By Brian Casey, LabPulse.com editorial director

February 13, 2019 -- Two recently published studies indicate that blood-based liquid biopsy can be used to track lung cancer treatment response by measuring levels of circulating tumor DNA (ctDNA) in patients who are receiving treatments such as immunotherapy. Both studies found that liquid biopsy worked better than imaging-based methods.

The results suggest that noninvasive tests using blood samples have the potential to change cancer therapy by evaluating treatment response more quickly, helping patients avoid treatments that are toxic or ineffective, according to Dr. Victor Velculescu, PhD, co-director of cancer biology at the Johns Hopkins Kimmel Cancer Center.

The studies, both published in Cancer Research, show how tracking treatment response by measuring ctDNA was more accurate for assessing tumor growth or shrinkage than other more traditional methods such as medical imaging.

In the first study by Velculescu, first author Jillian Phallen, and colleagues (published online December 20, 2018), blood samples were taken from a group of 28 adults who had non-small cell lung cancer (NCSLC). The patients were receiving treatments targeting epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2). Samples were taken before treatment and at subsequent intervals.

The researchers analyzed the blood samples to detect ctDNA given off by tumors into circulating blood. They also tracked tumor burden during therapy by detecting gene mutations and chromosomal changes in tumor cells.

The blood-sample measurements showed that 16 patients had almost complete elimination of detectable ctDNA as soon as one week after treatment. Eight patients who did not respond to therapy had limited changes in ctDNA levels and shorter progression-free survival.

Ultimately, measuring ctDNA detected patient response to treatment four weeks earlier and was more accurate than computed tomography (CT), the investigators reported.

In the second study (published online December 12, 2018), Velculescu, first author Dr. Valsamo Anagnostou, PhD, and colleagues tracked 38 patients with NCSLC who were receiving therapy targeting a protein known as programmed cell death 1 (PD-1); anti-PD-1 therapies boost the immune response against cancer cells.

The researchers measured ctDNA levels and immune blood cell changes in response to the therapy. They found that nine patients who had a clinical response to immunotherapy also showed a complete reduction in ctDNA levels immediately after therapy began. On the other hand, 10 patients who did not respond had no significant change or an increase in ctDNA levels.

What's more, the molecular response to therapy as measured by ctDNA levels more accurately predicted overall survival. Patients who didn't show a molecular response had shorter progression-free survival and overall survival than those who did have a response. Also, using ctDNA showed therapy response almost nine weeks earlier than using CT, the researchers reported.

"Our studies suggest that tests using blood samples will change the way cancer patients will be treated by helping to evaluate therapeutic responses more quickly and accurately, and avoid unneeded toxicity or ineffective treatments," Velculescu said in a release from Johns Hopkins.


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