A new blood test can detect changes in cancer cells, which will help doctors determine if a patient's treatment is working.
Researchers at Massachusetts General Hospital (MGH) in Boston have found that placing just a teaspoon of blood on a device called a CTC-chip, is enough for scientists to view tumour cells circulating in the bloodstream. The cells can be counted to determine if a patient's drug therapy is working, and can be observed for mutations.
"The CTC-chip opens up a whole new field of studying tumours in real time," Dr. Daniel Haber, director of the MGH Cancer Center and the study's senior author, said in a statement.
"When the device is ready for larger clinical trials, it should give us new options for 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."
The researchers studied this test on lung cancer patients and found that it could accurately detect changes in cancer cells.
Their research is published in the New England Journal of Medicine.
The next area of study will be to determine the accuracy of the test by using it on patients with a variety of different cancers.
If successful, doctors would be able to find out in a few days whether a patient is responding to treatment.
"If tumour genotypes don't remain static during therapy, it's essential to know exactly what you're treating at the time you are treating it," Haber said. "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 tumour, but the CTC-chip offers the promise of noninvasive continuous monitoring."
Abstract:
Detection of Mutations in EGFR in Circulating Lung-Cancer Cells
Shyamala Maheswaran, Ph.D., Lecia V. Sequist, M.D., M.P.H., Sunitha Nagrath, Ph.D., Lindsey Ulkus, B.S., Brian Brannigan, B.A., Chey V. Collura, M.S., Elizabeth Inserra, B.S., Sven Diederichs, Ph.D., A. John Iafrate, M.D., Ph.D., Daphne W. Bell, Ph.D., Subba Digumarthy, M.D., Alona Muzikansky, M.S., Daniel Irimia, Ph.D., Jeffrey Settleman, Ph.D., Ronald G. Tompkins, M.D., Thomas J. Lynch, M.D., Mehmet Toner, Ph.D., and Daniel A. Haber, M.D., Ph.D.
Background: The use of tyrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non-small-cell lung cancer is effective but limited by the emergence of drug-resistance mutations. Molecular characterization of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment.
Methods: We captured highly purified circulating tumor cells from the blood of patients with non-small-cell lung cancer using a microfluidic device containing microposts coated with antibodies against epithelial cells. We performed EGFR mutational analysis on DNA recovered from circulating tumor cells using allele-specific polymerase-chain-reaction amplification and compared the results with those from concurrently isolated free plasma DNA and from the original tumor-biopsy specimens.
Results: We isolated circulating tumor cells from 27 patients with metastatic non-small-cell lung cancer (median number, 74 cells per milliliter). We identified the expected EGFR activating mutation in circulating tumor cells from 11 of 12 patients (92%) and in matched free plasma DNA from 4 of 12 patients (33%) (P=0.009). We detected the T790M mutation, which confers drug resistance, in circulating tumor cells collected from patients with EGFR mutations who had received tyrosine kinase inhibitors. When T790M was detectable in pretreatment tumor-biopsy specimens, the presence of the mutation correlated with reduced progression-free survival (7.7 months vs. 16.5 months, P<0.001). Serial analysis of circulating tumor cells showed that a reduction in the number of captured cells was associated with a radiographic tumor response; an increase in the number of cells was associated with tumor progression, with the emergence of additional EGFR mutations in some cases.
Conclusions: Molecular analysis of circulating tumor cells from the blood of patients with lung cancer offers the possibility of monitoring changes in epithelial tumor genotypes during the course of treatment.
