Blood test shows promise for identifying genetic abnormalities in tumors

A technique for reading the genetic abnormalities in patient tumors with a simple blood test has passed a critical test of accuracy and reliability. The Dana-Farber Cancer Institute scientists who developed the technique will be reporting their results at the annual meeting of the American Society of Clinical Oncology (ASCO) on Saturday, May 31, 2014.

The technique, known as plasma genotyping, utilizes free-floating tumor DNA in patients’ bloodstreams, rather than surgically removed tumor tissue, as material for analysis of a tumor’s genetic makeup. Because it can be performed quickly, plasma genotyping may enable physicians to track the emergence of new gene mutations in tumors and promptly prescribe the appropriate targeted therapies. The quantitative nature of the technique may also allow for monitoring of patients’ response to treatment.

In the study, researchers tested the technique in 45 patients with advanced non-small cell lung cancer (NSCLC) whose tumors had become resistant to the drug erlotinib. Each patient had a re-biopsy (second removal of a tumor tissue sample) and a collection of plasma (the liquid portion of blood). The re-biopsy tissue was analyzed for mutations in the gene EGFR, which often takes an abnormal form in NSCLC and which is specifically targeted by erlotinib. Floating DNA was extracted from the plasma samples and analyzed for three mutations in EGFR, including a mutation known as T790, which can allow tumors to become resistant to erlotinib.

The researchers found that the plasma genotyping assay was able to detect the EGFR T790 mutation with high accuracy – a positive result was correct 95 percent of the time. Repeat plasma testing was also performed in a subset of patients on treatment, and those with a response to treatment had a dramatic decrease in concentration of the tumor mutation. These data suggest that this assay is capable of initially providing clinically useful results, while also providing insight into whether a treatment is working.

“It’s the application that makes it so intriguing, because obtaining a biopsy at the time of progression (especially in lung cancer) is not always medically feasible and carries risks,” said Cloud Paweletz, PhD, of the Belfer Institute for Applied Cancer Science at Dana-Farber, who leads the laboratory development of this technology.

The researchers also piloted the plasma genotyping technique in a group of patients with advanced NSCLC who had not previously had their tumor tissue genetically analyzed. In 17 members of this group, the technique identified EGFR mutations in three patients, with a median turnaround time of three days, up to 19 days before standard genotyping techniques confirmed the result.

“This assay has the potential to rapidly and noninvasively identify tumor genotype, efficiently matching the right patient to the right drug,” suggested Geoffrey R. Oxnard, MD, medical oncologist at the Lowe Center for Thoracic Oncology at Dana-Farber, who is leading the clinical development of this technology. “In some cases, it may eliminate the need for repeat biopsies altogether.”

This study was supported in part by the National Cancer Institute at the National Institutes of Health (R01-CA135257), by the Conquer Cancer Foundation of ASCO (Career Development Award), by the Standing-Younger Cancer Research Foundation, research funding from Genentech, and the Canadian Association of Medical Oncology.