Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localised pancreatic cancer
- Lee, B; Lipton, L; COHEN, J; Tie, J; Javed, AA; Li, L; Goldstein, D; Burge, M; Cooray, P; Nagrial, A; Tebbutt, NC; Thomson, B; Nikfarjam, M; Harris, M; Haydon, A; Lawrence, B; Wm Tai, D; Simons, K; Lennon, AM; Wolfgang, CL; Tomasetti, C; Papadopoulos, N; Kinzler, KW; Vogelstein, B; Gibbs, P;
Publication Year 2019-09-01, Volume 30, Issue #9, Page 1472-1478
- Journal Title
- Annals of Oncology
- Publication Type
- Journal Article
- BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
- Oxford Academic
- WEHI Research Division(s)
- Personalised Oncology
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-07-01 12:57:16Last Modified: 2019-10-11 03:40:25