scholarly journals SOURCE-PANC: A Prediction Model for Patients With Metastatic Pancreatic Ductal Adenocarcinoma Based on Nationwide Population-Based Data

2021 ◽  
Vol 19 (9) ◽  
pp. 1045-1053
Author(s):  
Héctor G. van den Boorn ◽  
Willemieke P.M. Dijksterhuis ◽  
Lydia G.M. van der Geest ◽  
Judith de Vos-Geelen ◽  
Marc G. Besselink ◽  
...  
Keyword(s):  
Prediction Model ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cross Validation ◽  
Cox Regression ◽  
Performance Status ◽  
Treatment Strategies ◽  
Population Based ◽  
Ductal Adenocarcinoma ◽  
Treatment Characteristics ◽  
Netherlands Cancer Registry

Background: A prediction model for overall survival (OS) in metastatic pancreatic ductal adenocarcinoma (PDAC) including patient and treatment characteristics is currently not available, but it could be valuable for supporting clinicians in patient communication about expectations and prognosis. We aimed to develop a prediction model for OS in metastatic PDAC, called SOURCE-PANC, based on nationwide population-based data. Materials and Methods: Data on patients diagnosed with synchronous metastatic PDAC in 2015 through 2018 were retrieved from the Netherlands Cancer Registry. A multivariate Cox regression model was created to predict OS for various treatment strategies. Available patient, tumor, and treatment characteristics were used to compose the model. Treatment strategies were categorized as systemic treatment (subdivided into FOLFIRINOX, gemcitabine/nab-paclitaxel, and gemcitabine monotherapy), biliary drainage, and best supportive care only. Validation was performed according to a temporal internal–external cross-validation scheme. The predictive quality was assessed with the C-index and calibration. Results: Data for 4,739 patients were included in the model. Sixteen predictors were included: age, sex, performance status, laboratory values (albumin, bilirubin, CA19-9, lactate dehydrogenase), clinical tumor and nodal stage, tumor sublocation, presence of distant lymph node metastases, liver or peritoneal metastases, number of metastatic sites, and treatment strategy. The model demonstrated a C-index of 0.72 in the internal–external cross-validation and showed good calibration, with the intercept and slope 95% confidence intervals including the ideal values of 0 and 1, respectively. Conclusions: A population-based prediction model for OS was developed for patients with metastatic PDAC and showed good performance. The predictors that were included in the model comprised both baseline patient and tumor characteristics and type of treatment. SOURCE-PANC will be incorporated in an electronic decision support tool to support shared decision-making in clinical practice.

scholarly journals Liver Metastases in Newly Diagnosed Pancreatic Ductal Adenocarcinoma: A Population Based Analysis

2020 ◽  
Author(s):  
Guoyi Wu ◽  
Xiaoben Pan ◽  
Baohua Wang ◽  
Xiaolei Zhu ◽  
Jing Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Metastases ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Size ◽  
Cox Regression ◽  
Population Based ◽  
The Body ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Factors Associated

Abstract Background Estimates of the incidence and prognosis of developing liver metastases at the pancreatic ductal adenocarcinoma (PDAC) diagnosis are lacking.Methods In this study, we analyzed the association of liver metastases and the PDAC patients outcome. The risk factors associated with liver metastases in PDAC patients were analyzed using multivariable logistic regression analysis. The overall survival (OS) was estimated using Kaplan-Meier curves and log-rank test. Cox regression was performed to identify factors associated with OS.Results Patients with primary PDAC in the tail of the pancreas had a higher incidence of liver metastases (62.2%) than those with PDAC in the head (28.6%). Female gender, younger age, primary PDAC in the body or tail of the pancreas, and larger primary PDAC tumor size were positively associated with the occurrence of liver metastases. The median survival of patients with liver metastases was significantly shorter than that of patients without liver metastases. Older age, unmarried status, primary PDAC in the tail of the pancreas, and tumor size ≥4 cm were risk factors for OS in the liver metastases cohort.Conclusions Population-based estimates of the incidence and prognosis of PDAC with liver metastases may help decide whether diffusion-weighted magnetic resonance imaging should be performed in patients with primary PDAC in the tail or body of the pancreas. The location of primary PDAC should be considered during the diagnosis and treatment of primary PDAC.

A High C-Reactive Protein Level on Postoperative Day 7 is Associated with Poor Survival of Patients with Pancreatic Ductal Adenocarcinoma after Resection

2021 ◽  
pp. 000313482110234
Author(s):  
Masaji Tani ◽  
Hiroya Iida ◽  
Hiromitsu Maehira ◽  
Haruki Mori ◽  
Toru Miyake ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Median Overall Survival ◽  
Cox Regression ◽  
Ductal Adenocarcinoma ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Retrospective View ◽  
Node Metastases ◽  
Common Malignancy

Introduction Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy. While inflammation-related biomarkers influence patient survival after resection, it has not been known whether postoperative inflammations affect the survival of PDAC patients or not. Methods It was investigated whether the universal biomarkers on postoperative day (POD) 7 affect the survival of PDAC patients in the retrospective view, and univariate and multivariate analyses were performed via the Cox regression method. Results Overall, 108 consecutive patients underwent resection; 98 (90.7%) had T3 disease and 73 (67.6%) had lymph node metastases. Thirty-four patients (31.5%) experienced postoperative complications. Compared with preoperative values, the white blood cell count and C-reactive protein (CRP) level on POD 7 were significantly elevated ( P < .001 for both); conversely, the lymphocyte count was significantly reduced ( P < .001). Among 108 patients, 72 received adjuvant chemotherapy. The median overall survival was 21.0 months; the 5-year survival rate was 22.3%. On multivariate analysis, receiving adjuvant chemotherapy and low CRP levels on POD 7 (<7.6 mg/dL) were prognosticators of better survival. However, the CD classification was not a prognosticator of survival after resection. Conclusions Adjuvant chemotherapy and postoperative low CRP levels on POD 7 were prognosticators of better survival of PDAC patients after resection. Surgeons should be aware of managing postoperative infections because a high postoperative CRP level is related with unfavorable survival.

scholarly journals Prognostic Nomogram for Patients With Pancreatic Ductal Adenocarcinoma of Pancreatic Head After Pancreaticoduodenectomy

2021 ◽  
Vol 15 ◽  
pp. 117955492110241
Author(s):  
Hongkai Zhuang ◽  
Zixuan Zhou ◽  
Zuyi Ma ◽  
Shanzhou Huang ◽  
Yuanfeng Gong ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Perineural Invasion ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Cox Regression Analysis ◽  
Ajcc Stage

Background: The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) of pancreatic head remains poor, even after potentially curative R0 resection. The aim of this study was to develop an accurate model to predict patients’ prognosis for PDAC of pancreatic head following pancreaticoduodenectomy. Methods: We retrospectively reviewed 112 patients with PDAC of pancreatic head after pancreaticoduodenectomy in Guangdong Provincial People’s Hospital between 2014 and 2018. Results: Five prognostic factors were identified using univariate Cox regression analysis, including age, histologic grade, American Joint Committee on Cancer (AJCC) Stage 8th, total bilirubin (TBIL), CA19-9. Using all subset analysis and multivariate Cox regression analysis, we developed a nomogram consisted of age, AJCC Stage 8th, perineural invasion, TBIL, and CA19-9, which had higher C-indexes for OS (0.73) and RFS (0.69) compared with AJCC Stage 8th alone (OS: 0.66; RFS: 0.67). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the nomogram for OS and RFS were significantly higher than other single parameter, which are AJCC Stage 8th, age, perineural invasion, TBIL, and CA19-9. Importantly, our nomogram displayed higher C-index for OS than previous reported models, indicating a better predictive value of our model. Conclusions: A simple and practical nomogram for patient prognosis in PDAC of pancreatic head following pancreaticoduodenectomy was established, which shows satisfactory predictive efficacy and deserves further evaluation in the future.

scholarly journals Development and Verification of the Hypoxia- and Immune-Associated Prognostic Signature for Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongjie Chen ◽  
Hui Huang ◽  
Longjun Zang ◽  
Wenzhe Gao ◽  
Hongwei Zhu ◽  
...  
Keyword(s):  
High Risk ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Risk Score ◽  
Cox Regression ◽  
Pearson Correlation ◽  
Risk Groups ◽  
Low Risk ◽  
Ductal Adenocarcinoma ◽  
Prognostic Signature ◽  
Score Model

We aim to construct a hypoxia- and immune-associated risk score model to predict the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). By unsupervised consensus clustering algorithms, we generate two different hypoxia clusters. Then, we screened out 682 hypoxia-associated and 528 immune-associated PDAC differentially expressed genes (DEGs) of PDAC using Pearson correlation analysis based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression project (GTEx) dataset. Seven hypoxia and immune-associated signature genes (S100A16, PPP3CA, SEMA3C, PLAU, IL18, GDF11, and NR0B1) were identified to construct a risk score model using the Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, which stratified patients into high- and low-risk groups and were further validated in the GEO and ICGC cohort. Patients in the low-risk group showed superior overall survival (OS) to their high-risk counterparts (p &lt; 0.05). Moreover, it was suggested by multivariate Cox regression that our constructed hypoxia-associated and immune-associated prognosis signature might be used as the independent factor for prognosis prediction (p &lt; 0.001). By CIBERSORT and ESTIMATE algorithms, we discovered that patients in high-risk groups had lower immune score, stromal score, and immune checkpoint expression such as PD-L1, and different immunocyte infiltration states compared with those low-risk patients. The mutation spectrum also differs between high- and low-risk groups. To sum up, our hypoxia- and immune-associated prognostic signature can be used as an approach to stratify the risk of PDAC.

scholarly journals Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Xin Zhao ◽  
Di Cao ◽  
Zhangyong Ren ◽  
Zhe Liu ◽  
Shaocheng Lv ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Dipeptidyl Peptidase ◽  
Ductal Adenocarcinoma ◽  
Gene Promoters ◽  
Cox Regression Analysis

Abstract Background: Hypermethylation of gene promoters plays an important role in tumorigenesis. The present study aimed to identify and validate promoter methylation-driven genes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC). Methods: Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing polymerase chain reaction (BSP) in paired tumor and normal tissues of 72 PDAC patients. Kaplan−Meier survival analyses were performed to evaluate the clinical value of PMDGs. Results: In GSE49149, the β-value of the dipeptidyl peptidase like 6 (DPP6) promoter was significantly higher in tumor compared with normal samples (0.50 vs. 0.24, P&lt;0.001). In the PDAC cohort of TCGA, the methylation level of the DPP6 promoter was negatively correlated with mRNA expression (r = −0.54, P&lt;0.001). In a multivariate Cox regression analysis, hypermethylation of the DPP6 promoter was an independent risk factor for PDAC (hazard ratio (HR) = 543.91, P=0.002). The results of BSP revealed that the number of methylated CG sites in the DPP6 promoter was greater in tumor samples than in normal samples (7.43 vs. 2.78, P&lt;0.001). The methylation level of the DPP6 promoter was moderately effective at distinguishing tumor from normal samples (area under ROC curve (AUC) = 0.74, P&lt;0.001). Hypermethylation of the DPP6 promoter was associated with poor overall (HR = 3.61, P&lt;0.001) and disease-free (HR = 2.01, P=0.016) survivals for PDAC patients. Conclusion: These results indicate that DPP6 promoter methylation is a potential prognostic biomarker for PDAC.

scholarly journals Complete Radiologic Response of Metastatic Pancreatic Ductal Adenocarcinoma to Microwave Ablation Combined with Second-Line Palliative Chemotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Hakon Blomstrand ◽  
Karin Adolfsson ◽  
Per Sandström ◽  
Bergthor Björnsson
Keyword(s):  
Adjuvant Chemotherapy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Palliative Chemotherapy ◽  
Lung Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
Ductal Adenocarcinoma ◽  
Second Line ◽  
First Line

Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis, especially for the majority of patients diagnosed with metastatic disease. The primary option for palliative treatment is chemotherapy, and responses beyond first-line treatment are rare and typically short. Here, we report a case of a 63-year-old woman with PDAC in the head of the pancreas who was initially successfully treated by pancreaticoduodenectomy followed by adjuvant chemotherapy with gemcitabine. However, disease recurrence with liver and para-aortic lymph node metastases was detected only two months after the completion of adjuvant chemotherapy. First-line palliative chemotherapy with gemcitabine-nab/paclitaxel was commenced. The results were discouraging, with disease progression (liver and lung metastases) detected at the first evaluation; the progression-free survival was just two months (64 days). Surprisingly, the response to second-line palliative chemotherapy with 5-fluorouracil-oxaliplatin was excellent; in combination with the ablation of a liver metastasis, this treatment regimen resulted in a complete radiological response and an 11-month treatment-free interval with a sustained good performance status.

Temporal trends of pancreatic ductal adenocarcinoma in young adults in the United States: A Population-Based Study

2020 ◽  
Vol 44 (2) ◽  
pp. 204-210
Author(s):  
Mohamed M. Gad ◽  
Anas M. Saad ◽  
Muneer J. Al-Husseini ◽  
Youssef M. Abdel-Gawad ◽  
Obai M. Alsalhani ◽  
...  
Keyword(s):  
United States ◽  
Young Adults ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Temporal Trends ◽  
The United States ◽  
Population Based ◽  
Ductal Adenocarcinoma ◽  
Population Based Study

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2

2019 ◽  
Vol 37 (3) ◽  
pp. 230-238 ◽  
Author(s):  
Teresa Macarulla ◽  
Roberto Pazo-Cid ◽  
Carmen Guillén-Ponce ◽  
Rafael López ◽  
Ruth Vera ◽  
...  
Keyword(s):  
Phase I ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Ductal Adenocarcinoma ◽  
Tolerability Profile ◽  
Ecog Performance Status ◽  
Actuarial Survival ◽  
Number Of Patients

Purpose Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS. Patients and Methods In the phase I part of this study, patients were randomly assigned to one of the following four parallel GA treatment arms (six patients per arm): a biweekly schedule of NAB-paclitaxel (150 mg/m2 [arm A] or 125 mg/m2 [arm C]) plus gemcitabine 1,000 mg/m2 or a standard schedule of 3 weeks on and 1 week off of NAB-paclitaxel (100 mg/m2 [arm B] or 125 mg/m2 [arm D]) plus gemcitabine 1,000 mg/m2. The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study, the primary end point of which was 6-month actuarial survival. Results Arms B and D were selected for the phase II part of the study. A total of 221 patients (111 patients in arm B and 110 patients in arm D) were enrolled. Baseline characteristics including median age (71 and 68 years in arms B and D, respectively), sex (51% and 55% men in arms B and D, respectively), and metastatic disease (88% and 84% in arms B and D, respectively) were comparable between arms. The most frequent grade 3 or 4 toxicities in arms B and D were anemia (12% and 7%, respectively), neutropenia (32% and 30%, respectively), thrombocytopenia (7% and 11%, respectively), asthenia (14% and 16%, respectively), and neurotoxicity (11% and 16%, respectively). In arms B and D, there were no significant differences in response rate (24% and 28%, respectively), median progression-free survival (5.7 and 6.7 months, respectively), and 6-month overall survival (63% and 69%, respectively). Conclusion NAB-paclitaxel administered at either 100 and 125 mg/m2 in combination with gemcitabine on days 1, 8, and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS.

Morphological classification of pancreatic ductal adenocarcinoma that predicts molecular subtypes and correlates with clinical outcome

Gut ◽  
2019 ◽  
Vol 69 (2) ◽  
pp. 317-328 ◽  
Author(s):  
Sangeetha N Kalimuthu ◽  
Gavin W Wilson ◽  
Robert C Grant ◽  
Matthew Seto ◽  
Grainne O’Kane ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Subtypes ◽  
Differentially Expressed Gene ◽  
Biological Significance ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Rna Seq ◽  
Gene Signatures ◽  
Significant Difference ◽  
Morphological Patterns

IntroductionTranscriptional analyses have identified several distinct molecular subtypes in pancreatic ductal adenocarcinoma (PDAC) that have prognostic and potential therapeutic significance. However, to date, an indepth, clinicomorphological correlation of these molecular subtypes has not been performed. We sought to identify specific morphological patterns to compare with known molecular subtypes, interrogate their biological significance, and furthermore reappraise the current grading system in PDAC.DesignWe first assessed 86 primary, chemotherapy-naive PDAC resection specimens with matched RNA-Seq data for specific, reproducible morphological patterns. Differential expression was applied to the gene expression data using the morphological features. We next compared the differentially expressed gene signatures with previously published molecular subtypes. Overall survival (OS) was correlated with the morphological and molecular subtypes.ResultsWe identified four morphological patterns that segregated into two components (‘gland forming’ and ‘non-gland forming’) based on the presence/absence of well-formed glands. A morphological cut-off (≥40% ‘non-gland forming’) was established using RNA-Seq data, which identified two groups (A and B) with gene signatures that correlated with known molecular subtypes. There was a significant difference in OS between the groups. The morphological groups remained significantly prognostic within cancers that were moderately differentiated and classified as ‘classical’ using RNA-Seq.ConclusionOur study has demonstrated that PDACs can be morphologically classified into distinct and biologically relevant categories which predict known molecular subtypes. These results provide the basis for an improved taxonomy of PDAC, which may lend itself to future treatment strategies and the development of deep learning models.

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