Dataset Information

Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC.

Methods

We used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA. Samples were collected from 105 patients who underwent pancreatoduodenectomy for PDAC at a single institution. Overall survival (OS) was analysed according to the presence of ctDNA.

Results

Among the 105 cases, ctDNA was detected in 33 (31%) plasma samples. The median OS durations were 13.6 months for patients with ctDNA (ctDNA+) and 27.6 months for patients without ctDNA. Patients who were ctDNA+ had a significantly poorer prognosis with respect to OS (P<0.0001).

Conclusions

Our findings suggested that the presence of ctDNA in plasma samples could be an important and powerful predictor of poor survival in patients with PDAC. Accordingly, ctDNA detection might be a promising approach with respect to PDAC treatment.

SUBMITTER: Hadano N

PROVIDER: S-EPMC4931379 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer.

Hadano Naoto N Murakami Yoshiaki Y Uemura Kenichiro K Hashimoto Yasusi Y Kondo Naru N Nakagawa Naoya N Sueda Taijiro T Hiyama Eiso E

British journal of cancer 20160609 1

<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC.<h4>Methods</h4>We used droplet digital poly ...[more]

PMID: 27280632

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Project description:Increasing lymph node ratio (LNR) (ratio of metastatic lymph nodes to the total number of harvested lymph nodes) and extramural vascular invasion (EMVI) have been proposed as adverse prognostic indicators in colorectal cancer, although their use remains variable and controversial. The aim of the present study was to assess the prognostic value of LNR and EMVI in predicting survival for patients undergoing curative colon cancer resection.Between 2006 and 2012, 922 patients underwent curative colon cancer resection. Surgical technique and pathological assessment did not change during the study period. Clinical and pathological data were collected from a prospectively maintained database. The primary outcome measure was overall survival and disease-free survival. LNR was separated into five categories based on three previously calculated cutoff values: LNR 0 (no lymph nodes involved), LNR 1 (ratio 0.01<0.17), LNR 2 (ratio 0.18-0.41), LNR 3 (ratio 0.42-0.69), and LNR 4 (ratio >0.70).Nine hundred and twenty-two patients underwent colon cancer resection. The median follow-up for survivors was 52.8 months (IQR 34.6-77.6). The median total number of lymph nodes harvested was 16 (IQR13-22). On multivariate analysis, both pN and LNR were strongly associated with overall and disease-free survival. Using the Akaike information criterion (AIC), LNR had greater prognostic value compared with pN. For overall survival, compared with patients in LNR category 0, hazard ratios (95% CI) for those in categories 1, 2, 3 and 4 were 1.37 (1.03,1.82), 2.37 (1.70,3.30), 2.40 (1.57,3.65) and 5.51 (3.16,9.58), respectively. For disease-free survival, patients had hazard ratios (95% CI) of 1.78 (1.25,2.52), 3.79 (2.56,5.61), 2.60 (1.50,4.48) and 4.76 (2.21,10.27), respectively. The presence of EMVI was a significant predictor of decreased overall and disease-free survival (P<0.001).This study demonstrated, in the presence of high surgical, oncology and pathological standards, EMVI and increasing LNR were independent predictors of decreased overall and disease-free survival for patients undergoing curative colon cancer resection. LNR was superior to pN stage in predicting overall and disease-free survival.

Project description:BackgroundCirculating angiogenic cytokines (CACs) have been confirmed as prognostic biomarkers and therapeutic targets in several solid tumors. However, their role as prognostic biomarkers in resected pancreatic ductal adenocarcinoma (PDAC) is unknown.ResultsThe expression of CACs in patients with PDAC differs from those with CP both pre- and postoperatively. Correlation analyses show significant correlations between circulating levels of CACs: VEGF was correlated with IL-6 (r = 0.457), FGF (r = 0.44), G-CSF (r = 0.543), HGF (r = 0.586) and SDF-1α (r = 0.784) before the surgery. The circulating levels of TNF-α correlated with the serum concentration of IL-4 before (r= 0.656) and after the resection (r = 0.776 on POD 3, r = 0.865 on POD 7). Gender did not show any correlation with serum levels of CAC, except for significantly higher levels of EGF in males (P = 0.002). Other clinicopathological variables such as age (< 65 vs. > 65 years), T, N, or UICC stage did not have an association with the cytokine levels. The multivariate model including the entire angiogenic panel revealed that postoperative increasing levels of EGF (P = 0.023), PDGFA-A (P = 0.024), TNF-α (P = 0.001) and IL-8 (P = 0.049) were associated with a favorable prognosis, whereas elevating levels of VEGF (P = 0.005) correlated with a poor cancer-specific survival.Materials and methodsPreoperative and postoperative blood samples were collected in patients undergoing surgery for PDAC (n = 40) or chronic pancreatitis (CP; n = 9). Serum levels of 13 angiogenic cytokines (IL-4, IL-6, FGF-b, G-CSF, TNF-α, VEGF, HGF, SDF-1α, IL-8, EGF, Ang-1, PDGF-AA and PlGF) were analyzed using ELISA and Multiplex. Prognostic factors were identified by a Cox proportional hazards model.ConclusionsPostoperative changes of serum levels of certain angiogenic cytokines correlate with patients' prognosis after resection for pancreatic cancer. CACs should thus be considered as biomarkers in patients with resected pancreatic cancer.

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Dataset Information

Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer.

Background

Methods

Results

Conclusions

Publications

Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer.

Similar Datasets

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