Circulating tumor DNA predicts pancreatic-cancer outcomes

Last Updated: 2018-09-27

By Reuters Staff

NEW YORK (Reuters Health) - Circulating tumor-cell DNA (ctDNA) and exosome DNA (exoDNA) from "liquid biopsies" predict progression and survival in patients with pancreatic cancer, researchers report.

CtDNA has been shown to predict relapse in breast, colorectal and lung cancer patients, but it remains unclear whether ctDNA or exoDNA - tumor DNA in the form of microvesicles - has prognostic value in pancreatic cancer.

Dr. Hector Alvarez and colleagues from the University of Texas MD Anderson Cancer Center, in Houston, used liquid biopsies from 194 patients undergoing treatment for localized (n=71) or metastatic (n=123) pancreatic ductal adenocarcinoma (PDAC) to investigate the utility of ctDNA and exoDNA for predicting outcomes.

KRAS-detection rates at baseline were 61% in exoDNA and 53% in ctDNA in patients with metastases and 38% and 34%, respectively, in patients with localized disease, the team reports in Gastroenterology, online September 18.

Mutation-detection rates were substantially lower among patients with other pancreatic lesions: 12% and 16%, respectively, for pancreatic cysts and 25% and 17%, respectively, for non-neoplastic pancreatic disease.

ExoKRAS mutant allele fraction (MAF) declined after neoadjuvant therapy and after tumor resection, but increased or did not change in patients who were not surgical candidates.

Compared with no detection, the presence of detectable ctDNA (that is, with any mutant KRAS) was associated with significantly shorter progression-free survival (PFS), with a hazard ratio 1.93, and overall survival (OS), with a hazard ratio of 2.36.

Similarly, patients with exoKRAS MAF higher than 5% had significantly reduced PFS and OS.

On multivariate analysis, exoKRAS MAF of 5% or higher was the only significant predictor of PFS and the only individual predictor of OS. Both exoKRAS 5% and higher and detectable ctDNA were significant predictors of poorer OS when occurring in combination with CA19-9 levels of 300 or higher at baseline.

ExoKRAS also predicted radiological progression, whereas ctDNA did not.

"Our study in a relatively large cohort of PDAC patients, comprised of both metastatic and localized disease, reiterates the predictive and prognostic value of liquid biopsies in this malignancy," the researchers conclude.

"In contrast to the challenges of repetitive tissue biopsies for visceral cancers, serial liquid biopsies may provide an attractive alternative strategy to map tumor evolution in real time, providing an unprecedented insight into how the PDAC genome adapts to, and eventually becomes recalcitrant, to therapy," they add.

Dr. Alvarez did not respond to a request for comments.

SOURCE: https://bit.ly/2N6pXKX

Gastroenterology 2018.