Prognostic Role of Circulating Tumor DNA in Resectable Pancreatic Cancer

Aim: The prognosis of resectable pancreatic cancer patients with the same stage of disease is highly variable. The purpose of this study is to establish a scoring system for preoperative screening of resectable patients. Materials & methods: The clinical information and laboratory tests of 105 resectable patients with pancreatic cancer were enrolled and analyzed. Results: The consistency of clinical stage and pathological stage was poor (κ = 0.193; p < 0.003). We performed a comprehensive scoring system with KRAS mutations in circulating tumor DNA (mut KRAS ctDNA) for the resectable patients. Patients with higher scores were more prone to early postoperative recurrence and poorer prognosis. Conclusion: The scoring system can help preoperatively screen out resectable patients who are prone to early postoperative recurrence.

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Comparative circulating tumor DNA levels for KRAS mutations in patients with nonresectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.288 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 288-288 ◽

Cited By ~ 2

Author(s):

Julia S. Johansen ◽

Cecile Rose T. Vibat ◽

Dan Calatayud ◽

Benny Vittrup Jensen ◽

Jane Preuss Hasselby ◽

...

Keyword(s):

Patient Outcome ◽

Pancreatic Cancer ◽

Cancer Patients ◽

Kras Mutation ◽

Circulating Tumor Dna ◽

Resectable Pancreatic Cancer ◽

Kras Mutations ◽

Study Objective ◽

Wide Range ◽

Tumor Dna

288 Background: Non-resectable pancreatic cancer patients have a wide range of median time for overall survival (OS). Currently there is a lack of diagnostic tools to predict patient outcome at diagnosis. KRAS mutations are present in the vast majority of pancreatic tumors. The study objective was to determine if quantitative baseline and longitudinal monitoring of KRAS mutations from plasma circulating tumor DNA (ctDNA) could be used to stratify patients for predicting outcome. Methods: Plasma was prospectively collected from the Danish BIOPAC study for non-resectable pancreatic cancer patients undergoing treatment with gemcitabine or FOLFIRINOX. Feasibility of monitoring ctDNA KRAS mutations was assessed in 10 patients with long OS (median 493 days; range 360-1031) and 10 patients with short OS (median 66 days; range 21-136). KRAS G12A/C/D/R/S/V, and G13D mutations were PCR enriched, sequenced by massively parallel deep sequencing, quantitated and standardized by reporting number of copies detected per 105 genome equivalents (GE). Results: In a pilot study of 20 patients, all 18 patients with evaluable DNA had detectable KRAS mutations. Of 18 patients, 12 had baseline plus longitudinal time points (7 short, 5 long OS). Mutant KRAS copies were higher for short OS (median=994; range 0-34305 copies/105 GE) vs. with long OS (median 196; range, 34-278 copies/105 GE). Longitudinally, KRAS mutation levels remained mostly low with long OS (last time point median 204; range 8-873 copies/105 GE) vs. short OS where levels increased or remained high (median 2363; range 71-47919 copies/105 GE). Identical KRAS mutations were consistently detected for a given patient with short OS. However, long OS patients had variable KRAS mutations in longitudinal analysis. Conclusions: High levels of ctDNA KRAS mutations at diagnosis and post-treatment elevation of KRAS mutations were more associated with short OS. Different levels of KRAS mutation at diagnosis may predict patient outcome and could reflect distinct underlying tumor biology. Expansion of this prospective-retrospective biomarker cohort will be reported.

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