Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/21125
Title: Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localised pancreatic cancer.
Authors: Lee, B;Lipton, L;Cohen, J;Tie, J;Javed, A A;Li, L;Goldstein, D;Burge, M;Cooray, P;Nagrial, A;Tebbutt, N C;Thomson, B;Nikfarjam, Merhdad;Harris, M;Haydon, A;Lawrence, B;Wm Tai, D;Simons, K;Lennon, A M;Wolfgang, C L;Tomasetti, C;Papadopoulos, N;Kinzler, K W;Vogelstein, B;Gibbs, P
Affiliation: Division of Systems Biology & Personalised Medicine, Walter & Eliza Hall Institute (WEHI), Melbourne, Australia
Department of Medical Oncology, Prince of Wales Hospital, Randwick, Australia
Department of Medical Oncology, Royal Brisbane Hospital, Brisbane, Australia
Department of Medical Oncology, Crown Princess Mary Cancer Centre Westmead, Australia
Department of Surgery, Royal Melbourne Hospital, Melbourne, Australia
Department of Medical Oncology, Monash Medical Centre, Clayton, Australia
Department of Medical Oncology, Alfred Hospital, Australia
Centre for Epidemiology & Biostatistics, University of Melbourne, Melbourne, Australia
Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Australia
Department of Medical Oncology, Western Health, Melbourne, Australia
Department of Medical Oncology, Cabrini Health, Malvern, Australia
Department of Medical Oncology, Eastern Health, Melbourne, Australia
Department of Medical Oncology, Olivia Newton John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
Ludwig Centre and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Centre, Baltimore, USA.
Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, USA.
Department of Medical Oncology, Auckland City Hospital, New Zealand.
Department of Medical Oncology, National Cancer Centre, Singapore.
Ludwig Centre and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Centre, Baltimore, USA.
Ludwig Centre and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Centre, Baltimore, USA. Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, USA.
Ludwig Centre and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Centre, Baltimore, USA.
Issue Date: 28-Jun-2019
EDate: 2019-06-28
Citation: Annals of oncology : official journal of the European Society for Medical Oncology 2019; online first: 28 June
Abstract: In early-stage pancreatic cancer there are no currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical utility of circulating tumour DNA (ctDNA) analysis to inform adjuvant therapy decision making. Patients considered by the multidisciplinary team to have resectable pancreatic adenocarcinoma were enrolled. Pre- and post-operative samples for ctDNA analysis were collected. PCR-based-SafeSeqS assays were used to identify mutations at codon 12, 13 and 61 of KRAS in the primary pancreatic tumor and to detect ctDNA. Results of ctDNA analysis were correlated with CA19-9, recurrence-free and overall survival. Patient management was per standard of care, blinded to ctDNA data. Of 112 patients consented pre-operatively, 81 (72%) underwent resection. KRAS mutations were identified in 91% (38/42) of available tumor samples. Of available plasma samples (N=42), KRAS mutated ctDNA was detected in 62% (23/37) pre-operative and 37% (13/35) post-operative cases. At a median follow-up of 38.4 months, ctDNA detection in the pre- operative setting was associated with inferior recurrence free survival (Hazard Ratio (HR) 4.1; P=0.002) and overall survival (HR 4.1; P=0.015). Detectable ctDNA following curative intent resection was associated with inferior recurrence free survival (HR 5.4; P<0.0001) and overall survival (HR 4.0; P=0.003). Recurrence occurred in 13/13 (100%) patients with detectable ctDNA post-operatively, including in seven that received gemcitabine-based adjuvant chemotherapy. ctDNA studies in localized pancreatic cancer are challenging, with a substantial number of patients not able to undergo resection, not having sufficient tumor tissue for analysis or not completing per protocol sample collection. ctDNA analysis, pre- and/or post-surgery, is a promising prognostic marker. Studies of ctDNA guided therapy are justified, including of treatment intensification strategies for patients with detectable ctDNA post-operatively who appear at very high risk of recurrence despite gemcitabine-based adjuvant therapy.
URI: http://ahro.austin.org.au/austinjspui/handle/1/21125
DOI: 10.1093/annonc/mdz200
ORCID: 0000-0003-4866-276X
PubMed URL: 31250894
Type: Journal Article
Subjects: Adjuvant therapy
Biomarkers
Circulating Tumor DNA (ctDNA)
Liquid Biopsy
Pancreatic Ductal Adenocarcinoma (PDAC)
Pancreatic cancer
Appears in Collections:Journal articles

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