tbuckley/cabot-search huggingface dataset:
Meta-analysis of chemoradiation therapy in locally advanced pancreatic cancer.
Authors: Amit Mahipal, William J. Fulp, Chenwi Ambe
Journal: Journal of Clinical Oncology (2014)

e15241 Background: Pancreatic cancer is the fourth most common cause of cancer deaths in the US. Despite the fact that the radiotherapy in addition to chemotherapy (CT) is frequently employed, the role of chemoradiation (CRT) therapy in the treatment of locally advanced pancreatic cancer (LAPC) remains controversial. The majority of the data evaluating the efficacy of this approach is primarily derived from small randomized trials. Methods: We conducted a systemic review and metanalysis to assess the effect of radiation treatment in addition to CT in patients with LAPC. Only randomized controlled trials that compared CRT to CT and reported time to event summary were included in this study. Primary outcome was overall survival (OS). Using previously published methods, we calculated the time to event (OS) for each study summarized by the log hazard ratio (HR) and its variance. Comprehensive Meta Analysis Version 2.2 was used for the analysis. Due to significant heterogeneity, random effects models statistics were used. Also sensitivity analysis was conducted by comparing the five random effects models, each obtained by removing a single study. Results: Five eligible studies were included with a total of 593 patients (CT, N=298; CRT, N=295). Three of the studies favored CRT over chemotherapy alone and two studies did not demonstrate any difference between the two arms (Table 1). Funnel plot analysis did not demonstrate publication bias. Overall there was a trend towards a survival benefit with the addition of radiation to CT (HR: 0.848, CI: 0.708-1.014, p = 0.071). No significant differences in overall results were seen with sensitivity analysis. Conclusions: The addition of radiation therapy to chemotherapy in the treatment of LAPC was not associated with significant survival advantage. Larger randomized controlled trials are needed to further clarify the role of radiation in this setting. Summary of the clinical trials included in the metanalysis Study N (CT) N (CRT) HR CI Klassen et al (1985) 44 47 1.25 0.83-1.88 GISTG (1988) 21 22 0.40 0.23-0.70 Chauffert et al (2008) 60 59 0.54 0.31-0.96 Loehrer et al (2011) 37 34 0.63 0.39-1.02 LPA-07 (2013) 136 133 1.03 0.79-1.34
Contraceptive recommendations for young women during cancer treatment: Examining contraceptive knowledge of pediatric oncology clinicians.
Authors: Sloane L. York, Yasmin Gosiengfiao, Barbara Lockart, Sara Barnato Giordano, Kristin Smith, Jessica Kiley
Journal: Journal of Clinical Oncology (2014)

10089 Background: Adolescent and young adult women with cancer have specific reproductive health needs and may seek guidance from oncology clinicians. This study examined oncology clinicians’ reported contraceptive recommendations and contraceptive knowledge. Methods: Oncology clinicians caring for women aged 13-45 completed an online survey. This secondary analysis reports on pediatric clinicians’ contraceptive knowledge by identifying typical failure rates of 10 contraceptives and safety of 4 hormonal contraceptives using case scenarios. Knowledge score was determined by averaging the percent correct on safety and efficacy questions. Results: 518 respondents were included. Most were practicing pediatric oncologists (52.3%) or advanced practice clinicians (42.5%). Participants practiced a mean of 12.5 years and most (64.1%) saw 3-10 reproductive-aged female patients per month. Most (82.0%) reported regularly recommending a woman use contraception during treatment. Over half (53.2%) stated they were comfortable with contraceptive counseling, 69.9% provided contraception in the past year, and 67.1% wanted more information on contraception. Almost half (47.3%) stated they do not discuss pregnancy planning and 233 (45.0%) had cared for at least one pregnant cancer patient. Total knowledge score was 47.4% (95% CI: 45.8, 49.0). Participants identified 61.9% of contraceptives’ safety (95% CI: 60.0, 64.2). 87.1% identified combined oral contraceptives as unsafe after pulmonary embolism. For a nulliparous woman with AML, 30.4% correctly identified the safety of the levonorgestrel intrauterine device (IUD) and 28.9% for the copper IUD. Participants identified 32.6% (95% CI: 31.0, 34.2) of 10 contraceptives’ efficacy. 19.4% correctly identified condoms’ efficacy, 12% for oral contraceptive pills, and 34.8% for depot-medroxyprogesterone acetate. Almost half correctly identified the failure rate of IUDs (46.1%). Most over-estimated the effectiveness of contraceptives. Conclusions: Pediatric oncology clinicians report recommending contraception during cancer treatment, but may lack comprehensive knowledge for counseling their patients.
Phase II study of fosaprepitant plus 5HT3 receptor antagonists plus dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: Hoosier Oncology Group QL12-153.
Authors: Costantine Albany, Nasser H. Hanna, Joel Picus, Ralph J. Hauke, Christopher A. Fausel, Ziyue Liu, Mary J. Brames, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2014)

TPS4594 Background: Germ cell tumors (GCT) account for 1% of malignancies of American males. Cisplatin combination chemotherapy is the cornerstone for curative therapy in metastatic GCT. Cisplatin is administered for 5 consecutive days, and it is appropriately categorized as highly emetogenic chemotherapy (HEC). Clinical and basic research over the past 25 years has led to steady improvements in the control of chemotherapy-induced nausea and vomiting (CINV). All of the guidelines (ASCO, MASCC and NCCN) unanimously suggest a combination of a 5-HT3RA, dexamethasone, and aprepitant for the prevention of acute and delayed CINV with single day HEC. However, there is paucity of studies and no clear guidelines evaluating multiday cisplatin-induced nausea and vomiting compared to single day cisplatin. We have published a randomized double-blind phase III trial testing whether the addition of aprepitant to standard 5HT3RA plus dexamethasone would provide additional protection in this patient population. Aprepitant was given for 5 consecutive days, starting on day 3 of chemotherapy; aprepitant 125mg PO (or matched placebo) was given on day 3, then 80mg PO on days 4-7. The complete response rate (CR) was 42% in the aprepitant arm vs. 13% in the placebo arm (p<0.0001), 80% of patients experienced no emetic episodes on days 1-5 on the aprepitant arm vs. just 52% on the placebo arm (p<0.0001).(J Clin Oncol. 2012 Nov 10;30(32):3998-4003. doi: 10.1200/JCO.2011.39.5558.) Methods: The current study is a single arm phase II study to evaluate the efficacy of combining fosaprepitant with a 5HT3RA + dexamethasone. This is the first clinical trial evaluating fosaprepitant in patients receiving multiday cisplatin. The primary objective is the Complete Response (CR) rate (no emetic episodes or use of rescue medications). Secondary objectives are the incidence of vomiting or retching via patient log and the patient’s self-reported assessment of nausea Days 1-8 using a 0-100mm visual analog scale (VAS). Clinical trial information: NCT01736917.
Effect of metformin and 5-fluorouracil on nucleolin expression and microRNAs in hepatic cancer cell lines.
Authors: Ahmad Raafat Bassiouny, Amira Zaky
Journal: Journal of Clinical Oncology (2014)

e22163 Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies and has an increasing incidence in Egypt. The identification of new effective therapies for HCC is urgently needed. To date, efforts to modulate the altered expression of miRNA levels for therapeutic purposes have been challenging to implement in HCC. Methods: The aim of the present study was to evaluate the impacts of a long-term exposure on HepG2, and Huh7 HCC cells to clinically relevant concentrations of metformin (6–30 μM) and 5-fluorouracil (5-FU), on the level of nucleolin, a eukaryotic nucleolar phosphoprotein, and to study miR-21, miR-221, and miR-222 expressions causally involved in HCC progression, and drug resistance. Results: Culturing HepG2, and Huh7 cells with 30 µM metformin decreased the survival to 69.2% and 75.6% respectively. Metformin increased the chemosensitivity of cancer cells in vitro, and significantly enhanced the 5-FU-induced growth inhibition of HepG2, and Huh7 cells. Both metformin and 5-FU treatment leads to suppression of nucleolin and marked inhibition of miR-21, miR-221, and miR-222 expression. Metformin suppressed cell growth and induced apoptosis in a dose dependent manner of HepG2, and Huh7 cells in vitro. Flow cytometric analysis showed that metformin treatment was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Conclusions: Our preclinical investigation underscores the complexity of nucleolin’s actions on microRNAs.Metformin kills cancer cells and eradicates cancer stem cells, possibly by inhibiting nucleolin expression through the alteration of microRNAs.
Serocorrelates of protection against infant group B streptococcus disease
Authors: Kirsty Le Doare, Beate Kampmann, Johan Vekemans, Paul T Heath, David Goldblatt, Moon H Nahm, Carol Baker, Morven S Edwards, Gaurav Kwatra, Nick Andrews, Shabir A Madhi, Ajoke Sobanjo ter Meulen, Annaliesa S Anderson, Bart Corsaro, Per Fischer, Andrew Gorringe
Journal: The Lancet Infectious Diseases (2019)
A Phase I Study of Molibresib (GSK525762), a Selective Bromodomain (BRD) and Extra Terminal Protein (BET) Inhibitor: Results from Part 1 of a Phase I/II Open Label Single Agent Study in Subjects with Non-Hodgkin's Lymphoma (NHL)
Authors: Michael Dickinson, Manali Kamdar, Brian J.P Huntly, Carlos Fernández De Larrea, Raul Cordoba, Maria-Victoria Mateos, Adrián Alegre, Won-Seog Kim, Jin Seok Kim, Mark Dawson, Paul Sung-Hao Yeh, Faisal Basheer, Paolo Gallipoli, Aristeidis Chaidos, Alejandro Martín, Thierry Horner, James Winnberg, Lijoy K Mathew, Jeffrey Botbyl, Natalie Karpinich, Brandon E. Kremer, Arindam Dhar, Anastasios Karadimitris
Journal: Blood (2018)
A pharmacist-led medication assessment to identify prevalence and associations with potentially inappropriate medications (PIMs) in ambulatory senior adults with cancer.
Authors: Ginah Nightingale, Emily Hajjar, Kristine Swartz, Jocelyn Andrel-Sendecki, Andrew E. Chapman
Journal: Journal of Clinical Oncology (2014)

e20516 Background: PIM use in seniors is a public health problem linked to billions in health expenditures; cancer-related therapies further escalate its prevalence and complexity. Existing studies are limited by antiquated criteria and inherent pitfalls of patient self-report/chart extraction (versus a pharmacist-led assessment). Objectives: 1) Identify prevalence and associations with PIM use; 2) Determine the most inclusive PIM criteria. Methods: This retrospective study involved 248 patients (aged ≥ 60 years) referred for a geriatric-oncology assessment in January 2011 through June 2013 (data from physician/pharmacist electronic notes). Patients brought medications (prescription, non-prescription, herbals) for the pharmacist-led assessment. PIM use was determined by 2012 Beers, the Screening tool of older persons' potentially inappropriate prescriptions (STOPP) and the Healthcare and data information set (HEDIS) criteria. Results: Mean age was 79.9 years [range 61-98]; 64% women, 74% Caucasian, 87% solid tumor, mean comorbidities, 7.69); only 234 patients (evaluated by pharmacists) were included in the final analysis. PIM prevalence was 51% (n = 119). Beers, STOPP and HEDIS classified 173 PIMs equivalent to 8% of total medications (n = 2163). Mean PIM use was 0.74 (SD 0.89), range [(0-4)]. The proportion of PIMs used (0, 1, 2, 3, 4) was 49%, 34%, 12%, 4% and 1%, respectively. Significant associations with PIM use (versus no-PIM) were polypharmacy (P < 0.001) and increased comorbidities (P = 0.005), specifically cardiovascular (P = 0.014), gastrointestinal (P = 0.013), neurologic (P = 0.020), and psychiatric (P < 0.001) conditions. BEERs and STOPP were most inclusive capturing 120 (69%) and 119 (69%) PIMs versus 58 (34%) with HEDIS. 67 (39%) PIMs were jointly identified by Beers and STOPP. Conclusions: A pharmacist-led medication assessment identified a high prevalence of PIM use associated with polypharmacy and increased comorbidities. A modified PIM tool that integrates Beers and STOPP and considers cancer diagnosis, prognosis and cancer-related therapy is needed to identify and prevent PIM use in this vulnerable population.
Prognostic value of routinely determined tumor infiltrating lymphocytes in triple-negative breast cancer.
Authors: Jana Pahole Golicnik, Barbara Gazic, Tanja Ovcaricek, Erika Matos, Simona Borstnar
Journal: Journal of Clinical Oncology (2014)

1125 Background: Tumor infiltrating lymphocytes (TIL) was suggested to influence disease outcome in triple negative breast cancer (TNBC). Our hypothesis was that TIL determined by routine histopathological examination (RHE) is a prognostic and predictive factor in TNBC. Methods: Clinical and pathological data from 267 consecutively diagnosed and treated patients (pts) with TNBC from the year 2000 to 2006 was retrospectively collected. On RHE, lymphocytic infiltration was evaluated morphologically on H and E slides. Lymphocytic infiltration of the stroma surrounding the tumor or the tumor nests inside the tumor mass was scored as mild, moderate or intensive. The prognostic and predictive impact of TIL was calculated using Cox model. Results: The median age of pts was 56 years, 38.6% being premenopausal, 57.3% had tumors >2cm, 80.5% grade 3, 46.1% nodal involvement, and in 23.2% of pts lymphovascular invasion (LVI) was present. TIL was determined in 240 tumors; in 187 (78%) mild or moderate and in 53 (22%) intensive TIL was described. In the whole group of pts 79.8% received chemotherapy, among them 56.5% anthracycline based (A) only, 14.5% A and taxane (AT), 23.8% cyclophosphamide-methotrexate-fluorouracil (CMF) and 5.1 % other schemes. At a median follow-up of 10 years 93 pts progressed. Ten-year disease free survival (DFS) of pts with intensive TIL was 80.8 %, comparing with 60.5% in other pts (p=0.02). The differences in 10-year DFS for pts with intensive TIL was almost significantly better when treated with A (intensive TIL vs other 82.4% vs 62.7%, p=0.06), however this difference was not significant in the CMF group (85.7% vs 66.5%, p=0.16) while the opposite was noted in the AT group (62.5% and 68.8%, p= 0.69). Conclusions: In pts with TNBC intensive TIL determined on RHE predicts better disease outcome. In addition, pts with intensive TIL may benefit more from adjuvant A compared with AT. Estimated DFS hazard ratios, 95% CI and p-values for the Cox multivariate model. Variable HR (95%CI) p TIL (intensive vs other) 0.45 (0.22-0.93) 0.03 Grade (1+2 vs 3) 0.88 (0.67-1.15) 0.34 Size (>20 mm vs <20 mm) 1.63 (0.98-2.72) 0.06 Lymph nodes (positive vs negative) 2.39 (1.45-3.92) <0.01 LVI (yes vs no) 1.17 (0.70-1.96) 0.54
Comparison of different cationic polymers efficacy in fabrication of alginate multilayer microcapsules
Authors: Fariba Hajifathaliha, Arash Mahboubi, Leila Nematollahi, Elham Mohit, Noushin Bolourchian
Journal: Asian Journal of Pharmaceutical Sciences (2018)

In past decades, alginate-based multilayer microcapsules have been given important attention in various pharmaceutical investigations. Alginate-poly l lysine-alginate (APA) is studied the most. Due to the similarity between the structure of polyethyleneimine (PEI) and poly-L-lysine (PLL) and also lower price of PEI than PLL, this study was conducted to compare the efficacy of linear (LPEI) and branch (BPEI) forms of PEI with PLL as covering layers in fabrication of microcapsules. The microcapsules were fabricated using electrostatic bead generator and their shape/size, surface roughness, mechanical strength, and interlayer interactions were also investigated using optical microscopy, AFM, explosion test and FTIR, respectively. Furthermore, cytotoxicity was evaluated by comparing the two anionic final covering layers alginate (Alg) and sodium cellulose sulphate (NCS) using MTT test. BPEI was excluded from the rest of the study due to its less capacity to strengthen the microcapsules and also the aggregation of the resultant alginate-BPEI-alginate microcapsules, while LPEI showed properties similar to PLL. MTT test also showed that NCS has no superiority over Alg as final covering layer. Therefore, it is concluded that, LPEI could be considered as a more cost effective alternative to PLL and a promising subject for future studies.
Relationships between head and neck cancer patients and their caregivers: Focus on psychological distress and quality of life.
Authors: Gianmauro Numico, Mario Airoldi, Massimiliano Garzaro, Claudia Bartoli, Luca Raimondo, Antonella Varetto, Paolo Leombruni, Riccardo Torta, Giancarlo Pecorari
Journal: Journal of Clinical Oncology (2014)

e20571 Background: Family caregiver’s (Cg) distress and its relationship with patient’s (Pt) psychological asset is a hot topic. CG of HNSCC Pts is still un-investigated. Aim of this cross-sectional study was to evaluate mutual influence between HNC Pt and CG in term of quality of life (QoL) and psychological well-being and differences depending on type treatment. Methods: Sixty couples Pt-CG were enrolled and divided in 3 groups basing on type of treatment: Group A = ipopharyngeal cancer Pts surgically treated (N=20); Group B = oropharyngeal cancer Pts surgically treated (N=20); Group C = oropharyngeal and ipopharyngeal cancer Pts treated with radio-chemotherapy (N=20). Pt’s inclusion criteria: histological diagnosis of SCC, stage III-IV, curative treatment, no evidence of disease at the enrolment. Pts and CGs were evaluated by means of StayTrait Anxiety Inventory Manual (Y1 and Y2), Beck Depression Inventory and Montgomery-Asberg Depression Rating Scale, EORTC-QLQ-C30 and Head and Neck35 module and Caregiver QoL Index Cancer. Results: Comparing overall QoL and psychological asset (anxiety and depression) of Pts and CGs belonging to Group A, B and C we observed no statistically significant differences due to treatment. However treatment produces statistically significant differences in some items of Pt’s QoL (Table). Moreover our data shows that there is not an association between overall QoL of Pts and CGs; psychological asset shows same tendency. Furthermore, it comes out that “Trouble whit social eating” produces an increase in Pt’s depression (p=0,009) that is strongly associated with a poor CG’s QoL (p=0,017). Conclusions: Our cohort of couples seems to show a different behaviour if compared to other literature data analysing the relationship within such dyads in other types of tumours. In conclusion, we hypothesize that other variables, present before tumour onset, could influence the thorny equilibrium of Pt-CG dyad. Group B Group A Group C p-values Trouble with social contact Mean 21.45 8.4 4.7 0.001 IC 12.8;30.1 3.2;13.6 0.3;9.1 Dry mouth Mean 13.3 24.95 39.95 0.017 IC 2.7;23.9 10.7;39.2 25.1;54.8 Sticky saliva Mean 23.3 36.5 46.6 0.034 IC 10.8;35.8 23.2;49.8 33.7;59.5
Abstract 18248: Sequential His Bundle and Left Ventricular Pacing: A Novel Alternative for Cardiac Resynchronization
Authors: Amrish Deshmukh, Tasha Wadsworth, Mary Romanyshyn, Pramod Deshmukh
Journal: Circulation (2017)

Introduction: The fusion of left ventricular (LV) pacing with intrinsic conduction can provide superior cardiac resynchronization compared to biventricular pacing in patients with left bundle branch block (LBBB). However, the timing of intrinsic ventricular activation depends on AV nodal conduction. Selective His bundle pacing (HBP) preserves intrinsic conduction independent of AV nodal conduction and allows constant fusion with LV pacing. Hypothesis: We hypothesized that HBP with sequential LV pacing would provide superior cardiac resynchronization compared to biventricular pacing. Methods: Patients with QRS>120 milliseconds, LBBB, and ejection fraction≤ 35% underwent simultaneous placement of HBP and biventricular pacing leads when HBP alone did not induce cardiac resynchronization. Patients with AF underwent AV nodal ablation. Devices were programmed for HBP and LV pacing based on optimal fusion of intracardiac electrograms. Results: A total of 10 patients, 9 males, age 80.0±8.4 years, 50% with AF, 60%...
Mutational Analysis of 472 Urothelial Carcinoma Across Grades and Anatomic Sites
Authors: Amin H. Nassar, Renato Umeton, Jaegil Kim, Kevin Lundgren, Lauren Harshman, Eliezer M. Van Allen, Mark Preston, Fei Dong, Joaquim Bellmunt, Kent W. Mouw, Toni K. Choueiri, Guru Sonpavde, David J. Kwiatkowski
Journal: Clinical Cancer Research (2018)

The purpose of this study is to characterize the mutational landscape across the spectrum of urothelial carcinoma (UC) to identify mutational features and potential therapeutic targets.Using targeted exome sequencing (n = 237 genes), we analyzed the mutation spectra of 82 low-grade nonmuscle-invasive bladder cancers (LG-NMIBC), 126 high-grade (HG) NMIBC, 199 muscle-invasive bladder cancers (MIBC), 10 LG-upper tract urothelial cancers (LG-UTUC), and 55 HG-UTUC.FGFR3 and KDM6A mutations were significantly more common in LG-NMIBC (72% and 44%, respectively) versus other bladder subtypes. FGFR3 alterations were also enriched in LG-UTUC versus HG-UTUC tumors (80% vs. 16%). In contrast, TP53 and RB1 mutations were significantly more frequent in all 3 HG urothelial carcinoma subtypes than in LG-NIMBC (45%-58% vs. 4%; 9%-22% vs. 0; respectively). Among LG-NMIBC tumors, KDM6A mutations were more common in women than in men (71% vs. 38%). HG-NMIBC and MIBC had higher tumor mutational burden (TMB) than LG-NMIBC (P = 0.001 and P < 0.01, respectively). DNA-damage repair (DDR) alterations were associated with a higher TMB in HG-NMIBC and MIBC tumors, and these two tumor types were also enriched for an APOBEC mutational signature compared with LG-NMIBC and HG-UTUC. Alterations in FGFR3, PIK3CA, and EP300 correlated with worse overall survival in HG-UTUC and occurred concurrently.Our analysis suggests that a fraction of MIBCs likely arise from precursor lesions other than LG-NMIBC. KDM6A mutations are twice as common in women with LG-NIMBC than those in men. DDR gene mutations and APOBEC mutagenesis drive mutations in HG-NMIBC and MIBC. UTUC has a distinct mutation profile from bladder cancer.
Abstract 18924: Porcine Model of Aortic Coarctation: Treatment With Novel Biodegradable Stent Up to 12mm Diameter
Authors: Surendranath R Veeram Reddy, Tre R Welch, Jian Wang, Matthew Riegel, James Richardson, Joseph M Forbess, Alan W Nugent
Journal: Circulation (2016)

Introduction: A novel double opposing helical (DH) biodegradable stent (BDS) made of poly-l-lactic-acid can be fabricated to larger diameters needed for use in congenital heart disease. Study aims were: 1. Create a model of coarctation of aorta (CoA) in minipigs. 2. Evaluate feasibility of stent implantation (DH BDS and metal) and assess mid-term results and inflammatory profile. Hypothesis: DH BDS will maintain structural integrity to treat porcine CoA. Methods: Via left lateral thoracotomy, CoA was created in 7 Yucatan minipigs (7-9 kg) by resecting a portion of the aortic wall. Stents were implanted 6-8 weeks later. Assessment included: angiography, intravascular ultrasound and histopathology. Results: All 7 animals survived the CoA creation surgery and underwent successful stent implantation (4 DH BDS and 3 metal) via carotid (5) and femoral (2) access. 1 planned non-survival animal underwent a 10-mm metal stent implantation that successfully relieved the CoA. The remaining 6 minipigs underwent succes...