Massachusetts General Hospital (MGH) investigators have developed a microchip-based device that detects and analyzes circulating tumor cells (CTCs) to determine the genetic signature of lung tumors. It allowed the identification of those appropriate for targeted treatment and helped monitor genetic changes that occur during therapy, according to the MGH team.
Genetic analysis of CTCs from mutation-positive tumors detected these mutations 92% of the time. In addition to the primary mutation that leads to initial tumor development and sensitivity to a group of drugs called TKIs, the CTC-chip also detected a secondary mutation associated with treatment resistance in some participants including those whose tumors originally responded to treatment but later resumed growing.
The CTC-chip was used to analyze blood samples from 27 patients; 23 had EGFR mutations and four did not. CTCs were identified in samples from all patients. Blood samples were taken at regular intervals during the course of treatment from four patients with mutation-positive tumors.
In all these patients, levels of CTCs dropped sharply after TKI treatment started and began rising when tumors resumed growing. In one patient, adding more chemotherapy caused CTC levels to drop again as the tumor continued shrinking.
Throughout the course of therapy, the tumors' genetic makeup continued to evolve. The most common resistance mutations emerged in tumors where it was not initially present. Also, new activating mutations, the type that causes a tumor to develop in the first place, appeared in seven patients' tumors. This indicates that these cancers are more genetically complex than expected and that continuing to monitor tumor genotype throughout the course of treatment may be crucial, the scientists explain.
"If tumor genotypes don't remain static during therapy, it's essential to know exactly what you're treating at the time you are treating it," says Daniel Haber, M.D., director of the MGH Cancer Center and the study's senior author. "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."
A pilot study of the device called the CTC-chip will appear in the July 24 issue of The New England Journal of Medicine and was published July 2 online.