bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anorectal neuroendocrine carcinoma (NEC): Patient characteristics and treatment outcomes.
Authors: Ueberroth Benjamin Edward , Liu Alex John , Halfdanarson Thorvardur Ragnar , Sonbol Mohamad Bassam 
Published: May 2020

e16702 Background: There are only a few reports examining the treatment patterns for poorly differentiated rectal/anal NEC. In this study, we sought to report treatment and survival outcomes for patients with NEC of the anus and rectum seen at Mayo Clinic. Methods: We identified patients with a primary NEC of the anus or rectum using Mayo Clinic databases (Minnesota, Arizona, Florida) from the year 2000 to present. NEC identified within polyps on colonoscopy was excluded from this study. Patients’ demographics were compiled. Kaplan Meier analyses were performed to evaluate overall survival (OS) for all patients, as well as subgroups with locoregional disease (LRD) and metastatic disease at diagnosis. Progression free survival (PFS) was also evaluated for patients with LRD treated with chemoradiation therapy (CRT). Results: 38 patients with NEC of the anus/rectum were identified with a median age of 55.5 years. 23 patients (61%) had metastatic disease at diagnosis and 15 (39%) had LRD. The most common site of metastasis was the liver (n = 20). Patients with metastatic disease at presentation had significantly shorter OS compared to patients with LRD (median OS 10.4 vs. 18.9 months, p = 0.039; HR 2.46, 95% CI [1.001-6.050]). 34 total patients received chemotherapy (ORR 11.8%), with platinum + etoposide (EP) being the most common first-line chemotherapy (n = 26). 10 of 15 patients with LRD received CRT (9 with EP and 1 with 5-FU) with median PFS of 6.3 months (95% CI 2.3-16.5 months), a 1-year PFS rate of 20%, and median OS of 18.6 months (95% CI 13.5-23.7 months). 2/10 received induction chemotherapy prior to CRT with 6/10 undergoing primary tumor resection (1 prior to CRT and 5 after CRT). Only 3 CRT patients were living at time of analysis (all underwent surgical resection), 2 without any active disease, 1 who achieved complete response with CRT then suffered recurrence and is still undergoing treatment. Conclusions: NEC of the anus and rectum is an aggressive malignancy with most patients experiencing metastatic disease at presentation and poor response to chemotherapy at all stages. Even those with LRD experience a very poor prognosis with OS of 18.9 months from diagnosis. For LRD, most patients underwent CRT with only a short-lived response (median PFS 6.3 months). Those achieving sustained response also underwent surgical resection. Overall, prognosis is poor for all stages and further study on a large scale is warranted to better characterize this rare, aggressive malignancy.
Prolongation of the average survival time in pancreatic cancer (a new measure of effect): Pooled analysis of adjuvant chemotherapy trials.
Authors: Ceballos Barbancho Eduardo , Sánchez Robles Galo 
Published: May 2020

e16723 Background: With the aim of improving the prognosis of the disease, in recent years attempts have been made to optimize the adjuvant treatment of pancreatic cancer, having demonstrated the usefulness of chemotherapy in several phase III trials: CONKO-001, JASPAC-01, ESPAC -4 and PRODIGE. Methods: The method to measure the Area Under the Curve (AUC) is universally known. When the curve is not homogeneous, the AUC is calculated using the traditional method of breaking down the total area into a sum of many polygons. We have calculated the AUC through pixel counting using Image J, which is an image processing application, programmed in Java, developed in the National Institutes of Health and free to access. To estimate the consistency between the pixels and the sum of polygons, we have performed several curves with linear edges to measure the AUC through the sums of the polygons, and then by counting pixels with the Image J application. We have verified that the results are similar, so the pixel count can be used to replace the sum of polygons, especially when the curves are not homogeneous. Entering the areas obtained with Image J in the worksheet, made for this purpose, and available for free at evalmed.es, the measures of the effect are automatically obtained: prolongation of the average surival time (PtS), prolongation of the average event free time (PtSLEv) and time lived without an event (PtvSEV). Results: The median follow-up in all studies was 60 months, with the exception of CONKO-001, for which we have data at an average follow-up time of 136 months, however for our comparative purpose we cite the results in the first 60 months. -CONKO-001: PtS was 5.1 months (24.2 observation vs 29.3 gemcitabine). PtSLEv was 9.6 months (13 observation vs 22.6 gemcitabine). PtvSEv was 22.57 months. -JASPAC-01: PtS was 9.04 months (32.4 gemcitabine vs 41.5 gemcitabine + S1). PtSLEv was 9.75 months (21.6 gemcitabine vs 31.4 gemcitabine + S1). PtvSEv was 31.38 months. -ESPAC-4: PtS was 3.2 months (34 gemcitabine vs 37.2 gemcitabine + capecitabine). PtSLEv was 2.7 months (25.6 gemcitabine + 28.3 gemcitabine + capecitabine). PtvSEv was 24.92 months. -PRODIGE: PtS was 6 months (37 gemcitabine vs 43 FOLFIRINOX). PtSLEv was 8.9 months (22.4 gemcitabine vs 31.2 FOLFIRINOX). PtvSEv was 31.23 months. Conclusions: In the adjuvant treatment with chemotherapy in pancreatic cancer, the transit from observation to gemcitabine, and from here to the most intensive schedules, has meant or contributed an important advance for patients in terms of PtS, PtSLEv and PtvSEv.
A real-world comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine to nab-paclitaxel in treatment of advanced stage pancreatic cancer.
Authors: Shaik Abdul Rashid Shaik Abdul Samad , Cohen Steven , Micaily Ida 
Published: May 2020

e16728 Background: Pancreatic adenocarcinoma is a dreaded malignancy accounting for 7% of all cancer related deaths in the United States. The two most used chemotherapeutic regimens are a combination of 5- fluorouracil, leucovorin, oxaliplatin and irinotecan (FFX) and a combination of gemcitabine nab paclitaxel (GN). Both improve survival when compared to gemcitabine alone but have not been compared directly. Methods: Retrospective chart review of 83 chemotherapy naïve patients with metastatic cancer of exocrine pancreas who underwent chemotherapy between February 2011 and June 2017. Patients who completed at least one cycle of chemotherapy regimen were included. Characteristics, efficacy and adverse events between the two regimens were compared using appropriate statistical analyses. Results: 83 patients met selection criteria. 39 patients received FFX and 44 received GN. Mean age of FFX and GN patients was 69.7 (SD 8.7) (Median 66) and 72.3 (SD 8.8) (Median 69) yrs respectively (p = 0.100). The proportion of patients with ECOG performance scale ≤1 receiving FFX vs. GN was 50.8% vs. 49.2% and > 2 receiving FFX vs. GN was 33.3% vs 66.7% (p = .286). Of the 23 patients > 75 yrs., 7 received FFX and 16 received GN (p = .086). Median overall survival was 10.1 months (95% CI: 5.4-18.7) in FFX and 7.2 months in GN (95% CI: 5.4-11.3) [p = 0.037]. Median survival based on site of tumor was 10.2 months (95% CI: 6.7-13.8) in head and 10.1 months (95% CI: 4.3-14.7) in body and tail tumors [p = 0.776]. Incidence of vomiting in FFX / GN was 94.1% / 73.7% (p =.027), vomiting requiring hospital admission was 55.9% / 21.1% (p = 0.003). Other events requiring admission included: diarrhea 31.4% / 17.9%; anemia 5.7% / 10.3%; thrombocytopenia 11.4% / 7.7%; febrile neutropenia 28.6% / 12.8% and acute kidney injury 25.7% / 15.4%; no statistically significant differences between groups. Conclusions: Patients treated with FFX had a longer survival in this retrospective review. FFX is associated with an increased incidence of vomiting requiring hospitalization. FFX remains a preferred regimen in treating patients with good performance status regardless of age.
Clinical trials in pancreatic cancer: A comprehensive analysis.
Authors: Katayama Erryk Stephan , Hue Jonathan J. , Bajor David Lawrence , Ocuin Lee Mayer , Ammori John Brian , Hardacre Jeffrey , Winter Jordan Michael 
Published: May 2020

e16730 Background: Pancreatic cancer is the most aggressive of common cancers and desperately in need of novel therapies. Unlike many other common cancers, there have been no new paradigm-changing therapies in the past 40 years beyond chemotherapy. The most urgent question in the field then is what is coming down the pike? In this study, we perform the first comprehensive analysis of the current clinical trial landscape in pancreatic cancer to better understand the pipeline of new therapies. Methods: We queried clinicaltrials.gov for registered pancreatic cancer clinical trials. Studies were curated and categorized according to the phase of study, the clinical stage of the study population, the type of the intervention under investigation, and the biologic mechanism targeted by the therapy. This compendium revealed the full landscape of investigational therapeutic trials. Results: As of May 18, 2019, there were 440 total trials testing 600 distinct interventions. 104 of these trials spanned multiple phases, yielding 544 trials across phases. These included 38 trials (8.6%) in phase III testing, 269 (61%) in phase II, and 237 (54%) in phase I. With respect to therapeutic category, 186 (31%) were investigating immunotherapies, 66 (11%) targeted cell signaling pathways, 140 (23%) targeted cell cycle or DNA biology, and 32 (5%) targeted metabolic pathways. Of the 38 phase III trials, only 10 are currently testing novel drugs that are not already FDA approved or routinely used in patients for another indication. Conclusions: A large number of novel therapeutic strategies are currently under investigation. They include a broad range of therapies targeting diverse biologic processes. However, only a small number of novel therapies are in late-stage testing, suggesting that future progress is likely several years away, and dependent on the success of early-stage trials. [Table: see text]
Oncogenic roles of CEACAM6 in pancreatic ductal adenocarcinoma.
Authors: Mahadevan Daruka , Pandey Ritu , Chen Yuliang , Essif Jacob , Al-Khinji Aisha 
Published: May 2020

e16744 Background: Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a cell adhesion receptor of the Ig-superfamily overexpressed in human Pancreatic Ductal Adenocarcinoma (PDA), enriching to the classical activated stroma subtype. CEACAM6 has multifaceted roles in PDA and is a poor prognostic maker (Pandey et al. Sci Rep 2019). We report functional correlative studies across PDA cell lines with high vs KO vs low of CEACAM6 and a PDX model with a therapeutic Mab. Methods: RNA-Seq and microarray expression data of PDA cell lines were downloaded from GEO using R (4.3), normalized and log transformed for analysis: CEACAM6 high vs. low were assessed for differential gene expression changes. Correlation of CEACAM6 levels with genes of interest was studied and compared with the CEACAM6 KO proteomic profile of HPAF-II cells. CEACAM6 WT vs. KO cells were profiled for protein kinase (PK) activity (PAMChip) and gene expression changes by RNA-Seq. NSG-CD34+ mice bearing PDX were evaluated with a humanized anti-CEACAM6 Mab for anti-tumor activity. Results: Differential expression analyses between PDA cell lines with low vs KO vs high CEACAM6 resulted in identifying similar markers changing in quantitative proteomics. KRT20, SYTL1, SKIL, CES1P1, MAN1A1 were down-regulated and HMOX1, CPNE2, ABCD1 were up-regulated in CEACAM6 low or KO cell lines. Specific PKs are upregulated in CEACAM6 KO enriching to the TK family (EPH A1, 3, 4, 8 and HCK), AGC family (e.g. AKT, PKA) and cellular apoptosis (e.g. BAD). RNA-Seq of CEACAM6 WT vs KO cells reconfirmed the up-regulation of MMP1, IL2RG, ATP6V0D2 and low expression of KRT20, AGK and MAN1A1 in CEACAM6 KO cells. Pharmacologic inhibition with a humanized anti-CEACAM6 scFv-Fc (IgG4) in PDA PDX of NSG CD34+ mice demonstrated ~55% tumor growth inhibition (TGI) with enhanced survival of > 14 days vs. control. Conclusions: CEACAM6 is expressed exclusively in primates and humans and plays multifaceted oncogenic roles in PDA pathogenesis. When CEACAM6 is disrupted, ECM proteins are altered reshaping the stroma, activating specific PKs and priming apoptosis. The therapeutic anti-CEACAM6 Mab possesses anti-tumor activity with associated cellular apoptosis and increased mouse survival.
Germline ATM mutations on survival in metastatic pancreatic cancer patients.
Authors: Gower Arjan , Gresham Gillian , Haladjian Nanor , Lee John , Ng Camille , Mehta Sejal , Hendifar Andrew Eugene 
Published: May 2020

e16746 Background: Ataxia telangiectasia mutated (ATM) protein is a DNA damage repair enzyme and regulates normal cell-cycle mechanisms. Germline ATM mutations are associated with increased risk for developing pancreatic cancer (PC), occurring in approximately 2% of PC patients (pts). The role of germline ATM mutations in PC is not well defined. The objective of this study was to compare survival outcomes in patients with germline ATM mutations compared to somatic ATM mutations in PC. Methods: Tumor genomic profiling was completed in 144 PC patients at a single institution in the US, where pts were included in the analysis if they had either germline ATM mutations or somatic ATM mutations. Clinical outcomes were compared between pts with germline ATM mutations and pts with somatic ATM mutations only. Adjusted Cox regression models were fit to evaluate the impact of ATM mutation on overall survival (OS), calculated from treatment (tx) initiation to death, and progression free survival (PFS) calculated from tx initiation to first progression. Results: From 144 PC pts evaluated, 7 pts (4.9%) had germline ATM mutations, all of whom presented with metastatic disease, and 14 pts (9.7%) with somatic ATM mutations only, of whom 10 presented with metastatic disease and 4 who initially presented with locally advanced PC. The majority of pts (15/21), including all 7 pts with germline ATM mutations and 8 with somatic ATM mutations, were treated with first line gemcitabine and abraxane. Median OS was not reached in patients with germline mutations, and 11 months for patients with somatic mutations. Pts with germline ATM mutations had significantly higher OS (HR: 0.12, 95% CI 0.03-0.62, p = 0.01) and PFS (HR:0.26, 95%CI 0.07-0.91, p = 0.04) compared to patients with somatic ATM mutations only after adjusting for age, sex, and first-line tx. Conclusions: Pts with germline ATM mutations may experience greater survival benefit from tx compared to those with only somatic ATM mutations. Further research into the underlying mechanism is warranted.
Novel targeted and sustained drug delivery therapy for localized pancreatic cancer: Validation in porcine models and minimally invasive surgical feasibility in human cadavers.
Authors: Lashof-Sullivan Margaret , Kim Michael Paul , Tzeng Ching-Wei David , Indolfi Laura 
Published: May 2020

e16747 Background: As systemic therapy improves, control of localized pancreatic adenocarcinoma (PDAC) remains a major challenge. Up to 40% of patients present with locally advanced and borderline resectable tumors, for whom enhanced local downsizing of disease could improve resection rates and survival. PanTher is developing a locally targeted drug delivery product (PTM-101) to treat localized PDAC by directly delivering chemotherapy to the primary tumor. PTM-101 is a bioresorbable polymeric patch containing paclitaxel surgically placed onto the tumor. It biodegrades, resulting in sustained localized release of drug. In murine orthotopic patient-derived xenograft models a 60% increase in OS and inhibition of metastasis was achieved after single treatment. Here we validate and de-risk PTM-101 implantation in standard OR settings in large animals and human cadavers to prepare for a phase 1 study. Methods: We conducted two 30-day studies in porcine models to assess safety, toxicity and biodistribution. Parameters included body weights, hematology, urinalyses, drug levels in the blood and at the implantation site and histomorphologic evaluation. To validate the feasibility of minimally invasive surgical insertion, we conducted a follow-up study in three human cadavers. In each case, PTM-101 was laparoscopically placed directly on the pancreas. Results: We surgically implanted PTM-101 without complications and our approach ensures localized drug delivery with extreme control of drug biodistribution. Importantly, no detectable levels of drug were present in the blood any time during the 30-day treatment, confirming our targeted delivery. PTM-101 was consistently and effectively placed during a minimally invasive surgery without substantial increase in procedure time. PTM-101 conforms fully to pancreatic tissue, allowing for close contact with the intended tissue for drug delivery, and can cover the areas of the pancreas where critical involvements of tumors with vasculature are commonly found. Conclusions: By changing the route of administration to target just the area of interest, PTM-101 can increase the amount of drug reaching the tumor with the aim to enhance therapeutic efficacy. This could open the door to clinically relevant applications in PDAC patients: (i)pre-operatively as neoadjuvant treatment to control progression and downsize locally advanced and borderline anatomy to improve resectability; or (ii)post-resection to reduce the rate of local recurrence.
Cytokines as a prognostic biomarker of overall survival in pancreatic cancer.
Authors: Tan Harold Nathan Choa , Velasco Rogelio Nona , San Juan Michael Ducusin , Cornelio Gerardo H. 
Published: May 2020

e16753 Background: Pancreatic cancer is an aggressive malignancy with a dismal 5-year survival rate of only 9%. Novel biomarkers are urgently needed to improve the survival outcomes of patients with this dreaded disease. Cytokines serve a key role in tumor development and metastasis in pancreatic cancer, with each cytokine demonstrating unique functionality in the tumor microenvironment. This meta-analysis examined the role of cytokines in prognosticating overall survival (OS) of pancreatic cancer patients. Methods: Relevant literature were identified via electronic search of PubMed, EMBASE, Google Scholar and Cochrane Library databases up to January 1, 2020. Employing Review Manager 5.3, pooled hazard ratios and 95% confidence intervals were computed. Results: A total of 18 studies comprising 1920 patients were included. Pooled analysis showed worse OS among patients with high T-helper 1 (Th1) cytokines, with a hazard ratio of 1.48 (95% CI 1.27-1.74, p < 0.00001). High T-helper 2 (Th2) cytokines also demonstrated significant association with poor OS, with a hazard ratio of 1.62 (95% CI 1.12–2.34, p = 0.01). In terms of individual cytokines, high IL-6 correlated with inferior OS, with a hazard ratio of 2.73 (95% CI 2.18-3.43, p < 0.00001). Similarly, high IL-12 were linked with worse OS, with a hazard ratio of 1.85 (95% CI 1.26-2.72, p = 0.002). Other individual cytokines were not significantly associated with OS. Conclusions: Cytokines show promise as a prognostic biomarker in pancreatic cancer. Th1 and Th2 cytokines portend worse overall survival outcomes. In particular, high levels of IL-6 and IL-12 can potentially prognosticate patients with poor overall survival. Further prospective studies are encouraged to delineate the role of cytokines in mediating treatment outcomes in this deadly disease.
Myosteatosis to predict postoperative morbidity in pancreatic ductal adenocarcinoma patients receiving neoadjuvant chemotherapy.
Authors: Louie Raphael , Aleixo Gabriel , Deal Allison Mary , Damone Emily , Tremont-Portelli Jaclyn , Nyrop Kirsten A. , Williams Grant Richard , Yeh Jen Jen , Yu Hyeon , Kim Hong Jin , Muss Hyman B. 
Published: May 2020

e16754 Background: Myosteatosis (adipose deposits in muscle) can be detected on cross-sectional imaging through variations in Skeletal Muscle Density (SMD). Patients with myosteatosis tend to have lower overall survival, increased chemotherapy toxicity, and shorter progression-free intervals across cancer types. We investigated whether changes in myosteatosis during neoadjuvant chemotherapy can predict postoperative morbidity risk in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: This is a retrospective cohort study from 2014-2019 of patients with biopsy-proven PDAC who completed neoadjuvant chemotherapy and R0/1 resection (R1: margin < 1mm or microscopically positive). We obtained preoperative patient (age at diagnosis, baseline body mass index (BMI), sex, race, comorbidities) and treatment data (neoadjuvant chemotherapy regimen and duration, time from completion of systemic therapy to surgery, type of operation). Primary outcomes were postoperative complications and 90-day readmission. Average SMD was measured using imaging analysis software at the L3 level on axial abdominal CT scans at the time of diagnosis and at completion of neoadjuvant therapy (SliceOmatic TomoVision QC, Can). We defined SMDΔ as the decrease in SMD during neoadjuvant chemotherapy. Descriptive statistics and Student’s t-test were performed with STATA. Results: We identified 44 patients who received neoadjuvant chemotherapy, achieved a R0/1 resection, and had available CT scans for body composition evaluation. The postoperative complication rate was 43% (n = 19) and 90-day readmission rate was 30% (n = 13). Lower SMD at diagnosis was associated with increased postoperative delirium (p < 0.01) and 90-day readmission (p = 0.02). Greater SMDΔ was associated with increased ICU utilization (p < 0.01) and tube feeding upon discharge (p = 0.03). There was no significant association between preoperative BMI or albumin and our primary outcomes. Conclusions: Preoperative SMD and SMDΔ, rather than albumin or BMI, can predict postoperative morbidity in PDAC patients who received neoadjuvant chemotherapy. This study provides the framework for future studies to develop and validate a tool to predict postoperative morbidity risk in these patients.