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Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer.

ABSTRACT: BACKGROUND:In early-stage pancreatic cancer, there are currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical utility of circulating tumor DNA (ctDNA) analysis to inform adjuvant therapy decision making. MATERIALS AND 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 (OS). 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 (RFS) [hazard ratio (HR) 4.1; P?=?0.002)] and OS (HR 4.1; P?=?0.015). Detectable ctDNA following curative intent resection was associated with inferior RFS (HR 5.4; P?

SUBMITTER: Lee B

PROVIDER: S-EPMC6771221 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer.

Lee B B Lipton L L Cohen J J Tie J J Javed A A AA Li L L Goldstein D D Burge M M Cooray P P Nagrial A A Tebbutt N C NC Thomson B B Nikfarjam M M Harris M M Haydon A A Lawrence B B Tai D W M DWM Simons K K Lennon A M AM Wolfgang C L CL Tomasetti C C Papadopoulos N N Kinzler K W KW Vogelstein B B Gibbs P P

Annals of oncology : official journal of the European Society for Medical Oncology 20190901 9

<h4>Background</h4>In early-stage pancreatic cancer, there are currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical utility of circulating tumor DNA (ctDNA) analysis to inform adjuvant therapy decision making.<h4>Materials and methods</h4>Patients considered by the multidisciplinary team to have resectable pancreatic adenocarcinoma were enrolled. Pre- and post-operative samples for ctDNA analysis were ...[more]

PMID: 31250894

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Project description:BackgroundThe pre-adjuvant chemotherapy (PAC) status of postoperative pancreatic ductal adenocarcinoma (PDAC) patients has not been studied and elaborated well previously.MethodThe association of PAC variables and prognoses was explored using a multivariable Cox model, restricted cubic spline analysis, and correlation analysis. The main outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcome was chemotherapy completeness (CHC).ResultsA total of 401 eligible patients were enrolled in sequential surgery and chemotherapy. The chemotherapy regimen, PAC fasting blood glucose (FBG), and elevated fasting blood glucose (eFBG) status were associated with CHC (regimen types: p = 0.005, continuous FBG: p = 0.014, eFBG status: p = 0.012). Early administration of adjuvant chemotherapy (<34 days) was a risk factor for the limited OS and PFS (OS: aHR: 1.61 [1.09-2.38], p = 0.016; PFS: aHR: 1.91 [1.29-2.82], p = 0.001). Patients with higher PAC body mass index (BMI), receiving Gemcap regimen, and with lower PAC tumor marker value were observed with better survival prognoses (PAC BMI: OS: 0.927 [0.875-0.983], p = 0.011; Gemcap: OS: 0.533 [0.312-0.913], p = 0.022; Gemcap: PFS: 0.560 [0.341-0.922], p = 0.023; PAC CA125: OS: 1.004 [1.002-1.006], p < 0.001; PAC CA125: PFS: 1.003 [1.000-1.005], p = 0.031; PAC CEA: OS: 1.050 [1.026-1.074], p < 0.001). The BMI decrease was mainly concentrated in the first 3 months of chemotherapy courses (first 3 months: p < 0.001; latter 3 months: p = 0.097). And CEA, compared to CA125 and CA199, was a better prognostic indicator (CEA: first 3 months: PFS p = 0.011, OS p < 0.001; latter 3 months: PFS p = 0.024, OS p = 0.041).ConclusionPDAC patients should be treated with adjuvant chemotherapy over 34 postoperative days. PAC sarcopenia was a risk factor for OS, but not PFS and limited CHC. Those with higher PAC FBG levels were more likely to finish chemotherapy. CEA, compared to CA125 and CA199, was a better prognostic indicator.

Dataset Information

Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer.

Publications

Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer.

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