Title:	Assessment of mutation burden after clinical intervention in pancreatic ductal adenocarcinomas (PDAC), and biliary tract cancers (BTC) via profiling circulating tumor DNA (ctDNA).
Authors:	Pittella-Silva, Fabio Motoya, Masayo Kimura, Yasutoshi Nakamura, Toru Low, Siew-Kee Nakamura, Yusuke
metadata.dc.contributor.affiliation:	Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan Universidade de Brasília, Faculdade de Ciências da Saúde Department of Gastroenterology and Hepatology, Sapporo Medical University, Sapporo, Japan Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan Department of Gastroenterological Surgery, Hokkaido University, Sapporo, Japan Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
Assunto::	Mutação genética Pâncreas - câncer Adenocarcinoma Tumores Câncer - tratamento
Issue Date:	25-May-2020
Publisher:	American Society of Clinical Oncology
Citation:	PITTELLA-SILVA, Fabio et al. Assessment of mutation burden after clinical intervention in pancreatic ductal adenocarcinomas (PDAC), and biliary tract cancers (BTC) via profiling circulating tumor DNA (ctDNA). Journal of Clinical Oncology, v. 38, n. 15 supl., e15529, 25 maio 2020. DOI: 10.1200/JCO.2020.38.15_suppl.e15529.
Abstract:	Background: PDAC and BTC have very poor prognosis with limited treatment options. Blood-based monitoring of ctDNA may have great potential to improve early detection of relapse or failure to chemotherapy and to possibly identify actionable genetic alterations. Methods: We performed targeted sequencing using NGS with Ion S5 Oncomine PanCancer gene panel to investigate mutations in 52 genes in 42 PDAC and 24 BTC patients. Blood samples were obtained from PDAC and BTC cases before the first intervention (baseline) as well as 2-4 weeks later to evaluate cfDNA mutations after surgery or chemotherapy. Actionable alterations with potential therapeutic relevance was defined as those with possible treatments within OncoKB system. We also compared the amount of cfDNA and mutant allele detection rates in pre-, intra- and post-operative samples. Results: Overall detection of ctDNA alterations in baseline samples was 74% (31/42) in PDAC cases. Alterations including SNVs and CNVs were detected among 15 genes; mutations in TP53 (53%), KRAS (41%) and SMAD4 (10%) were most commonly identified. Overall detection rate in BTC patients was 83% (20/24) comprising 9 genes; frequent mutations were observed in TP53 (58%) and KRAS (33%). Decrease in MAF (mutant allele frequency) was observed in 64% (18/28) of PDAC cases after the treatment and that of CA19-9 was observed in 50% (14/28) of the cases. In BTC pts, reduction of MAF was observed in 60% of the cases after surgery. Potentially actionable mutations were observed in 38% of PDAC samples and in 25% of BTC samples. Interestingly, the amounts of cfDNA were 4-fold higher in intraoperative samples compared to pre- and post-operative samples indicating release of cfDNA during surgery, possibly by tissue damage. Conclusions: We have shown the feasibility to assess minimum residual tumor cells or drug response by liquid biopsy in both PDAC and BTC which may improve the clinical management.
DOI:	10.1200/JCO.2020.38.15_suppl.e15529
metadata.dc.relation.publisherversion:	https://ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.e15529
Appears in Collections:	Artigos publicados em periódicos e afins

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