bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early progression (progr) in patients (pts) with metastatic pancreatic cancer (mPaC) and a germline BRCA mutation (gBRCAm): Phase III POLO trial of olaparib (O) versus placebo (P).
Authors: Macarulla Teresa , Kindler Hedy L. , Hammel Pascal , Reni Michele , Van Cutsem Eric , Hall Michael J. , Park Joon Oh , Hochhauser Daniel , Arnold Dirk , Oh Do-Youn , Reinacher-Schick Anke C. , Tortora Giampaolo , Algül Hana , O'Reilly Eileen Mary , McGuinness David , Cui Karen , Schlienger Katia , Locker Gershon Y. , Golan Talia 
Published: February 2020

750 Background: In POLO (NCT02184195), maintenance O was associated with significant progr-free survival benefit vs P in pts with a gBRCAm and mPaC (Golan NEJM 2019). Early progr or death (within 4 months [m]) occurs in ~35−45% of pts on standard-of-care first-line (1L) chemotherapy for mPaC (Conroy NEJM 2011; von Hoff NEJM 2013); however, predictive factors are currently unknown and early progr has not been addressed in the maintenance setting. We examined factors potentially associated with early progr in POLO. Methods: Following ≥16 weeks of 1L platinum-based chemotherapy (PBC) without progr, pts were randomized to maintenance O (tablets; 300 mg bd) or P until progr or unacceptable toxicity. Early progr was defined as progr (by blinded independent central review) or death within 4 m of randomization. A stepwise logistic regression model included baseline (BL) factors age, albumin, lactate dehydrogenase (LDH), global health status (GHS) and physical functioning (PhysF) as continuous variables, and discrete variables listed in the Table. Results: 62/154 randomized pts (40%) were defined as early progressors (EP; Table). Due to missing BL data, the multivariate analysis included 127 pts (56 EPs [44%]). Lower BL PhysF score (continuous) was significantly associated with early progr ( P= 0.02); no difference for partial/complete response (PR/CR) vs stable disease (SD). Conclusions: While small sample size limited analysis power, PhysF score was the only BL factor significantly associated with early progr in pts with a gBRCAm and mPaC in the POLO trial of maintenance O vs P. Clinical trial information: NCT02184195 . [Table: see text]
Evaluation of the ratio of plasma fibrinogen to platelet in resectable pancreatic cancer.
Authors: Arakawa Yusuke , Shimada Mitsuo , Morine Yuji , Imura Satoru , Ikemoto Tetsuya , Saito Yu , Yamada Shinichiro , Yoshikawa Masato , Miyazaki Katsuki 
Published: February 2020

756 Background: Several prognostic factors were reported in pancreatic cancer such as neutrophil lymphocyte ratio (NLR), platelet lymphocyte ration (PLR) modified GPS. Fibrinogen platelet ratio (FPR) was reported as one of the prognostic factor of resectable gastric cancer (Surgery today 2019). In this report, the FPR was evaluated in patients with resectable pancreatic cancer. Methods: Between 2004 and 2019, one hundred and sixty-three patients in our institution with curative resection for pancreatic cancer were enrolled in this retrospective study. The cases of non-curative resection were excluded. The FPR was calculated with the preoperative plasma fibrinogen and the platelet counts. Cut-off value was decided with ROC curve. The patients were divided into high and low FPR group according to cut-off value. Results: The cut-off value of FPR was 25.51. In age, gender, BMI, operative factors including operative type, amount of blood loss and operative time, there was no significant difference between these two groups. Patients in low FPR group had significantly better overall survival (OS) rates and relapse-free survival (RFS) rates compared with high FPR group (p < 0.05). On multivariate analysis, the high FPR, CA19-9 > 300 U/ml and receipt of adjuvant chemotherapy were independent risk factor of post-operative recurrence. Conclusions: The FPR might be a prognostic factor of patients with resectable pancreatic cancer.
Impact of CDKN2A/b status in pancreatic cancer (PC).
Authors: Annunzio Kaitlin , Griffiths Claire , Arapi Igli , Lasowski Matthew , Singavi Arun K. , Dua Kulwinder , Khan Abdul H. , Ritch Paul S. , Kamgar Mandana , Thomas James P. , Hall William Adrian , Erickson Beth , Tsai Susan , Christians Kathleen K. , Evans Douglas B. , Urrutia Raul , Szabo Aniko , George Ben 
Published: February 2020

759 Background: PC is a lethal disease with limited treatment options. We utilized Comprehensive Genomic Profiling (CGP) to identify putative prognostic and/or predictive biomarkers. Methods: We retrospectively reviewed PC patients (pts) at our institution who underwent CGP utilizing the Foundation One assay. CGP was performed on hybrid-capture, adaptor ligation-based libraries for up to 315 genes plus 47 introns from 19 genes frequently rearranged in cancer. PC pts were categorized by clinical stage – localized (resectable and borderline resectable PC; LPC), locally advanced (LAPC) and metastatic (mPC). Effect of gene alterations (GAs) with at least 10% prevalence were analyzed. The marginal effect of each gene on radiographic response and survival outcomes was estimated using proportional odds and multivariate Cox regression analysis, respectively, adjusting for stage. Results: Ninety-three pts were identified - median age was 63, 55% were male, and 50% were smokers. Clinical stage at diagnosis was LPC, LAPC and mPC in 42 (45%), 23 (25%) and 28 (30%) pts, respectively. The most commonly altered genes were KRAS (94%), TP53 (75%), CDKN2A (41.2%) and SMAD4 (32.9%). All patients were microsatellite stable and the median tumor mutational burden was 1.7. 5-FU (52%) or Gemcitabine (46%) based chemotherapy combinations were utilized as the first systemic therapy. Median overall survival for patients with LPC, LAPC and mPC were 30.7, 28.8 and 9.6 months respectively. Thirty-eight (91%) pts with LPC underwent curative intent surgery compared to 15 (65%) pts with LAPC (p = 0.019). Thirty-five (95%) pts with wild type (WT) CDKN2A and 47 (94%) pts with WT CDKN2B underwent curative intent surgery compared to 13 (65%) and 1(14%) pt(s) with GAs in CDKN2A and CDKN2B respectively (p = 0.003 and p < 0.0001 respectively). The response to chemotherapy was statistically significantly higher in pts with WT CDKN2A (53%) and CDKN2B (48%) compared to pts with GAs in CDKN2A (19%) and CDKN2B (12%) (p = 0.03 and p = 0.05, respectively). Conclusions: GAs in CDKN2A/B may have a predictive and possibly a prognostic impact. The clinical validity and biological relevance of these findings need to be further explored in larger studies.
Analysis of associations of CXCR3 ligands with immune microenvironment and aggressiveness in murine and human pancreatic ductal adenocarcinoma.
Authors: Cannon Andrew , Thompson Christopher M , Atri Pranita , Bhatia Rakesh , Kumar Sushil , Batra Surinder 
Published: February 2020

762 Background: The complex milieu of cytokines within pancreatic ductal adenocarcinoma (PDAC) promotes tumor progression and immune suppression thereby contributing to the dismal prognosis of patients with PDAC. However, the roles of many cytokines, including CXCR3 ligands, in PDAC have not been thoroughly investigated. Methods: Bioinformatics analyses of PDAC microarray and TCGA datasets were used to identify cytokines overexpressed in PDAC, their association with patient survival as well as the expression of cognate cytokine receptors. Comparative analysis of cytokine expression in KrasLSL-G12D-P53LSL-R172H-Pdx1-Cre (KPC) and KrasLSL-G12D-Pdx1-Cre (KC) murine PDAC models were used to validate these findings. Pathway and CIBERSORT analyses were employed to determine mechanistic basis of altered survival associated with cytokines of interest. Results: Of the 149 cytokines analyzed, CXCR3 ligands CXCL9 and CXCL10 were highly and consistently overexpressed in PDAC datasets. Concurrently, CXCL9, CXCL10 and PF4 were overexpressed in the aggressive KPC murine model compared to the indolent KC model. CXCR3 showed robust expression in PDAC in microarray, TCGA and IHC analyses. Interestingly, high expression of CXCR3 ligands was associated with shorter overall survival (p = 0.04 for CXCL9, 10 and 11 and p = 0.02 for PF4) while high expression of CXCR3 was associated with increased overall survival (p = 0.03). Pathway analysis of genes correlated with CXCR3 and/or its ligands showed that CXCR3 ligands may promote T-cell exhaustion (p < 0.001). Finally, CIBERSORT analysis of TCGA data demonstrated that high CXCR3 expression was associated with increased CD8 T-cell and naïve B-cell signatures and loss of plasma cells signatures. High CXCR3 ligand expression was associated with increased CD8 T-cell, and M1 macrophage, and loss of NK-cell signatures(p < 0.05). Conclusions: CXCR3 ligands are overexpressed in PDAC and are associated with poor survival, likely related to alterations in tumor immune infiltrate/activity and may represent targets to augment anti-tumor immunity.
Association of neutrophil, platelet, and lymphocyte ratios with prognosis in metastatic pancreatic cancer.
Authors: Allen Jessica , Cernik Colin , Bajwa Suhaib , Saeed Anwaar , Kasi Anup 
Published: February 2020

767 Background: High mortality associated with pancreatic ductal adenocarcinoma (PDA) warrants research into prognostic factors. We examined the relationship between the daily rate of change of CA19-9 over the first 90 days of treatment (DRC90) and pretreatment levels of neutrophils, lymphocytes, and platelets with overall survival (OS) and progression free survival (PFS) in patients with stage IV PDA that received chemotherapy. Methods: We retrospectively evaluated 102 locally advanced and metastatic PDA patients treated at KU Cancer Center between Jan 2011 and Sep 2019. We compared the ratio of pretreatment absolute neutrophil count to pretreatment absolute lymphocyte count (NLR) and the ratio between pretreatment platelet count to pretreatment absolute lymphocyte count (PLR) with OS and PFS. We also compared DRC90 to OS and PFS. Log-rank trend test using the mean of NLR, PLR, and DRC90 as the threshold for two groups within each variable. Results: Baseline demographics are shown in the table. Pts with ≥ mean NLR (4.6) had significantly lower OS [p = 0.0444] and PFS [p = 0.0483] than Pts below the mean. Pts with PLR ≥ mean (3.9) did not have significantly different OS [p = 0.507] or PFS [p = 0.643] than Pts below the mean. Pts with DRC90 ≥ mean (-1%) did not have significantly different OS [p = 0.342] or PFS [p = 0.313] than Pts below the mean. Conclusions: Pts with NLR ≥ mean (4.6) had significantly lower OS and PFS than Pts with NLR below the mean. This implies the possibility of NLR as a prognostic marker in PDA that could guide treatment approach but needs validation in a larger cohort. [Table: see text]
Clinical outcomes of first-line FOLFIRINOX versus gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Healthcare System.
Authors: Patel Timil , Srikumar Thejal , Miccio Joseph Anthony , Lacy Jill , Stein Stacey , Kortmansky Jeremy S. , Staugaard Carol , Gambaccini Melissa , Axtmayer Alfredo , Cecchini Michael 
Published: February 2020

769 Background: FOLFIRINOX (FFX) and Gemcitabine plus nab-paclitaxel (GN) are established first line (1L) therapies for metastatic pancreatic cancer (MPC) but real-world data on their comparative effectiveness is limited. Methods: All cases of MPC treated with 1L FFX or GN at Yale Smilow Cancer Hospital and the affiliated community care centers (CCC) from January 2011 – April 2019 were reviewed. Patient (pt) demographics, prior therapy, initial and subsequent dose reductions (DR), time to treatment discontinuation (TTD), overall survival (OS), and second line (2L) treatment data were manually abstracted from the electronic medical record. Categorical and continuous variables were compared between 1L FFX and GN cohorts via the Chi-squared and Wilcoxon rank-sum tests. Median OS was calculated by the Kaplan-Meier method. Results: We identified 363 MPC pts treated with 1L FFX or GN; 269 (74%) pts were treated with FFX and 94 (26%) with GN as 1L therapy. 204 (56%) pts were treated at the main campus and 159 (44%) at a CCC. Demographics and baseline characteristics (FFX/GN) were as follows: gender (male) 55% / 41%; race (white) 82% / 77%; age < 76 90% / 71% ( P < 0.001). 332 (91%) of pts received no prior therapy; 21 (6%) had prior surgery plus adjuvant gemcitabine and 10 (3%) had surgery alone. 98% of FFX-treated pts were treated with upfront DR, compared to 78% of GN-treated pts ( P= 0.003). 78% and 53% of FFX-treated and GN-treated pts, respectively, had subsequent DR ( P< 0.001). Median TTD was 4.8 months with FFX and 3.4 months with GN ( P= 0.0029) and the median OS was 11.3 months with FFX versus 7.2 months with GN ( P < 0.0001). After 1L, 33% and 61% of FFX- and GN-treated pts, respectively, received no further chemotherapy ( P< 0.001). Conclusions: In the largest manually abstracted retrospective analysis to date, MPC pts treated with 1L FFX were younger, more likely to receive 2L therapy, and had increased survival compared to pts treated with GN. The OS of pts treated with FFX was similar to the OS reported by Conroy et al despite upfront dose attenuations in 98% of pts. A randomized trial is needed to confirm optimal sequencing of chemotherapy in MPC.
Feasibility of pharmacist co-management for patients prescribed oral anticancer therapy for gastrointestinal cancers.
Authors: Cao Cathy , Cleary James M. , Patel Anuj K. , Yurgelun Matthew B. , Ng Kimmie , Perez Kimberly , Rubinson Douglas Adam , Wolpin Brian M. , Meyerhardt Jeffrey A. , McCleary Nadine Jackson 
Published: February 2020

77 Background: There is an increased use of oral anti-cancer therapies (OACTs) for treatment of gastrointestinal (GI) cancers. While OACTs provide convenience compared to IV agents, they carry similar risks for drug-drug interactions (DDI), toxicities, and unique challenges like adherence and drug access. Patients on OACTs have fewer touch-points with clinicians, requiring more patient ownership of treatment. Pharmacist co-management of pts has been shown to be successful in teaching and monitoring of IV therapy. We sought to assess feasibility of pharmacist co-management for pts prescribed OACTs for treatment of GI cancers. Methods: In 2019, the Dana-Farber GI Cancer Center (GCC) had an embedded pharmacist 8 hrs/week to help with co-management of pts on OACTs. The pharmacist provided (1) in-person and telephone teaching; (2) comprehensive medication reconciliation; (3) DDI review; and (4) supportive care recommendations. Patients were identified by reviewing provider schedules and through provider referrals. The initial teach visit was one-on-one with each patient before initiation, with joint visits with providers thereafter for monitoring and adherence checks. Data were collected to quantify the types of support/recommendation provided by pharmacist and the impact on clinical workflow. Results: After 4 months in the GCC clinic, the pharmacist has co-managed 26 new pts, 61% seen in-person. In initial visits, the pharmacist identified 3 DDI, updated 15 medication lists, and assisted 11 pts/or providers with drug access and drug information. The pharmacist saw 10 of 26 pts for follow up, totaling 21 encounters. The pharmacist assisted in 17 of the 21 encounters with drug access and drug information. Pharmacist spent 20 min/pt on teaching. For follow-up visits, the pharmacist did not additional incur clinic resources as patients were seen with providers. Conclusions: Pharmacist co-management of patients on OACTs is feasible and offers an added safety resource to pts and providers from initial teaching to monitoring. Future research will focus on the impacts of co-management on clinical outcomes, such as the use of emergency/hospital visits, the duration of therapy, and adherence.
Is adjuvant chemotherapy beneficial for stage II-III goblet cell tumors of the appendix?
Authors: Zakka Katerina Mary , Williamson Shayla , Jiang Renjian , Alese Olatunji B. , Shaib Walid Labib , Wu Christina , Behera Madhusmita , El-Rayes Bassel F. , Akce Mehmet 
Published: February 2020

796 Background: Goblet cell tumors (GCT) of the appendix are very rare tumors constituting 2.5%-5% of all primary appendiceal neoplasms. Role of adjuvant chemotherapy (AC) is not established for GCT. This study aims to evaluate the impact of AC in stage II-III appendiceal GCT. Methods: Patients with pathological stage II and III GCT who underwent surgical resection between 2006 and 2015 were identified from the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8243/3, 8245/3 and C18.1. Patients treated with neoadjuvant systemic and/or radiation therapy and adjuvant radiation were excluded. Univariate and multivariable analyses were conducted, and Kaplan-Meier Curves were used to compare overall survival (OS) based on treatment received with Log-rank test. Results: A total of 1,046 patients were identified. 53.7% males and 89.0% Caucasian; median age 56 (range, 20-90) years. Distribution across pathological stages II-III was 83.6% (N = 874) and 16.4% (N = 172) consecutively. 8.3% (N = 73) of stage II and 50.6% (N = 87) of stage III patients received AC. In the total cohort, AC was not associated with better OS compared to no AC in univariate analysis (HR 1.84; 95% CI 1.26-2.67; p = 0.001) or multivariable analysis (HR 0.94; 95% CI 0.57-1.52; p = 0.790). For stage II patients, AC was not associated with better OS in univariate (HR 1.24; 95% CI 0.60-2.57; p = 0.562) or multivariable analyses (HR 1.67; 95% CI 0.76-3.64; p = 0.199). Similarly, in stage III patients, AC was not associated with better OS in univariate (HR 0.78; 95% CI 0.48-1.29; p = 0.340) or multivariable analyses (HR 0.55; 95% CI 0.28-1.04; p = 0.067). In the entire cohort 5-year OS for patients that received AC was 83.9% (80.3%, 86.9%) versus 70.7% (60.9%, 78.5%) (p = 0.001) with no AC. For stage II patients, 5-year OS was 77.3% with AC vs. 87.7% with no AC (p = 0.562). For stage III patients, 5-year OS was 64.8% with AC vs. 54.4% with no AC (p = 0.340). Conclusions: AC was not associated with improved 5-year OS in patients with pathological stage II and III GCT compared to no AC.
Nationwide large-scale investigation of microsatellite instability status in more than 18,000 patients with various advanced solid cancers.
Authors: Akagi Kiwamu , Oki Eiji , Taniguchi Hiroya , Nakatani Kaname , Aoki Daisuke , Kuwata Takeshi , Yoshino Takayuki 
Published: February 2020

803 Background: The recent success of immunotherapy in high-frequency microsatellite instability (MSI-H) and/or mismatch repair protein deficient (MMR-D) tumors now supports testing for MSI in all advanced solid tumors. We previously reported using the quasi-monomorphic variation range (QMVR), the MSI status can be determined without matched normal DNA (Bando H, et al. Cancer Sci. 2018). Here, we investigate the proportion of the MSI status across various advanced solid tumors by this method. Methods: The MSI analysis was performed centrally by CLIA-certified, CAP-accredited, the single laboratory using tumor DNA from formalin-fixed paraffin embedded (FFPE) tissues with the MSI test kit (FALCO), which includes fluorescent-labelled primers for co-amplification of five mononucleotide markers (NR-21, BAT-25, MONO-27, NR-24 and BAT-26). The MSI-H was defined as positive if 2 or more makers showed instable. Results: A total of 18,250 patients with advanced solid tumors were registered from Dec 2018 to Aug 2019, and the MSI status was confirmed in 18,088 patients (99%). Among them, 51.9% were male, with median of 62.0 y/o. Overall prevalence of the MSI-H was3.3% (2.3% in male and 4.5% in female); the highest was 16.2% (149/916) in endometrial cancer, followed by 13% (13/100) in small intestinal cancer, 5.9% (74/1277) in gastric cancer, 3.3% (236/7190) in colorectal cancer, 2.6% (4/154) in prostate cancer, 2.5% (20/806) in ovarian cancer, 2.1% (9/426) in cervical cancer, 1.6% (13/831) in biliary tract cancer, 1.5% (4/271) in hepatocellular carcinoma, 0.9% (16/1852) in pancreas cancer. Interestingly, among biliary tract cancers, all MSI-H cases were arising from gall bladder (13/152) but no other sites. High prevalence was observed in cancer of teens or twenties (7.9%) and over 80y/o (5.6%), compare with others (3.0%) in this study (p < 0.001, both). Conclusions: These data show the MSI-H advanced solid tumors are distributed across a much broader tumor spectrum, and confirm the clinical relevance of the screening in patients with most advanced solid tumors, which can select patients sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.
Female representation in clinical trials leading to FDA cancer drug approvals for gastrointestinal (GI) cancers between 2008 to 2018.
Authors: Mendis Shehara Ramyalini , Anand Seerat , Dasari Arvind , Unger Joseph M. , Gothwal Anirudh , Ellis Lee M. , Varadhachary Gauri Rajani , Kopetz Scott , Overman Michael J. , Raghav Kanwal Pratap Singh , Loree Jonathan M. 
Published: February 2020

809 Background: Proportionate representation of women in health research is an area for improvement. This study aims to assess the representation of women in gastrointestinal (GI) cancer clinical trials leading to FDA cancer drug approvals over the past 10 years. Methods: FDA cancer drug approvals between 07/2008-06/2018 were identified and trial reports supporting approvals sourced. The ratio of female to male (F:M) enrollment was compared with F:M cancer incidence in the U.S., and U.S. cancer prevalence and mortality. Results: Although F:M enrollment for all 229 trials leading to FDA cancer drug approvals in this period was similar to overall F:M cancer incidence in the U.S. (0.89 vs 0.86; Odds Ratio for female enrollment (OR) 1.05, 95% Confidence Interval (CI) 1.03-1.06, P<0.0001), in 17 trials that led to drug approvals in GI cancers there was lower F:M trial enrollment compared to cumulative U.S. incidence at those tumor sites (0.55 vs 0.79, OR 0.71, 95% CI 0.68-0.74, P<0.0001). F:M enrollment and U.S. incidence by the main GI tumor sites where approvals occurred is shown in Table. Female enrollment rates were also lower than U.S. female cancer mortality and prevalence rates in these tumor sites (P<0.0001 for all). Female enrollment in GI trials fell between 2008-2013 and 2014-2018 (38 vs 33%, OR 0.80, 95% CI 0.74-0.87, P<0.0001). Conclusions: Although disparity in female enrollment may be improving across combined FDA cancer drug approval trials, underrepresentation of females has persisted in GI cancer trials when compared to F:M cancer incidence, prevalence and mortality in the U.S. More work is required to determine the drivers of this disparity, in order to mitigate it. [Table: see text]