Clinical significance of monitoring KRAS in tissue and plasma of pancreatic cancer patients.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 745-745
Author(s):  
Fumiaki Watanabe ◽  
Koichi Suzuki ◽  
Toshiki Rikiyama
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Prognostic Biomarker ◽  
Pancreatic Tumors ◽  
Curative Surgery ◽  
Tumor Tissues ◽  
Polymerase Chain ◽  
Predictive And Prognostic Biomarker ◽  
Digital Polymerase Chain Reaction ◽  
Tumor Dna

745 Background: KRAS monitoringprovides valuable information for early diagnosis and prediction of treatment outcome in colorectal cancer. KRASmutation is observed in only half of colon cancer patients, whereas it is detected in 90% of pancreatic cancer patients. Therefore, investigating tumor DNA in plasma by KRAS monitoringmay be even more valuablein pancreatic cancerpatients. In this study, we elucidated the clinicalsignificance of KRASmonitoring in pancreatic cancer patients during treatment. Methods: KRASin tumor tissues was analyzed for mutations by Scorpion ARMS or RASKET in 83 patients with pancreatic tumors. KRASin plasma was analyzed for mutations(G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61L, and Q61H) using droplet digital polymerase chain reaction in 88 patients who underwent the curative surgery (N = 45) or the chemotherapy (N = 33) and who had KRAS mutation in their tissues. Results: KRASmutation in tumor tissues was detected in 74 of 83 patients (89.2%). These 74 patients showed significantly poorer prognosis (MST; 32) than the seven patients without mutation (p = 0.03), whose MST were 193. Monitoring of KRASin plasma revealed KRASmutation in 35 of 88 patients (39.8%). In patients who underwent the chemotherapy (N = 33), 2years OS of patients who detected KRASmutation in plasma (N = 23) was 16.4% and them which not detected it (N = 10) was 53.3% (p = 0.18). But in the curative resection group (N = 45), 3years OS of patients who detected KRASmutation in plasma (N = 12) was 16.7% and them which not detected it (N = 33) was 68.2% (p = 0.00). Conclusions: KRASmutation in tissue and plasma could be a valuable predictive and prognostic biomarker in pancreatic cancer patients.

Clinical significance of monitoring KRAS in the blood of pancreatic cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23042-e23042
Author(s):  
Fumiaki Watanabe ◽  
Koichi Suzuki ◽  
Kosuke Ichida ◽  
Yuji Takayama ◽  
Taro Fukui ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Kras Mutation ◽  
Tumor Biology ◽  
Pancreatic Tumors ◽  
Tumor Tissues ◽  
Polymerase Chain ◽  
Predictive And Prognostic Biomarker ◽  
Digital Polymerase Chain Reaction

e23042 Background: KRAS monitoring provides valuable information for early diagnosis and prediction of treatment outcome in colorectal cancer. KRAS mutation is observed in only half of colon cancer patients, whereas it is detected in 90% of pancreatic cancer patients. Therefore, investigating tumor DNA in blood by KRAS monitoring may be even more valuable in pancreatic cancer patients. In this study, we elucidated the clinical significance of KRAS monitoring in pancreatic cancer patients during treatment. Methods: KRAS in tumor tissues was analyzed for mutations by Scorpion ARMS or RASKET in 38 patients with pancreatic tumors. KRAS in blood was analyzed for mutations (G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61L, and Q61H) using droplet digital polymerase chain reaction in 23 patients who underwent chemotherapy and who had KRAS mutation in their tissues. Results: KRAS mutation in tumor tissues was detected in 27 of 38 patients (71.1%). These 27 patients showed significantly poorer prognosis (24.4 months median overall survival time [MST]) than the six patients without mutation (p = 0.04), who were all alive. Patients with mutation of 12D in tumor tissues showed better prognosis than patients with other types of mutation; thus, mutation of 12D may have a different biological effect to other mutations. Monitoring of KRAS in blood revealed KRAS mutation in 14 of 23 patients (60.9%). These 14 patients exhibited significantly poorer treatment outcomes than patients without mutation. The MST of patients with KRAS mutation in their blood was significantly shorter than that of patients without KRAS mutation (17.7 months vs. 44.3 months, p = 0.03). Conclusions: KRAS mutation in blood could be a valuable predictive and prognostic biomarker in pancreatic cancer patients who undergo chemotherapy. Additionally, assessment of KRAS in tumor tissues may provide information about individual tumor biology.

Clinical significance of monitoring KRAS in tissue and serum of pancreatic cancer patients.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 286-286
Author(s):  
Fumiaki Watanabe ◽  
Koichi Suzuki ◽  
Hideki Ishikawa ◽  
Yuhei Endo ◽  
Kosuke Ichida ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Kras Mutation ◽  
Tumor Biology ◽  
Pancreatic Tumors ◽  
Curative Surgery ◽  
Kras Mutations ◽  
Tumor Tissues ◽  
Predictive And Prognostic Biomarker

286 Background: KRAS monitoring provides valuable information for early diagnosis and prediction of treatment outcome in colorectal cancer. KRAS mutation is observed in only half of colon cancer patients, whereas it is detected in 90% of pancreatic cancer patients. Therefore, investigating tumor DNA in serum by KRAS monitoring may be even more valuable in pancreatic cancer patients. In this study, we elucidated the clinical significance of KRAS monitoring in pancreatic cancer patients during treatment. Methods: KRAS in tumor tissues was analyzed for mutations by Scorpion ARMS or RASKET in 69 patients with pancreatic tumors. KRAS in serum was analyzed for mutations (G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61L, and Q61H) using droplet digital polymerase chain reaction in 58 patients who underwent the curative surgery (N = 39) or the chemotherapy (N = 19) and who had KRAS mutation in their tissues. Results: KRAS mutation in tumor tissues was detected in 62 of 69 patients (92.5%). These 62 patients showed significantly poorer prognosis (3years overall survival; 43.9%) than the seven patients without mutation (p = 0.03), who were all alive. Monitoring of KRAS in serum revealed KRAS mutation in 22 of 58 patients (37.9%). In patients who underwent the chemotherapy (N = 19), 2years OS of patients who detected KRAS mutation in serum (N = 9) was 0% and them which not detected it (N = 10) was 46.7% (p = 0.01). And in the curative resection group (N = 39), we detected KRAS mutations in serum among recurrent patients after surgery, but did not detect them among non-recurrent patients. Conclusions: KRAS mutation in serum could be a valuable predictive and prognostic biomarker in pancreatic cancer patients. Additionally, assessment of KRAS in tumor tissues may provide information about individual tumor biology. So, monitoring KRAS status of patients with pancreatic cancer may be useful of the treatment strategy.

scholarly journals The Origin of Tumor DNA in Urine of Urogenital Cancer Patients: Local Shedding and Transrenal Excretion

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 535
Author(s):  
Anouk E. Hentschel ◽  
Rianne van den Helder ◽  
Nienke E. van Trommel ◽  
Annina P. van Splunter ◽  
Robert A. A. van Boerdonk ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Bladder Tumor ◽  
Great Promise ◽  
Tumor Tissues ◽  
Catheter Urine ◽  
Tumor Dna ◽  
Urogenital Cancers

In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.

scholarly journals Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker

2016 ◽  
Vol 23 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Daniel Pietrasz ◽  
Nicolas Pécuchet ◽  
Fanny Garlan ◽  
Audrey Didelot ◽  
Olivier Dubreuil ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 516 ◽  
Author(s):  
François-Clément Bidard ◽  
Nicolas Kiavue ◽  
Marc Ychou ◽  
Luc Cabel ◽  
Marc-Henri Stern ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Circulating Tumor Cell ◽  
Circulating Tumor Dna ◽  
Detection Sensitivity ◽  
Clinical Validity ◽  
Mutational Status ◽  
Prospective Phase ◽  
Polymerase Chain ◽  
Digital Polymerase Chain Reaction ◽  
Tumor Dna

The management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection. CRC patients with potentially resectable LM were treated with first-line triplet or doublet chemotherapy combined with targeted therapy. CTC (Cellsearch®) and Kirsten RAt Sarcoma (KRAS) ctDNA (droplet digital polymerase chain reaction (PCR)) levels were assessed at inclusion, after 4 weeks of therapy and before LM surgery. 153 patients were enrolled. The proportion of patients with high CTC counts (≥3 CTC/7.5mL) decreased during therapy: 19% (25/132) at baseline, 3% (3/108) at week 4 and 0/57 before surgery. ctDNA detection sensitivity at baseline was 91% (N=42/46) and also decreased during treatment. Interestingly, persistently detectable KRAS ctDNA (p = 0.01) at 4 weeks was associated with a lower R0/R1 LM resection rate. Among patients who had a R0/R1 LM resection, those with detectable ctDNA levels before liver surgery had a shorter overall survival (p < 0.001). In CRC patients with limited metastatic spread, ctDNA could be used as liquid biopsy tool. Therefore, ctDNA detection could help to select patients eligible for LM resection.

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

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 288-288 ◽  
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.

The clinical significance of KRAS monitoring in tumor tissues and blood of patients with pancreatic tumor.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 334-334 ◽  
Author(s):  
Fumiaki Watanabe ◽  
Koichi Suzuki ◽  
Kosuke Ichida ◽  
Yuji Takayama ◽  
Taro Fukui ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Treatment Outcome ◽  
Clinical Significance ◽  
Kras Mutation ◽  
Poor Prognosis ◽  
Pancreatic Tumor ◽  
Pancreatic Tumors ◽  
Tumor Tissues ◽  
Kras Status

334 Background: Monitoring of gene alterations in blood to track circulating tumor DNAs has been attempted for a clinical application. For example, KRAS monitoring in colorectal cancer provides a valuable biomarker for diagnosis and prediction of treatment outcome. While half of of colon cancer has RAS mutation, 90% of pancreatic cancer shows KRAS mutation, suggesting that most of pancreatic cancer is a good candidate for KRAS monitoring. In this study, we elucidated the clinical significance of KRASmonitoring in patients with pancreatic tumor during treatments. Methods: KRAS mutation in tumor tissues was determined by Scorpion ARMS or RASKET methods in 39 patients with pancreatic tumors. KRASmutation in blood (G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61L, Q61H) were investigated by using droplet digital polymerase chain reaction (ddPCR) in 24 patients treated with chemotherapy. Results: KRAS assessment in tumor tissues showed 33 patients with mutation and 6 patients without mutation. Thirty-three patients with mutation showed significantly poor prognosis of 49% in three years overall survival (OS) as compared with 100% in 6 patients with mutation (p=0.02). KRAS assessment in blood revealed that KRAS mutation was detected in 14 patients, but no detection was seen in 10 patients. Patients harboring KRAS mutation in blood exhibited significantly poor treatment outcome, including 12 patients with progressive disease, as compared with 10 patients without detection of mutation, including 6 patients with any treatment responses (stable disease in 4 patients and partial response in 2 patients, p=0.03). Fourteen patients with mutation in blood displayed poor prognosis of 20% in three years overall survival (OS), comparing to 69% in 10 patients without mutation in blood (p=0.06). Conclusions: KRAS status in tumor tissues was involved in prognosis; in addition, KRAS status in blood was implicated in treatment response of chemotherapy in patients with pancreatic tumor. KRAS monitoring in tumor tissues and blood provides useful information for the treatment strategy including chemotherapy in patients with pancreatic tumor.

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