GENEVA – The tests widely available today that use a cancer patient’s tumor DNA that circulates in the blood to detect a treatment-altering lung cancer mutation vary widely in sensitivity, meaning that using circulating DNA to identify a clinically important mutation should be limited to when biopsying the primary does not yield enough DNA for testing.
“It is important to use robust and sensitive methods” when trying to match treatment to the molecular specificities of each patient’s tumor, Dr. Martin Reck said at the European Lung Cancer Conference.
Results from a study that prospectively compared DNA analysis for mutations in the epidermal growth factor receptor (EGFR) gene in tumor biopsies from 1,162 patients with advanced non–small cell lung cancer with DNA analysis of circulating tumor DNA (ctDNA) from the same patients showed that ctDNA analysis had 46% sensitivity, compared with tumor biopsy DNA, reported Dr. Reck, a thoracic oncologist at the Lung Clinic in Grosshandsdorf, Germany. This high level of false-negative results with ctDNA analysis produced a positive predictive value of 78%. In contrast, ctDNA has a specificity of 97% and a negative predictive value of 90%.
The results from the international study, which included 881 patients from seven European countries plus 281 patients from Japan, highlighted the divergent concordance among EGFR mutation comparisons of ctDNA and biopsy DNA depending on which DNA tests were used. Participating physicians could order whichever genetic analyses they wanted. A subanalysis of the study showed, for example, that among the 138 patients whose tumor and ctDNAs were both evaluated for EGFR mutations using the therascreen test marketed by QIAGEN the concordance rose to 95%, the sensitivity of ctDNA was 73%, and the positive predictive value was 94%, Dr. Reck reported.
The Europe-Japan Diagnostic Study for EGFR Testing (ASSESS) enrolled patients with either newly diagnosed, locally advanced stage IIIA or IIIB metastatic non–small cell lung cancer or patients with recurrent non–small cell lung cancer following surgical resection. Patients averaged about 67 years old, and about 85% had stage IV disease. The genetic analyses identified EGFR mutations in 31% of the Japanese patients and in 12% of those in Europe.
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