Circulating free DNA as biomarker and source for mutation detection in metastatic XXXX .

@entity1 @entity5 @entity984 @entity73 @entity14 @entity1098
BACKGROUND: Circulating cell-free DNA (cfDNA) in plasma has shown potential as biomarker in various @entity5 and could become an importance source for @entity5 mutation detection. The objectives of our study were to establish a normal range of cfDNA in a cohort of healthy individuals and to compare this with four cohorts of metastatic @entity14 (mCRC) @entity1 . We also investigated the prognostic value of cfDNA and analysed the @entity5 -specific @entity984 mutations in the plasma. METHODS: The study was a prospective biomarker evaluation in four consecutive Phase II trials, including 229 @entity1 with chemotherapy refractory mCRC and 100 healthy individuals. Plasma was obtained from an @entity1098 blood-sample, and the total number of DNA alleles and @entity984 mutated alleles were assessed using an in-house ARMS-qPCR as previously described. RESULTS: Median cfDNA levels were higher in mCRC compared to controls (p < 0.0001). ROC analysis revealed an AUC of 0.9486 (p<0.00001). Data showed @entity73 with increasing levels of baseline cfDNA both when categorising @entity1 by quartiles of cfDNA and into low or high cfDNA groups based on the upper normal range of the control group (Median OS 10.2 (8.3-11.7) and 5.2 (4.6-5.9) months, respectively, HR 1.78, p = 0.0006). Multivariate analysis confirmed an independent prognostic value of cfDNA (HR 1.5 (95% CI 1.3-1.7) for each increase in the cfDNA quartile). The overall concordance of @entity984 mutations in plasma and tissue was high (85%). CONCLUSIONS: These data confirm the prognostic value of cfDNA measurement in plasma and utility for mutation detection with the method presented.
