bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation and culture of circulating pancreatic cancer tumor cells using a microfilter.
Authors: Furukawa Atsuko , Shimomura Osamu , Araki Kazuhisa , Mori Tomoko , Oda Tatsuya , Matsusaka Satoshi 
Published: June 2022

e16230 Background: The presence and number of circulating tumor cells (CTCs) are reportedly associated with prognosis but the rarity of CTCs in peripheral circulation limits the ability of conventional technologies to provide fully accurate analyses. The purpose of this study was thus to establish a novel approach to capture and culture the CTCs using a microfilter device. Methods: This was a prospective study in preoperative patients with pancreatic cancer at the University of Tsukuba Hospital after approved by the Institutional Review Board. Five ml of whole blood was collected from each patient into an EDTA-treated collection tube before pumping through an 8μm pore microfilter. Cells isolated on the filter were stained with PE-conjugated anti-EpCAM, FITC-conjugated anti-CD45 and Hoechst 33342. The filter was then transferred to a 35mm dish and cultured with 20%FBS-IMDM-F12 medium containing 2%Matrigel- EGF-FGF-B27 for 4-6 weeks. Cells were visualized with an automatic fluorescence microscope. A CTC was defined as an intact round oval cell with a visible nucleus, positive staining for EpCAM and negative staining for CD45. Results: A total of 9 patients [male/female; 4/5, median age;71 (39-78), Stage 0/IA/IIA/IIB; 1/3/3/2, preoperative chemotherapy/chemoradiation; 1/2] were enrolled. CTCs were captured in 8 out of 9 cases and cultured CTCs were kept viable for 4-6 weeks in 6 out of 9 cases. CTCs formed colonies by 4-6 weeks of culture, colonies were expanding and blood cells disappeared. No cultured CTCs were observed in the two cases who received preoperative chemotherapy. Conclusions: We successfully developed a novel culture method of patient CTC using a microfilter device. Our system supports the possibility of accurate detection and proliferation of CTCs on microfilters. Cultured CTCs could be used for patient-specific drug susceptibility testing and mutational profiles for future cancer patients.
Emerging immuno-therapies for advanced pancreatic cancer: An overview of available literature.
Authors: Masood Adeel , Ehsan Hamid , Iqbal Qamar , Amin Saher Nasir , Wilson Melissa 
Published: June 2022

e16231 Background: Pancreatic cancer is the 11th most common cancer and represents 3.2% of all new cancer cases. But it is the third leading cause of cancer-related deaths with a five-year relative survival of only 10.8%. More than 50% of patients diagnosed with metastatic disease at initial presentation have 5-year relative survival of only 3.0%. Here, we explore the recent literature for the emerging role of immunotherapies and their outcomes for advanced pancreatic cancer. Methods: The literature search was conducted on PubMed, Embase, Cochrane, and ClinicalTrials.gov from inception to January 2022 using MeSH terms' pancreatic neoplasms', 'immunotherapy,' and 'therapeutics'. The final analysis includes nine clinical trials that meet the inclusion criteria regarding immunotherapy for metastatic pancreatic cancer. Results: The combination of pembrolizumab and trametinib with stereotactic radiotherapy (SBRT) reported a median progression-free survival (PFS) and overall survival (OS) of 25 and 18 months compared to gemcitabine and SBRT combination of 22 and 16 months, respectively. Another study reported a median OS of 18 months with nivolumab along with operative irreversible electroporation to increase the bioavailability of nivolumab in the cancer cells. The EGFR targeted CAR T cells therapy was evaluated in 14 patients with advanced pancreatic cancer with a median OS of five months and an overall response rate (ORR) of 29%. Sotigalimab, an agonistic CD40 antibody combined with nivolumab, was found to have an ORR of 58%, PFS of 12 months, and OS of 20 months after a follow-up of almost 18 months. On the contrary, Bruton's tyrosine kinase inhibitors such as Acalabrutinib and Ibrutinib were found to have no OS benefit (median OS 3.8 and 5.3 months, respectively). Conclusions: Due to the high mortality associated with advanced pancreatic cancer, there is increasing interest in Novel immunotherapies-based approaches, with some showing promising results.[Table: see text]
Toripalimab combined with nab-paclitaxel/gemcitabine as first-line treatment for advanced pancreatic adenocarcinoma: Updated results of a phase Ib/II clinical study.
Authors: Cheng Ke , Lv Wanrui , Li Xiaofen , Chang Chen , Cao Dan 
Published: June 2022

e16244 Background: Much controversy remains regarding the immune-checkpoint-inhibitor plus Nab-paclitaxel/gemcitabine (AG) as the treatment in advanced pancreatic ductal adenocarcinoma (aPDAC). We assess safety and efficacy of toripalimab plus AG in aPDAC, this was the updated results of the study. Methods: This was a phase Ib/II clinical study of toripalimab plus AG as first-line treatment for aPDAC. Toripalimab (240mg, Q3W), combined with AG (nab-paclitaxel 125 mg/m2, d1, d8 plus gemcitabine 1000 mg/m2, d1, d8) were administrated until the disease progresses/unacceptable toxicity or receiving toripalimab maintenance treatment. The primary endpoints were safety and OS; the secondary endpoints were ORR, DCR and PFS. Predictive biomarkers including gene mutations based on next-generation sequencing and PD-L1 expression were assessed. Results: Until January 2022, 55 chemotherapy-naïve aPDAC evaluable patients (beyond 90% patients with metastatic lesions) to safety and response, ECOG PS≤2 were enrolled. The ORR was 29.1%, the DCR was 90.9%, including 15 patients with PR and 1 patient with CR, 34 patients with SD respectively. 33 patients were alive and 16 patients were still ongoing study. Median PFS was 5.0 months (95% CI: 4.033-5.967), the 6-month PFS rate was 56.4%; median OS was 10.0 months (95% CI: 6.321-13.679), the 1-year OS rate was 69.1%. 2 cases of pseudoprogression were observed. The most frequent treatment related adverse events (TRAE) were anemia (90.1%, G3/4: 9.1%), hypoproteinemia (73%, G3/4: 5.5%), AST elevation (61.0%, G3/4: 3.6%), ALT elevation (60%, G3/4: 5.5%), hypothyroidism (51%, G3/4: 0%), leukocytopenia (45.4%, G3/4: 5.5%), neutropenia (44%, G3/4: 9.1%), nausea (44%, G3/4: 3.6%), rash (38.1%, G3/4: 0%). And 23 patients (41.8%) experienced grade 3/4 TRAE. In the biomarker analysis, all 55 patients were MMR-proficient status; 37 patients were evaluated for PD-L1 expression, PD-L1 positive cases (PD-L1 TPS > 1% and/or CPS > 2, n = 12, 6 patients achieved PR) compared with PD-L1 negative cases (n = 25) presented higher ORR (50% vs 16%). 44 patients were investigated for NGS in 55 evaluable patients, KRAS mutation (86.4%) was the most frequently mutated genes (KRAS G12D = 20 patients, KRAS G12V = 13 patients, KRAS G12R = 4 patients, KRAS G12C = 1 patients), and germline BRCA2 mutation was observed in one patient. The correlation between gene mutation and efficacy and prognosis is under analyzed. Conclusions: The updated results of this phase Ib/II study has met our preset primary endpoint with 69.1% in 1-year OS rate, provided promising evidence that toripalimab in combination with AG has a manageable safety profile and expected antitumor activity. The correlation between biomarkers with clinical efficacy are under investigation. The results supported ongoing combined treatment in aPDAC patients. Clinical trial information: ChiCTR2000032293.
Racial disparities in surgical outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing pancreas surgery.
Authors: Saad Mariam , Gartrelle Kendyll , Shah Rupen A. , Clark Julie , Steffes Christopher P. , Kwon David S. 
Published: June 2022

e16255 Background: Previous studies have suggested disparity in PDAC survival in African American (AA) compared to non-AA patients. Pancreas surgery is associated with significant morbidity, and technical outcomes are known to impact survival; however, there is little reported data on surgical outcomes by race. We sought to evaluate the effect of race on surgical outcomes and survival in an urban tertiary care center for patients with PDAC undergoing pancreas surgery. Methods: A retrospective single-center analysis of PDAC patients undergoing pancreas resection between January 2013 and September 2021 was performed. Patient demographics, Clavien-Dindo (CD) complications, readmission, and mortality in the 30- and 90- day period were collected and stratified by race. Univariate and multivariate analyses were performed. Results: Among 180 patients, 145 (81%) were non-AA and 35 (19%) were AA. Demographic and pre-operative characteristics were found to be similar between the two groups. 30-day ED visits, postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), and intra-abdominal abscess (IAA) were found to be significant on univariate analysis in the AA cohort. On multivariate analysis, 30-day ED visit (OR 4.5; 95% CI 1.3-15.8; p = 0.02), POPF (OR 4.5; 95% CI 1.3-14.8; p = 0.015), and IAA (OR 4.4; 95% CI 1.12-17.3; p = 0.033) were still significantly higher in the AA cohort while DGE lost its significance. Median overall survival and disease-free survival showed no significant difference on Kaplan-Meier curves. There was no statistical difference in local, regional, or metastatic recurrence patterns between the two groups (distant metastasis 36% in non-AA and 37% in AA). Conclusions: AA undergoing pancreas surgery for PDAC were noted to have higher incidence of POPF and IAA as well as ED visits compared to non-AA patients. However, no significant difference was seen in reoperation rates, major CD complications, recurrences, or survival. Exploring tumor biology, and preoperative treatment algorithms may shed additional insight on the differences in surgical outcomes in this patient cohort.[Table: see text]
Do patients with metastatic pancreatic adenocarcinoma to the lung have improved survival?
Authors: Ebrahimi Aren , Shadarevian Melanie , Cham Jason , Hermel David Jacob , Spierling Bagsic Samantha R. , Sigal Darren 
Published: June 2022

e16257 Background: Pancreatic ductal adenocarcinoma (PDAC) is a genetically heterogeneous disease often diagnosed with synchronous metastatic disease involving the liver. Tumors with extra-abdominal spread that bypass the liver are thought to represent a unique molecular subgroup of the disease. Specifically, those with isolated pulmonary metastatic disease are thought to have a more favorable clinical phenotype. We sought to retrospectively investigate whether patients with isolated pulmonary metastases had improved survival compared to those with disease involving the liver. Methods: We conducted a retrospective review of patients with pathologically confirmed PDAC treated between the years 2010 and 2020 at a Scripps Health hospital. The final study sample included only patients with pulmonary and/or liver primary metastases (N = 175). Analyses were conducted on subgroups defined by metastatic sites of disease in the liver only, lung only and combined liver+lung. Primary and secondary outcome analyses compared isolated lung versus liver/liver+lung. Primary endpoint was overall survival (OS), defined as from the date of diagnosis to date of death or most recent follow up. Progression free survival (PFS) was also analyzed as a secondary endpoint and defined as from the date of diagnosis to date of radiographic progression. Each survival outcome was analyzed using Cox Proportional Hazards tests. Results: No statistically significant differences were seen in OS (HR 0.67, CI 0.44–1.03; p= 0.069) or PFS (HR 1.05, CI 0.68–1.65; p= 0.816) between patients with primary lung metastases compared to those with either liver or liver+lung metastases (reported as hazard ratios of liver/liver+lung relative to lung only). However, a trend towards improved OS was seen for patients with isolated lung metastasis and the kaplan-meier curve for OS showed improved survival for these patients at 3 years, with crossing of the survival curves around 5 years from time of diagnosis. Conclusions: There appears to be a unique clinical phenotype in patients with PDAC presenting with isolated pulmonary disease. Though there was not a statistically significant difference in OS and PFS seen in our population, there was a trend towards improved overall survival compared to those with hepatic involvement. These findings highlight a potential prognostic indicator of metastatic PDAC and further subgroup analysis will help characterize clinical variations that may lead to these differences in tumor biology.[Table: see text]
A phase I study of gemcitabine/nab-paclitaxel/S-1 chemotherapy in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma.
Authors: Chang Chen , Li Xiaofen , Cheng Ke , Cai Zhaolun , Xiong Junjie , Lv Wanrui , Li Ruizhen , Zhang Pei , Cao Dan 
Published: June 2022

e16261 Background: Systemic chemotherapy is the primary treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinomas (PDAC). More effective treatment options are highly awaited . The aim of this study was to evaluate the toxicity and feasibility of triweekly gemcitabine/nab-paclitaxel/S-1 (GAS) chemotherapy in patients with locally advanced or metastatic PDAC, determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of S-1 in this regimen, and explore the preliminary efficacy. Methods: Eligible patients with locally advanced or metastatic PDAC received GAS chemotherapy on a 21-day cycle. Fixed-dose of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) were given intravenously on days 1 and 8. Different doses of S-1 were given orally twice daily from day 1 to day 14 within a 3+3 dose escalation design. According to patients` body surface area, the dose-escalation design was as follows: patients with a body surface area of 1.25–1.5 m2 received S-1 40 mg/d initially and the dose was increased to 60 mg or 80 mg. Patients with a body surface area of more than 1.5 m2 received S-1 60 mg/d initially and the dose was increased to 80 mg or 100 mg. The primary endpoints were to evaluate the toxicity and determine the DLT and MTD of S-1. The secondary endpoint was to evaluate efficacy. Results: A total of 21 eligible patients were included. Due to the infrequence of patients with a body surface area of 1.25–1.5 m2, only 2 patients were included in cohort of S-1 40 mg. The dose-escalation for patients in this group failed to be enrolled completely. For patients with a body surface area of more than 1.5 m2, 3 DLTs in 7 patients were detected at cohort of S-1 100 mg (grade 3 thrombocytopenia with hemorrhage, grade 3 rash, and grade 3 mucositis/stomatitis). S-1 80 mg/d (body surface area: > 1.5 m2) was considered to be the MTD in GAS chemotherapy (21-day cycle). No grade 4 adverse events (AEs) or treatment-related deaths were observed. The most common occurring hematologic AE of any grade was anemia (38.1%). The most frequent nonhematologic AEs of any grade were peripheral neuropathy (38.1%), dyspepsia (23.8%), constipation (23.8%), and alopecia (23.8%). After 2 cycles of GAS chemotherapy, the objective response rate was 36.8% and the disease control rate was 94.7%. The median progression-free survival was 5.3 (95% CI, 4.6 to 6.0) months and the median overall survival was 10.3 (95% CI, 8.1 to 12.5) months. Conclusions: GAS chemotherapy (21-day cycle) with nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2, and S-1 80 mg/d (body surface area: > 1.5 m2) was detected with the acceptable toxicity and significant clinical control in patients with locally advanced or metastatic PDAC. It is valuable to conduct further phase II trials. Clinical trial information: ChiCTR1900027833.
Impact of site-specific metastases on survival outcomes in pancreatic adenocarcinoma (PDAC) patients: A national analysis.
Authors: Nikravesh Nima , Gresham Gillian , Anderson Eric , Elmadbouh Omer , Thomassian Shant , Moshayedi Natalie , Davelaar John , Lo Simon , Gaddam Srinivas , Nissen Nicholas , Kosari Kambiz , Gangi Alexandra , Pandol Stephen Jacob , Gong Jun , Hendifar Andrew Eugene , Osipov Arsen 
Published: June 2022

e16270 Background: PDAC is the third most fatal cancer, where most patients present with metastases at diagnosis. Previous studies, including a retrospective analysis from our single-center experience, suggests survival rates are significantly higher for those with lung-only metastases (mets) when compared to liver metastasis or other sites of metastases (liver+other). The objective of this analysis is to explore this difference based on sites and metastasis and the impact of chemotherapy from a national cohort. Methods: We identified PDAC patients (>18years) from with metastases to either 1) lung-only; 2) liver+other sites in the National Cancer Database diagnosed between 2010 and 2015.We analyzed patient characteristics, demographics, type of chemotherapy, and survival outcomes. Kaplan Meir survival curves were generated, and Cox proportional hazard models adjusted for age and sex were fit to evaluate associations between met site and survival. Survival was calculated from time of diagnosis to death and compared across mets site, receipt of chemotherapy, and treatment and type (single versus multi-agent). Results: 15359 PDAC patients were included in the analysis [51.6% male 48.4% female, mean age 69 years] of which 4512 (29.4%) patients had lung only mets and 10847 (70.6%) had liver + other mets. Median survival was 5.72 and 2.37 months for lung only vs. liver+other mets, respectively (log rank p<0.001). From a subset population of 8440 patients who received chemotherapy, median survival of 9.4 and 4.9 months for lung only and liver+other mets was observed, respectively [Table]. Median OS for single agent chemotherapy was 4.4 months (n=2637), with patients with lung only mets having a median OS of 7.1 months and those with liver+other mets having a median OS of 3.6 months. Median OS for patients treated with multi-agent chemotherapy (n=5380) was 7.4 months, with lung only met patients having a median OS of 11.6 months and those with liver+other mets having a median OS of 6.1 months. Hazard ratios (HR) and 95% confidence intervals (CI) are displayed in the table. Conclusions: In a national cohort, patients with metastatic PDAC and lung-only metastasis had improved survival when compared with liver +other metastasis. Further contemporary research is needed to understand the underlying biology that dictates the survival difference between lung metastasis vs other sites of metastatic disease in pancreatic cancer.[Table: see text]
Access to care in patients with pancreatic adenocarcinoma by race/ethnicity in an academic center in the Bronx, NY.
Authors: Brodsky Michael , Wei John X , Castagna Francesco , Jou Erin , Shusterman Michael , Goel Sanjay , Acuna-Villaorduna Ana 
Published: June 2022

e16280 Background: Racial disparities in the overall survival (OS) of patients with pancreatic adenocarcinoma (PDAC) have been previously reported. Large population datasets suggest that Non-Hispanic Blacks (NHB) have decreased OS when compared to non-Hispanic Whites (NHW), and Hispanics. It is unclear whether this is related to biologic features or differences in access to care. This study was aimed to compare time to treatment in a racially-diverse cohort of patients with PDAC in an academic center in the Bronx, NY. Methods: Patients diagnosed with PDAC between 2015 and 2021, available race/ethnicity (NHW, NHB or Hispanic) who received treatment at Montefiore Medical Center were identified. Data including demographics (age, gender, BMI), clinical features (date of diagnosis, presentation [localized/metastatic], tumor location, grade), first-treatment received (surgery or chemotherapy) and outcomes (vital status, date of death) were collected manually. Time to first treatment was compared between racial/ethnic groups using the Kruskal-Wallis test. Results: Of 226 patients diagnosed with PDAC, there were 46 (20.4%), 77 (34.1%) and 103 (45.6%) NHW, NHB and Hispanics respectively. The frequency of metastatic disease was higher in Hispanics and NHB compared to NHW (42.7% vs. 46.7% vs. 22.2%, p = 0.02). Median time to first treatment did not differ significantly among racial/ethnic groups in the overall cohort and stratified by disease presentation. Conclusions: There were no differences in access to care among racial/ethnic groups in this cohort. A higher frequency of metastatic disease at presentation among NHB and Hispanics might be explained by more aggressive biology. Further evaluation of the molecular profile in this cohort is warranted.[Table: see text]
Impact of antibiotics on stage IV pancreatic ductal adenocarcinoma treated with gemcitabine or 5-fluorouracil.
Authors: Fulop Daniel Jeremy , Zylberberg Haley , Wu Linda , Aronson Anne , Labiner Arielle , Cohen Deirdre Jill , Sigel Keith Magnus , Lucas Aimee L. 
Published: June 2022

e16292 Background: Recent studies have suggested a role for the tumor microbiome in conferring chemoresistance to gemcitabine (GEM) in patients with pancreatic ductal adenocarcinoma (PDAC). One proposed resistance mechanism is the presence of bacterial enzymes that metabolize GEM, but not 5-fluorouracil (5-FU). We therefore assessed the impact of antibiotic receipt in the month before and after initiation of either GEM- or 5-FU-based chemotherapy on PDAC overall survival (OS). Methods: We used the SEER-Medicare database to identify adults >66 years old with stage IV PDAC treated with either first-line GEM or 5-FU between 2007-2017. Antibiotic receipt was defined as a claim for >5 days of oral antibiotics or >1 intravenous antibiotic in the month before or after chemotherapy initiation. Demographic and clinical characteristics were compared using chi-squared and student t-tests, and univariable survival was assessed using Kaplan-Meier methods. Propensity scores (PS) were created to account for potential allocation bias in the receipt of antibiotics. We fit PS-adjusted Cox proportional-hazard models to evaluate the association between antibiotic receipt and OS. Results: We identified 3,990 stage IV PDAC patients treated with first-line GEM-based (n = 3,219) or 5-FU-based (n = 771) chemotherapy, of whom 2,318 (58.1%) received antibiotics. In univariable analyses, antibiotic receipt in the month surrounding chemotherapy initiation was associated with improved median OS in patients treated with GEM (214 days vs 199 days, p = 0.04) but not in patients treated with 5-FU (255 days vs 284 days, P = 0.14). In PS-adjusted multivariable analyses, the significant association between antibiotic receipt and improved OS in patients who received GEM remained (HR 0.89, 95% CI 0.83-0.96). However, no significant association between antibiotic receipt and OS was seen in patients treated with 5-FU (1.10, 95% CI 0.94-1.28). Conclusions: Antibiotic receipt in the month before or after chemotherapy initiation was associated with improved OS in stage IV PDAC patients who received GEM but not 5-FU. These findings support the concept that antibiotics may impact the activity of GEM-metabolizing bacteria proposed to confer chemoresistance. Further studies are needed to characterize the potential role for antibiotics in PDAC treatment.[Table: see text]