Circulating Tumor DNA Panel Can Detect Early-Stage Lung Cancers

June 6, 2016

A targeted-sequencing gene panel that includes EGFR, KRAS, PIK3CA, and other mutations from circulating tumor DNA detects stage I non–small-cell lung cancer and might outperform existing tumor markers.

CHICAGO-A targeted-sequencing gene panel that includes EGFR, KRAS, PIK3CA, and other mutations from circulating tumor DNA (ctDNA) detects stage I non–small-cell lung cancer (NSCLC) and might outperform existing tumor markers’ positive predictive value (PPV), according to a prospective study presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 8514).

“This prospective study demonstrates the feasibility of identifying plasma ctDNA in stage I lung cancer patients via targeted sequencing, demonstrating a potential utility of ctDNA in the management of early-stage NSCLC,” reported lead author Kezhong Chen, MD, and coauthors from Peking University People’s Hospital and Sun Valley Biotechnology, Inc, in Beijing, China, in a poster presentation.

To evaluate plasma ctDNA’s sensitivity, specificity, PPV, and concordance with tumor DNA, and ctDNA concentrations’ association with clinical tumor aggressiveness, the research team paired presurgical plasma and frozen tumor tissue for 46 patients with stage I NSCLC (87% adenocarcinoma; 13% SCC) and conducted targeted sequencing using the Ion Personal Genome Machine System and Ion AmpliSeq Cancer Panel. They compared PPV with circulating tumor proteins CA 125, CA 19-9, CEA, CYFRA 21-1, and NSE. Pathologic tumor stage was IA for 30 (65%) and IB in 16 (35%) of patients.

The panel’s overall sensitivity and specificity were 78.6% and 55.6%, respectively. PPV was 68.4% (95% CI, 43.5%–44%) for stage IA tumors and 81.8% (95% CI, 47.8%–96.8%) for stage IB tumors.

“Plasma ctDNA had a higher positive predictive value than currently used tumor biomarkers in early-stage NSCLC,” Dr. Chen and colleagues wrote.

Higher ctDNA concentrations were also significantly associated with clinical features of tumor aggressiveness, including CT consistency, tumor histology (squamous > adenocarcinoma), extent of invasion of vasculature or visceral pleura, older patient age (> 65 years), and patient sex (female > male), they reported.

“There is high concordance between ctDNA and tumor DNA in stage I patients,” commented Denise Aberle, MD, professor of radiology and bioengineering at the David Geffen School of Medicine at UCLA in Los Angeles, who led a panel discussion of the study. “ctDNA has higher PPV than routine tumor markers.”

Potential sources of discordance between ctDNA and tumor DNA in the study included specimen processing (analytical platform), dilution of ctDNA by lysis of normal cells and circulating enzymes, and sampling error in small tumor samples that did not reflect tumor heterogeneity, Dr. Aberle noted.