Survival Of Pancreatic Adenocarcinoma Patients Research Articles

Construction of an RNA-Binding Protein-Related Prognostic Model for Pancreatic Adenocarcinoma Based on TCGA and GTEx Databases.

Background: Recently, RNA-binding proteins (RBPs) were reported to interact with target mRNA to regulate gene posttranscriptional expression, and RBP-mediated RNA modification can regulate the expression and function of proto-oncogenes and tumor suppressor genes. We systematically analyzed the expression of RBPs in pancreatic adenocarcinoma (PAAD) and constructed an RBP-associated prognostic risk model.Methods: Gene expression data of normal pancreatic samples as well as PAAD samples were downloaded from TCGA-PAAD and GTEx databases. Wilcoxon test and univariate Cox analysis were, respectively, applied to screen differential expression RBPs (DE-RBPs) and prognostic-associated RBPs (pRBPs). Functional enrichment was analyzed by GO, KEGG, and GSEA. Protein–protein interaction (PPI) network was constructed by STRING online database. Modeling RBPs were selected by multivariate Cox analysis. Kaplan–Meier survival and Cox analysis were applied to evaluate the effects of risk score on the overall survival of PAAD patients. ROC curves and validation cohort were applied to verify the accuracy of the model. Nomogram was applied for predicting 1-, 3-, and 5-year overall survival (OS) of PAAD patients. At last, modeling RBPs were further analyzed to explore their differential expression, prognostic value, as well as enrichment pathways in PAAD.Results: RBPs (453) were differentially expressed in normal and tumor samples, besides, 28 of which were prognostic associated. DE-RBPs (453) are functionally associated with ribosome, ribonuclease, spliceosome, etc. Eight RBPs (PABPC1, PRPF6, OAS1, RBM5, LSM12, IPO7, FXR1, and RBM6) were identified to construct a prognostic risk model. Higher risk score not only predicted poor prognosis but also was an independent poor prognostic indicator, which was verified by ROC curves and validation cohort. Eight modeling RBPs were confirmed to be significantly differentially expressed between normal and tumor samples from RNA and protein level. Besides, all of eight RBPs were related with overall survival of PAAD patients.Conclusions: We successfully constructed an RBP-associated prognostic risk model in PAAD, which has a potential clinical application prospect.

Psoas muscle mass, nutritional status, inflammation, and their relationship with prognosis in patients with pancreatic adenocarcinoma.

Introduction: some factors have been shown to be associated with survival in patients with pancreatic adenocarcinoma. Recently, some studies suggested that malnutrition, muscle mass, and inflammation might have an effect on survival in patients with pancreatic malignancy. Objectives: to investigate the association between psoas muscle mass, inflammation, nutritional status at the time of diagnosis, and survival in patients with pancreatic adenocarcinoma. Methods: this retrospective study included 219 patients diagnosed with pancreatic carcinoma. The nutritional status, inflammation, and psoas muscle mass of the patients at the time of diagnosis were evaluated. Nutritional status was assessed using the Prognostic Nutritional Index (PNI). Leucocyte count and neutrophil/lymphocyte ratio (NLR) were used for inflammation assessment. Psoas muscle mass was calculated by using abdominal computed tomography images of the patients. Results: the mean age of patients (80 female and 139 male) was 66.6 ± 11.7 years. According to the PNI results, 155 patients had a normal nutritional status (70 %), whereas 64 patients were malnourished (30 %). The survival of the patients with normal nutritional status was significantly longer than that of those who were malnourished (p < 0.001). There was no significant relationship between psoas muscle area, leucocyte count, NLR, and survival time. Conclusion: the survival of pancreatic adenocarcinoma patients with malnutrition at the time of diagnosis was significantly shorter than for patients without malnutrition.

An evaluation of treatments and survival rates for pancreatic adenocarcinoma through survival analysis with inverse probability of treatment weighting: a population-based study

Abstract Objective: This study conducted inverse probability of treatment weighting (IPTW) survival analysis to examine survival in pancreatic adenocarcinoma patients. Methods: In this population-based study, data from the Surveillance, Epidemiology, and End Results program of the United States were analyzed to identify patients diagnosed with adenocarcinoma of the pancreas 2004 to 2014. Differences in survival rates were examined among patients who underwent pancreatectomy alone, radiotherapy alone, and those who had pancreatectomy plus adjuvant radiotherapy. Kaplan–Meier estimates and Cox proportional hazards models with the IPTW were performed to determine the effect of different treatments on overall and cancer-specific survival. This study was approved by the Ethics Review Board of Weifang Medical University. Results: A total of 8191 patients were included, with 3409 taking pancreatectomy only, 2865 taking radiotherapy only, and 1917 taking pancreatectomy plus adjuvant radiotherapy. Patients who received surgery plus adjuvant radiotherapy had statistically a higher survival rate than those who received the other 2 treatments. Survival analysis with the IPTW for the 3 different groups showed that the difference in median overall survival time among these patient groups was significant. Conclusion: Using IPTW survival analysis, the present study shows that surgery with adjuvant radiotherapy is significantly associated with improved overall and cancer-specific survival among patients with pancreatic adenocarcinoma.

Conditional Survival in Pancreatic Adenocarcinoma Patients Treated with Neoadjuvant FOLFIRINOX and Chemoradiation

Sekigami, Yurie MD; Michelakos, Theodoros MD; Kontos, Filippos MD; Qadan, Motaz MD PhD, FACS; Antonio Catalano, Onofrio MD; Deshpande, Vikram MBBS; Lillemoe, Keith D. MD, FACS; Rosa Ferrone, Cristina MD, FACS Author Information

The impact of immunotherapy on the survival of pancreatic adenocarcinoma patients who do not receive definitive surgery of the tumor

Background and PurposeImmunotherapy has shown great efficacy in many cancers, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The objective of this study was to investigate the impact of immunotherapy on the overall survival of PDAC patients who did not receive definitive surgery of the pancreatic primary tumor site using the National Cancer Database (NCDB). Materials and MethodsPatients with pancreatic adenocarcinoma who did not receive surgery were identified from NCDB. Cox proportional hazard models were employed to assess the impact of immunotherapy on survival after adjusting for age at diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, year of diagnosis, and treatment types such as chemotherapy and radiation therapy. ResultsOf 263,886 patients who were analyzed, 911 (0.35%) received immunotherapy. Among patients who received chemotherapy (101,546), and chemoradiation (30,226) therapy, 555/101,546 (0.55%) received chemotherapy plus immunotherapy, and 299/3,022 (9.9%) received chemoradiation plus immunotherapy. In a multivariable analysis adjusted for the factors mentioned above, immunotherapy was associated with significantly improved OS (HR: 0.866 (0.800–0.937); P < 0.001) compared to no immunotherapy. Chemotherapy plus immunotherapy was significantly associated with improved OS (HR: 0.848 (0.766–0.938); P < 0.001) compared to chemotherapy without immunotherapy. Further, chemoradiation plus immunotherapy was associated with significantly improved OS (HR: 0.813 (0.707–0.936); P < 0.001) compared to chemoradiation alone. ConclusionIn this study, the addition of immunotherapy to chemotherapy and chemoradiation therapy was associated with significantly improved OS in PDAC patients without definitive surgery. The study warrants future clinical trials of immunotherapy in PDAC.

The impact of immunotherapy on the survival of pancreatic adenocarcinoma patients who received definitive surgery of the pancreatic tumor: a retrospective analysis of the National Cancer Database

BackgroundImmunotherapy has paved the way for new therapeutic opportunities in cancer but has failed to show any efficacy in Pancreatic Adenocarcinoma (PDAC), and its therapeutic role remains unclear. The objective of this study is to examine the impact of immunotherapy in combination with chemotherapy, RT, and chemoradiation on the overall survival (OS) of PDAC patients who received definitive surgery of the tumor using the National Cancer Database (NCDB).MethodsPatients with PDAC who received definitive surgery of the pancreatic tumor and were diagnosed between 2004 and 2016 from the NCDB were identified. Cox proportional hazard analysis was used to assess the survival difference between patients who received chemotherapy plus immunotherapy and chemoradiation therapy plus immunotherapy and their counterparts who only receive these treatments without immunotherapy. The multivariable analysis was adjusted for age of diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, year of diagnosis, and treatment types such as chemotherapy and radiation therapy.ResultsIn total, 63,154 PDAC patients who received definitive surgery of the tumor were included in the analysis. Among the 63,154 patients, 636 (1.01%) received immunotherapy. Among patients who received chemotherapy (21,355), and chemoradiation (21,875), 157/21,355 (0.74%) received chemotherapy plus immunotherapy, and 451/21,875 (2.06%) received chemoradiation plus immunotherapy. Patients who received chemoradiation plus immunotherapy had significantly improved median OS compared to patients who only received chemoradiation with an absolute median OS benefit of 5.7 [29.31 vs. 23.66, p < 0.0001] months. In the multivariable analysis, patients who received immunotherapy had significantly improved OS compared to patients who did not receive immunotherapy (HR: 0.900; CI: 0.814–0.995; P < 0.039). Patients who received chemoradiation plus immunotherapy had significantly improved OS compared to their counterparts who only received chemoradiation without immunotherapy (HR: 0.852 CI: 0.757–0.958; P < 0.008).ConclusionsIn this study, the addition of immunotherapy to chemoradiation therapy was associated with significantly improved OS in PDAC patients who received definitive surgery. The study warrants further future clinical trials of immunotherapy in PDAC.

Abstract B110: Racial disparities in pancreatic adenocarcinoma survival. Do they exist for patients who already survived their first year?

Abstract Purpose: Population-based studies indicated that prognosis of pancreatic adenocarcinoma (PAC) is worse in black patients compared to other races. Nonetheless, survival probabilities can change over time based on number of years (yr.) already survived by patients; a concept called conditional survival. This study explored the dynamic changes in risk according to patient characteristics, particularly race, on survival of PAC patients using cancer-specific survival (CSS) estimates. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for data on adult patients with non-metastatic PAC, diagnosed between 1988 and 2010. Patient characteristics, such as age, race, tumor grade, and stage were collected at the time of diagnosis. CSS probabilities, as well as Cox proportional hazard ratios (HRs), were computed at the time of diagnosis (Actuarial CSS and baseline HR), and after already surviving 1 to 6 yr. after diagnosis (Conditional CSS and HR). Harrell’s concordance index (C-index) was used to measure the cross-validation accuracy of the Cox models. Results: Our search retrieved data on 20,491 patients, with a mean age at diagnosis of 67.2 yr. Most of the patients were White (81.6%), followed by Black (12%) and Asians/Pacific Islander (6.4%). The stage was T1-2N0M0 in 15.9%, T3-4N0M0 in 41.8%, and T1-4N1M0 in 42.3% of patients. The 3-yr actuarial CSS calculated from time of diagnosis was significantly different across racial groups, at 11%, 10%, and 13% for Whites, Blacks, and Asians, respectively (P &amp;lt; 0.01). Conversely, for patients who already survived 1 yr. after diagnosis, the probability of surviving an additional 2 yr. was similar across races, at 26.2%, 27.1%, and 29.9%, for Whites, Blacks, and Asians, respectively (P = 0.218). As patients survived for longer periods of time following diagnosis, conditional CSS estimates increased similarly across different races; for White, Black, and Asian patients who already survived 3 yr. after diagnosis, the probability of surviving an additional 2 yr. was 62.6%, 60.5%, and 62.1%, respectively (P = 0.532). In multivariate cox models, the prognostic effect of race lost significance if patients already survived ≥1 yr. after diagnosis (Baseline HR = 1.114, 95%CI [1.045- 1.187], mean C-index = 67%; conditional HR at 1 yr = 1.015, 95%CI [0.919- 1.12], mean C-index = 60%). The prognostic effect of tumor grade, site, and age lost significance if patients already survived ≥2, ≥4, and ≥6 yr. after diagnosis, respectively. Tumor stage maintained its prognostic significance over time (conditional HR at 6 yr = 1.522, 95%CI [1.049- 2.208], mean C-index = 59%). Conclusion: Racial disparities in survival outcomes exist at the time of diagnosis for PAC patients. However, the survival impact of these disparities does not seem to persist over time. Other variables, such as age, tumor grade, stage, and treatment received should be taken into account when predicting future prognosis of PAC patients who have already survived ≥ 1 yr. after diagnosis. Citation Format: Anas M Saad, Maha AT Elsebaie, Mohamed Amgad, Muneer J Al-Husseini, Kyrillus S Shohdy, Omar Abdel-Rahman. Racial disparities in pancreatic adenocarcinoma survival. Do they exist for patients who already survived their first year? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B110.

Identification of prognostic splicing factors and exploration of their potential regulatory mechanisms in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD), the most common subtype of pancreatic cancer, is a highly lethal disease. In this study, we integrated the expression profiles of splicing factors (SFs) of PAAD from RNA-sequencing data to provide a comprehensive view of the clinical significance of SFs. A prognostic index (PI) based on SFs was developed using the least absolute shrinkage and selection operator (LASSO) COX analysis. The PI exhibited excellent performance in predicting the status of overall survival of PAAD patients. We also used the percent spliced in (PSI) value obtained from SpliceSeq software to quantify different types of alternative splicing (AS). The prognostic value of AS events was explored using univariate COX and LASSO COX analyses; AS-based PIs were also proposed. The integration of prognosis-associated SFs and AS events suggested the potential regulatory mechanisms of splicing processes in PAAD. This study defined the markedly clinical significance of SFs and provided novel insight into their potential regulatory mechanisms.

Preoperative CA19-9 levels predict disease-free survival and overall survival in pancreatic adenocarcinoma patients after resection.

BackgroundThis study investigates the association between the preoperative serum CA19-9 and the effects of adjuvant chemotherapy (CT), and its impact on survival in patients undergoing curative resection for pancreatic adenocarcinoma (PAC).MethodsFrom January 01, 2015 to June 30, 2017, we retrospectively reviewed 421 PAC patients who underwent radical resection. The association between preoperative CA19-9 and disease-free survival (DFS), and overall survival (OS) was analyzed using Kaplan-Meier method and Cox proportional hazards model.ResultsA total of 354 patients eligible for this study were classified into three groups according to preoperative CA19-9: G1 (≤87 U/mL), G2 (87–322 U/mL) and G3 (>322 U/mL), in tertiles. Multivariable analysis showed preoperative CA19-9 and adjuvant CT were both independent predictors of DFS and OS. Subgroup analyses showed the multivariable-adjusted hazard ratios (HR) of DFS for patients treated with adjuvant CT were 0.54 (95% CI, 0.33–0.86), 0.63 (95% CI, 0.40–0.97) and 0.32 (95% CI, 0.21–0.49) in G1, G2 and G3, respectively. A trend of decreasing HR of recurrence risk was observed in the higher preoperative CA 19-9 group treated with CT.ConclusionsHigh preoperative CA19-9 is an emerging biomarker that identifies a more aggressive PAC subgroup, which might benefit more from postoperative CT.

The Rho/MRTF pathway inhibitor CCG-222740 reduces stellate cell activation and modulates immune cell populations in KrasG12D; Pdx1-Cre (KC) mice

The stromal reaction in pancreatic cancer creates a physical barrier that blocks therapeutic intervention and creates an immunosuppressive tumor microenvironment. The Rho/myocardin-related transcription factor (MRTF) pathway is implicated in the hyper-activation of fibroblasts in fibrotic diseases and the activation of pancreatic stellate cells. In this study we use CCG-222740, a small molecule, designed as a Rho/MRTF pathway inhibitor. This compound decreases the activation of stellate cells in vitro and in vivo, by reducing the levels of alpha smooth muscle actin (α-SMA) expression. CCG-222740 also modulates inflammatory components of the pancreas in KC mice (LSL-KrasG12D/+; Pdx-1-Cre) stimulated with caerulein. It decreases the infiltration of macrophages and increases CD4 T cells and B cells. Analysis of the pancreatic adenocarcinoma (PDA) TCGA dataset revealed a correlation between elevated RhoA, RhoC and MRTF expression and decreased survival in PDA patients. Moreover, a MRTF signature is correlated with a Th2 cell signature in human PDA tumors.

Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study

BackgroundPancreatic exocrine insufficiency (PEI) and malnutrition are prevalent among patients with pancreatic adenocarcinoma. Pancreatic enzyme replacement therapy (PERT) can correct PEI but its use among patients with pancreatic cancer is unclear as are effects upon survival. This population-based study sought to address these issues MethodsSubjects with pancreatic adenocarcinoma were identified from the UK Clinical Practice Research Datalink (CPRD). Propensity score matching generated matched pairs of subjects who did and did not receive PERT. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables ResultsPERT use among the whole cohort (987/4554) was 21.7%. Some 1614 subjects generated 807 matched pairs. This resulted in a total, censored follow-up period of 1643 years. There were 1403 deaths in total, representing unadjusted mortality rates of 748 and 994 deaths per 1000 person-years for PERT-treated cases and their matched non-PERT-treated controls, respectively. With reference to the observed survival in pancreatic adenocarcinoma patients, adjusted median survival time was 262% greater in PERT-treated cases (survival time ratio (STR) = 2.62, 95% CI 2.27–3.02) when compared with matched, non-PERT-treated controls. Survival remained significantly greater among subjects receiving PERT regardless of the studied subgroup with respect to use of surgery or chemotherapy ConclusionsThis population based study observes that the majority of patients with pancreatic adenocarcinoma do not receive PERT. PERT is associated with increased survival among patients with pancreatic adenocarcinoma suggesting a lack of clinical awareness and potential benefit of addressing malnutrition among these patients

From morphological resection to biological benefits: decision and reflection in the treatment of pancreatic adenocarcinoma

Pancreatic adenocarcinoma (PAC) is a highly lethal disease for human being. Surgery in the past 100 years, novel drug combination and neoadjuvant therapy haven′t changed the prognosis of PAC fundamentally. Traditionally, authors only focused on the treatment in term of morphological changes, while it′s tumor biology that will ultimately determine the long-term survival of PAC patients. Surgeons should continuously pursue the radical resection of pancreatic cancer, however, with the guidance of tumor biology. Omics′ researches, artificial intelligence and next generation platform of translational study will improve our understanding and treatment for PAC. Key words: Pancreas; Neoplasms; Morphology; Biology

Robotic total pancreatectomy with splenectomy: technique and outcomes.

Robotic total pancreatectomy (TP) represents a minimally invasive approach to a major intra-abdominal operation. Its utility, technique, and outcomes are evolving. In this video, we describe a systematic approach to a robotic total pancreatectomy performed for multifocal intraductal papillary mucinous neoplasm (IPMN). Additionally, we reviewed the National Cancer Database (NCDB) to examine the outcomes of robotic TP compared to laparoscopic and open TP between 2010 and 2014. The patient is a 61-year-old female who was diagnosed with multifocal IPMN. A total of 6 robotic ports were placed and the da Vinci Xi robotic system was used with the patient supine. The approach entailed as follows: (1) Diagnostic laparoscopy; (2) Entry into the lesser sac; (3) Division of the short gastric vessels; (4) Exposure and dissection of the inferior pancreas border; (5) Dissection and transection of the splenic artery; (6) Mobilization of the pancreas tail/spleen; (7) Exposure of the splenic vein-superior mesenteric vein confluence; (8) Kocher maneuver; (9) Release of the ligament of Treitz and transection of the proximal jejunum; (10) Transection of the distal stomach; (11) Portal lymphadenectomy; (12) Dissection and transection of the gastroduodenal artery; (13) Superior mesenteric vein exposure/dissection of the uncinate process; (14) Hepaticojejunostomy; (15) Cholecystectomy; and (16) Gastrojejunostomy. NCDB database review of 73 patients who underwent robotic TP revealed similar rates of margin negative resections and retrieved lymph nodes between robotic, laparoscopic, and open TP, whereas robotic and laparoscopic TP were associated with shorter in-hospital stay and reduced mortality at 30 and 90days compared to open TP. Overall median survival of pancreatic adenocarcinoma patients who underwent TP was similar between robotic, laparoscopic, and open approaches. Robotic total pancreatectomy with splenectomy offers a minimally invasive approach to a major abdominal operation and is feasible in a stepwise, reproducible technique. It is associated with improved postoperative outcomes and equivalent oncologic outcomes compared to open TP.

Expression of LDL receptor-related proteins (LRPs) in common solid malignancies correlates with patient survival.

LDL receptor-related proteins (LRPs) are transmembrane receptors involved in endocytosis, cell-signaling, and trafficking of other cellular proteins. Considerable work has focused on LRPs in the fields of vascular biology and neurobiology. How these receptors affect cancer progression in humans remains largely unknown. Herein, we mined provisional databases in The Cancer Genome Atlas (TCGA) to compare expression of thirteen LRPs in ten common solid malignancies in patients. Our first goal was to determine the abundance of LRP mRNAs in each type of cancer. Our second goal was to determine whether expression of LRPs is associated with improved or worsened patient survival. In total, data from 4,629 patients were mined. In nine of ten cancers studied, the most abundantly expressed LRP was LRP1; however, a correlation between LRP1 mRNA expression and patient survival was observed only in bladder urothelial carcinoma. In this malignancy, high levels of LRP1 mRNA were associated with worsened patient survival. High levels of LDL receptor (LDLR) mRNA were associated with decreased patient survival in pancreatic adenocarcinoma. High levels of LRP10 mRNA were associated with decreased patient survival in hepatocellular carcinoma, lung adenocarcinoma, and pancreatic adenocarcinoma. LRP2 was the only LRP for which high levels of mRNA expression correlated with improved patient survival. This correlation was observed in renal clear cell carcinoma. Insights into LRP gene expression in human cancers and their effects on patient survival should guide future research.

Cell-free DNA promoter hypermethylation in plasma as a predictive marker for survival of patients with pancreatic adenocarcinoma.

IntroductionFew prognostic biomarkers are available for pancreatic cancer. The aim of this study is to examine the correlation between the survival of pancreatic adenocarcinoma patients and hypermethylated genes in plasma-derived cell-free DNA.MethodsConsecutive patients with pancreatic adenocarcinoma were prospectively included and staged according to the TNM classification. Methylation-specific PCR of 28 genes was conducted. A survival prediction model independent of cancer stage and stage-specific survival prediction models were developed by multivariable Cox regression analysis using backward stepwise selection.ResultsNinety-five patients with pancreatic adenocarcinoma were included. Patients with more than 10 hypermethylated genes had a HR of 2.03 (95% CI; 1.15-3.57) compared to patients with fewer hypermethylated genes. Three survival prediction models were developed: Total group; (American Society of Anesthesiologists score (ASA)=3, GSTP1, SFRP2, BNC1, SFRP1, TFPI2, and WNT5A) Risk groups 2, 3 and 4 had a HR of 2.65 (95% CI; 1.24-5.66), 4.34 (95% CI; 1.98-9.51) and 21.19 (95% CI; 8.61-52.15), respectively, compared to risk group 1. Stage I-II; (ASA=3, SFRP2, and MESTv2) Risk groups 2, 3 and 4 had a HR of 4.83 (95% CI; 2.01-11.57), 9.12 (95% CI; 2.18-38.25) and 70.90 (95% CI; 12.63-397.96), respectively, compared to risk group 1. Stage IV; (BMP3, NPTX2, SFRP1, and MGMT) Risk group 2 had a HR of 5.23 (95% CI; 2.13-12.82) compared to risk group 1.ConclusionPrediction models based on cell-free DNA hypermethylation stratified pancreatic adenocarcinoma patients into risk groups according to survival. The models have the potential to work as prognostic biomarkers. However, further validation of the results is required to substantiate the findings.

An Evaluation of Artificial Neural Networks in Predicting Pancreatic Cancer Survival

ObjectiveThis study aims to evaluate the development of an artificial neural network (ANN) method for predicting the survival likelihood of pancreatic adenocarcinoma patients. The ANN predictive model should produce results with a 90% sensitivity. MethodsA prospective examination of the records for 283 consecutive pancreatic adenocarcinoma patients is used to identify 219 records with complete data. These records are then used to create two unique samples which are then used to train and validate an ANN predictive model. Numerous network architectures are evaluated, following recommended ANN development protocols. ResultsSeveral backpropagation-trained ANNs were produced that satisfied the 90% sensitivity requirement. An ANN model with over a 91% sensitivity is selected because even though it did not have the highest sensitivity, it was able to achieve over 38% specificity. ConclusionsANN models can accurately predict the 7-month survival of pancreatic adenocarcinoma patients, both with and without resection, at a 91% sensitivity and 38% specificity. This implies that ANN models may be useful objective decision tools in complex treatment decisions. This information may be used by patients and surgeons in determining optimal treatment plans that minimize regret and improve the quality of life for these patients.

Su1282 - An Evaluation of Artificial Neural Networks in Predicting Pancreatic Cancer Survival

This study aims to evaluate the development of an artificial neural network (ANN) method for predicting the survival likelihood of pancreatic adenocarcinoma patients. The ANN predictive model should produce results with a 90% sensitivity. A prospective examination of the records for 283 consecutive pancreatic adenocarcinoma patients is used to identify 219 records with complete data. These records are then used to create two unique samples which are then used to train and validate an ANN predictive model. Numerous network architectures are evaluated, following recommended ANN development protocols. Several backpropagation-trained ANNs were produced that satisfied the 90% sensitivity requirement. An ANN model with over a 91% sensitivity is selected because even though it did not have the highest sensitivity, it was able to achieve over 38% specificity. ANN models can accurately predict the 7-month survival of pancreatic adenocarcinoma patients, both with and without resection, at a 91% sensitivity and 38% specificity. This implies that ANN models may be useful objective decision tools in complex treatment decisions. This information may be used by patients and surgeons in determining optimal treatment plans that minimize regret and improve the quality of life for these patients.

The Promise of Gene Therapy for Pancreatic Cancer.

Unlike for other digestive cancer entities, chemotherapy, radiotherapy, and targeted therapies have, so far, largely failed to improve patient survival in pancreatic adenocarcinoma (PDAC), which remains the fourth leading cause of cancer-related death in Europe and the United States. In this context, gene therapy may offer a new avenue for patients with PDAC. In this review, we explore the research currently ongoing in French laboratories aimed at defeating PDAC using nonviral therapeutic gene delivery, targeted transgene expression, or oncolytic virotherapy that recently or will soon bridge the gap between experimental models of cancer and clinical trials. These studies are likely to change clinical practice or thinking about PDAC management, as they represent a major advance not only for PDAC but may also significantly influence the field of gene-based molecular treatment of cancer.

Aberrant Expression miR-196a Is Associated With Abnormal Apoptosis, Invasion, and Proliferation of Pancreatic Cancer Cells

MiR-196a levels inversely correlated with survival in pancreatic adenocarcinoma patients. However, the functional contributions of miR-196a to pancreatic cancer remain unclear. Three lentiviral vectors encoding microRNA miR-196a precursor, inhibitor, and scrambled microRNA oligomer were transfected into Panc-1 cells, respectively. Then we explored the regulation of inhibitor of growth 5 (ING5) expression by miR-196a and its impact on apoptosis, invasion, and growth of pancreatic cancer cells. The lentiviral transfected Panc-1 cells were surgically implanted into the pancreas of mice. In vivo tumor growth and ING5 expression were measured. Down-regulation of ING5 expression was detected in cells transfected with miR-196a precursor (P < 0.01), accompanied by less apoptosis, increased invasion, and proliferation compared with control cells (P < 0.05). Cells transfected with miR-196a inhibitor revealed an opposite trend. Smaller detectable tumors were found in only 60% of mice after implantation of Lenti.miR-196a inhibitor-transfected Panc-1 cells compared with controls (360.7 ± 303.6 mm vs 511.58 ± 365.9 mm in controls; P < 0.01). Our results provide experimental evidence to support aberrant expression of miR-196a is associated with abnormal apoptosis, invasion, and proliferation of pancreatic cancer cells.

Impact of epidermal growth factor receptor (EGFR) kinase mutations, EGFR gene amplifications, and KRAS mutations on survival of pancreatic adenocarcinoma

Erlotinib, in combination with gemcitabine, has shown clinical benefits in pancreatic adenocarcinoma patients. The presence of EGFR mutations and increased EGFR copy numbers in pancreatic adenocarcinoma was explored. Sixty-six pancreatic cancer patients were included in the analysis. The EGFR mutation was analyzed by DNA sequencing of exons 18-21 in the tyrosine kinase domain. KRAS mutation was analyzed by sequencing codons 12, 13, and 61. Quantitative real-time polymerase chain reaction was performed to analyze the copy number of EGFR. In the current study the EGFR mutation was harbored in only 1 (1.5%) of the 66 inoperable or metastatic pancreatic adenocarcinoma patients. Amino acid substitution was detected in exon 20 of the EGFR gene. Increased EGFR copy numbers (> or =3.0 per cell) were detected in 26 (41%) patients. There was only 1 patient, who had a highly increased EGFR copy number (> or =6.0 per cell), who died, 2.1 months from the date of diagnosis. The EGFR amplification did not significantly influence survival in pancreatic adenocarcinoma patients (P = .935). Thirty-two (49%) of the 65 pancreatic adenocarcinomas examined harbored a point mutation in codons 12 (n = 31) and 61 (n = 1) of the KRAS gene. The presence of a point mutation in codon 12 adversely influenced survival of pancreatic cancer patients (P = .030). The incidence of somatic mutations in the tyrosine kinase domains of EGFR was very low and the increased gene copy number of EGFR did not significantly influence survival.