bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic significance of exosomal markers (CD63 and CD9) expression using immunohistochemistry in patients with pancreatic ductal adenocarcinoma.
Authors: Khushman Moh'd M. , Bhardwaj Arun , Patel Girijesh K. , Laurini Javier , Roveda Kelly , Donnell Robert , Sherling Kelley , Case Brittany , Tan Marcus Chuan Beng , Thompson Lee W. , Nelson Cindy , Wyatt Mary , Patton Mary , Singh Seema , Wang Bin , Taylor William R. , Singh Ajay 
Published: January 2019

342 Background: Exosomes are important mediators of intercellular communications and play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are exosomal markers. In patients with pancreatic ductal adenocarcinoma (PDAC), positive correlation between CD9 expression and overall survival (OS) was reported. CD63 expression was conserved in all patients with no reported prognostic significance. This study explored the prognostic significance of CD63 and CD9 expression using immunohistochemistry (IHC) in patients with PDAC of mixed racial background. Methods: Between 2012 and 2016, 49 patients with PDAC had available tissues for CD63 and CD9 staining using IHC. Two pathologists independently scored CD63 and CD9 expression. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean Quick-score (Intensity X Percentage of staining) was calculated. Results: Median age was 64 (range 42-85). 53% are males. 67% Caucasians, 27% African Americans (AA) and 6% are other ethnicities. 41% had stage IV while 59% had stage I-III. The mean CD63 and CD9 Q scores are higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites (185 vs 102, p = 0.0002) and (48 vs 11, p = 0.0418) respectively. We fitted accelerated failure-time models to investigate the impacts of the covariates CD63 and CD9 on progression free survival (PFS) and OS. CD63 has significant impact on PFS (p = 0.0058) and OS (p = 0.0012). The higher the CD63 Q score, the longer the PFS and OS. CD9 doesn’t have significant impact on PFS (p = 0.8950) or OS (p = 0.7182). The mean CD63 and CD9 Q scores are slightly higher in AA compared to Caucasians (157 vs 149, p = 0.76) and (45 vs 29, p = 0.43) respectively. Conclusions: CD63 and CD9 expression is higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites. There is correlation between CD63 expression (but not CD9 in this cohort) and PFS and OS. To our knowledge, this is the first study to show prognostic significance of CD63 expression in patients with PDAC using IHC. A trend of higher expression of CD63 and CD9 among AA compared to Caucasians was noticed.
Long-term outcomes of liver transplantation (LT) for the treatment of neuroendocrine liver metastases (NELM): The Mayo Clinic experience.
Authors: Sonbol Mohamad Bassam , Buras Matthew , Ahn Daniel H. , Borad Mitesh J. , Gores Gregory J. , Mathur Amit , Heimbach Julie , DeLeon Thomas , Taner C.Burcin , Halfdanarson Thorvardur Ragnar , Hobday Timothy J. , Ramanathan Ramesh K. , Mody Kabir , Stucky Chee-Chee H. , Truty Mark J. , Moss Adyr A , Bekaii-Saab Tanios S. 
Published: January 2019

355 Background: In this study, we sought to determine the prognostic factors impacting survival of patients with NELM who underwent LT at Mayo Clinic. Methods: We performed a three-site retrospective analysis of patients with unresectable NELM treated with LT from 1990 -2017. Cases were identified from clinical databases at Mayo Clinic. Data on demographics, timing of diagnosis and transplant, extent of liver involvement, and tumor grade, were extracted. Extent of liver involvement was calculated using previously validated standardized volumetry with high defined as > 25% increase in the weight of the extracted liver at the time of the transplant as compared to the standard liver volume. Survival was calculated using the Kaplan–Meier method. Results: We identified 37 patients. Median age at LT was 47 (range 17.0-64.0), male: female (73% vs. 27%, respectively). Primary tumor site was in the pancreas in 51.3% and in the small bowels in 43.2%; 78.4% had NELM at presentation. While primary tumor resection was done at the time of LT in 5 (13.9%) cases, most patients (80.6%) had ˃6-months interval between primary tumor resection and LT surgery. Prior to LT, 25 (74.3%) patients received somatostatin analogues and 18 (61.3%) had liver-directed therapy. Median time from diagnosis to transplant was 33.6 months (0-246). High extent of liver involvement was identified in 12 patients (33.3%). Disease-Free Survival (DFS) at 3, 5, and 10 years was 56.8%, 43.1%, and 22.4% respectively. Overall-survival (OS) at 3, 5, and 10 years was 86.9%, 79.6%, and 52.6% respectively. High extent of liver involvement at the time of transplantation was associated with inferior DFS and OS and patients˃45 years-old at the time of transplantation had worse DFS. Patients whose disease met the OPTN (Organ Procurement and Transplantation Network) criteria for NELM transplantation had significantly better DFS and OS with median 10-year OS of 80.7 % vs. 17%. Conclusions: LT is a reasonable therapeutic option for selected patients with unresectable NELM with 10-year OS of 52.6%. High extent of liver involvement was associated with worse long-term outcomes while meeting OPTN criteria resulted in best outcomes.
Healthcare utilization and costs associated with GI cancers in the United States.
Authors: Deng Aileen , Basu Mallick Atrayee 
Published: January 2019

361 Background: In 2009, adults had 4.7 million cancer-related hospitalizations. Adult hospital stays with cancer identified as the principal diagnosis cost $20.1 billion and accounted for 6% of adult inpatient hospital costs. GI cancer-related healthcare utilization has not been well-defined. The aim of this study was to evaluate the trends in the incidence and costs of GI cancer-related hospital admissions in the U.S. Methods: We reviewed the National Inpatient Sample Database (NIS) from 1997-2014. All patients with principle discharge diagnoses of esophageal, stomach, colon, rectum and anus, liver and intrahepatic bile duct and pancreas cancer were analyzed. Temporal trends in the number of hospital admissions, length of stay, hospitalization cost and mortality rates were obtained by HCUPnet. Results: GI cancer-related hospital admissions decreased from 230,537 in 1997 to 221,220 in 2014. Although the number of hospital admissions decreased for esophageal (12,157 to 11,885), stomach (23,528 to 21,800), colon (110,939 to 90,135), rectum and anus cancer (43,807 to 40,160), it has increased for liver and intrahepatic bile duct (11,243 to 21,775, p < 0.001) and pancreas cancer (28,862 to 35,465, p < 0.001). While the mean length of stay decreased from 9.6 days in 1997 to 7.6 days in 2014, the mean hospital charges per patient (adjusted for inflation) increased 127% from $34,747 in 1997 to $78,742 in 2014. The highest increase in mean hospital charges per patient were in liver and intrahepatic bile duct ($27,128 to $74,619 (175%), p < 0.001), rectum and anus ($32,566 to $80,789 (148%), p < 0.001) and pancreas cancer ($33,562 to $75,981 (126%), p < 0.001). Conclusions: GI cancer-related hospital admissions decreased from 1997 to 2014. Despite decrease in the mean length of hospital stay, the costs of hospitalizations have increased substantially, especially in liver and intrahepatic bile duct, rectum and anus and pancreas cancer. Our study suggests that shorter length of stay alone has not reduced costs of hospitalizations in GI cancers. There remains a growing need to understand healthcare costs and to develop effective value-based interventions in GI cancer-related hospital admissions.
Tremelimumab in combination with microwave ablation in patients with refractory biliary tract cancer (BTC).
Authors: Xie Changqing , Fioravanti Suzanne , Walker Melissa , Mabry Donna , Kleiner David E , Wood Brad J. , Levy Elliot B , Krishnasamy Venkatesh P , Steinberg Seth M. , Duffy Austin G. , Greten Tim F. 
Published: January 2019

365 Background: Treatment option for patients with advanced BTC is limited and prognosis is poor with a median survival of less than 1 year in the locally advanced or metastatic setting. It has been shown deregulation of the immune system plays an important role in the pathogenesis of BTC. This study aimed to investigate whether tremelimumab (Treme), anti-CTLA4, could be combined safely and feasibly with microwave ablation therapy to enhance the effect of anti-CTLA4 treatment in patients with advanced BTC. Methods: Patients with refractory BTC were enrolled in a study of monthly Treme (10mg/kg, IV, 6 doses), followed by 3-monthly infusions until off-treatment criteria were met. On day 36, patients underwent subtotal microwave ablation. Staging image was performed every 8 weeks. Adverse events (AEs) were collected and managed. Tumor samples and peripheral blood samples were collected to perform immune monitoring. Results: Twenty patients with refractory BTC were enrolled. Male: female ratio was 10:10 with median age 56.5 years (range 37-67). Six patients had extrahepatic cholangiocarcinoma (ECC), two patients had gallbladder cancer, whereas the remaining 12 patients had intrahepatic cholangiocarcinoma (ICC). No dose-limiting toxicities were encountered. The common AEs included lymphocytopenia, colitis, adrenal insufficiency, anemia, and elevated transaminases. The most common clinical toxicity was diarrhea. Sixteen patients were evaluable for response analysis, one (6%) patient achieved a confirmed partial response (lasting for 8 months), 6 (37.5%) achieved stable disease with the longest lasting for 9.2 months. Among all 20 patients, median progression free survival, time to progression, and overall survival were 3.4 months (95% CI 2.5-5.2 months), 3.3 months (95% CI: 2.5-4.6 months) and 6.0 months (95% CI 3.8-8.8 months) respectively in this small pilot cohort. T cell receptor (TCR) b screening showed Treme expanded TCR repertoire though non-significantly. RNA seq is ongoing and will be presented. Conclusions: Treme in combination with tumor ablation is a potential new treatment for patients with advanced BTC. TCR repertoire expansion induced by Treme may contribute to treatment benefit. Clinical trial information: NCT01853618.
Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) with a novel radiopaque (RO) drug eluting bead (DEB).
Authors: Lencioni Riccardo , Fraud Tatiana , Doshi Mehul , Venkat Shree , Echenique Ana , Narayanan Govindarajan 
Published: January 2019

366 Background: Preclinical studies have suggested that RO beads may offer advantages over standard microspheres used for TACE of HCC. The ability to image bead distribution during the procedure is expected to improve the coverage of the tumor minimizing off-target delivery. We conducted a retrospective analysis of efficacy and safety of RO DEB-TACE in patients with HCC. Methods: Forty-eight patients (38 males and 10 females, median age 64 years) with nodular, noninvasive HCC unsuitable for curative treatments, Child-Pugh A (n = 29) or B (n = 19) liver functional status, and ECOG PS 0-1 received DEB-TACE with injection of 2-4 ml of 70-150-micron RO microspheres (LC Bead LUMI; BTG-Biocompatibles) loaded with 37.5 mg/ml doxorubicin. Thirty-seven of 48 patients (77%) had unilobar disease and 11 of 48 (23%) bilobar tumors. The baseline sum tumor diameter was 5.3±2.6 cm (range, 1.2-14.5 cm). The primary endpoint was tumor response by mRECIST. Secondary endpoints were time to progression (TTP), overall survival (OS), and safety. Results: The number of treatments was 1 in 28 patients (58%), 2 in 16 (33%), and 3 in 4 (8%). The mean doxorubicin dose per treatment was 43.9±34.4mg (range, 3.3-150 mg). Best response was CR, PR, SD, and PD in 32, 10, 4 and 2 patients, respectively, for an objective response rate (ORR) of 87.5%. Median TTP was 8.5 months (95% CI, 6.7-not reached). Median OS was not reached in Child class A patients; in class B patients it was 19.5 months (95% CI, 6.0-not reached). There was one treatment-emergent grade 5 AE unrelated to treatment. Grade 3/4 AEs included pain (n = 4), fatigue (n = 2), and fever (n = 1). Grade 3/4 laboratory abnormalities were thrombocytopenia (n = 9), leukopenia (n = 3), elevation of transaminases (n = 3) or bilirubin (n = 3), and anemia (n = 2). Conclusions: In this first clinical study, treatment with RO DEB-TACE resulted in a high ORR and was well tolerated. The encouraging efficacy signal requires confirmation with long-term survival data.
Subgroup analysis by baseline pain intensity (BPI) and analgesic use (BAU) in NAPOLI-1: A phase III study of liposomal irinotecan (nal IRI)±5-fluorouracil/ leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy.
Authors: Macarulla Teresa Mercade , Siveke Jens T. , Dean Andrew Peter , Hubner Richard , Blanc Jean-Frédéric , Cunningham David , Chen Li-Tzong , Mirakhur Beloo , Chen Jie , de Jong Floris A , Wang-Gillam Andrea 
Published: January 2019

379 Background: We report an exploratory, post hoc subgroup analysis in pts with BPI and BAU data receiving nal-IRI+5-FU/LV, nal-IRI or 5-FU/LV in NAPOLI-1 (NCT01494506). In this pivotal trial, nal-IRI+5-FU/LV improved median OS (mOS) vs. 5-FU/LV (6.1 vs. 4.2 mo [HR=0.67; p=0.012]). Methods: BPI/BAU included an average of 3-7 days pt-recorded data before randomisation. Greater values indicated greater pain for BPI using a 100 mm visual analogue scale. BAU was converted to morphine equivalent mg/day. Results: Of 417 ITT pts, 295 had BPI and 299 had BAU data. Mean and median BPI were 28.6 and 25.0, respectively, and BAU were 33.3 and 8.1 mg/day, respectively. The percentage of pts with KPS ≥ 80 was higher in ≤ mean/≤ median (n=159/148) BPI groups vs. > mean/> median (n=136/147) BPI groups (96-97 vs. 83%) and in ≤mean/≤median (n=207/150) BAU groups vs. > mean/> median (n=92/149) BAU groups (95-97 vs. 82-85%). mOS and median PFS (mPFS) were higher for nal-IRI+5-FU/LV vs 5-FU/LV in all groups, with ≤ mean/≤ median BPI or BAU showing better outcomes vs. > mean/> median BPI or BAU (Table). Conclusions: BPI and BAU appear to have a prognostic effect on outcomes in mPDAC pts in the NAPOLI-1 study. No predictive effect was observed, with nal-IRI+5-FU/LV showing higher mOS vs. 5-FU/LV in all groups. Clinical trial information: NCT01494506. [Table: see text]
RXÂ 3117: Activity of an oral antimetabolite nucleoside in subjects with pancreatic cancerâ€“Preliminary results of stage II of the phase Ia/IIb study.
Authors: Chung Vincent M. , Merchan Jaime R. , Ocean Allyson J. , Rasco Drew W. , Babiker Hani M. , Oliff Ira , Paluri Ravi Kumar , Roman Eloy , Poore Julie , Benaim Ely 
Published: January 2019

396 Background: RX-3117 is an oral small-molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 2 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 2 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle. Eligible subjects (aged ≥ 18 years) had relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% of evaluable subjects with a partial response rate or better. Results: As of Sep 2017, 44 subjects have been enrolled (22 females, 22 males). The median age was 68 years, ECOG performance statuses were 0 (13 subjects) and 1 (31 subjects) and 6 subjects had received 4 or more prior therapies. One subject had an unconfirmed partial response and 21 subjects met the primary endpoint of stable disease with a duration of 30-224 days. The most frequent adverse events were mild to moderate anemia (19%), mild to moderate fatigue (15%), mild to moderate diarrhea (11%), and severe anemia (9%). Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. The study continues to enroll subjects with advanced pancreatic cancer into stage 2. A phase 2 study with nab-paclitaxel in first-line patients with advanced pancreatic cancer has been started. Clinical trial information: NCT02030067.
Folfirinox versus gemcitabine/nab-paclitaxel for neoadjuvant treatment of resectable and borderline resectable pancreatic adenocarcinoma: A propensity matched analysis.
Authors: Dhir Mashaal , Zenati Mazen S , Hamad Ahmad , Singhi Aatur D. , Bahary Nathan , Hogg Melissa Ellen , Zeh Herbert , Zureikat Amer H. 
Published: January 2019

402 Background: Comparative effectiveness of FOLFIRINOX and Gemcitabine/nab-paclitaxel (G-nP) in the neoadjuvant treatment (NAT) of pancreatic ductal adenocarcinoma (PDA), remains unknown. The aim of this study was to perform a propensity matched analysis of neoadjuvant FOLFRINOX vs G-nP for resectable(R) and borderline resectable (BR) PDA. Methods: A single institution retrospective review of all R and BR PDA patients who underwent resection after NAT with FOLFIRINOX or G-nP was performed. Comparative effectiveness analysis was conducted using inverse-probability-weighted estimators. Primary endpoint was overall survival (OS) from the time of diagnosis. Results: A total of 193 patients (FOLFIRINOX=73, G-nP=120) who underwent resection from 01/11-03/17 were included. Median OS was 28.9 months (95% CI 26.1-39.7). Patients treated with FOLFIRINOX were younger (median age 63 vs. 69 y), had less comorbidities (median CCI 4 vs. 5), more frequent BR disease (79 vs. 59%), and larger tumors (median CT size 2.9 v 2.7 cm) compared to G-nP (all p < 0.05). Duration of NAT was similar and both regimens were equally effective in achieving a 50% or 80% decline in CA19-9 (logistic regression, P 0.9). Rates of R0 resection were also similar (80%), but folfirnox was associated with a reduction in pN1 disease (56% vs. 72%, p =0.028). Receipt of adjuvant therapy was similar in both groups (74 vs. 75%, p =0.79). In a multivariable cox regression analysis utilizing only preoperative variables (FOLFIRINOX v G-nP, age, gender, CT tumor size, BR vs. R, pre NAT CA19-9 and number of NAT cycles), only the number of neoadjuvant cycles was an independent predictor of survival (HR 0.49, 95% CI 0.34-0.71, p < 0.001). In a propensity matched analysis of 166 patients using the same preoperative variables, the average treatment effect of FOLFIRINOX was to increase OS by 4.9 months above G-nP (p=0.012). Conclusions: FOLFIRINOX and Gem Abraxane are viable options for neoadjuvant treatment of PDA. In this study, FOLFIRINOX was associated with a 4.9 month improvement in OS when compared to G-nP in the neoadjuvant setting after adjusting for covariates.
Resection of pancreatic cancer following induction chemotherapy.
Authors: Shaib Walid Labib , Sayegh Layal , Alese Olatunji , Maithel Shishir , Cardona Kenneth , Sarmiento Juan , Belalcazar Astrid , Ip Andrew , Qu Yuesheng , Akce Mehmet , Zhang Chao , Wu Christina Sing-Ying , Chen Zhengjia , El-Rayes Bassel F. 
Published: January 2019

406 Background: Survival of resectable pancreas cancer (RPC) treated with resection and adjuvant therapy is 22-28 months (mo). Locally advanced unresectable pancreatic cancer (LAPC) treated with combination chemotherapy have a median survival of 24 mo. The objective of this project is to evaluate the effect of neoadjuvant treatment on survival outcome of localized PC. Methods: Charts of localized PC patients treated at Emory University from 2009 to 2016 were reviewed. Information on demographics, stage and treatment was collected. Survival rates were estimated by Kaplan-Meier method and compared with log-rank test. A Cox proportional hazard model was fitted to estimate the adjusted effect of treatment on overall survival(OS). Results: A total of 415 patients were included; 144 RPC, 158 borderline resectable (BRPC) and 108 LAPC. Stage was determined at the multidisciplinary conference. The median age was 67.7 years (30-92); 49% male, and 63% Caucasians. The median OS for RPC, BRPC, and LAPC was 16.9, 14.6 and 10.9 mo, respectively. Stage, type of chemotherapy and age were significant predictors of OS after adjusting for gender, race, age, surgery, stage, chemotherapy, margins and radiation. Of the 144 RPC, 137 underwent surgery and 3 received neoadjuvant treatment; 73 RPC were followed in outside facility with missing follow up data. Of the 71 RPC treated at Emory; 91% received adjuvant gemcitabine. Of the 158 BRPC, 84 underwent surgery; 44 received FOLFIRINOX neoadjuvant therapy, 23 received gemcitabine/nab-paclitaxel, and 16 received gemcitabine single agent. BRPC patients who underwent resection had a median OS of 18.5 mo (95%CI: 14.2, 26.4), significantly longer than RPC (P = 0.044). Combination chemotherapy was significantly associated with improved OS at 36 mo (38.9%) when compared to single agent gemcitabine (6.3% at 36 mo) (p = 0.009). BRPC patients who received FOLFORINOX and surgery had a median OS of 31.5 mo. Conclusions: Overall survival of BRPC patients who undergo resection after FOLFIRINOX is significantly improved (more than doubled) compared to upfront resection for RPC. Preoperative therapy provides the best approach for systemic disease early in the course of treatment.
Oxaliplatin (OX), chronomodulated capecitabine, and UGT1A1 genotype-directed dosing of irinotecan (IR) triplet chemotherapy (OXIRI) in patients (pts) with advanced pancreatic cancer (APC).
Authors: Seet Amanda Oon Lim , Chen Sylvia , Yu Yingnan , Choo Su Pin , Tai David Wai-Meng , Lam Justina Yick Ching , Chang Yvonne , Chowbay Balram , Ng Matthew CH 
Published: January 2019

411 Background: The FOLFIRINOX regimen is highly active in APC, but its use is limited by toxicity. Irinotecan (IR) toxicity is correlated with UGT1A1 genotype status and chronomodulated delivery of fluoropyrimidines may reduce toxicity and increase efficacy. We have presented the dose escalation (DES) of OXIRI. In dose expansion (DXP), several pts required dose reduction after cycle 1 and we evaluated a lower starting dose. We now present data of the recommended Phase II dose (RP2D) and DES combined. Methods: Pts with APC and ECOG performance status ≤2, adequate organ function were enrolled. Previous OX or IR exposure was disallowed. During DES, APC pts homozygous for UGT1A1*6/*6 or UGT1A1*28/*28 were excluded. During DXP, only pts progressing on ≥ 1 line prior chemo was allowed and IR was dosed according to UGT1A1 genotype. At RP2D, pts received iv OX 37.5mg/m2 and IR 50mg/m2 on D1, 8 and po capecitabine 2650mg once at midnight on D1-14 every 21D until progression. Results: A total of 25 pts were enrolled, 17 in DES and 8 in DXP, 21 had metastatic and 4 had locally advanced APC. Male:Female 11:14, median (range) age and ECOG PS was 65yrs (50-77) and 0 (0-1) respectively. Pts with 0, 1 or 2 lines of prior chemo were 4 (16%) , 14 (56%) and 7(28%) respectively. Grade 3/4 AEs (≥5%) related to OXIRI were neutropenia (32%), anaemia (12%), diarrhoea (16%). No events of febrile neutropenia were reported. At data cut-off on 31 Aug 2017, 4 pts are on study. Median progression-free and overall survival was 22 and 35 wks respectively. Response rate (RR) was 5/25 (20%, overall); 5/20 (25%, evaluable pts) including 1 complete response and 1 unconfirmed partial response. Disease control rate for ≥ 12wks was 16/25 (64%) with 3 pts > 52wks. CA19-9 decrease of ≥ 20% was seen in 9/25 pts. Conclusions: OXIRI is an active regimen with RR of 20% despite 84% of pts having prior chemo, with disease control for ≥ 12wks in 64% of pts. Predominant toxicity was neutropenia. This study was supported by the National Medical Research Council Singapore. Clinical trial information: NCT02368860.