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Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma
Author(s) -
Strijker Marin,
Soer Eline C.,
Pastena Matteo,
Creemers Aafke,
Balduzzi Alberto,
Beagan Jamie J.,
Busch Olivier R.,
Delden Otto M.,
Halfwerk Hans,
Hooft Jeanin E.,
Lienden Krijn P.,
Marchegiani Giovanni,
Meijer Sybren L.,
Noesel Carel J.,
Reinten Roy J.,
Roos Eva,
Schokker Sandor,
Verheij Joanne,
Vijver Marc J.,
Waasdorp Cynthia,
Wilmink Johanna W.,
Ylstra Bauke,
Besselink Marc G.,
Bijlsma Maarten F.,
Dijk Frederike,
Laarhoven Hanneke W.
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32586
Subject(s) - hazard ratio , medicine , confidence interval , circulating tumor dna , gastroenterology , oncology , adenocarcinoma , proportional hazards model , pancreatic ductal adenocarcinoma , regimen , pancreatic cancer , cancer
Circulating tumor DNA (ctDNA) is assumed to reflect tumor burden and has been suggested as a tool for prognostication and follow‐up in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). However, the prognostic value of ctDNA and its relation with tumor burden has yet to be substantiated, especially in mPDAC. In this retrospective analysis of prospectively collected samples, cell‐free DNA from plasma samples of 58 treatment‐naive mPDAC patients was isolated and sequenced using a custom‐made pancreatobiliary NGS panel. Pathogenic mutations were detected in 26/58 (44.8%) samples. Cross‐check with droplet digital PCR showed good agreement in Bland–Altman analysis ( p = 0.217, nonsignificance indicating good agreement). In patients with liver metastases, ctDNA was more frequently detected (24/37, p < 0.001). Tumor volume (3D reconstructions from imaging) and ctDNA variant allele frequency (VAF) were correlated (Spearman's ρ = 0.544, p < 0.001). Median overall survival (OS) was 3.2 (95% confidence interval [CI] 1.6–4.9) versus 8.4 (95% CI 1.6–15.1) months in patients with detectable versus undetectable ctDNA ( p = 0.005). Both ctDNA VAF and tumor volume independently predicted OS after adjustment for carbohydrate antigen 19.9 and treatment regimen (hazard ratio [HR] 1.05, 95% CI 1.01–1.09, p = 0.005; HR 1.00, 95% CI 1.01–1.05, p = 0.003). In conclusion, our study showed that ctDNA detection rates are higher in patients with larger tumor volume and liver metastases. Nevertheless, measurements may diverge and, thus, can provide complementary information. Both ctDNA VAF and tumor volume were strong predictors of OS.