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

ABSTRACT: 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?

SUBMITTER: Strijker M

PROVIDER: S-EPMC7004068 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Strijker Marin M Soer Eline C EC de Pastena Matteo M Creemers Aafke A Balduzzi Alberto A Beagan Jamie J JJ Busch Olivier R OR van Delden Otto M OM Halfwerk Hans H van Hooft Jeanin E JE van Lienden Krijn P KP Marchegiani Giovanni G Meijer Sybren L SL van Noesel Carel J CJ Reinten Roy J RJ Roos Eva E Schokker Sandor S Verheij Joanne J van de Vijver Marc J MJ Waasdorp Cynthia C Wilmink Johanna W JW Ylstra Bauke B Besselink Marc G MG Bijlsma Maarten F MF Dijk Frederike F van Laarhoven Hanneke W HW

International journal of cancer 20190813 5

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 c ...[more]

PMID: 31340061

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced stage, with systemic therapy being the mainstay of treatment. Survival continues to be limited, typically less than 1 year. The PDAC microenvironment is characterized by a paucity of malignant epithelial cells, abundant stroma with predominantly immunosuppressive T cells and myelosuppressive-type macrophages (M2), and hypovascularity. The current treatment options for metastatic PDAC are modified (m)FOLFIRINOX /FOLFIRINOX or nab-paclitaxel and gemcitabine in patients with good performance status (PS) (ECOG 0-1/KPS 70-100%) and gemcitabine with or without a second agent for those with ECOG PS 2-3. New therapies are emerging, and the current guidelines endorse both germline and somatic testing in PDAC to evaluate actionable findings. Important themes related to new therapeutic approaches include DNA damage repair strategies, immunotherapy, targeting the stroma, and cancer-cell metabolism. Targeted therapy alone (outside small genomically defined subsets) or in combination with standard cytotoxic therapy, thus far, has proven disappointing in PDAC; however, novel therapies are evolving with increased integration of genomic profiling along with a better understanding of the tumor microenvironment and immunology. A small but important sub-group of patients have some of these agents available in the clinics for use. Olaparib was recently approved by the US Food and Drug Administration for maintenance therapy in germline BRCA1/2 mutated PDAC following demonstration of survival benefit in a phase 3 trial. Pembrolizumab is approved for patients with defects in mismatch repair/microsatellite instability. PDAC with wild-type KRAS represents a unique subgroup who have enrichment of potentially targetable oncogenic drivers. Small-molecule inhibitors including ERBB inhibitors (e.g., afatinib, MCLA-128), TRK inhibitors (e.g., larotrectinib, entrectinib), ALK/ROS inhibitor (e.g., crizotinib), and BRAF/MEK inhibitors are in development. In a small subset of patients with the KRASG12C mutation, a KRASG12C inhibitor, AMG510, and other agents are being investigated. Major efforts are underway to effectively target the tumor microenvironment and to integrate immunotherapy into the treatment of PDAC, and although thus far the impact has been modest to ineffective, nonetheless, there is optimism that some of the challenges will be overcome.

Dataset Information

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

Publications

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

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