bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical predictors of second-line chemotherapy (ChT) benefit in pancreatic cancer (PC).
Authors: Pokataev Ilya , Bazin Igor , Fedyanin Mikhail , Tryakin Alexey , Popova Anna , Rumyantsev Alexey , Sekhina Olga , Patutko Yury , Fainstein Igor , Tjulandin Sergei 
Published: September 2018

e15733 Background: Second line ChT is shown to improve outcome in selected patients with PC; however there are no approved models predicting its benefit. This retrospective study was aimed to evaluate prognostic factors in patients with PC who had disease progression following 1st line ChT and their value in prediction of 2nd line ChT benefit. Methods: Records of PC patients treated in N.N. Blokhin Russian Cancer Research Center since 2000 to 2015 were analyzed. Inclusion criteria for this retrospective analysis were: morphologically confirmed PC, disease progression after 1st line ChT or adjuvant / induction ChT with ChT-free interval <6 months. The most common clinical factors were evaluated for prognostic significance in the Cox proportional hazards model with overall survival (OS) as the end-point. OS was calculated from the date of progression following previous ChT. Cutoff values for quantitative variables were determined using ROC curve analyses. Results: Records of 172 patients matched the inclusion criteria. Second line ChT was administered in 110 (64%) patients (47% of them received gemcitabine- and/or platinum-based doublets). The Cox multivariate analysis identified two independent prognostic factors: Karnofsky performance status (KPS) ≤70% and neutrophil-to-lymphocyte ratio (NLR) >5 at the time of disease progression after 1st line ChT (Table). Administration of 2nd line ChT improved outcome of patients with favorable prognosis (score ≤1): median OS increased from 1.7 to 5.5 months in groups without (n=23) and with (n=90) ChT, respectively (p=0.02). In patients with poor prognosis (score>1) there were no benefit by administration of 2nd line ChT: medians OS were 2.3 and 1.7 months in groups with (n=20) and without (n=39) ChT, respectively (p=0.23). Conclusions: This novel prognostic model can potentially predict 2nd line ChT benefit in patients with PC, however it needs to be validated in further trials. [Table: see text]
NAMPT expression in stage I/II pancreatic ductal adenocarcinoma.
Authors: Davis Katelynn , Dunseth Craig , Mott Sarah L , Bellizzi Andrew , Chan Carlos Hou Fai 
Published: September 2018

e15735 Background: NAD (nicotinamide adenine dinucleotide), a vital cofactor in redox reactions and a substrate for many enzymes, plays a critical role in cellular metabolism. NAMPT (nicotinamide phosphoribosyltransferase) is a key enzyme that regenerates NAD from its metabolites. NAMPT has been shown to be overexpressed in some cancers, and inhibition of NAMPT in pancreas cancer cell lines and xenografts has been shown to decrease cell growth, making it an attractive potential therapeutic target. Here we correlate NAMPT expression in a large cohort of stage I/II pancreatic ductal adenocarcinomas (PDA) with clinical outcomes and pathologic features. Methods: NAMPT immunohistochemistry (IHC) was performed on tissue microarrays of 250 PDAs. Tumors had been arrayed in triplicate. Each core was evaluated for staining intensity of cancer cells (0 = no staining, 1+ = weak, 2+ = moderate, 3+ = strong), and a mean score was calculated for each case; cases with fewer than 2 cores were excluded. Fisher’s exact and Wilcoxon rank sum tests were used for categorical and continuous variables, respectively. Recurrence-free survival (RFS) and overall survival (OS) differences were evaluated using Cox regression. This study was conducted under an approved IRB protocol. Results: 197 PDAs had at least 2 TMA cores with identifiable cancer cells. The mean IHC score was 0.53 (range 0 to 2.33). While 121/197 PDAs (61%) were positive, only 18/197 (9%) had a score > 1. Stage II tumors had a higher mean score than stage I tumors (0.57 vs 0.31; P = 0.03) and were more likely to be positive (66% of 148 vs 41% of 22; P = 0.03). However, RFS and OS were not significantly different between NAMPT-positive vs NAMPT-negative PDAs. Conclusions: NAMPT expression was detected in 61% of stage I/II PDAs. Frequency and extent of expression correlated with overall stage, suggesting a role in cancer progression. Although NAMPT expression did not correlate with RFS and OS in this study, given its frequent expression in PDA, it represents a potential therapeutic target.
Early-onset pancreatic ductal adenocarcinoma (PDAC) at Memorial Sloan Kettering Cancer Center (MSKCC).
Authors: Kunte Siddharth , Sangli Swathi , Lemor Alejandro , Lowery Maeve Aine , Yu Kenneth H. , Abou-Alfa Ghassan K. , Varghese Anna M. , O'Reilly Eileen Mary 
Published: September 2018

e15736 Background: PDAC is a leading and rising cause of cancer-related mortality. There is infrequent description of patients and outcomes with PDAC diagnosed aged <=50 years old (Early onset PC: EOPC). We reviewed the epidemiology, risk factors, oncologic outcomes and genomic data of EOPC pts at MSKCC. Methods: Using an institutional dataline search, N=364 patients were identified with EOPC between 2008-2014 at MSKCC. N= 282 were included in final analysis based on data completeness. Results: Baseline characteristics are summarized in table 1. The average patient was male, aged between 40- 50 years, BMI 24 and had metastatic disease at diagnosis. Family history of malignancy was present in N= 216 patients. The median overall survival (OS) for stages IIA, IIB, III and IV was 19.2, 21.8, 18.8 and 9.7 months respectively. Age, gender, diabetes and smoking history did not have a significant impact on OS. No difference in OS was noted between the groups who received gemcitabine based first-line chemotherapy compared to those with 5-fluorouracil based regimen in metastatic disease (9.9 vs 12 months, p= 0.315). Conclusions: EOPC represents a small subset of patients with PDAC and very rarely arises < 30 years of age. For this MSKCC cohort, outcomes appear similar to patients with average age onset PDAC. Further analyses on genomic characteristics may provide insight into outcomes and genetic underpinnings of EOPC. [Table: see text]
Modified FOLFIRINOX (mFOLFIRINOX) as second-line chemotherapy in pancreatic adenocarcinoma.
Authors: Dean Andrew Peter , Higgs Domenic , James Alex , Van Gemert Tegan , James Alena Talia 
Published: September 2018

e15747 Background: FOLFIRINOX is a highly effective combination chemotherapy regimen with the reputation of only being tolerable to young patients with good performance status. As the original ACCORD study was carried out at specific French university hospitals with patients performance status 0 or 1 many oncologists feel uncomfortable administering mFOLFIRINOX as a second-line therapy. We have previously reported our experience in 24 patients ages 27 - 84 where we concluded that dose modified FOLFIRINOX can be safely administered to elderly patients with appropriate initial dose reductions and subsequent escalation. There is a lack of consensus on a standard second-line regimen for metastatic pancreatic cancer. We conducted a review of dose intensity and outcome for all patients treated with 2nd or 3rd-line mFOLFIRINOX for pancreatic adenocarcinoma at St John of God Hospital, Subiaco, Western Australia in order to assess efficacy and tolerability Methods: Electronic records were used to identify 35 patients who had received 1st-line gemcitabine-based chemotherapy who then went on to receive 2nd or 3rd line mFOLFIRINOX. Case files, laboratory and radiology records were then examined to determine outcomes and toxicities. Results: 35 patients were identified with an age range of 27- 85, both locally advanced and metastatic disease, with 12 over the age of 70. All patients except 2 had gemcitabine plus abraxane in the first line setting. Dose intensity was 65% for oxaliplatin, 68% for irinotecan, 18% for bolus 5-FU and 68% fir infusional 5FU. Toxicity was acceptable with a grade 3 toxicity rate of 10%. Overall survival in this group ranged from 5-67 months (median 23 months for locally advanced / 15 months for metastatic). Notably, 20 patients received greater than 6 cycles of treatment and 8 patients received more than 12 cycles. One patient has received 70 cycles. Conclusions: Our experience demonstrates the safety, tolerability and efficacy of mFolfirinox as a second-line therapy after gemcitabine failure. The disease control rate, even with the reduction in dose intensity, suggests that modified Folfirinox should be formally tested in the 2nd line setting in a clinical trial.
Effect of chemotherapy on survival of patients with recurrent pancreatic ductal adenocarcinoma (PDAC) following surgical therapy.
Authors: Gbolahan Olumide B. , Tong Yan , O'Neil Bert H. , Shahda Safi 
Published: September 2018

e15748 Background: Patients with recurrent PDAC are treated similarly to patients with de novo metastatic disease. The aim of this study is to report the outcome of patients with recurrent PDAC following initial definitive resection and adjuvant therapy. Methods: Patients were identified from an IRB approved, retrospective database at Indiana University that contained patient and tumor characteristics, adjuvant therapy and all treatment for metastatic disease. Follow-up was updated as of 6/2014. Overall survival (OS) from recurrence until death or last follow up was estimated using the Kaplan Meier method. Results: Between 2008-2014, 451 patients with resectable PDAC and available follow up data were identified, of whom 234 had documented relapse. Patient/tumor characteristics were as follows: median age: 64.2 years (25-89), 54% male, 76% LN+, 24% positive margins, 66% and 85% with lymphovascular and perineural invasion respectively. 69% of patients received adjuvant gemcitabine (GEM). Median time to relapse was 10 months. 60% of patients received at least 1 line of systemic therapy and 18% received 2 lines. Chemotherapy was GEM-based: 33%, 5FU-based 33%, or both 33% and 1% other treatment. Median OS from time of relapse was significantly improved following chemotherapy compared to no chemotherapy (10 months vs 3 months, P < 0.0001). Median OS for 5FU based and GEM based treatment was 6 and 8 months, respectively (P = 0.09). Those who received both had mOS of 14 months (95% C.I 10-17months, P < 0.0001). On univariate analysis, chemotherapy, regardless of type was associated with a survival benefit. Conclusions: Chemotherapy appears to be associated with survival benefit for patients with relapsed PDAC following initial curative therapy. Survival in our retrospective study appears similar to reported literature for de novo metastatic disease.
The effects of pioglitazone treatment on pancreatic cancer-related insulin resistance.
Authors: Stern Jennifer , Arriaga Yull Edwin , Gupta Arjun , Verma Udit N. , Karri Sirisha , Syed Samira K. , Khosama Leticia , Mansour John C. , Scherer Philipp , Beg Muhammad Shaalan 
Published: September 2018

e15752 Background: Insulin resistance (IR) in pancreatic cancer (PC) patients is associated with cachexia and poor outcome. Pioglitazone (PIO) improves insulin sensitivity via activation of peroxisome proliferator-activated receptor (PPAR gamma). Effects of PIO on insulin sensitivity, glucose homeostasis, and circulating adipokine levels in PC have not been examined. Methods: Patients with metastatic PC were administered PIO 45mg/day orally for 8 weeks concurrent with chemotherapy. Patients with known DM at enrollment were identified Fasting plasma was collected at baseline, weeks 2, 4, 6, 8 of pioglitazone treatment and at 2 weeks-post treatment. The primary objective was to describe changes in indicators of IR, including glucoregulatory hormone levels, glucose tolerance, and inflammatory cytokines. Results: Fourteen patients (age 64y), with a mean BMI of 28 were enrolled. Mean adiponectin increased from baseline to week 8 of treatment (14.2± 3.3 and 46.9±11.4µg/ml, respectively, P ≤ 0.01), and returned to baseline levels at 2 weeks post-treatment (15.1±1.9 µg/ml). Markers of IR (serum glucose, insulin, glucagon, and response to an oral glucose bolus) did not correlate with tumor size, inflammatory cytokine levels, GM-CSF, or CA19-9. A dichotomous response to PIO treatment was observed between non-diabetic and T2DM patients. Fasting insulin increased 70.6±31.3% from baseline to treatment week 8 in patients with T2DM. In contrast, treatment of non-diabetic patients decreased fasting insulin by 40.2±6.3%, demonstrating a significant, P ≤ 0.01, difference in treatment response between PC patients with or without T2DM. Conclusions: We have demonstrated that PC patients respond to 8 weeks of PIO treatment with a significant rise in the insulin sensitizing adipokine, Adiponectin, with a complete wash-out after 2 weeks of cessation. PIO results in opposing fasting insulin responses in non-diabetic and DM patients suggests that diabetes status plays a significant role in the glucoregulatory effects of PIO treatment in PC patients. Clinical trial information Clinical trial information: NCT01838317.
Survival after recurrence following curative intent resection of pancreatic adenocarcinoma.
Authors: Ellsworth Susannah G. , Stanley Melissa , House Michael Garrett , Nakeeb Attila , Shahda Safi , Schmidt Christian , Zyromski Nicholas J , O'Neil Bert H. , Sehdev Amikar 
Published: September 2018

e15760 Background: Limited data exist on outcomes after recurrence after curative intent resection for pancreatic adenocarcinoma (PC). We analyzed the prognostic significance of time to recurrence and associated factors in patients with post-pancreatectomy recurrence. Methods: Patients with a documented recurrence were identified from a prospectively maintained database of all patients undergoing pancreatectomy for PC between 2009-2015 at Indiana University Simon Cancer Center. Patients were divided into early (≤12 mos after surgery) and late recurrence ( > 12 mos after surgery) groups. Demographic (age, race, sex) and clinical (CA19-9, bilirubin, tumor location, diabetes at presentation, ECOG performance status, margin status, adjuvant radiation, and adjuvant and metastatic chemotherapy) data were obtained by manual chart abstraction and the IUSCC cancer registry. The primary outcome was survival after recurrence (SAR- time from recurrence to death). Chi-square was used for univariate analysis (except t-test for age). SAR was estimated with the Kaplan-Meier method and 95% CI. Cox proportional-hazard model was used for multivariate analysis (MVA). Results: Of 437 patients undergoing surgical resection for PC, 235 had documented recurrence. More patients had an early recurrence (ER) as compared to late recurrence (LR; 58.3% vs 41.7%). Median SAR was significantly shorter in ER vs LR patients (6.2 vs 8.6 months; HR, 0.71; 95% CI, 0.53-0.95; P = 0.02). Median age was higher in ER vs LR groups (64.7 and 64.2 years, P = 0.002). Diabetes at presentation was more common in ER vs LR group (42.3% vs 30.6%, P = 0.09). ER patients were significantly less likely to have received adjuvant chemotherapy (70.7% vs 84.7%, P = 0.02) or adjuvant radiation (17.8% vs 40%, P < .001). MVA showed a trend towards longer SAR in LR vs ER group (adjusted HR = 0.75, 95% CI, 0.55-0.1.03, p = 0.08) however age, adjuvant chemotherapy, adjuvant radiation and diabetes at presentation were not significant predictors of SAR. Conclusions: Early recurrence after resection of PC is associated with poor SAR. Patients with early recurrence tend to be older, diabetic at presentation and were less likely to have received adjuvant chemotherapy or adjuvant radiation.
Association between lymph node examination and nodal staging for pancreatic adenocarcinoma: A population-based analysis.
Authors: Xu Rui-hua , Wang Zi-Xian , Qiu Miaozhen , Jin Ying , He Ming-ming , Wang Feng , Wang Fenghua 
Published: September 2018

e15772 Background: The minimum number of examined lymph nodes (ELNs) for accurate nodal staging remains controversial and has not been recommended by the NCCN guidelines for pancreatic adenocarcinoma (PADC). We aimed to evaluate the time trends in the ELN count and the proportion of node-positive PADC (N+%), as well as determine the minimal threshold for the ELN count. Methods: We analyzed 9258 patients with resectable PADC between 2000 and 2012 in the SEER database (18 registries). Changes in the ELN count and N+% over time were evaluated using the Spearman correlation analysis and the Cochran-Armitage test, respectively. Multivariable logistic and Cox models were used to evaluate the association between the ELN count and N+% and overall survival after adjusted for clinicopathologic features (i.e., race/ethnicity, sex, age, marital status, SEER region, year of diagnosis, tumor grade, tumor site, 8th AJCC T stage, and surgical type). Restricted cubic spline modeling was used to handle possible nonlinear effects of the ELN count as a continuous covariate in the multivariable models. Structural breakpoints, which were considered the threshold of clinical impact, were determined by the Chow test. Results: The median ELN count increased from 9 (interquartile range: 5−15) in 2000 to 16 (11−23) in 2012 ( Ptrend < 0.001), and the N+% increased from 61.1% to 67.2% ( Ptrend < 0.001). An increased ELN count was associated with a nonlinear increase in N+% ( P < 0.001), and the Chow test revealed a threshold ELN count of 8 (ORadjusted for ≥ 8 vs. < 8 ELNs, 2.42 [95% CI, 2.19−2.68]). The 8-ELN threshold was confirmed in patients with declared N0 disease: A larger number of ELNs was correlated with a nonlinear increase in overall survival among these patients ( P < 0.001), with the threshold ELN count also being 8 (HRadjustedfor ≥ 8 vs. < 8 ELNs, 0.79 [95% CI, 0.75−0.87]). Moreover, the 8-ELN threshold remained valid regardless of T stage and year of diagnosis. Conclusions: Lymph node examination has increased markedly over time and was associated with an overall shift toward higher-staged PADC. We recommend 8 ELNs as the cut point for improvement of prognostic accuracy and quality measurement of lymph node examination.
Chromogranin A levels to predict survival in resectable pancreatic neuroendocrine tumors.
Authors: Tariq Khurram Bilal , Roberts Brandon , Nayak Kapoor Asha 
Published: September 2018

e15775 Background: To determine whether Chromogranin A (CGA) predicts outcome after Cytoreductive Surgery (CRS) for Pancreatic Neuroendocrine Tumors (PNETs). CGA is used by clinicians to monitor progression of disease and response to treatment, but has not been objectively evaluated. Methods: A retrospective study of patients with PNETs seen at the Georgia Cancer Center, formerly the Medical College of Georgia, from 1980 to 2011 was performed. All patients who had CGA concentrations measured were evaluated (n = 126). Data relating to diagnosis, therapies, and survival outcome were noted. Patients with resectable and unresectable disease were included. Those with unresectable disease where evaluated for receiving Octreotide treatment. Results: The initial patient pool yielded a group (n = 118) with 72% (n = 85) having undergone Cytoreductive Surgery (CRS). Within the CRS group decreased survival was noted in patients with an elevated CGA level 4 months post-operatively (p = 0.002) and an elevated median CGA level of > 224ng/ml correlated with a shorter survival time (p = < 0.005). Increased survival was seen in CRS patients with median CGA levels of < 200ng/ml between 4-12 months post-operatively with a 4 year survival of 91.08%. The median time to death was 80.27 months. Elevated CGA levels in CRS patients correlated with a survival probability of 63.25% at 4 years with a median death of 48.25 months. Overall 28% of the total patient group had unresectable disease (n = 33): 61% of this subgroup (n = 20) received Octreotide therapy and exhibited significant decrease in CGA level at a median of 3.6 months (p = < 0.024); no correlation existed between CGA levels and survival. Conclusions: PNETs amenable to resection by Cytoreductive Surgery (CRS) and had a median Chromogranin A (CGA) level < 200 ng/ml measured post-operatively after 4 months showed increased survival. No correlation existed between CGA levels and survival in patients with unresected disease despite Octreotide therapy lowering CGA levels. As such, CGA is predictive of survival in patients with resectable PNETs and worthy of prospective study.
A clinical prediction model to assess risk for pancreatic cancer among patients with new-onset diabetes.
Authors: Boursi Ben , Finkelman Brian S. , Giantonio Bruce J. , Haynes Kevin , Rustgi Anil K. , Rhim Andrew , Mamtani Ronac , Yang Yu-Xiao 
Published: September 2018

e15780 Background: Approximately 50% of all patients with pancreatic ductal adenocarcinoma (PDA) develop diabetes mellitus (DM) prior to cancer diagnosis. Targeted screening for PDA among those with new-onset diabetes may allow earlier diagnosis. We sought to develop and validate a PDA risk prediction model to identify high-risk individuals among those with new-onset diabetes. Methods: We conducted a retrospective cohort study in a population representative database from the UK. Individuals with incident diabetes after the age of 35 and ≥3 years of follow-up after DM diagnosis were eligible for inclusion. Candidate predictors consisted of epidemiological and clinical characteristics available at the time of diabetes diagnosis. Variables with p-value<0.25 in the univariable analyses were further evaluated using backward stepwise approach. Model discrimination was assessed using ROC curve analysis. Calibration was evaluated using the Hosmer–Lemeshow test. Results were internally validated using a bootstrapping procedure. Results: The study included 109,385 patients with new-onset diabetes. Among them, 390 (0.4%) were diagnosed with PDA within 3 years. The final model (AUC 0.82, 95% CI: 0.75-0.89) included age, BMI, BMI change, smoking, HbA1C, cholesterol, hemoglobin, creatinine and alkaline phosphatase, and use of PPI and anti-diabetic medication. Bootstrapping validation showed negligible optimism. If the predicted risk threshold for definitive PDA screening was set at 1% over 3 years, only 6.19% of the new-onset diabetes population would undergo definitive screening, and the corresponding sensitivity, specificity and positive predictive value would be 44.7%, 94.0%, and 2.6% respectively. Conclusions: A risk model based on widely available clinical parameters can help target PDA screening in patients with new-onset diabetes.