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. 2017 Sep 26;117(7):1017-1025.
doi: 10.1038/bjc.2017.250. Epub 2017 Aug 3.

Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

David Sefrioui  1   2 , France Blanchard  3 , Emmanuel Toure  3 , Paul Basile  1 , Ludivine Beaussire  2 , Claire Dolfus  3 , Anne Perdrix  2   4 , Marianne Paresy  3 , Michel Antonietti  1 , Isabelle Iwanicki-Caron  1 , Raied Alhameedi  1 , Stephane Lecleire  1 , Alice Gangloff  1 , Lilian Schwarz  5 , Florian Clatot  2   6 , Jean-Jacques Tuech  5 , Thierry Frébourg  2   7 , Fabrice Jardin  2   8 , Jean-Christophe Sabourin  2   3 , Nasrin Sarafan-Vasseur  2 , Pierre Michel  1   2 , Frédéric Di Fiore  1   2   6
Affiliations

Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

David Sefrioui et al. Br J Cancer. .

Abstract

Background: The direct comparison of CA19.9, circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has never been performed for the diagnosis of solid pancreatic tumours (SPTs).

Methods: We included 68 patients with a SPT referred for EUS-FNA. CTCs were analysed using size-based platform and ctDNA using digital PCR. The sensitivity, specificity, negative and positive predictive values were evaluated for each marker and their combination.

Results: SPTs corresponded to 58 malignant tumours (52 pancreatic adenocarcinoma (PA) and 6 others) and 10 benign lesions. The sensitivity and specificity for PA diagnosis were 73% and 88% for EUS-FNA, 67% and 80% for CTC, 65% and 75% for ctDNA and 79% and 93% for CA19.9, respectively. The positivity of at least 2 markers was associated with a sensitivity and specificity of 78% and 91%, respectively. CtDNA was the only marker associated with overall survival (median 5.2 months for ctDNA+ vs 11.0 months for ctDNA-, P=0.01).

Conclusions: CA19.9 alone and in combination with ctDNA and/or CTC analysis may represent an efficient method for diagnosing PA in patients with SPTs. Further studies including a larger cohort of patients with both malignant and benign lesions will be necessary to confirm these promising results.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representation of circulating tumour DNA detection with ddPCR for two patients with pancreatic adenocarcinoma and a KRAS mutation (p.G12D for patient 47 and p.G12V for patient 63). The graphs in (A and C) illustrate the data obtained with multiplex assays, and the graphs in (B and D) illustrate the data obtained with simplex assays. The blue and green dots represent droplets containing amplified mutant and wild-type alleles, respectively. The red dots correspond to droplets containing both mutant and wild-type alleles. The gray dots correspond to wells containing no alleles (no amplification). % circulating tumour DNA represents the fraction of mutant allele/total allele (wild-type allele+mutant allele). Abbreviation: ctDNA, circulating tumour DNA.
Figure 2
Figure 2
Comparison of results obtained with the multiplex and simplex analyses. The graph illustrates the concordance of the allelic frequency (r2=0.995) between the 23 samples that tested positive in the multiplex and simplex analyses.
Figure 3
Figure 3
Overall survival of patients with pancreatic adenocarcinoma according to circulating biomarkers at baseline. (A) Kaplan–Maier survival curve stratified by the presence (black line) or absence (red line) of CTCs. (B) Kaplan–Maier survival curve stratified by the CTC level above (black line) or below (red line) the median value (4 CTC ml−1). (C) Kaplan–Maier survival curve stratified by the presence (black line) or absence (red line) of ctDNA. (D) Kaplan–Maier survival curve stratified by the ctDNA level above (black line) or below (red line) the median allelic frequency value (0.75%). (E) Kaplan–Maier survival curve stratified by the cfDNA level above (black line) or below (red line) the median value (59.5 ng ml−1) expressed as ng ml−1 of plasma. (F) Kaplan–Maier survival curve stratified by the CA19.9 level above (black line) or below (red line) the median value (174 UI l−1).
See this image and copyright information in PMC

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