique more efficient on the larger scale that would be needed for clinical trials. For information on innovative lung cancer research, see "What's New in Non-Small Cell Lung Cancer Research and Treatment?"

Citation: "Detection of Mutations in EGFR in Circulating Lung-Cancer Cells." Published online July 2, 2008 in the New England Journal of Medicine. First authors: Shyamala Maheswaren, PhD; Lecia V. Sequist, MD, MPH; Sunitha Nagrath, PhD, Massachusetts General Hospital Cancer Center.