bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial, ethnic, and sex-based disparities among high-risk individuals undergoing pancreatic cancer surveillance.
Authors: Klute Kelsey , Lucas Aimee L. , Brand Randall , Everett Jessica N. , Farrell James J. , Hawthorne Kieran , Kaul Vivek , Kupfer Sonia S. , Paiella Salvatore , Simeone Diane M. , Sussman Daniel A. , Zogopoulos George , Kastrinos Fay , Katona Bryson W ,   and the PRECEDE Consortium
Published: January 2023

687 Background: The international, multi-center Pancreatic Cancer Early Detection (PRECEDE) Consortium enrolls high-risk individuals (HRIs) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Enrollment began in 2020, and despite challenges related to the COVID-19 pandemic, the PRECEDE Consortium rapidly accrued a large cohort of HRIs. The purpose of this study is to describe the characteristics of this cohort and assess racial, ethnic, and sex-based disparities. Methods: The PRECEDE Consortium (NCT04970056) is a prospective, multicenter study focused on improving survival from PDAC through early detection. Data from all HRIs who met criteria for PDAC surveillance and enrolled between May 2020 - March 2022 were collected and included in the analysis. Results: During the study period, 1299 HRIs enrolled in PRECEDE at 32 centers. HRIs were excluded if enrollment data was incomplete or criteria for PDAC surveillance were not met. Of 1113 who were included, 47.2% met criteria for familial pancreatic cancer (FPC) and 45.4% had a family history of PDAC along with a PV in a PDAC-risk gene (BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, MSH6, PMS2, or EPCAM). The remainder had familial atypical mole melanoma syndrome (5.7%), Peutz-Jeghers syndrome (1.6%), or hereditary pancreatitis (0.2%). More females than males enrolled (65.9% vs. 33.5%). The distribution of HRIs by race and ethnicity is depicted; the majority identified as white (87.7%). Study participants were primarily from the US (82.7%), the median age was 61 (27-85) and 18.5% had Ashkenazi Jewish ancestry. Nearly all HRIs consented to allow access to imaging data (99.6%), collection of germline DNA (97.7%), and biosample collection (99.5%). There were no race, ethnicity, or sex-based differences in rates of consent for collection of imaging, DNA, or biosamples. Conclusions: Enrollment of HRIs in prospective studies of PDAC surveillance is essential for advancing early detection research in PDAC. A distinct advantage of the PRECEDE Consortium for examining enrollment disparities is that recruitment began in 2020, providing a unique and current snapshot of the international PDAC surveillance landscape. Despite the recent attention on addressing disparities in healthcare delivery, significant racial, ethnic, and sex-based disparities persisted in the cohort of HRIs enrolled in the PRECEDE Consortium. Ensuring that the diversity of participants in the PRECEDE Consortium mirrors the communities served by participating centers is crucial. Further examining and addressing the reasons for these disparities is a major focus of the PRECEDE Consortium moving forward. [Table: see text]
Use of glycoproteome profiles to detect advanced adenomas and colorectal cancer.
Authors: Desai Khushbu , Mitchell Alan , Shah Ankita , Chandrasekar Dharini , Xu Gege , Lindpaintner Klaus , Serie Dan , Pearce Tillman E. , Hommes Daniel 
Published: January 2023

69 Background: Colorectal cancer (CRC) remains a leading cancer despite current screening modalities. Precancerous lesions, or Advanced Adenomas (AA), commonly precede invasive cancer development by years. Newer technologies use circulating tumor DNA and/or proteins for CRC detection but have not been able to effectively detect AA. Aberrant protein glycosylation is associated with (pre-)malignant lesions. To detect glycoproteome profiles associated with the occurrence of AA, we studied serum glycoproteins in AA/CRC. Methods: A novel platform combining liquid-chromatography/mass-spectrometry (LC-MS) and artificial-intelligence (AI)-powered data processing allowing high resolution, high throughput glycoproteomic profiling was used to identify glycoprotein biomarkers in peripheral blood. Samples were sourced from biorepositories and included patients diagnosed with CRC, AA, ulcerative colitis (UC) and controls. The samples were split into a training (50%) and a hold-out testing set (50%) for the development of a machine learning (ML)-based multivariable predictive model. Statistical analysis was performed on normalized data to identify biomarkers differentiating AAs and different stages of CRC from controls. Results: We studied 563 patient samples: 196 controls (mean age 51.7; 52% female); 32 AA (mean age 68.6; 53% female); 247 CRC (mean age 65.6; 50% female) and 88 UC (mean age 44.1; 47% female). There were 250 differentially abundant (FDR < 0.05) glycopeptides/peptides when comparing CRC and AA samples with healthy and UC controls. A subset was assessed, generating a six (6) biomarker ML classification model. This model was applied to the hold-out test and achieved an overall sensitivity of 91.4% and specificity of 91.8% for predicting AA/CRC versus healthy/UC with an area under the receiver operating characteristic of 0.962. AA and CRC separately were predicted with a sensitivity of 84.4% and 92.8%, respectively, relative to healthy/UC with sensitivities for CRC stage 1/2 and stage 3/4 being 91.2% and 93.2%, respectively). Conclusions: Glycoproteomic serum profiles accurately detect precancerous AA in addition to CRC and offer a new approach to effective CRC screening. We will have completed an interim analysis of a large prospective observational study at the time of the meeting. Clinical trial information: NCT05445570 . [Table: see text]
Assessment of an emergency 14-day (d) integrative supportive care program (14-EISCP) followed by early chemotherapy (CTx) in symptomatic patients (pts) with advanced pancreatic ductal adenocarcinoma (aPDAC): A prospective ARCAD cohort study.
Authors: Rousseau Benoit , Falcoz Antoine , Toullec Clemence , Lecomte Thierry , Lambert Aurélien , Tournigand Christophe , Guerin-Meyer Veronique , Louvet Christophe , Trouilloud Isabelle , Rinaldi Yves , Coriat Romain , Dauba Jerome , Neuzillet Cindy , Andre Thierry , Bachet Jean-Baptiste , Cros Jerome , De La Fouchardiere Christelle , Garcia-Larnicol Marie-Line , De Gramont Aimery , Hammel Pascal 
Published: January 2023

700 Background: Pts with aPDAC often have general health impairment due to high symptom burden at diagnosis. We investigated prospectively the clinical benefit (CB) of an EISCP followed by CTx as early as suspicion of aPDAC in pts with ECOG performance status (PS)≥2. Methods: In this multicenter study, PS≥2 pts with pathologically confirmed or suspected aPDAC on imaging were included at first oncology visit (V1) in a personalized 14-d EISCP including pain, nutritional, diagnostic/stenting procedures. Post-EISCP PS≤1 pts received mFOLFIRINOX or gemcitabine(Gem)/Nab-paclitaxel(NP), PS≥2 received mFOLFOX7 or investigator choice CTx or best supportive care (BSC). The primary endpoint was the 14-EISCP success on both feasibility of procedures within 14-d±2 and CB defined by post-EISCP PS≤1, ≥5 points improvement of either fatigue/pain/global health EORTC QLQ-C15-PAL quality of life (QOL) scores, or CTx start ≤30d, aiming 59% success for clinical relevance. Secondary endpoint included uni/multivariate median overall survival (mOS) analyses. Results: As of 07/2022, 106 pts were included; 93 pts were evaluable for primary endpoint: male 46%, mean age 74 yrs, PS2/3 79%/21%, metastases (M1) 62%, pathological diagnosis needed 53%, biliary stenting 16%. V1 mean QOL global health score was 48±23. mOS was 4.1 months (IC95 2.8-5.7). The 14-d feasibility was achieved in 71%. Post-EISCP CB was observed in 82% of pts: 13%, PS improvement to 0/1, 23% QOL improvement and/or 73% CTx start ≤30-d. Eight pts (9%) died during the EISCP. The primary endpoint was achieved in 59% of pts (n=55). Overall, 17 pts (16%) received mFOLFIRINOX/GemNP, 32 (30%) FOLFOX, 29 (27%) Gem or 5FU alone, and 28 (27%) BSC. OS analyses are shown. At d30, pts receiving CTx had a mean change of QOL global health score from 51±23 to 60±23. Conclusions: In PS≥2 pts with aPDAC, a personalized 14-EISCP is feasible and lead to a meaningful CB allowing the administration of doublet/triplet CTx in nearly half of the pts. Pts starting CTx within 30d had improved OS. Clinical trial information: NCT02979483 . [Table: see text]
Camrelizumab combined with apatinib and albumin-bound paclitaxel followed by camrelizumab plus apatinib as first-line therapy for unresectable or metastatic pancreatic cancer.
Authors: Shen Bo , Wu Yuan 
Published: January 2023

703 Background: Pancreatic carcinoma has complex immunosuppressive tumor microenvironment that acts to insulate the tumor against an effective cytotoxic immune response. Apatinib (small molecular agent targeting the VEGFR-2), has shown the potential additive or synergistic antitumor effects with camrelizumab (anti-PD-1 agent) in vitro study. The inhibition of VEGF signaling pathway could trigger immune suppression provoked. Considering the anti-PD-1 agent plus antiangiogenic drug might avoid the substantial cumulative toxicities and obtain well tolerance, the specific and optimized therapeutic agents and treatment strategy to carry out chemotherapy-free strategy as maintenance or sequential (switch maintenance) therapy is hopeful and noteworthy. Methods: In this single-arm, single-center, exploratory study, patients (pts) who were pathologically or cytologically diagnosed as unresectable or metastatic pancreatic cancer and had not received systemic treatment before, with an ECOG performance status of 0-2. Pts received camrelizumab (200 mg intravenously once every 3 weeks) plus albumin-bound paclitaxel (125 mg/m2 intravenously on day 1,8 every 3 weeks) and apatinib (250 mg once daily orally on days 1–21 of each 3-week cycle) for 4–6 cycles, and pts without progressive disease (PD) after completing 4–6 cycles of initial camrelizumab plus albumin-bound paclitaxel and apatinib were administrated subsequent camrelizumab (200 mg intravenously once in 3 weeks) plus apatinib (250 mg once daily orally on days 1–21 of each 3-week cycle). Primary endpoint was progressionfree survival (PFS) by RECIST 1.1. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: From 09/2021 to 08/2022 13 pts were enrolled (median age 60, 77% male). At data cutoff, 5 pts continued to receive subsequent camrelizumab plus apatinib, 12 pts were included in the efficacy analysis. The ORR was 16.7%, with confirmed 2 (16.7%) PR. SD were 9 (75.0%) with a DCR of 91.7%. All pts experienced treatment-related AEs (TRAEs), the ≥grade 3 TRAEs were GGT increased (31%), blood bilirubin increased (8%), alanine aminotransferase increased (8%), aspartate aminotransferase increased (8%), alkaline phosphatase increased (8%), creatinine increased (8%), hypoesthesia (8%) and malaise (8%). Of 13 patients, 5 (38%) had TRAEs leading to any treatment interruption, and 5 (38%) patients had TRAEs leading to any dose reduction, respectively. None patient died because of TRAEs. Conclusions: Camrelizumab combined with apatinib and albumin-bound paclitaxel followed by camrelizumab plus apatinib demonstrated encouraging antitumor activity and manageable toxicity as firstline therapy for patients with unresectable or metastatic pancreatic cancer. Clinical trial information: ChiCTR2100045844 .
Incidence and clinical characteristics of patients with LAPC and mesenteric vein thrombosis and current treatment paradigm.
Authors: Zureikat Amer H. , Pishvaian Michael J. , Lopez Charles D. , Meredith Kenneth , Zervos Emmanuel E. , Hatoum Hassan , Chung Ki Y. , Tsobanoudis Alex , Berg Daniel James , Ucar Antonio , Nazemzadeh Reza , Bates Susan Elaine , Goodman Karyn A. , Johnson Thor , Parikh Nainesh , Kouri Brian , Laing Christopher , Boone Brian A. , Qureshi Imtiaz , Agah Ramtin 
Published: January 2023

714 Background: Mesenteric venous thrombosis (MVT), defined as complete occlusion of the Superior Mesenteric Vein (SMV) or Main Portal Vein (MPV) is often incidentally identified on CT or MRI in patients with Locally Advanced Pancreatic Cancer (LAPC). There is very limited data describing the incidence and treatment of MVT in large studies in this patient population. Herein, we seek to establish the incidence of MVT and the treatment response in patients with LAPC. Methods: We conducted an analysis on 180 subjects with interpretable baseline imaging for MVT enrolled in the randomized Phase III TIGeR-PaC clinical trial (NCT03257033). Subjects who completed 4 Cycles of induction treatment (3 cycles of IV gemcitabine/nab-paclitaxel and 1 cycle of IMRT or SBRT) prior to randomization were analyzed. Baseline and end of induction CT scans were read by a board-certified radiologist to determine presence of MVT. Severe MVT was defined as complete occlusion of MPV and/or SMV. For patients who completed induction the end of induction CT was used to assess down staging of MVT. We analyzed the mean age between patients with and without MVT using a Mann-Whitney test and performed a contingency table with Pearson Chi-Square statistics to analyze tumor location. Results: Out of a total of 180 patients, 91 patients presented with severe MVT at baseline (50%). There was no difference in age (67 vs. 69) or sex (44% male vs. 39% male) for patients with and without MVT. The location of the tumor in the head of the pancreas was more prevalent in both groups (62% vs 53%, respectively). Out of 112 patients who completed induction, 60 presented with MVT at baseline (53%). Seventeen of these patients (28%) demonstrated partial or complete resolution of MVT during induction; most resolved MVT after the first 2 cycles of chemotherapy (15/17). Only a minority of these patients were on anticoagulation therapy (10/60, 17%). Conclusions: Severe MVT is much more prevalent in patients with LAPC than previously reported. Anticoagulation is underutilized in this cohort; however, chemotherapy may have a beneficial effect in downstaging MVT beyond anticoagulation. Clinical trial information: NCT03257033 .
Efficacy of sequential perioperative FOLFIRNOX plus gemcitabine nab-paclitaxel for resected pancreatic and periampullary cancers.
Authors: Cen Putao , Chan Kok Hoe , Wray Curtis Jackson , Thosani Nirav , Bynon John , Rowe Julie Haewon 
Published: January 2023

724 Background: Perioperative chemotherapy with single regimen either FOLFIRINOX (FFX) or gemcitabine/nab-paclitaxel (Gem/NabP) is the current standard of care for pancreatic and periampullary cancers (PC) with overall survival (OS) of 2-3 years without pre-selected CA19-9 level. Sequential chemotherapy with FFX plus Gem/NabP has recently been investigated in metastatic PC and shown to improve OS. We investigated the outcome of patients who received sequential perioperative chemotherapy FFX plus Gem/NabP. Methods: Patients treated with curative intent surgery for PC who received perioperative sequential chemotherapy FFX plus Gem/NabP (each regimen was given at least two months) were identified. OS and recurrence-free survival (RFS) were calculated from the date of initial treatment (neoadjuvant chemotherapy or resection) to the date of last follow-up/death or recurrence via Kaplan-Meier analysis. Results: A total of 29 patients were identified: 24 (83%) patients had pancreatic cancer, 5 (17%) patients had periampullary cancer; 16 (55%) patients received neoadjuvant chemotherapy FFX plus Gem/NabP; 13 (45%) patients underwent upfront surgery and received adjuvant FFX plus Gem/NabP chemotherapy; 22 (76%) patients had resectable disease, the rest 7 (24%) patients had borderline or unresectable disease were all in the neoadjuvant cohort; node positivity was higher in the adjuvant cohort (n=8, 62%) than in the neoadjuvant cohort (n=8, 50%); 5 (17%) patients were found to have homologous recombination deficiency (HRD: BRCA2, CHEK, BARD, ATM) and received PARP inhibitors as part of the perioperative therapy combination. 10 (34%) patients had CA19-9 ≥ 500. Median age was 65 years (range, 45-79 years), 20 (69%) were male. During the study period, 4 (14%) patients died, and 6 (21%) patients had disease recurrence. Median RFS and OS were not reached with a median follow-up of 28 months (range, 10.9–119 months). The longest RFS was 10 years. The 2-years RFS and OS for the entire cohort was 76.7% and 88.8%, respectively. There was no statistical difference in RFS (log rank HR 1.72, 95% CI 0.23-13.15) or OS (log rank HR 0.99, 95% CI 0.20-4.93) for patients in the neoadjuvant cohort versus adjuvant cohort. Conclusions: Sequential perioperative chemotherapy combined FFX plus Gem/NabP for resected PC is effective and potentially prolongs survival, compared to historical controls who received single regimen.[Table: see text]
A pilot study for single cell RNA-sequencing of patient-derived pancreatobiliary cancer organoid.
Authors: Kim Bomi , Seo Minseok , Park Sinwoo , Park Jiho , Jin Jeonghwa , Park Jinkyeong , Lee Jong-Chan , Hwang Jin-Hyeok , Kim Jaihwan 
Published: January 2023

739 Background: For precision medicine, patient-derived organoid (PDO) is regarded as one of the promising models. However, current PDOs were mainly derived from surgical specimens. We aimed to analyze the single cell RNA-sequencing (scRNA-seq) of PDO from various sampling methods with different pathologic outcomes. Methods: In 2021, three pancreatic cancer and one gallbladder cancer samples were collected from surgical specimen, endoscopic ultrasound guided-fine needle biopsy (EUS-FNB), and endoscopic retrograde cholangiopancreatography (ERCP)-guided biopsy. The samples were mechanically dissociated with dissociation buffer and incubated using shaking incubator. Dissociated cells were seeded into growth factor reduced Matrigel. From these PDOs, we generated scRNA-seq data in each experimental design, and corrected batch effects that could occur when multiple samples are considered simultaneously in downstream analysis. Marker genes representing each cell subcluster were identified, and statistical hypothesis tests were performed to identify genes differentially expressed according to differences in biopsy methods and/or pathological results. Results: We found the optimal 8 types of sub cell-type clusters with a resolution parameter of 0.3 in clustering analysis based on the Uniform Manifold Approximation and Projection (UMAP) algorithm in terms of silhouette score. As a result of examining the expression levels of KRT19, a marker gene for malignant ductal cells, and RGS5, a stellate marker gene, which showed the same pattern as the existing PDAC transcriptome studies, it was confirmed that most of the cells derived from PDOs were malignant ductal cells. Finally, we identified a heterogeneous effect on gene expression patterns in ductal cells depending on not only pathological positivity, but also biopsy methods for organoid. Conclusions: According to our scRNA-seq, most cells were malignant cells and EUS-FNB could be a good sampling method for PDOs. However, further analysis about a heterogeneous effect on gene expression patterns is necessary.[Table: see text]
KRAS WT pancreatic adenocarcinomas: Another disease?
Authors: Ben-Ammar Imen , Ducreux Michel , Boige Valérie , Hollebecque Antoine , Tarabay Anthony , Smolenschi Cristina , Gelli Maximiliano , Tanguy Marie Laure , Valery Marine , Rouleau Etienne , Barbe Rémy , Boileve Alice , Fuerea Alina Cristina 
Published: January 2023

750 Background: KRAS mutation is the most common molecular alteration (MA) in pancreatic adenocarcinoma (PDAC), and only 8-10% of patients (pts) harbor KRAS wild-type tumors (WT). This study describes clinical and molecular features of KRAS WT PDAC and compares it to mutant KRAS (m KRAS) PDAC. Methods: A retrospective chart review of clinical/molecular data was performed on all pts with PDAC who had contributive molecular profile at Gustave Roussy. KRAS status was determined on tumor molecular profiling as part of routine care using an in-house panel or Foundation Medicine NGS either on tissue (63%) or liquid biopsy (37%). Results: Overall, 41 pts with KRAS WT PDAC were compared to 197 pts with mKRAS PDAC. Median OS (mOS) from initial diagnosis was significantly higher in the KRAS WT group compared to mKRAS group (32.8 months (mts), CI95% [25.9-NR] vs 21.5 mts, CI95% [18.8-24.9] respectively), as mOS from metastatic diagnosis, 26 mts, CI95% [15.7-NR] for KRAS WT pts vs 17.7 mts CI95% [15.5-19.3] for mKRAS (all p<0.05)). After adjustment on gender, age, metastasis status at diagnosis, hazard ratio (HR) of OS from metastatic stage diagnosis associated with KRAS status was 1.9 [1.1;3.4], p=0.02 (similar for 1st line PFS and OS from initial diagnosis). MA were found in 31 KRAS WT pts (76%). KRAS WT and m KRAS pts harbored different molecular profiles with less alterations of TP53, SMAD4 and CDKN2A/B (p<0.05) in KRAS WT tumors, but more of BRAF (p<0.05), PALB2, RET and BRIP1 (p=NS) alterations. Interestingly, 3 MSI tumors were found in the KRAS WT group (one received immunotherapy), vs none in m KRAS group). Tumor mutational burden was similar (2.00 Mut/Mb in KRAS WT pts vs 2.7 Mut/Mb in m KRAS pts). Based on ESCAT classification, a putative therapeutic target (ESCAT I-IV, other than KRAS) was identified in 15 (36%) KRAS WT pts and 65 (33%) m KRAS pts, thus enriching the therapeutic panel for these patients. Indeed, for example 9 (22%) KRAS WT pts received an oriented therapy after palliative treatments (such as anti-RET or anti-PARPs) and showed higher survival rates compared to KRAS WT pts who did not (mOS from diagnosis in months NR (14.2; NR) and 28.3 (26; NR) respectively). Conclusions: In our cohort of 238 PDAC, we confirm that KRAS is a prognostic factor of OS. KRAS WT PDAC have a significantly longer OS compared to m KRAS. Moreover, 36% of KRAS WT PDAC pts had a potentially actionable MA, and 9 pts displayed higher survival rates after receiving oriented therapies. This study suggests that KRAS WT PDAC should be eligible for a large molecular screening.[Table: see text]