bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ciprofloxacin plus gemcitabine-based chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma: A pilot study of microbiome manipulation.
Authors: Cheo Seng Wee , Lee Jonathan WJ , Walsh Robert John , Sundar Raghav , Choo Joan RE , Chan Gloria , Yong Wei-Peng , Meah Wee Yang , Khor Chiea Chuen , Chee Cheng Ean 
Published: January 2022

570 Background: Gemcitabine-based chemotherapy is an approved therapy for treatment-naïve metastatic pancreatic ductal adenocarcinoma (PDAC). Inherent resistance to gemcitabine inevitably leads to cancer progression and shorter survival. It has been demonstrated that bacteria are a component of the PDAC tumor microenvironment and may play a critical role in mediating resistance to chemotherapy. Hence, the coadministration of an antibiotic to chemotherapy may potentiate antitumour drug responses. We conducted a pilot study to assess the efficacy and safety of ciprofloxacin plus gemcitabine-based chemotherapy in patients with treatment naïve metastatic PDAC. We also aimed to study gut microbiome changes during treatment with ciprofloxacin. Methods: This was a single arm study conducted at the National University Cancer Institute, Singapore. Patients (pts) with histologically confirmed metastatic PDAC were treated with nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on days 1, 8, and 15 every 4 weeks, in combination with oral ciprofloxacin 500 mg twice daily. Treatment was continued until disease progression or intolerable toxicity. DNA extraction, 16S rRNA amplification and sequencing for bacteria were performed on pre- and post-treatment stool samples. Primary endpoint of this study was response rate and safety of the treatment combination. Secondary endpoints included progression free survival (PFS), overall survival (OS) and microbiome changes after treatment with ciprofloxacin. Results: From Mar 2019 – Feb 2021, 8 pts were recruited. Median age was 71 years old. Best response was stable disease in 5 (62.5%) pts and 3 pts had progressive disease (PD). Median PFS and OS were 4.3 and 15.4 months, respectively. 2 pts developed grade 4 neutropenia and 1 pt had grade 3 febrile neutropenia. Rash was common with 50% of pts developed grade 1/2 rash. No additional toxicities from ciprofloxacin were observed. Preliminary stool analysis showed significant differences in individual bacterial strains across all timepoints in the PD vs. SD groups. There was also an increased abundance in gammaproteobacteria resistant to ciprofloxacin treatment in pts with PD. Conclusions: Gemcitabine-based chemotherapy plus ciprofloxacin demonstrated clinical activity and acceptable safety profile in PDAC. Our study also highlighted that gut microbiome may play a critical role in mediating resistance to chemotherapy. Clinical trial information: NCT04523987.
Can stereotactic ablative radiotherapy for oligometastatic pancreatic cancer help avoid perpetual chemotherapy and improve outcomes?
Authors: Elamir Ahmed , Karalis John D , Sanford Nina Niu , Polanco Patricio , Porembka Matthew R. , Timmerman Robert D. , Ligorio Matteo , Beg Muhammad Shaalan , Aguilera Todd Anthony 
Published: January 2022

571 Background: The oligometastatic state is increasing recognized and improved outcomes after local regional therapies have been observed in many malignancies, however there is a paucity of data on outcomes of patients with limited extent pancreatic ductal adenocarcinoma (PDAC). We hypothesize oligometastatic pancreatic cancer (OPanc) with 1-5 metastases would benefit from stereotactic ablative radiotherapy (SABR) to all active sites of disease, can improve outcome, and offer time off chemotherapy. Here in, we report our institutional experience of treating OPanc with SABR to evaluate the outcome and feasibility of the approach and compare outcomes with other institutional cohorts. Methods: A retrospective review was conducted on patients with stage IV PDAC who received SABR after noted to have OPanc. Patients with a histological diagnosis of PDAC, number of metastases ranging between 1-5, and who received SABR to all active disease at time of treatment were included. We identified a comparable group of 16 patients with similar metastatic burden but did not receive SABR. Overall survival and time off chemotherapy were evaluated in addition to assessment of each patients’ disease course. Results: Fourteen patients met the inclusion criteria. Five patients had metastases confined to lung only and nine to the liver only. Median baseline CA 19-9 was 105 U/mL (range < 1, 921 U/mL). Eight patients had metachronous OPanc diagnosis. SABR was delivered to 22 metastatic tumors. Median progression free and overall survivals were 25 and 12.8 months, and 46 and 14.5 months for the SABR treated and the chemotherapy cohorts respectively. A total of 85.7% of patients that received SABR had a chemotherapy treatment break of greater than 6 months. Conclusions: Management of OPanc (1-5 lesions) with SABR as local regional therapy could improve outcomes in this selected population and warrants prospective evaluation.
Integrative analysis of KRAS-wildtype pancreatic ductal adenocarcinoma reveals unique similarities to extrahepatic cholangiocarcinoma.
Authors: Tsang Erica S , Topham James T. , Karasinska Joanna , Kalloger Steve , Csizmok Veronika , Williamson Laura , Wong Hui-Li , O'Kane Grainne M. , Loree Jonathan M. , Notta Faiyaz , Bathe Oliver F. , Tang Patricia A. , Goodwin Rachel Anne , Knox Jennifer J. , Gallinger Steven , Laskin Janessa J. , Marra Marco A. , Jones Steven J. M. , Schaeffer David F. , Renouf Daniel John 
Published: January 2022

587 Background: Oncogenic driver mutations in KRAS represent a hallmark genomic event in approximately 90% of pancreatic adenocarcinoma (PDAC). For the remaining 10% of patients with KRAS wildtype (wt) PDAC, distinct driver mutations have been described, but their transcriptional landscape has not been reported. Here, we leverage sequencing data from the PanGen trial to provide a comprehensive characterization of advanced KRASwt PDAC. Methods: 63 patients with advanced PDAC received whole genome and transcriptome sequencing prior to treatment for metastatic disease as part of the PanGen trial (NCT02869802). Clinical features, somatic mutation data and gene expression patterns were compared between KRASwt and mutant groups. PDAC samples were contrasted with 77 other metastatic carcinoma (colorectal and cholangiocarcinoma) samples from the Personalized OncoGenomics trial (NCT0215562). KRAS wt-associated genes were further investigated using 3 additional PDAC cohorts (COMPASS NCT02750657, TCGA, and ICGC). Results: 9 of 63 (14%) samples were KRASwt, with an earlier median age at diagnosis (51.4 vs. 60.9 years; p=0.03). Clinical features, including diabetes, family history of malignancy, and location of primary tumor, were comparable. CA 19-9 at baseline was lower in the KRASwt group, with median 58 vs. 4900 U/mL in the KRAS-mutant group ( p=0.03). Patients with KRASwt PDAC showed increased overall survival in univariable ( p=0.0024) and multivariable ( p=0.0089) analyses. 6 of 9 (67%) KRASwt tumors had fusions involving NRG1 (n = 3), FGFR2 (n = 1), BRAF (n = 1) or NTRK2 (n = 1), while known actionable fusions were not observed in KRAS mutant patients. KRASwt tumors showed increased expression of genes associated with cholangiocytes and grouped with cholangiocarcinoma samples in unsupervised clustering analysis. Validation using three independent PDAC cohorts revealed a core set of 70 KRAS wt-associated genes that converge on keratinization, ion transport, and hormone metabolism pathways. Conclusions: Patients with KRASwt PDAC show potentially targetable molecular traits with actionable fusions. We also highlight novel mutation and expression-based similarities between KRASwt PDAC and cholangiocarcinoma samples. Recurrent dysregulation of genes involved in cellular structure and metastasis provide impetus for further investigation into the developmental trajectory and potential therapeutic vulnerabilities of KRASwt PDAC.
Prognostic utility of preoperative and postoperative circulating tumor DNA (ctDNA) in resected pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.
Authors: Alqahtani Ali , Alloghbi Abdurahman , Yin Chao , Mukherji Reetu , Weinberg Benjamin Adam 
Published: January 2022

595 Background: Surgical resection offers the only chance of cure for localized pancreatic ductal adenocarcinoma (PDAC). Despite surgical resection, 80% of patients experience disease recurrence. There is growing evidence that support the prognostic role of perioperative KRAS-mutated circulating tumor DNA (ctDNA). We conducted a systematic review and meta-analysis to investigate the prognostic utility of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search of PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was performed in September 2021. We included studies that reported on the effects of preoperative and postoperative KRAS-mutated ctDNA on overall survival (OS) and/or relapse free survival (RFS) in resected PDAC. The random-effects model was used to calculate pooled OS and RFS hazard ratios (HRs) and 95% confidence intervals (CIs). Publication bias was assessed by visual inspection of a funnel plot of the included studies. Results: We identified 6,986 studies, and 13 studies were eligible for analysis. A total of 954 patients were included for the final evaluation. In the preoperative setting, positive ctDNA correlated with worse RFS in 8 studies (HR, 2.067; 95% CI, 1.346-3.174; P < 0.001) and worse OS in 10 studies (HR, 2.170; 95% CI, 1.451-3.245; P < 0.001) compared to negative ctDNA. In the postoperative setting, positive ctDNA correlated with worse RFS across 7 studies (HR, 2.986; 95% CI, 1.897-4.699; P <.001), and worse OS in 5 studies (HR, 5.812; 95% CI, 1.757-19.228; P = 0.004) compared to negative ctDNA. There was visible symmetry in the funnel plot of the studies included, suggesting no publication bias. Conclusions: In resected PDAC, preoperative and postoperative KRAS-mutated ctDNA positivity may be useful markers of poor prognosis in terms of RFS and OS. Clinically, KRAS-mutated ctDNA testing may also have implications when considering the aggressiveness and duration of adjuvant therapy in PDAC, although prospective trials are needed to assess this utility.
Plasma metabolomics to predict chemotherapy (CTX) response in advanced pancreatic cancer (PC) patients (pts) on enteral feeding for cachexia.
Authors: Muranaka Hayato , Moshayedi Natalie , Hendifar Andrew Eugene , Osipov Arsen , Placencio-Hickok Veronica , Stotland Aleksandr , Parker Sarah , Van Eyk Jennifer , Bhowmick Neil , Gong Jun 
Published: January 2022

600 Background: We evaluated the potential of plasma metabolites as predictors of response to CTX in a prospective cohort of pts who received enteral feeding for cachexia and advanced PC. Methods: The PANCAX-1 (NCT02400398) prospective trial enrolled 31 cachectic advanced PC pts to receive jejunal tube peptide-based diet for 12 weeks (wks) who were planned for palliative CTX. Out of 16 evaluable pts, 62.5% receiving enteral feeding met the primary endpoint of weight stability at 12 wks. As part of an exploratory analysis of the PANCAX-1 trial, serial blood samples were collected at 3 predefined timepoints over 12 wks of enteral feeding. Up to 219 plasma metabolites were analyzed by mass spectrometry and high-performance liquid chromatography. Analytes were compared by relative area under the curve (AUC) and differences evaluated by two-sample t-tests. The mean AUC was used in pts with metabolites measured from > 1 timepoint of collection. Pts were stratified by stable disease (SD), partial response (PR), or progressive disease (PD) as best overall response to standard CTX. Results: Of 31 pts with advanced PC prospectively enrolled for enteral feeding, there were 55 blood samples collected from 28 pts available for plasma metabolomics. 20/28 (71%) pts received first-line CTX, the majority of whom (90%) received gemcitabine-based CTX. There were 2 PRs (7%) and 10 with SD (36%) as best response to CTX. Overall, there were statistically significant differences in levels of intermediates involved in multiple metabolic pathways including glycolysis, the tricarboxylic acid (TCA) cycle, fatty acid synthesis, and nucleoside synthesis in pts with PR/SD vs. PD to CTX (all p < 0.05). When stratified by CTX regimen, PD to 5-fluorouracil-based CTX (e.g., FOLFIRINOX) was associated with decreased levels of essential amino acids (AAs, L-leucine, L-methionine, L-tryptophan) and non-essential AAs (L-arginine, L-serine, L-tyrosine, all p < 0.05). For gemcitabine-based CTX (e.g., gemcitabine/nab-paclitaxel), PD was associated with increased levels of intermediates of glycolysis (pyruvate), TCA cycle (L-glutamate), nucleoside synthesis (xanthine), and bile acid metabolism (taurocholic acid, all p < 0.05). Conclusions: We are the first to demonstrate the feasibility of plasma metabolomics in a prospective cohort of advanced PC pts on enteral feeding as their primary source of nutrition. Metabolic signatures unique to FOLFIRINOX or gemcitabine/nab-paclitaxel may be predictive of response and warrant further study.
Improved survival in patients with lung only recurrence after surgical resection of pancreatic ductal adenocarcinoma.
Authors: May Michael S. , Michel Alissa , Lee Tristan , Wong Winston , Jamison Jacob K.R. , Manrique David , Pan Samuel M , Hu Jianhua , Safyan Rachael A , Raufi Alexander , Kluger Michael , Bates Susan Elaine , Chabot John A. , Manji Gulam Abbas 
Published: January 2022

608 Background: Recurrence rates after resection of pancreatic ductal adenocarcinoma (PDA) can be up to 80%. Prior data suggests that initial site of recurrence influences prognosis. This study aims to compare survival of patients (pts) with resected PDA by initial site of recurrence. Methods: We retrospectively reviewed the demographics, treatments, recurrence and survival of 717 pts with PDA who underwent resection at Columbia University Irving Medical Center from 2011 to 2020 and were part of a tumor registry. Analyses were performed using Kaplan-Meier and paired T-tests. Results: Of 717 pts with resected PDA, 320 had confirmed recurrence. Median age at diagnosis was 67 years (yrs). Among pts with a single initial recurrence site, 36 recurred in lung, 97 in liver, 95 locally, and 23 in peritoneum. 58 pts had initial recurrence at 2 or more sites. Neoadjuvant treatment had been administered in 42%, 36%, 40%, 35%, and 22% of pts with lung, liver, local, peritoneal, and multiple sites at initial recurrence, respectively (p=0.21). Adjuvant treatment had been administered in 72%, 69%, 76%, 70%, and 72% of pts with lung, liver, local, peritoneal, and multiple sites at initial recurrence, respectively (p=0.88). Pts with initial lung recurrence had a significantly longer median overall survival (mOS), 4.39 yrs, compared to initial recurrence in the liver (1.98 yrs, p=0.02), peritoneum (2.19 yrs, p=0.0002), and at multiple sites (2.66 yrs, p=0.03). A significantly longer time from diagnosis to recurrence was observed in pts who had initial lung recurrence, compared to pts who had initial hepatic, peritoneal or multiple site recurrences. Pts with initial lung recurrence had a significantly longer time from first recurrence to death compared to pts with initial peritoneal recurrence. See Table for summary. Conclusions: Pts with resected PDA with initial pulmonary recurrence experience improved survival compared to those who recur at other distinct or multiple sites. The underlying pathways contributing to this improved survival need to be investigated further.[Table: see text]
Rural-urban disparities in mortality from gastrointestinal (GI) cancer.
Authors: Hussaini Syed , Blackford Amanda L. , Gupta Arjun 
Published: January 2022

644 Background: There are notable economic, social, and political challenges to rural healthcare delivery in the US. Patients with GI cancer have high symptom burden and complex needs, challenging healthcare infrastructure. We investigated U.S. rural-urban disparities in age-adjusted mortality rates (AAMRs) from GI cancers. Methods: We utilized the CDC Wonder database to analyze deaths from GI cancer from 1999 to 2019. Per the 2013 US Census classification, we created population categories using the NCHS Urban-Rural Classification Scheme: large metropolitan (population, ≥1 million), small-or-medium-sized metropolitan (50,000-999 999), and rural (<50,000) areas. We calculated AAMRs and stratified results by age, sex, and race/ethnicity. We estimated annual percentage change (APC) in AAMR using a linear regression model of the log-scale with interactions between subgroup and year to examine differential changes over time. Results: We identified 3,020,133 deaths from GI cancers. The overall APC in AAMR was -0.9%, 95%CI, -0.8 to -1.0%. Rural areas noted least improvement in AAMR (APC, -0.6%; 95% CI, -0.4 to -0.6%, interaction p < 0.001) compared to large (APC, -1.2%; 95% CI, -1.1 to -1.3%) and small-or-medium-sized (APC, -0.8%; 95% CI - 0.7 to -0.9%) metropolitans. AAMR in rural areas decreased from 49.2/100,000 in 1999 to 43.8/100,000 in 2019 (p < 0.001; 2019 rural AAMR was highest across all areas) (Table). Across all areas, men had greater AAMRs (p<0.001) and lower reduction in APC (interaction p < 0.001) than women. Non-Hispanic Black individuals (NHBs) had highest AAMRs among all racial/ethnic groups and across all areas (p<0.001). Among those with age≥65 years, NHBs had the highest AAMRs; 367.3/100,000 in 1999 and 266.7/100,000 in 2019, and NHBs living in rural areas had the lowest APC. All racial/ethnic groups saw reductions in AAMRs across all areas. Conclusions: In this national analysis over 2 decades, rural residents with GI cancer experienced greater mortality, and the least improvement in mortality over time. Our findings support ongoing congressional policy to urgently develop infrastructure and improve cancer care access in rural areas. [Table: see text]
Preferences and attitudes of cardiologists in the management of cancer patients.
Authors: Azar Ibrahim , Wang Stephani , Kenitz Jacqueline , Lombardo Dawn , Deaño Roderick , Shields Anthony Frank , Mahmood Syed S. , Philip Philip Agop , Al Hallak Mohammed Najeeb , Schulman-Marcus Joshua 
Published: January 2022

651 Background: With recent improvements in survival of cancer patients and emphasis on high-value care at end-of-life, the management of cardiovascular disease in patients with cancer is increasingly important. To our knowledge, there is no current US data examining how the presence and extent of cancer influence cardiologists’ decision-making for common cardiovascular conditions. Methods: An anonymous online vignette-based survey of cardiologists was conducted at five US institutions investigating how the extent of gastrointestinal and thoracic malignancies (prior/localized, metastatic) would influence treatment recommendation for atrial fibrillation (AF), aortic stenosis (AS), unstable angina (UA) and obstructive coronary artery disease (CAD). Results: Thirty-three percent (86/259) of cardiologists completed the survey between September and November 2019. Participants were 67% male, 51% below age 40, and 58% had five or more years of clinical experience. Majority of cardiologists practiced at teaching hospitals (72%) and were non-interventional (63%). Cardiologists were more likely to recommend procedural interventions in patients with localized cancer than with metastatic disease: AF (LAAO: 20% vs 8%), AS (AVR: 83% vs 11%), UA (LHC: 70% vs 27%) and obstructive CAD (PCI: 81% vs 38%) (Table). In patients with metastatic cancer, most cardiologists sought an oncology (82%) or a palliative care (69%) consult. Conclusions: Cardiologists were less likely to recommend invasive cardiovascular therapies to patients with metastatic cancer. This preference pattern likely reflects the influence of comorbidities and quality of life expectation on cardiologists’ treatment recommendations but may also be related to the stigma of advanced cancer. Better communication between cardiologists and oncologists is necessary to a personalized care of patients with cancer and cardiovascular disease that would maximize treatment benefit with least morbidity.[Table: see text]
Prognostic significance of exosomal programmed death-ligand 1 in advanced gastric cancer patients treated with first-line chemotherapy.
Authors: Shin Kabsoo , Kim Joori , Park Juyeon , Kim Ok Ran , Kang Nahyeon , Kim In-Ho 
Published: January 2022

Retraction The abstract by Shin et al entitled, “Prognostic significance of exosomal programmed death-ligand 1 in advanced gastric cancer patients treated with first-line chemotherapy,” ( Journal of Clinical Oncology 40, no. 4, suppl 665) published on February 1, 2022, has been retracted due to statistical errors that significantly changed the results and conclusion of the abstract. This abstract was retracted on November 4, 2022. 665 Background: Recent studies have found that exosomal PD-L1 could be associated with prognosis in several malignancies by its potential immunosuppressive role. Prognostic role of exosomal PD-L1 in advanced gastric cancer patients treated with systemic chemotherapy has not been well explored. The aim of the present study was to explore prognostic and predictive significance of exosomal PD-L1 in advanced gastric cancer patients. Methods: We prospectively collected plasma samples of patients with advanced gastric cancer receiving first-line chemotherapy at pre and post treatment. Combined ultracentrifugation with polymer-based precipitation was applied to isolate exosome and enzyme-linked immunosorbent assay(ELISA) was applied to measure exosomal PD-L1. The correlation between exosomal PD-L1 and circulating immune cells in the plasma was evaluated. Patients were divided into two groups according to pretreatment exosomal PD-L1 level. Survival analysis was performed using Kaplan-Meier method and multivariate analyses based on Cox-proportional hazards regression model. Results: A total of 99 patients were enrolled in the study, and serum samples collected at pre-treatment and post-treatment were pooled. Median value of the pre-treatment exosomal PD-L1 was 0.42 pg/ml (range 0.01 ̃3.75). Patients with pre-treatment exoPD-L1 < 0.42 pg/mL (exoPD-L1low) showed significantly better overall survival than those with exoPD-L1 ≥ 0.42 pg/mL(exoPD-L1high) (p = 0.033). Progression-free survival was not different between the groups (p = 0.754). exoPD-L1lowgroup showed significantly higher percentages of CD8+T cells than exoPD-L1high group. (p = 0.024). In multivariate analysis, pretreatment exosomal PD-L1, poorly differentiated tumors and No. of metastatic sites(≥2) were independent prognostic factors for overall survival. Conclusions: In summary, the level of pre-treatment exosomal PD-L1 could be used as a prognostic marker for patients with advanced gastric cancer receiving systemic chemotherapy.