Survival In Resected Pancreatic Cancer Research Articles

Prediction of short- and long-term survival in resectable pancreatic cancer using deep learning histology

Prediction of short- and long-term survival in resectable pancreatic cancer using deep learning histology

HPB P36 The influence of sarcopenia and systemic inflammation on survival in resected pancreatic cancer

Abstract Background Sarcopenia, cachexia and systemic inflammation are early hallmarks of pancreatic cancer (PC) which hamper systemic therapy and accelerate the terminal stages of the disease. The significant impact of sarcopenia on survival in PC has been demonstrated in numerous meta-analyses using standardised thresholds to define body composition measurements. We sought to determine the influence of sarcopenia and systemic inflammation on survival in our cohort of resected PC patients. We also interrogated the impact of the introduction of neoadjuvant therapy (NAT) protocols on survival, body composition and systemic inflammation. Finally we investigated the use of varying thresholds to define sarcopenia and the impact of this on survival. Methods Analysis of a prospectively maintained database of resected patients with PC accrued through the tertiary West of Scotland Pancreatic Unit was undertaken. Patients with cancer types other than pancreatic ductal adenocarcinoma were excluded. Body composition analysis was carried out using cross-sectional measurements of skeletal muscle area, skeletal muscle density and visceral fat area at the L3 level from pre-treatment or pre-operative CT scan using Slice-o-Matic software (Tomovision, Montreal). Disease-specific survival was used with Log-rank test for survival differences. Results 188 patients underwent resection between 2008–2020. 44.1% received NAT and 65.9% were resected up-front. Using Prado / Martin cutoffs of skeletal muscle index (SMI) to define sarcopenia demonstrated no significant survival difference in either cohort. Visceral obesity and myosteatosis (defined by Doyle / Martin) also demonstrated no significant survival difference. Modified thresholds tailored to our cohort were used and a median survival difference of 34.5 vs 23.1 months was identified (p < 0.001). Similarly for modified BMI-specific thresholds a median survival difference of 35.2 vs 22.8 months was identified (p < 0.001). On further analysis of the NAT cohort, 60.2% of patients exhibited gain in SMI with treatment and 39.8% of patients exhibited loss of SMI. There was a tendency towards poorer survival in the latter group however this was not significant. On further stratification of cohorts in to NAT and up-front resection it was revealed that the predictive effect of sarcopenia was entirely the effect of the up-front resected cohort, with little difference in survival between sarcopenic and non-sarcopenic groups in the NAT cohort. Median survival in all patients (NAT and up-front resection combined) increased from 27.4 months to 32.6 months (p = 0.016) with the introduction of NAT protocols in 2013. Conclusions Defining sarcopenia using modified thresholds tailored specifically to our cohort of patients demonstrates the significant impact of sarcopenia on survival in resected PC. The introduction of NAT protocols in 2013 has had a significant impact on survival, an effect which may be due to the selection of smaller tumours for up-front resection. Further work is needed as part of intention-to-treat analysis to identify patients who undergo NAT who do not progress to resection. Analysis of this cohort will validate our findings and shed further light on the impact of neoadjuvant therapy on sarcopenia and body composition. This analysis is ongoing and further novel data will be presented in September should this abstract be accepted.

Impact of classical and basal-like molecular subtypes on overall survival in resected pancreatic cancer in the SPACIOUS-2 multicentre study.

The recently identified classical and basal-like molecular subtypes of pancreatic cancer impact on overall survival (OS). However, the added value of routine subtyping in both clinical practice and randomized trials is still unclear, as most studies do not consider clinicopathological parameters. This study examined the clinical prognostic value of molecular subtyping in patients with resected pancreatic cancer. Subtypes were determined on fresh-frozen resected pancreatic cancer samples from three Dutch centres using the Purity Independent Subtyping of Tumours classification. Patient, treatment, and histopathological variables were compared between subtypes. The prognostic value of subtyping in (simulated) pre- and postoperative settings was assessed using Kaplan-Meier and Cox regression analyses. Of 199 patients with resected pancreatic cancer, 164 (82.4 per cent) were classified as the classical and 35 (17.6 per cent) as the basal-like subtype. Patients with a basal-like subtype had worse OS (11 versus 16 months (HR 1.49, 95 per cent c.i. 1.03 to 2.15; P = 0.035)) than patients with a classical subtype. In multivariable Cox regression analysis, including only clinical variables, the basal-like subtype was a statistically significant predictor for poor OS (HR 1.61, 95 per cent c.i. 1.11 to 2.34; P = 0.013). When histopathological variables were added to this model, the prognostic value of subtyping decreased (HR 1.49, 95 per cent c.i. 1.01 to 2.19; P = 0.045). The basal-like subtype was associated with worse OS in patients with resected pancreatic cancer. Adding molecular classification to inform on tumor biology may be used in patient stratification.

TH2.11 The influence of sarcopenia and systemic inflammation on survival in resected pancreatic cancer

Abstract Aims Sarcopenia, cachexia and systemic inflammation are early hallmarks of pancreatic cancer. The impact of these processes on survival has been demonstrated in other cancer types using image-based body composition analysis. We sought to determine the impact of sarcopenia and systemic inflammation on survival in pancreatic cancer. Methods A database of patients with pancreatic cancer undergoing resection with curative intent was maintained. Single-slice (L3) skeletal muscle index from pre-operative CT was used to define sarcopenia. Pre-operative systemic inflammation measures were curated (modified Glasgow Prognostic Score and neutrophil-lymphocyte ratio). Results 176 patients underwent resection. Median post-operative survival was 26.3 months and 95 were sarcopenic (54%). Sarcopenia was not associated with worse survival versus non-sarcopenia (median 24.2 months vs 27.4 months, p = 0.558). mGPS was raised in 52 patients (30%) however this was not associated with worse survival versus normal mGPS (median 26.2 months vs 26.6 months, p = 0.193). Raised NLR did not significantly influence survival. Conclusions Pancreatic cancer represents a complex biological process with survival likely influenced by tumour biology and the relationship between tumour epithelium and tumour microenvironment. Survival has previously been shown to be influenced by sarcopenia in all patients with pancreatic cancer, suggesting selection of “fitter” patients for resection in our cohort. Further understanding of tumour biology is needed to determine the relationship between tumour epithelium, tumour microenvironment, cachexia and systemic inflammation. Analysis of this relationship is ongoing and we envisage presenting results of this research in conjunction with this abstract if selected for presentation.

The influence of socioeconomic status on access to cancer care and survival in resectable pancreatic cancer: a systematic review and meta-analysis.

Socioeconomic status (SES) is an important factor affecting access to cancer care and survival. Its role in pancreatic cancer warrants scrutiny. A systematic review of major reference databases was undertaken. Categorization of the study population into low SES (LSES) and high SES (HSES) was based on the criteria employed in the individual studies. The outcome measures studied were stage of cancer presentation, access to care and overall survival. Meta-analysis was performed using random-effects models and trial sequential analysis (TSA) was used to assess the precision and conclusiveness of the results. Thirteen studies meeting inclusion criteria were included in the meta-analysis, which demonstrated that LSES was associated with significantly lower rates of presentation at a non-metastatic stage and poorer access to cancer care, viz. surgery, chemotherapy and radiation therapy. Despite heterogeneity, TSA supported the findings, displaying minimal type I error. As LSES is associated with delayed presentation, poorer access to care and poorer survival, SES should be considered a modifiable risk factor for poor outcomes in pancreatic cancer.

Prognostic value of SMAD4 in resectable pancreatic cancer

Abstract Introduction The tumor gene SMAD4 was genetically inactivated in approximately half of pancreatic cancer (PC) patients. The correlation of SMAD4 gene expression in PC and its prognosis remains inconclusive. The aim of this study was to evaluate the association between loss of SMAD4 expression and the outcome of resectable PC. Materials and Methods A systematic review of the relevant electronic databases was conducted between SMAD4 expression and the outcome of PC patients until December 2020, including PubMed, Web of Science, and the China Journal Net. A meta-analysis was performed using STATA 12.0 and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between SMAD4 gene expression and the prognosis of PC patients. Results Twelve studies were included. Our meta-analysis illustrated that there were no significant associations between the loss of SMAD4 gene expression and overall survival in resectable PC (HR=1.38, 95% CI 0.98–1.81). In addition, there was no evidence of publication bias, as showed by Begg's and Egger's test. There was no correlation between the loss of SMAD4 expression and local recurrence (OR=0.97, 95% CI 0.52–1.80, p=0.914), while the loss of SMAD4 gene expression was associated with increased risk of distant recurrence (OR=1.36, 95% CI 1.08–1.70, p=0.008). Conclusions After PC resection, the loss of SMAD4 gene expression was correlated with higher risk of distant recurrence, but not with local recurrence nor overall survival.

How many number of retrieved lymph nodes is required for accurate N-staging in resected pancreatic cancer?

Although N stage is important factor in survival of resected pancreatic cancer, appropriate number of retrieved lymph nodes for accurate staging is still controversial. From 1993 to 2019, 446 patients underwent pancreatectomy for pancreatic cancer were included. The binomial probability law was applied to define the minimum number of examined LNs (minELN). The prognostic factors for overall survival were analyzed. According to binomial probability law, 12 and 20 retrieved lymph nodes were found to be required accurate staging for pancreatic cancer. With node-positive disease, the median OS of patients with less than 12 ELNs was not significantly different to those with 12 or more ELNs (20 v. 18 months, p = 0.326). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes even when finding fewer than 12 ELNs (26 v. 19 months, p = 0.04) and more than 12 ELNs (22 v. 18 months, p = 0.01). On the other hand, with node-positive disease, the median OS of patients with less than 20 ELNs was not significantly different to those with 20 or more ELNs (20 v. 20 months, p = 0.78). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes in fewer than 20 ELNs (23 v. 17 months, p = 0.015), but SHOWED no significant IN MORE THAN 20 ELNs (22 v. 18 months, p = 0.07). AJCC (8TH) N-staging system in independent prognostic factor for long-term survival of resected pancreatic cancer.Retrieving 12 lymph nodes are appropriate for Nodal staging PDAC by using AJCC (8th) N stage.

External validation of three nomograms predicting survival using an international cohort of patients with resected pancreatic head ductal adenocarcinoma

Abstract Objective Lymph node ratio (LNR, positive lymph nodes/collected lymph nodes during surgery) was identified as an important prognostic factor of survival in resected pancreatic cancer. Several nomograms based on LNR were recently proposed to predict survival after pancreatoduodenectomy (PD). The present study aimed to externally validate 3 published nomograms using an international cohort. Methods Consecutive patients with ductal adenocarcinoma of the pancreatic head who underwent PD without neoadjuvant treatment from 6 tertiary centers in Europe and the USA were retrospectively collected from 2000 to 2017. Patients with metastases at diagnosis, R2 resection, missing data regarding LNR, and who died within 90 postoperative days were excluded. The 3 selected nomograms were the updated Amsterdam nomogram (including LNR, adjuvant therapy, margin status, and tumor grade), the nomogram by Pu et al. (including LNR, age, tumor grade, and T stage) and the nomogram by Li et al. (including LNR, age, tumor location, grade, size, and TNM stage). Overall survivals (OS) were calculated using Kaplan-Meier method. For the validation, calibration (Hosmer-Lemeshow test), discrimination capacity (ROC curves for 3-year OS), and clinical utility (sensitivity and specificity at the value of Youden index) were assessed. Results After exclusion of 95 patients with metastases, R2 resection, and who died within 90 postoperative days, 1167 patients were included. Median OS of the entire cohort was 23 months (95% confidence interval: 21-24). For the 3 nomograms, Kaplan-Meier curves showed significant diminution of OS with increasing scores (p < 0.01 for the 3 nomograms). All nomograms showed good calibration (non significant Hosmer-Lemeshow goodness-of-fit tests). For the updated Amsterdam nomogram, the area under the ROC curve (AUROC) for 3-year OS was 0.66. Sensitivity and specificity were 73% and 50%. Regarding the nomogram by Pu et al., the AUROC was 0.67. Sensitivity and specificity were 65% and 60%. For the nomogram by Li et al., the AUROC was 0.67, while sensitivity and specificity were 56% and 71%. Conclusion The 3 selected nomograms were validated using an external international cohort and displayed interesting and comparable predictive values. Those nomograms may be used in clinical practice to estimate survival after PD for ductal adenocarcinoma.

Preoperative chemoradiotherapy to improve overall survival in pancreatic cancer: Long-term results of the multicenter randomized phase III PREOPANC trial.

4016 Background: Preoperative chemoradiotherapy (CRT) may improve overall survival in resectable pancreatic cancer (RPC) and borderline resectable pancreatic cancer (BRPC). Long term results are presented. Methods: In this multicenter phase III trial, patients with RPC or BRPC were randomized between preoperative CRT, (gemcitabine 1000 mg/m2 weekly for 7 of 10 weeks, and 15x2.4 Gy radiotherapy in week 4 to 6), followed by surgery and four cycles of adjuvant gemcitabine (1000 mg/m2 weekly for 3 of 4 weeks), or immediate surgery followed by 6 cycles of adjuvant gemcitabine (1000 mg/m2 weekly for 3 of 4 weeks). Primary endpoint was overall survival by intention-to-treat (ITT). Results: From April 2013 to July 2017, 246 eligible patients were accrued by 16 Dutch centers and randomized, 119 to preoperative CRT and 127 to immediate surgery. After a median follow up of 56 months (35.3-92.0 months), 210 patients have died, 93 (78%) in the preoperative CRT arm and 117 (92%) in the immediate surgery arm. Three- and five-year overall survival ITT was 27.7% and 20.5% after preoperative CRT versus 16.5% and 6.5% after immediate surgery (HR 0.73; 95% CI 0.56 to 0.96; p = 0.025). In addition, disease-free survival (HR 0.70; p = 0.009) locoregional failure-free interval (HR 0.57; p = 0.004) and distant metastases free interval (HR 0.74; p = 0.071) improved after preoperative CRT. Also in the stratified subsets RPC and BRPC, preoperative CRT improved OS: RPC (n = 133, HR 0.79; 95% CI 0.54 to 1.16; P = 0.23). BRPC (n = 113, HR 0.67; 95% CI 0.45 to 0.99; p = 0.045). We could not demonstrate a difference in treatment effect between these subsets (interaction test p = 0.56). Conclusions: Preoperative gemcitabine-based CRT for RPC or BRPC improves long term overall survival compared to immediate surgery with adjuvant gemcitabine. Clinical trial information: NTR3709.

How many number of retrieved lymph nodes is required for accurate N-staging in resected pancreatic cancer?

Introduction Although N stage is important factor in survival of resected pancreatic cancer, appropriate number of retrieved lymph nodes for accurate staging is still controversial. Methods From 1993 to 2019, 446 patients underwent pancreatectomy for pancreatic cancer were included. The binomial probability law was applied to define the minimum number of examined LNs (minELN). The prognostic factors for overall survival were analyzed. Results According to binomial probability law, 12 and 20 retrieved lymph nodes were found to be required accurate staging for pancreatic cancer. With node-positive disease, the median OS of patients with less than 12 ELNs was not significantly different to those with 12 or more ELNs (20 v. 18 months, p = 0.326). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes even when finding fewer than 12 ELNs (26 v. 19 months, p = 0.04) and more than 12 ELNs (22 v. 18 months, p = 0.01). On the other hand, with node-positive disease, the median OS of patients with less than 20 ELNs was not significantly different to those with 20 or more ELNs (20 v. 20 months, p = 0.78). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes in fewer than 20 ELNs (23 v. 17 months, p = 0.015), but SHOWED no significant IN MORE THAN 20 ELNs (22 v. 18 months, p = 0.07). Conclusions AJCC (8TH) N-staging system in independent prognostic factor for long-term survival of resected pancreatic cancer.Retrieving 12 lymph nodes are appropriate for Nodal staging PDAC by using AJCC (8th) N stage.

External Validation of Three Nomograms Predicting Survival Using an International Cohort of Patients with Resected Pancreatic Head Ductal Adenocarcinoma

Purpose: Lymph node ratio (LNR, positive lymph nodes/collected lymph nodes during surgery) was identified as an important prognostic factor of survival in resected pancreatic cancer. Several nomograms based on LNR were recently proposed to predict survival after pancreatoduodenectomy (PD). The present study aimed to externally validate 3 published nomograms using an international cohort. Methods: Consecutive patients with ductal adenocarcinoma of the pancreatic head who underwent PD without neoadjuvant treatment were retrospectively collected from 6 tertiary centers in Europe and the USA from 2000 to 2017. Patients with metastases at diagnosis, R2 resection, missing data regarding LNR, and who died within 90 postoperative days were excluded. The 3 selected nomograms were the updated Amsterdam nomogram (including LNR, adjuvant therapy, margin status, and tumor grade), the nomogram by Pu et al. (including LNR, age, tumor grade, and T stage) and the nomogram by Li et al. (including LNR, age, tumor location, grade, size, and TNM stage). Overall survivals (OS) were calculated using Kaplan-Meier method. For the validation, calibration (Hosmer-Lemeshow test), discrimination capacity (ROC curves for 3-year OS), and clinical utility (sensitivity and specificity at the value of Youden index) were assessed. Results: After exclusion of 95 patients with metastases, R2 resection, and who died within 90 postoperative days, 1167 patients were included. Median OS of the entire cohort was 23 months (95% CI: 21-24). For the 3 nomograms, Kaplan-Meier curves showed significant diminution of OS with increasing scores (p<0.01 for the 3 nomograms). All nomograms showed good calibration (non significant Hosmer-Lemeshow goodness-of-fit tests). For the updated Amsterdam nomogram, the area under the ROC curve (AUROC) for 3-year OS was 0.66. Sensitivity and specificity were 73% and 50%. Regarding the nomogram by Pu et al., the AUROC was 0.67. Sensitivity and specificity were 65% and 60%. For the nomogram by Li et al., the AUROC was 0.67, while sensitivity and specificity were 56% and 71%. Conclusion: The 3 selected nomograms were validated using an external international cohort and displayed interesting and comparable predictive values. Those nomograms may be used in clinical practice to estimate survival after PD for ductal adenocarcinoma.

Angiotensin system inhibitor use is associated with longer survival in resected pancreatic cancer

Presenter: Hao Liu MD, PhD | University of Pittsburgh Medical Center Background: The renin-angiotensin system (RAS) has been correlated with pancreatic adenocarcinoma (PDAC) tumorigenesis and progression. Activities and inhibition of RAS may affect the response to systemic therapy and may correlate with clinical outcomes. Previous observational studies suggested that angiotensin system inhibitor (ASI) use is associated with prolonged survival in a subset of PDAC patients. Our present study focused on resected PDAC patients and further explored the protective effect of ASI. Methods: We conducted a single-institution retrospective analysis of resected PDAC patients between 2010-2019. Clinicopathological characteristics of all cases meeting inclusion criteria were reviewed. The effect of ASI on patient survivals was measured by Kaplan Meier analysis, Cox Proportional Hazards model, Propensity Score Matching (PSM), and inverse propensity score weight (IPW) analysis. The propensity score of ASI treatment was calculated, accounting for comorbidities and treatments received, including the use of beta-blockers, diuretics, metformin, and statins. Results: A total of 813 patients were included in the analysis. The average age was 67.0 (34 – 91) years with a median follow up of 20.2 (1.8 – 117.5) months. On average, ASI users were older (69.1 vs. 65.1y, p<0.001) and has higher Charlson comorbidity index (4.6 vs 5.4, p<0.001). However, the use of ASI was significantly associated with longer overall survival in univariate (HR = 0.78 [95%CI: 0.65-0.92], p = 0.004) and multivariate (HR = 0.73 [0.58-0.91], p = 0.005) adjusted analysis. In the propensity score-matched cohort of 637 patients, ASI use confirmed the association with longer overall survival (HR = 0.75 [0.59-0.94], p = 0.013) as well as longer disease-free progression in the liver (HR = 0.66 [0.45-0.95}, p = 0.026) and peritoneum (HR = 0.60 [0.36-0.98] p = 0.041) but not local recurrence-free survival (HR = 0.92 [0.62-1.34], p = 0.653). Lastly, IPW analysis on the whole cohort of 813 patients demonstrated ASI use to be associated with an average treatment effect on the treated (ATT) of HR = 0.67 [0.53-0.85] (p<0.001) for overall survival. Conclusion: In this single institute retrospective study focusing on resected PDAC patients, the use of ASI was associated with longer overall survival after adjusting for multiple clinicopathological parameters. Propensity score matching and inverse propensity score weighted analysis also showed that ASI use was associated with longer overall and progression-free survival. Further prospective trials on the impact of ASI on PDAC are needed.

Five gene signatures were identified in the prediction of overall survival in resectable pancreatic cancer

BackgroundAlthough genes have been previously detected in pancreatic cancer (PC), aberrant genes that play roles in resectable pancreatic cancer should be further assessed.MethodsMessenger RNA samples and clinicopathological data corrected with PC were downloaded from The Cancer Genome Atlas (TCGA). Resectable PC patients were randomly divided into a primary set and a validation set. Univariable Cox regression analysis, lasso-penalized Cox regression analysis, and multivariable Cox analysis were implemented to distinguish survival-related genes (SRGs). A risk score based on the SRGs was calculated by univariable Cox regression analysis. A genomic-clinical nomogram was established by integrating the risk score and clinicopathological data to predict overall survival (OS) in resectable PC.ResultsFive survival-related genes (AADAC, DEF8, HIST1H1C, MET, and CHFR) were significantly correlated with OS in resectable PC. The resectable PC patients, based on risk score, were sorted into a high-risk group that showed considerably unfavorable OS (p < 0.001) than the low-risk group, in both the primary set and the validation set. The concordance index (C-index) was calculated to evaluate the predictive performance of the nomogram were respectively in the primary set [0.696 (0.608–0.784)] and the validation set [0.682 (0.606–0.758)]. Additionally, gene set enrichment Analysis discovered several meaningful enriched pathways.ConclusionOur study identified five prognostic gene biomarkers for OS prediction and which facilitate postoperative molecular target therapy for the resectable PC, especially the nomic-clinical nomogram which may be used as an effective model for the postoperative OS evaluation and also an optimal therapeutic tool for the resectable PC.

A nomogram to preoperatively predict 1-year disease-specific survival in resected pancreatic cancer following neoadjuvant chemoradiation therapy.

ObjectiveThis study aimed to develop a nomogram to predict the 1-year survival of patients with pancreatic cancer who underwent pancreatectomy following neoadjuvant treatment with preoperatively detectable clinical parameters. Extended pancreatectomy is necessary to achieve complete tumor removal in borderline resectable and locally advanced pancreatic cancer. However, it increases postoperative morbidity and mortality rates, and should be balanced with potential benefit of long-term survival.MethodsThe medical records of patients who underwent pancreatectomy following neoadjuvant treatment from January 2005 to December 2016 at Severance Hospital were retrospectively reviewed. Medical records were collected from five international institutions from Japan and Singapore for external validation.ResultsA total of 113 patients were enrolled. The nomogram for predicting 1-year disease-specific survival was created based on 5 clinically detectable preoperative parameters as follows: age (year), symptom (no/yes), tumor size at initial diagnostic stage (cm), preoperative serum carbohydrate antigen (CA) 19-9 level after neoadjuvant treatment (<34/≥34 U/mL), and planned surgery [pancreaticoduodenectomy (PD) (pylorus-preserving PD)/distal pancreatectomy (DP)/total pancreatectomy]. Model performance was assessed for discrimination and calibration. The calibration plot showed good agreement between actual and predicted survival probabilities; the the Greenwood-Nam-D’Agostino (GND) goodness-of-fit test showed that the model was well calibrated (χ2=8.24, P=0.5099). A total of 84 patients were used for external validation. When correlating actual disease-specific survival and calculated 1-year disease-specific survival, there were significance differences according to the calculated probability of 1-year survival among the three groups (P=0.044). ConclusionsThe developed nomogram had quite acceptable accuracy and clinical feasibility in the decision-making process for the management of pancreatic cancer.

International validation of the Amsterdam model for survival prediction after resected pancreatic cancer

Background: A recent systematic review identified only two prediction models for survival in resectable pancreatic cancer of high methodological quality. The objective of this study was to validate one of these, the Amsterdam prediction model (including differentiation grade, positive lymph node ratio, margin status and adjuvant therapy), in a large international cohort. Methods: All consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000-2017 at 10 tertiary hospitals from 8 countries were included. Calibration and model performance for prediction of 3-year and 5-year survival were evaluated and compared to the 8th edition of the TNM staging system, using Uno’s C-statistic, the Receiver Operating Characteristics (ROC) curves and area under the curves (AUC). Results: A total of 2,203 patients were included (mean age 65 years, 54% male), with a median overall survival of 23.6 months. The validation cohort was demographically comparable to the design cohort, but had a higher lymph node yield (median of 19 vs. 8) and more N2 disease (22.0% vs. 40.3%), and a higher use of adjuvant therapy (76.0% vs. 35.1%). Calibration analysis demonstrated that the predictions of 3-year survival did not systematically deviate from the observed survival rates with a slope of 0.85 and an intercept of 0.04. Uno’s C-statistic was 0.65 in the validation cohort, compared to 0.67 in the derivation cohort. ROC-curves showed an AUC of 0.70 and 0.72 for 3- and 5-year survival, compared to 0.65 and 0.68 for the TNM 8, respectively. Analysis of model performance among the different countries demonstrated a robust C-statistic, ranging from 0.61 to 0.67. Conclusions: This international multicenter study validated the previous predictions of the Amsterdam model for 3- and 5-year survival after pancreatoduodenectomy for pancreatic cancer. Model performance was fairly accurate in terms of calibration and discrimination, and the model demonstrated robustness within the different countries.

Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer

Background: As more therapeutic options for pancreatic cancer are becoming available, there is a need to improve outcome prediction to support shared-decision making. A systematic evaluation of prediction models in resectable pancreatic cancer is lacking. Methods: This systematic review followed the CHARMS and PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched up to 11 October 2017. Studies reporting development or validation of models predicting survival in resectable pancreatic cancer were included. Models without performance measures, reviews, abstracts or more than 10% of patients not undergoing resection in postoperative models were excluded. Studies were appraised critically. Results: After screening 4403 studies, 22 (44 319 patients) were included. There were 19 model development/update studies and three validation studies, altogether concerning 21 individual models. Two studies were deemed at low risk of bias. Eight models were developed for the preoperative setting and 13 for the postoperative setting. Most frequently included parameters were differentiation grade (11 of 21 models), nodal status (8 of 21) and serum albumin (7 of 21). Treatment-related variables were included in three models. The c-statistic/area under the curve values ranged from 0.57 to 0.90. Based on study design, validation Methods and the availability of web-based calculators, two models were identified as the most promising. Conclusion: Although a large number of prediction models for resectable pancreatic cancer have been reported, most are at high risk of bias and have not been validated externally. This overview of prognostic factors provided practical recommendations that could help in designing easily applicable prediction models to support shared decision-making.

Diabetes mellitus is associated with unfavorable pathologic features, increased postoperative mortality, and worse long-term survival in resected pancreatic cancer

BackgroundThe risk of pancreatic ductal adenocarcinoma (PDAC) is increased in patients with diabetes mellitus (DM), particularly in those with new-onset DM. However, the impact of DM on outcomes following pancreatic surgery is not fully understood. We sought to explore the effects of DM on post-resection outcomes in patients undergoing either upfront resection or following neoadjuvant treatment (NAT). MethodsResections for PDAC between 2007 and 2016 were identified from a prospectively-maintained database. Data on demographics, pathology, and perioperative outcomes were compared between patients with or without DM. Survival analysis was performed using Kaplan-Meier curves and adjusted for confounders by a Cox-proportional hazards model. Results662 patients were identified, of whom 277 (41.8%) had DM. Diabetics were more likely to be male, had higher BMI, and higher ASA-scores. At pathology, DM was associated with larger tumors (30 vs. 26 mm; p = 0.041), higher rates of lymph-node involvement (69% vs. 59%; p = 0.031) and perineural invasion (88% vs. 82%; p = 0.026). Despite having similar rates of complications, diabetics experienced higher 30-day mortality (3.2% vs. 0.8%; p = 0.019). Median overall survival was worse in diabetic patients (18 vs. 34 months; p < 0.001); this effect was more pronounced in patients with NAT (18 vs. 54 months; p < 0.001). At multivariate analysis, DM was confirmed as an independent predictor of post-resection survival. ConclusionDM is a common comorbidity in PDAC and is associated with unfavorable pathology, as well as worse postoperative and oncologic outcomes. The blunted effect on survival is more pronounced in patients who undergo resection following NAT.

Silenced ZNF154 Is Associated with Longer Survival in Resectable Pancreatic Cancer.

Pancreatic cancer has become the third leading cause of cancer-related death in the Western world despite advances in therapy of other cancerous lesions. Late diagnosis due to a lack of symptoms during early disease allows metastatic spread of the tumor. Most patients are considered incurable because of metastasized disease. On a cellular level, pancreatic cancer proves to be rather resistant to chemotherapy. Hence, early detection and new therapeutic targets might improve outcomes. The detection of DNA promoter hypermethylation has been described as a method to identify putative genes of interest in cancer entities. These genes might serve as either biomarkers or might lead to a better understanding of the molecular mechanisms involved. We checked tumor specimens from 80 patients who had undergone pancreatic resection for promoter hypermethylation of the zinc finger protein ZNF154. Then, we further characterized the effects of ZNF154 on cell viability and gene expression by in vitro experiments. We found a significant association between ZNF154 hypermethylation and better survival in patients with resectable pancreatic cancer. Moreover, we suspect that the cell growth suppressor SLFN5 might be linked to a silenced ZNF154 in pancreatic cancer.

Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer.

As more therapeutic options for pancreatic cancer are becoming available, there is a need to improve outcome prediction to support shared decision-making. A systematic evaluation of prediction models in resectable pancreatic cancer is lacking. This systematic review followed the CHARMS and PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched up to 11 October 2017. Studies reporting development or validation of models predicting survival in resectable pancreatic cancer were included. Models without performance measures, reviews, abstracts or more than 10 per cent of patients not undergoing resection in postoperative models were excluded. Studies were appraised critically. After screening 4403 studies, 22 (44 319 patients) were included. There were 19 model development/update studies and three validation studies, altogether concerning 21 individual models. Two studies were deemed at low risk of bias. Eight models were developed for the preoperative setting and 13 for the postoperative setting. Most frequently included parameters were differentiation grade (11 of 21 models), nodal status (8 of 21) and serum albumin (7 of 21). Treatment-related variables were included in three models. The C-statistic/area under the curve values ranged from 0·57 to 0·90. Based on study design, validation methods and the availability of web-based calculators, two models were identified as the most promising. Although a large number of prediction models for resectable pancreatic cancer have been reported, most are at high risk of bias and have not been validated externally. This overview of prognostic factors provided practical recommendations that could help in designing easily applicable prediction models to support shared decision-making.

P-138 - Predictive factors for early relapse and survival in resected pancreatic cancer: A single institution experience

P-138 - Predictive factors for early relapse and survival in resected pancreatic cancer: A single institution experience