bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant neutrophil accumulation, IL-18 deposition, and active inflammasome in tumor regions of human pancreatic ductal adenocarcinoma.
Authors: Khattab Ahmed , Garciafigueroa Yesica , Phillips Brett , Patruni Sunita , Kamran Amir , Jayakrishnan Thejus , Khatoon Nazia , Mohy-ud-din Nabeeha , Monga Satdarshan P , Miller Stacey , Giannoukakis Nick , Monga Dulabh K. 
Published: May 2019

e15754 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients with a body-mass index (BMI) > 27 (obesity, n = 5) and BMI < 22 (normal, n = 5) were incubated with anti-human IL-18 and CD66b antibodies and detected using Alexa Fluor 488-conjugated donkey anti–mouse and Alexa Fluor 594-conjugated goat anti-rabbit secondary antibodies. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of CD66b+ neutrophils and IL-18 in all tissue sections. There is a significantly greater density of CD66b+ neutrophils and IL-18 in the tumor environment when compared to adjacent normal areas and IL-18+ signals appear to be deposited alongside the luminal area in a unique lasso-like pattern. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. There does not appear to be an association between tumor stage and TAN or IL-18 accumulation in the tumor area or the adjacent normal tissue in the tissues. Conclusions: Our data uniquely shows that CD66b+ neutrophils accumulate inside PDAC and this is associated with intra-tumoral active inflammasomes. The novel periductal deposition of IL-18 in the tumor areas may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.
Development of a radiomics nomogram based on the CE-CT features to predict the survival of upfront resectable patients with pancreatic head cancer and suspected venous invasion.
Authors: Shen Yinan , Tang Tianyu , Bai Xueli , Liang Tingbo 
Published: May 2019

e15760 Background: Pancreatic head adenocarcinoma is commonly diagnosed at an advanced stage when adjacent vascular invasion is present. This study aimed to establish a radiomics nomogram by integrating radiomics signature and clinical predictors to estimate overall survival(OS) in patients who underwent attempted curative resectional surgery for pancreatic head cancer with suspected peri-pancreatic venous invasion. Methods: Data on patients with pancreatic head adenocarcinoma and suspected peripancreatic invasion who underwent pancreatic resection with venous reconstruction were retrospectively collected from 2012 to 2016 at two academic institutions. A total of 396 radiomics features were extracted from pretreatment CE-CT images of each patient. Least absolute shrinkage and selection operator (LASSO) regression was applied to select optimal features and generate a radiomics signature. The radiomics nomogram was developed by integrating the radiomics signature and clinical predictors. The performance of radiomics nomogram validated in the cohort of patients of second institution. Results: Radiomics signatures were significantly associated with pancreatic head adenocarcinoma patients' survival time. The radiomics nomogram combined with clinical predictors(CA-199 value, Peripancreatic venous abnormalities and Lymph node staging) provided good predictive accuracy of survival on calibration curves. The C-index of the model in predicting overall survival (OS) was 0.836 for the validation cohort. Conclusions: The nomogram accurately predicted OS in patients with pancreatic head cancer with suspected peripancreatic venous invasion after attempted curative pancreatic resectional surgery. These findings might aid clinicians with treatment decision-making and improve precise medicine.
Comparison of FOLFIRINOX and gemcitabine with nab-paclitaxel in metastatic pancreatic cancer: Using Korean Pancreatic Cancer (K-PaC) Registry.
Authors: Lee Jong-Chan , Shin Dong Woo , Yang Se Yeol , Kim Min Jae , Kim Jaihwan , Woo Sang Myung , Lee Woo Jin , Choi Kui Son , Jung Jae Hyup , Kang Jingu , Hwang Jin-Hyeok 
Published: May 2019

e15762 Background: Although FOLFIRINOX and gemcitabine with nab-paclitaxel (GNP) are widely used in metastatic pancreatic cancer (MPC), the multi-center study comparing two regimens is rare. Recently, a multi-center, web-based registry for pancreatic cancer (K-PaC, Korean pancreatic cancer) was firstly launched in South Korea. We aimed to compare the clinical outcomes for FOLFIRINOX and GNP in MPC patients using K-PaC registry. Methods: In the K-PaC registry, we constructed the web-based database of anonymized 3,748 patients with histologically-proven pancreatic ductal adenocarcinoma. For this study, MPC patients who have received first-line FOLFIRINOX or GNP were enrolled. The baseline characteristics, overall survival (OS), grade III-IV toxicity, and other subgroup characteristics were analyzed. Results: From 2011 to 2017, a total of 413 (FOLFIRINOX 231 vs. GNP 182: with the same order below) patients met the eligible criteria. Median age was 63 year (60 vs. 68) and male were 46% (51% vs. 39%). Origins of tumor were head (41%), body (25%), and tail (34%). Major metastatic sites were liver (62%), peritoneum (32%), lung (18%), and others (34%), including multiple metastases. Median OS was 11.6 month (11.3 vs. 12.4, hazard ratio [HR] 0.91, confidence interval [CI] 0.71–1.16). The major hematologic toxicity was 32% of neutropenia (37% vs. 23% with P-value 0.116) and 12% of febrile neutropenia (16% vs. 10% with P-value 0.172). The major non-hematologic toxicity was 33% of fatigue (29% vs. 37% with P-value 0.455) and 28% of vomiting (27% vs. 29% with P-value 0.516). According to metastatic site, median OS by agents (months, FOLFIRINOX vs. GNP) were as follows: 9.5 vs. 10.2 with HR 0.898, CI 0.66–1.22 in liver; 11.8 vs. 12.5 with HR 0.90, CI 0.61–1.33 in lung; 9.1 vs. 12.6 with HR 0.94, HR 0.70–1.19 in peritoneal seeding. According to the sequential treatment, median OS of 1st-line FOLFIRINOX followed by GNP group (n = 53) was 11.2 month and that of 1st-line GNP followed by FOLFIRINOX group (n = 43) was 12.4 month (HR 0.82, CI 0.68–1.18). Conclusions: In this study using K-PaC registry in Korea, FOLFIRINOX and GNP showed comparable efficacy and toxicity. In the subgroup analysis, sequential treatment did not showed significant difference, but GNP showed a better trend in the group of peritoneal seeding.
Histology and stage at presentation among patients with rare pancreatic tumors: An exploratory analysis of the SEER database.
Authors: Subramoney Jay , Delgado David J. , Nguyen Victoria , Denneny Rachel Gray , George Brandon , Mitchell Edith P. 
Published: May 2019

e15774 Background: Rare pancreatic tumors account for approximately 15% of all pancreatic cancers (PCs) and 8,300 new cases diagnosed within the United States annually, while 85% of PCs diagnosed are classified as adenocarcinomas. Comparatively little research exists to analyze differences in diagnosis between rare PCs and the more common adenocarcinoma given greater clinical interest in the latter. The purpose of this study was to analyze the relationship between PC histology and stage at presentation with a focus on rare histologies. Methods: This study employed a retrospective cohort model using the NCI’s Surveillance, Epidemiology, and End Results (SEER) 1990-2015 database. We included patients diagnosed with PC aged 18+, with the comparator group being patients diagnosed with adenocarcinoma, and “rare” tumors defined as one of the following histologies: ductal, carcinoid, mucinous adenocarcinoma, and undetermined neoplasm. Stage was dichotomized (locoregional versus distant). Multivariable logistic regression was used to describe the association between tumor histology with initial stage at diagnosis, controlling for patient and tumor characteristics. Results: 90,764 PC patients were analyzed: 66.3% adenocarcinoma, 9.6% ductal carcinomas, 4.5% carcinoid, 3.8% mucinous, and 15.8% undetermined neoplasm. 54.7% of all cases were distantly metastasized at diagnosis. In multivariable analysis, pancreatic cancer patients with mucinous histology had greater odds of presenting at late-stage compared to those with adenocarcinoma: OR = 1.41, 95% CI = [1.31, 1.52]. Carcinoid and undetermined neoplasm odds for late stage presentation were not significant compared to adenocarcinoma: OR = 0.99, 95% CI = [0.92, 1.07] and OR = 1.01, 95% Cl = [0.97, 1.05] respectively. Ductal carcinoma was less likely than adenocarcinoma to present with late stage: OR = 0.38, CI = [0.36, 0.40]. Conclusions: We observed that mucinous histology had greater odds of late-stage diagnosis compared to those with adenocarcinoma. Patients with ductal carcinoma was less likely than those with adenocarcinoma to present with late stage. Further investigation is needed to explore the reasons for these differences.
Impact of KRAS mutations in clinical features and survival in pancreatic cancer patients: A single institution experience.
Authors: Saavedra Elizabeth Inga , Gomez Maria Auxiliadora , Cano Maria Teresa , Perdomo Eduardo , Toledano Marta , Aranda Enrique 
Published: May 2019

e15779 Background: Pancreatic cancer (PC) is currently one of the most lethal tumors. In recent years, although improvements have been developed in the detection and treatment of this disease, the 5-year survival is less than 10%. KRAS plays a key role in ras/mitogen-activated protein kinase signaling. Somatic mutation in KRAS mutations have been shown to be early events in the carcinogenesis of PC. KRAS mutations as a prognostic factor for PC remains inconclusive. Methods: We performed a retrospective study of our patients (pts) to demonstrate the impact of KRAS mutations in clinical features and survival in real-life clinical practice. This was an observational study of all patients with histological confirmed PC referred to Medical Oncology between April 2017 to December 2018 and followed until February 2019. KRAS mutations were analyzed by sequencing codons 12, 13, and 61 in diagnostic tumor tissues from formalin fixed paraffin embedded tissue using PCR and liquid biopsy test (BEAMing technology). Categorical variables were statistically analyzed with Fisher’s exact test and continuous variables with T-student for differences between both groups. Survival was analyzed by Kaplan–Meier estimation and log-rank testing while Cox regression was used to estimed hazard ratios. Results: Our study cohort was 64 pts. 43% of pts died, the most die at home (25%). Median follow-up was 552 days (18 months). Metastatic pts had an expected overall survival (OS) of 376 days, locally advanced 525 days and localized stage 592 days but not statistically significant difference (p = 0.11). Wild-type pts had an expected OS of 559 days and KRAS mutated 389 days with statistically significant difference. (p = 0.032). Conclusions: KRAS mutations are associated with a poorer survival in patients with pancreatic cancer in all stages. These results suggest that KRAS mutations may be an important biomarker in determining response and prognosis in patients with high risk and in developing specific treatments for these patients in clinical applications.[Table: see text]
A retrospective analysis of antibiotics usage and effect on overall survival and progressive free survival in patients with metastatic pancreatic cancer.
Authors: Mohindroo Chirayu , Rogers Jane E. , Hasanov Merve , Mizrahi Jonathan , Overman Michael J. , Varadhachary Gauri Rajani , Wolff Robert A. , Javle Milind M. , Fogelman David R. , Pant Shubham , McAllister Florencia 
Published: May 2019

e15781 Background: Recent studies have shown that the pancreatic ductal adenocarcinoma (PDAC)-associated gut microbiome can play a major in modulating responses to therapies. Antibiotics (ATB) can potentially alter the tumor and gut microbiota diversity and composition leading to modified responses to chemotherapeutic/immune therapy regimens and hence the survival. Methods: We retrospectively analyzed the clinical data of 148 patients (pts) with documented metastatic PDAC seen at MD Anderson Cancer (MDACC) from 2009 to 2017. Along with demographic and chemotherapy regimen details the duration, type and reason for antibiotic consumption for more than 3 days were recorded. Overall survival (OS) and Progression free survival (PFS) were calculated. Log-rank test and Gehan-Breslow-Wilcoxon test were used to check the statistical significance for OS and PFS. Confounding variables were also accounted. Results: We analyzed the data of 148 metastatic pancreatic cancer pts[mean age 62.73, 50.67% males 49.32% females, 75.6% white] out of which 135 patients received antibiotics. The infectious sources consisted of intraabdominal (n = 68), urinary (n = 36), respiratory (n = 57), skin/soft tissue infections (n = 26), blood related (n = 24), and others (n = 76). Beta lactams (n = 96) and Quinolones (n = 96) were the most commonly prescribed antibiotics. When comparing outcomes, we found out that the median OS for pts taking macrolides (n = 24) was 541 days compared to 341 days for pts not taking macrolides (n = 144) (HR = 0.6384, p value = 0.0191) . Median PFS for pts taking macrolides was 178 days versus 124 days in those not taking macrolides (HR = 0.6331, p value = 0.0188). The potential confounders were having a respiratory infection or the type of chemotherapy regimen. Conclusions: Macrolide consumption for > 3 days leads to a prolonged OS and PFS. Consistent with the preclinical evidence our data suggests a potential role for some antibiotics in modulating PDAC-associated gut microbiome. Hence, having implications on the survival of PDAC pts. [Table: see text]
Effect of targeting CD40 for DC vaccination in pancreatic adenocarcinoma.
Authors: Lau Sai Ping , van Montfoort Nadine , Kinderman Priscilla , Lukkes Melanie , Dumas Jasper , van Nimwegen Menno , Mustafa Dana , Vroman Heleen , van Hall Thorbald , van der Burg Sjoerd H. , Aerts Joachim G.J.V. , Dammeijer Floris , van Eijck Casper H.J. 
Published: May 2019

e15783 Background: Although immunotherapy yields striking results in various malignancies, results in pancreatic cancer have been disappointing. Both a highly immunosuppressive tumor microenvironment and a dense desmoplastic stroma have been found to prohibit proper T-cell infiltration in these tumors, thereby preventing immunotherapy efficacy. We hypothesize that a rational and translational multistep approach is needed to sensitize pancreatic cancer to immunotherapy. In an aggressive murine pancreatic ductal adenocarcinoma model, we assessed the effectiveness of dendritic cell (DC) vaccination in combination with αCD40 treatment, as these treatments are known to induce effector T cells and degrade stroma, respectively. Methods: Immune competent C57BL/6 mice were inoculated subcutaneously with pancreatic tumor cells (KPC3). Mice with established tumors were vaccinated with tumor-loaded monocyte derived DCs and consequently treated with αCD40 agonistic antibodies. Tumor sizes were monitored over time. Immune responses were determined by flow cytometry of cells in peripheral blood, spleen and tumor. NanoString Technologies were applied on tumor samples. Results: A significant delay in tumor growth was found in the combination therapy arm compared to untreated mice and mice treated with DCs or αCD40 alone. Monotherapy had no effect on tumor growth. Survival of mice treated with the combination therapy was also improved compared to untreated mice or mice treated with monotherapy (P < 0.001). Interim blood analysis showed significant increases in frequencies of activated and proliferating T cells in treated animals and those cells also displayed an effector memory phenotype. This was more pronounced for CD4 T cells in mice treated with DCs while αCD40 therapy induced a confined response in CD8 T cells. Increased frequencies of tumor infiltrating lymphocytes were found in all treated mice compared to untreated mice. mRNA expression analysis indicated less exhausted phenotype of intratumoral lymphoid cells in mice treated with DCs and αCD40 compared to monotherapy DCs or αCD40. Conclusions: These results demonstrate the potency of this novel form of combination immunotherapy and reveals a mechanistic insight into the requirements of effective immunotherapy in pancreatic cancer.
Modified FOLFIRINOX as a second-line treatment in pancreatic adenocarcinoma patients with poor performance status.
Authors: Das Adarsh , Dean Andrew Peter , Higgs Domenic 
Published: May 2019

e15796 Background: FOLFIRINOX is well known to be a highly effective treatment in pancreatic cancer for young patients with good performance status. As the original ACCORD study was carried out with patient’s performance status 0 or 1, many oncologists feel uncertain administering modified dose FOLFIRINOX (m-FOLFIRINOX) as a second-line therapy. We have previously reported our experience in 35 patients (aged 27 – 85) where we concluded that m-FOLFIRINOX can be administered safely with appropriate dose reductions. More recently, the systematic review and meta-analysis by Tong et al. concluded that m-FOLFIRINOX is a good choice of therapy even for those with poor performance status. This retrospective analysis assessed the efficacy of m-FOLFIRINOX in second-line treatment of pancreatic adenocarcinoma. Methods: Using an electronic database, patients with either locally advanced or metastatic pancreatic adenocarcinoma were identified who had received first-line gemcitabine plus nab-paclitaxel, followed by second-line m-FOLFIRINOX between January 2013 and July 2018. All patients had an ECOG performance status of 2 or less. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Fifty-two patients were identified, with 65% of the patients having metastatic pancreatic disease. Median age of patients was 75 (range, 27 – 86). Dose intensity of m-FOLFIRINOX was 65% for oxaliplatin, 68% for irinotecan, 18% for bolus 5-fluorouracil (5-FU) and 68% for infusional 5-FU. From diagnosis, the median OS of all patients was 45.0 months (95% CI, 25.0 – 63.0). The median OS of the locally advanced and metastatic pancreatic adenocarcinoma was 63.0 months (95% CI, 45.0 – 70.0) and 22.5 months (95% CI, 18.0, 38.0), respectively. Conclusions: Our study demonstrates the safety and efficacy of m-FOLFIRINOX as a second-line therapy after gemcitabine plus nab-paclitaxel failure. These findings correlate with the findings of Tong et al.’s findings of the benefits of m-FOLFIRINOX for advanced pancreatic cancer in patients with poor performance status.
Pilot study of [18F] fluorodexoyglucose positron emission tomography-magnetic resonance imaging (FDG-PET-MRI) for staging of muscle-invasive bladder cancer.
Authors: Eulitt Patrick , Altun Ersan , Sheikh Arif , Wong Terence Z. , Woods Michael , Rose Tracy L , Wallen Eric , Pruthi Raj , Smith Angela , Nielsen Matthew Edward , Whang Young E. , Kim William Y. , Godley Paul Alphonso , Basch Ethan M. , David Grace , Ramirez Juanita , Deal Allison Mary , Lee Joseph , Milowsky Matthew I. 
Published: May 2019

e16002 Background: Standard of care imaging for staging MIBC is computed tomography (CT) abdomen and pelvis despite poor diagnostic accuracy. The addition of FDG-PET to evaluate biologic activity has been shown to improve detection of metastatic bladder cancer. Better soft tissue characterization with MRI may improve detection of local disease. We hypothesized that simultaneous acquisition of FDG-PET and MRI images (PET-MRI) would allow for more accurate preoperative staging in patients with MIBC. Methods: 21 patients with MIBC and planned radical cystectomy with lymph node dissection were enrolled. Four radiologists (2 senior, 2 junior) with expertise in MRI and PET independently reviewed MRI and FDG-PET scans, respectively, to determine: 1) extent of the primary bladder tumor; and 2) involvement of local lymph nodes and distant sites of disease. Combined radiologist reads were performed (senior MRI and junior PET and vice versa). Imaging results were compared to surgical pathology. Results: 18 patients were included in the final analysis (3 PET-MRI scans excluded due to technical pitfalls with image acquisition). Final pathology revealed 10 patients (56%) with muscle invasion and only 2 patients (11%) with lymph node involvement. Combined analyses of PET-MRI accurately detected the extent of the primary tumor (sensitivity 0.84, specificity 0.50, PPV 0.70, NPV 0.70), but was less accurate for the detection of lymph node involvement (sensitivity 0.00, specificity 1.00, no calculable PPV, NPV 0.91). Senior MRI radiologist had improved PPV and NPV for extent of primary tumor compared to junior MRI radiologist (PPV 0.71 vs 0.56, NPV 0.83 vs. 0.50), and senior PET radiologist had improved PPV with similar NPV for extent of primary tumor (PPV 1.00 vs 0.78, NPV 0.50 vs 0.55). No patient was determined to have distant metastatic disease. Conclusions: To our knowledge, this is the first study exploring the use of PET-MRI for staging MIBC. This novel imaging modality demonstrated promise in detecting the extent of the primary tumor. Further investigation of FDG-PET-MRI is needed to better determine its potential utility in staging MIBC.
Carboplatin-based chemotherapy (C) versus immunotherapy (IO) in metastatic urothelial carcinoma (mUC).
Authors: Feld Emily , Harton Joanna , Meropol Neal J. , Adamson Blythe J.S. , Parikh Ravi Bharat , Galsky Matt D. , Cohen Aaron B. , Narayan Vivek , Christodouleas John Paul , Vaughn David J. , Hubbard Rebecca A. , Mamtani Ronac 
Published: May 2019

e16003 Background: There are limited data comparing first-line (1L) C versus IO in cisplatin-ineligible mUC patients. The primary evidence guiding treatment decisions was a May 2018 Food and Drug Administration (FDA) safety alert based on early review of two ongoing phase III trials, reporting shorter survival in PD-L1 negative patients receiving IO relative to chemotherapy. Final results from these trials are unknown and may not be applicable to a real-world cohort. Methods: We conducted a retrospective cohort study of mUC patients receiving 1L C or IO from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record-derived database. The primary outcome was overall survival (OS) from start of 1L treatment to date of death. We compared 12- and 36-month OS, and hazard ratios before and after 12 months. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier (KM) and Cox multivariable regression model estimates of comparative-effectiveness. Results: Of 2,243 patients, 562 received IO and 1,681 received C. Baseline characteristics were balanced between groups, with few exceptions (Table). In the first 12 months, IO was associated with an increased hazard of death compared to C (HR 1.38, 95% CI 1.16-1.66). Among patients who survived one year, survival was improved with IO compared to C (HR 0.50, 95% CI 0.27-0.92). Conclusions: In routine clinical practice, 1L IO was associated with inferior 12-month OS relative to C, but superior OS beyond 12 months. Clinicians and patients should carefully consider how to balance the early benefit of C against the late benefit of IO. Currently pending trial results will contribute additional evidence to inform treatment decision making. [Table: see text]