Blood Test Detects Genetic Mutations in Lung Cancer

A simple blood test can rapidly and accurately detect mutations in two key genes in non-small-cell lung tumors, demonstrating the test's potential as a clinical tool for identifying patients who can benefit from drugs targeting those mutations.

Non-small-cell lung tumors (NSCLC) are the most common form of lung cancer, diagnosed in more than 200,000 people in the USA each year. An estimated 30% of NSCLC patients have mutations in either of the genes included in a recent study, and can often be treated with targeted therapies.


Oncologists at the Dana-Farber Cancer Institute (Boston, MA, USA) and their associates prospectively enrolled 180 patients with NSCLC, 120 of whom were newly diagnosed, and 60 of whom had become resistant to a previous treatment, allowing the disease to recur. Participants' cell-free DNA was tested for mutations in the epidermal growth factor receptor (EGFR) and the Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) genes, and for a separate mutation in EGFR that allows tumor cells to become resistant to front- line targeted drugs.

The test was performed with a technique known as droplet digital polymerase chain reaction (ddPCR, Bio-Rad; Hercules, CA, USA), which counts the individual letters of the genetic code in cell-free DNA to determine if specific mutations are present. Each participant also underwent a conventional tissue biopsy to test for the same mutations. The results of the liquid biopsies were then compared to those of the tissue biopsies. Turnaround time for tissue genotyping was measured from the date of the initial genotyping order until the reporting of the final genotyping result.

The data showed that liquid biopsies returned results much more quickly. The median turnaround time for liquid biopsies was 3 days, compared to 12 days for tissue biopsies in newly diagnosed patients and 27 days in drug-resistant patients. Liquid biopsy was also found to be highly accurate. In newly diagnosed patients, the "predictive value" of plasma ddPCR was 100% for the primary EGFR mutation and the KRAS mutation, meaning that a patient who tested positive for either mutation was certain to have that mutation in his or her tumor. For patients with the EGFR resistance mutation, the predictive value of the ddPCR test was 79%, suggesting the blood test was able to find additional cases with the mutation that were missed using standard biopsies.

Lynette Sholl, MD, a pathologist, said, “The study data are compelling. We validated the authors' findings by cross-comparing results from liquid and tissue biopsies in 34 NSCLC patients. To work as a real-world clinical test, liquid biopsy needs to provide reliable, accurate data and be logistically practical. That's what we've seen with the ddPCR-based blood test. The test has great utility both for patients newly diagnosed with NSCLC and for those with a recurrence of the disease. It's fast, it's quantitative as it indicates the amount of mutant DNA in a sample, and it can be readily employed at a cancer treatment center.” The study was published on April 7, 2016, in the journal JAMA Oncology.

Related Links:
Dana-Farber Cancer Institute
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