Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma

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 substantia...

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Vydáno v:	International journal of cancer Ročník 146; číslo 5; s. 1445 - 1456
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Hoboken, USA John Wiley & Sons, Inc 01.03.2020 Wiley Subscription Services, Inc
Témata:	Adenocarcinoma Aged Biomarkers, Tumor - blood Biomarkers, Tumor - isolation & purification Cancer Carcinoma, Pancreatic Ductal - blood Carcinoma, Pancreatic Ductal - mortality Carcinoma, Pancreatic Ductal - secondary circulating tumor DNA Circulating Tumor DNA - blood Circulating Tumor DNA - isolation & purification Deoxyribonucleic acid DNA Female Follow-Up Studies Gene frequency High-Throughput Nucleotide Sequencing Humans KRAS Liver Liver Neoplasms - blood Liver Neoplasms - mortality Liver Neoplasms - secondary Male Medical research Metastases Metastasis Middle Aged Pancreas Pancreatic cancer Pancreatic Neoplasms - blood Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Prognosis Prospective Studies Retrospective Studies Tumor Burden Tumor Markers and Signatures tumor volume pancreatic cancer KRAS tumor volume prognosis circulating tumor DNA
ISSN:	0020-7136, 1097-0215, 1097-0215
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Shrnutí:	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. What's new? Circulating tumor DNA (ctDNA) attracts much interest as a possible prognostic tool for cancer. Here, the authors showed that the quantity of ctDNA correlated strongly with tumor volume in metastatic pancreatic ductal adenocarcinoma (mPDAC). They conducted a retrospective analysis using samples collected from 58 untreated mPDAC patients. For this study, the authors designed a pancreatobiliary NGS panel, which they used to test the patients’ cell‐free DNA, along with droplet digital PCR. Both ctDNA variant allele frequency and tumor volume predicted overall survival, they found.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 F.D. and H.W.L. shared senior authorship Conflict of interests: M.S. has received a travel grant sponsored by IPSEN. S.S. has received a travel grant (travel expenses and accommodation) from Roche. K.P.L. is a consultant for AngioDynamics and Cook. M.J.V. has received research funding from Seno Medical Instruments, is involved in Agendia and travel/accommodation expenses were paid by Hoffmann‐La Roche. J.W.W. has received research funding from Servier, Halozyme, Novartis, Celgene, Astra Zenica, Pfizer, Roche and Merck. B.Y. received a travel grant from Servier, and disclosed that one of the employees on the payroll of his group is paid by GenM. M.F.B. has received research funding from Celgene and acted as a consultant to Servier. H.W.L. has acted as a consultant for Celgene, Eli Lilly and Company, Nordic Pharma Group and Philips, has received research grants from, Amgen, Bayer Schering Pharma AG, Celgene, Eli Lilly and Company, GlaxoSmithKline Pharmaceuticals, Nordic Pharma Group, Philips, Roche Pharmaceuticals. M.S. and E.C.S. contributed equally to this work
ISSN:	0020-7136 1097-0215 1097-0215
DOI:	10.1002/ijc.32586