tbuckley/cabot-search huggingface dataset:
An open-label, first-in-human, dose escalation study of a novel CD3-CD123 bispecific T-cell engager administered as a single agent by intravenous infusion in patients with relapsed or refractory acute myeloid leukemia, B-cell acute lymphoblastic leukemia, or high risk myelodysplastic syndrome.
Authors: Nicolas Boissel, Stéphane de Botton, Xavier G. Thomas, Ercole Rao, Hélène Bonnevaux, Chantal Rubin-Carrez, Stéphane Guerif, Eric Beys, Alice Gosselin, Anne-Laure Bauchet, Valery Novikov, Elma Fernandes, Dmitri Wiederschain, Emanuel A. Palatinsky, Karl Hsu, Paula Goodman Fraenkel
Journal: Journal of Clinical Oncology (2018)

TPS7076 Background: Persistence of leukemic stem cells is an important cause of relapse in patients with acute myeloid leukemia (AML). CD123 (α-chain of the interleukin-3 receptor) is highly expressed on myeloid leukemic stem cells and blasts, and is present on B-cell acute lymphoblastic leukemia (B-ALL). With the goal of developing a therapeutic molecule active against leukemic stem cells and blasts, a novel bispecific T-cell engager (TCE) has been engineered incorporating the proprietary Cross-Over-Dual-Variable-Domain (CODV) format, a fully humanized Fc-silenced IgG1 backbone, and variable domains from two antibodies, targeting CD3 (T-cell co-receptor) and CD123, respectively. In nonclinical experiments, the TCE exhibited T-cell mediated cytotoxic activity against AML cells in vitro and in mouse models. Methods: This first-in-human trial will enroll patients with relapsed or refractory AML, B-ALL, or high risk myelodysplastic syndrome. The trial is starting at the minimum anticipated biological effect level (MABEL) dose, followed by an intrapatient dose escalation to a steady-state dose. The drug will be administered intravenously on a weekly basis with specific precautions to prevent and mitigate cytokine release syndrome. One patient will be treated at each of the first two dose levels, while subsequent dose levels will enlarge to a 3+3 design. Patients will be assessed for response, safety, and pharmacodynamic and pharmacokinetic endpoints. The primary objective of the dose escalation study is to determine a recommended phase 2 dose for a subsequent expansion cohort.
Perioperative positioning management in gynecologic cancer surgery: A national NOGGO-AGO intergroup survey.
Authors: Mareike Sporkmann, Jenny Katharina Wagner, Rolf Richter, Alexander Burges, Barbara Schmalfeldt, Hendrik Veldink, Irmela Schrettenbrunner, Klaus Pietzner, Jalid Sehouli
Journal: Journal of Clinical Oncology (2017)

e17046 Background: Perioperative positioning injuries occur in approximately 4% of all medical complications. The aim of the present survey was the analysis of positioning-management in gynecologic-oncological surgery, the process- and structure-reliability and the implementation of current guidelines into daily clinical practice. Methods: A multiple-choice anonymous questionnaire about the perioperative positioning management in gynecologic oncology was sent to all gynecological departments in Germany. Sixty questions were divided into five different parts: 1) descriptive information about the department, 2) focus on the pre- and 3) postoperative management, 4) on the quality management, and 5) information regarding the management of positioning in the operation room based on two fictional case examples in gynecologic oncology procedures. Results: 184 of 633 departments participated in the survey between June and September 2016. Complications related to intraoperative positioning occurred in 48.4% of all participating departments, independent from department size. Knowledge of the current guideline on positioning did not impact the incidence of complications. The positioning of the patient was mentioned in the team-time-out procedure in 66.1% of the participating departments. No difference was found between high-volume and low-volume gynecologic oncologic operative departments with regard to the use of supportive tools such as anti-thrombotic leg pumps. The vast majority with 92.7% included information of positioning injuries into the written informed consent. Knowledge of the guideline or a previous legal dispute did not influence the willingness to inform about possible positioning-related complications. Conclusions: Our survey shows, that the awareness of perioperative positioning management in gynecologic cancer surgery is high throughout all sizes departments in Germany. Almost half of all 184 participating departments report positioning-related complications in the previous 12 months, stressing the importance of this often underrated topic.
Baseline PET-CT functional parameters to identify low-grade versus grade 3A follicular lymphoma.
Authors: Ajay Major, Andrew Hammes, Rustain Morgan, Diana Abbott, Manali K. Kamdar
Journal: Journal of Clinical Oncology (2018)

e19541 Background: Fluorodeoxyglucose-positron emission tomography with computed tomography (PET-CT) is the preferred staging modality in patients (pts) with follicular lymphoma (FL). PET-CT parameters maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and total metabolic tumor volume (TMTV) have been studied to assess prognosis and detect occult transformation. FL is divided into low-grade (1-2; LG) and high-grade (3A; HG) with LG managed conservatively and HG treated aggressively. Differentiation of LG and HG FL is limited by inter-observer variability and heterogeneity of disease grades at different sites. This study aimed to determine if PET-CT parameters can differentiate between LG and HG FL. Methods: We performed a retrospective review of pts aged > 18 years with FL grades 1, 2 and 3A from 2009-2017 who obtained a PET-CT prior to any therapy. Pts with grade 3B and transformed lymphoma were excluded. SUVmax, TLG and TMTV values were generated from PET-CT using MIM software. Poisson regression and receiver operating characteristic (ROC) curves were used to compare PET-CT variables between LG and HG. Using regression models, PET-CT variables were correlated with stage, number of nodal sites, tumor burden, marrow involvement and Ki67. Results: 49 FL pts were identified, 38 LG and 11 HG. All PET-CT variables were significantly higher in HG than LG: SUVmax by 24% (p = .03), TLG by 27% (p < .001), and TMTV by 45% (p < .001). PET-CT variables differentiate between LG and HG FL on ROC curves with the following sensitivity/specificity and cutoff: SUVmax 0.7/0.6, cutoff 9.3; TLG 0.8/0.7, cutoff 543; and TMTV 0.7/0.7, cutoff 141. TMTV was significantly correlated with increasing stage (p = .01) and number of nodal sites (p = .01). SUVmax, TLG and TMTV were significantly correlated with high tumor burden (p < .03). None of the variables correlated with Ki97 or marrow involvement. Conclusions: PET-CT parameters SUVmax, TLG and TMTV have utility in predicting LG versus HG FL, with TMTV having a significant correlation with stage, tumor burden, and number of nodal sites. Our findings suggest that functional imaging parameters can serve as non-pathologic tools in identifying grades of FL.
Preference for People-First Language Among Patients Seeking Bariatric Surgery
Authors: Rebecca L. Pearl, Kaylah Walton, Kelly C. Allison, Jena Shaw Tronieri, Thomas A. Wadden
Journal: JAMA Surgery (2018)

This survey study evaluates responses to people-first language and terms for describing a body mass index of 40 or more among patients seeking bariatric surgery and explores patients' receptivity to discussing weight stigma in weight management.
Association between microRNAs expression in primary breast cancer and presence of circulating tumor cells (CTC) in peripheral blood.
Authors: Michal Mego, Matus Hajduk, Marian Karaba, Gabriel Minarik, Juraj Benca, Tatiana Sedlackova, Gabriela Repiska, Lucia Krasnicanova, Denisa Manasova, Silvia Jurisova, Jozef Sufliarsky, Daniel Pindak, Lubos Klucar, James M. Reuben, Jozef Mardiak
Journal: Journal of Clinical Oncology (2017)

e23022 Background: CTCs play major role in tumor dissemination and progression and represent one of the key component of metastatic cascade. MicroRNAs (miRs) are involved in regulation in several biological processes in cancer including invasion, epithelial-mesenchymal transition (EMT) and disease progression. The aim of this study was to identify miRs in primary tumor associated with presence of CTCs in peripheral blood (PB) in non-metastatic breast cancer patients. Methods: This translational study included 79 patients with primary breast cancer for whom fresh frozen tumor tissue and status of CTCs in peripheral blood were available. CTCs were detected before surgery by qRT-PCR assay for expression of epithelial (CK19) or epithelial-mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, ZEB1). Total RNA was extracted from fresh frozen primary tumor and the expression profiles were obtained using Human microRNA Microarray v21.0 (Agilent Technologies). Results: We analyzed 48 (60.8%) tumor samples from patients with presence of CTCs in PB and 31 (39.2%) tumors with non-detectable CTCs. From CTCs positive patients, in 20 (41.7%) of them epithelial CTCs (EP_CTC) were detected while in 28 (38.3%) CTCs with EMT (CTC_EMT) phenotype were present. We identified 178 miRs that were expressed at significantly different levels (FDR &lt; 0.05) in tumors with presence of any type of CTCs in PB compared to tumors with non-detectable CTCs. We also identified 174 and 137 miRs (33 overlapping) that were expressed at significantly different levels in tumors with EP_CTCs and CTC_EMT, respectively, compared to tumors with non-detectable CTCs. Overlapping miRs with highest different levels in expression (FDR &lt; 0.01) were miR-3137, miR-3138, miR-3168, miR-605-5p, miR-6165 and miR-6790-5p. Conclusions: We identified for the first time miRs expressed in primary tumor associated with CTCs in peripheral blood in breast cancer patients. Moreover, we identified miRs specifically associated with various subpopulations of CTCs. We suppose, that these miRs could be involved in tumor dissemination and might lead to identification of new therapeutic targets. Study was supported by APVV-14-0327.
Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories
Authors: Sarah J. Mitchell, Michel Bernier, Julie A. Mattison, Miguel A. Aon, Tamzin A. Kaiser, R. Michael Anson, Yuji Ikeno, Rozalyn M. Anderson, Donald K. Ingram, Rafael de Cabo
Journal: Cell Metabolism (2018)
Pilot study of a comprehensive precision medicine platform for children with high-risk cancer.
Authors: Loretta Lau, Jennifer Byrne, Paul G Ekert, Tim Failes, Andrew Fellowes, Jamie Fletcher, Andrew Gifford, Michelle Haber, Amit Kumar, Richard Lock, Glenn Marshall, Geoffrey Brian McCowage, Emily Mould, Murray Norris, Toby Trahair, Maria Tsoli, Vanessa Tyrrell, Carol Wadham, Jinhan Xie, David Simon Ziegler
Journal: Journal of Clinical Oncology (2017)

10539 Background: Genomic analyses can identify actionable mutations in a subset of childhood cancers. However it has been challenging to translate actionable mutations into substantial benefits for adult cancers despite high mutation frequency. Methods: To test whether we could enhance identification of personalised therapies for high risk (HR) childhood cancers we conducted a pilot study (TARGET) evaluating a novel, comprehensive precision medicine platform incorporating molecular profiling, in vitro and in vivo drug testing. Results: We evaluated the first 29 patients with HR cancer (expected survival &lt; 30%) enrolled prospectively over 15 months. Samples were collected from 15 CNS tumors, 10 solid tumors and 4 leukemias. All samples underwent targeted DNA sequencing. Pathogenic or likely pathogenic mutations were found in 59% (17/29) of tumors. 41% (12/29) had potentially actionable mutations. RNA-sequencing was performed on 27 samples. Previously described fusions were identified in 19% (5/27; 1 targetable, 1 clinical relevant and 3 diagnostic fusions). 37% (10/27) of samples also had actionable aberrations related to copy number changes or RNA expression. In vitro culture and establishment of patient-derived xenograft (PDX) were attempted in 19 and 21 fresh samples, respectively. The success rate of establishing a primary culture was 42% (8/19) and PDX engraftment rate was 67% (14/21). At least 1 drug hit was identified in 5 (56%) of the 9 samples screened using a high throughput drug screen of up to 165 compounds. Drug testing has been completed in 4 PDXs and was informative in all 4 cases allowing prioritisation of treatment recommendations. Genomic analysis in combination with RNA-seq, in vitro drug screening and PDX drug testing enriched the analysis and increased the ability to make personalised treatment recommendations from 41% (targeted panel alone) to 66%. Conclusions: This pilot study demonstrates that this novel, comprehensive platform is feasible and has the potential to improve outcome for HR childhood cancers. A multicentre study testing the implementation of the platform on a national level (PRISM trial) will open for Australian children with HR cancer under the Zero Childhood Cancer Program in 2017.
TCT-834 Risk Stratification Using the ACEF Score in Patients Undergoing Percutaneous or Surgical Left Main Revascularization: Insights From the EXCEL Trial
Authors: Bimmer Claessen, Roxana Mehran, Marie-Claude Morice, Martin Leon, David Taggart, Bernard Gersh, David Kandzari, Ori Ben-Yehuda, Ovidiu Dressler, Yangbo Liu, A. Pieter Kappetein, Patrick Serruys, Joseph Sabik, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Effect of pegfilgrastim on-body injector (OBI) on cancer care: A real-world health system and interrupted time series analysis.
Authors: Junji Lin, Aylin Yucel, Mark S. Walker, Nancy Perrin, Charles Bowers, Maxine D. Fisher, Mark Bensink, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2018)

e18859 Background: Pegfilgrastim prophylaxis reduces risk of febrile neutropenia (FN) and administration is recommended at least 24 h after cytotoxic chemotherapy. The pegfilgrastim (Neulasta) OBI enables automatic next-day administration without a return clinic visit. This study describes the impact of OBI introduction on attended next-day visits (ANDV) and scheduled next-day visits (SNDV) for pegfilgrastim prophylaxis in a real-world setting. Methods: Medical records of adults at high/intermediate FN risk based on regimen and individual risk factors who initiated myelosuppressive chemotherapy 1 Jan 2015-29 Jun 2017 were retrospectively collected from a large mid-south US community oncology practice. At-risk cycles (ARCs) in which NCCN recommends pegfilgrastim prophylaxis were identified. Prevalence of ANDV and SNDV for pegfilgrastim injection were assessed as ANDV or SNDV divided by total ARCs in the corresponding period. Interrupted time series (ITS) analysis was used to assess longitudinal OBI effects on ANDV and SNDV by evaluating the coefficient (b) and statistical significance. Pre-OBI (prior to 14 Jul 2016), transition (14 Jul 2016-7 Sep 2016), and post-OBI (after 7 Sep 2016) periods were assessed. Results: The study included 706 patients. Mean (SD) age was 57.9 (12.3) years; 84.7% were female; 53.4% had breast cancer, 20.3% had ovarian cancer, 17.4% had lung cancer, and 8.9% had NHL. 3274 ARCs were identified (67.7% pre-OBI, 6.4% transition, 25.9% post-OBI). In the post-OBI period, prevalence of ANDV decreased 86.4% and SNDV decreased 81.1% relative to the pre-OBI period (Table). ITS (adjusted for transition period & covariates) showed that ANDV (b = -30.1, P < 0.0001) and SNDV (b = -35.1, P < 0.0001) significantly declined immediately after the transition, and the decline continued throughout the post-OBI period (ANDV: b = -0.6, P = 0.21; SNDV: b = -0.9, P = 0.01). Conclusions: OBI introduction significantly reduced the need to schedule, or for patients to attend, return clinic visits for pegfilgrastim prophylaxis in a community oncology practice. Pre-OBI Transition Post-OBI ARCs 2216 210 848 ANDV n 1072 59 56 Prevalence, % 48.4 28.1 6.6 SNDV n 1313 69 95 Prevalence, % 59.3 32.9 11.2
Abstract P239: Adipose Tissue Palmitoleic Acid is Inversely Associated With Nonfatal Acute Myocardial Infarction in the Costa Rica Heart Study
Authors: Danny Luan, Dongqing Wang, Hannia Campos, Ana Baylin
Journal: Circulation (2018)

Background: Animal models have shown that adipose-derived palmitoleic acid may act as a lipokine by conferring resistance to diet-induced obesity; however, human epidemiologic studies investigating this relationship thus far have not provided data in support of this hypothesis. Because metabolic syndrome and cardiovascular disease are intricately linked with the former being a major risk factor for the latter, we hypothesized that adipose-derived palmitoleic acid may be inversely associated with myocardial infarction. Objective: We examined whether adipose tissue palmitoleic acid was associated with nonfatal acute myocardial infarction in a representative population of Costa Rican adults. Methods: Odds ratios of nonfatal acute myocardial infarction by quintiles of adipose tissue palmitoleic acid were calculated using conditional logistic regression in a case-control study of 1,828 cases and 1,828 controls matched by age, sex, and area of residence. Results: We observed an inverse relationship between nonfatal acute myocardial infarction and adipose tissue palmitoleic acid (OR for highest quintile compared to lowest quintile of palmitoleic acid: 0.54; 95% CI: 0.37, 0.79; P for trend: 0.0007). We additionally observed a significant positive association between adipose tissue palmitoleic acid and high-density lipoprotein (HDL) cholesterol, an important cardiometabolic risk factor for myocardial infarction. Conclusions: These data support the conclusion that adipose-derived palmitoleic acid may behave as a lipokine in the context of human myocardial infarction. This protective association may be partially explained by the increase in HDL cholesterol across quartiles of palmitoleic acid in our population of Costa Rican adults.
The activity of the conjugated antimetabolite 5-FdU-ECyd against platinum-resistant ovarian cancer.
Authors: Pauline Wimberger, Barbara Klink, Konrad Gruetzmann, Julian Puppe, Daniel Klotz, Evelin Schroeck, Jan Dominik Kuhlmann, Sarah Schott
Journal: Journal of Clinical Oncology (2017)

e17077 Background: Primary or secondary resistance to platinum-based chemotherapy is an important clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, the development of innovative drugs against platinum resistance is urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and is subsequently cleaved into several active cytostatic metabolites. Our in vitro study evaluates the effects of the conjugated antimetabolite 5-FdU-ECyd, consisting of 2-deoxy-5-fluorouridine (5-FdU) and ethynylcytidine (ECyd), on platinum-resistant OC cells. Methods: In vitro assays and RNA-Seq (Illumina) were applied for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis as well as independent platinum-resistant Skov-3-IP OC cells. Results: Nano molar 5-FdU-ECyd concentrations induced a rapid dose-dependent decline of cell viability in platinum-sensitive and platinum-resistant OC cells. The cytotoxicity of 5-FdU-ECyd was accompanied by the formation of DNA double strand breaks and by the induction of apoptosis, indicated by a strong increase of pro-apoptotic molecular markers (caspase-3/7 activation, PARP-cleavage). Moreover, 5-FdU-ECyd efficiently decreased cell migration of platinum-resistant OC cells and inhibited other tumor-associated cellular functions, such as clonogenic or spheroidal growth. Transcriptome analysis indicated that, independently of platinum-resistance status, 5-FdU-ECyd influences distinct cellular pathways, involved in cell cycle regulation, apoptosis, DNA-damage response and RNA/pyrimidine metabolism. Combination treatment of 5-FdU-ECyd and platin did not show a synergistic cellular response, suggesting the potential use of 5-FdU-ECyd as a monotherapeutic agent. Conclusions: Our data provide a rationale to characterize the effect of 5-FdU-ECyd in a pre-clinical in vivo setting. We hypothesize that this conjugate is a promising therapeutic option for OC patients with resistance to conventional platinum-based chemotherapy.
Clinical trial in progress: A phase 3 study of maintenance bi-shRNA-furin/GM-CSF-expressing autologous tumor cell vaccine in women with stage IIIb-IV high-grade epithelial ovarian cancer.
Authors: Jonathan Oh, Minal A. Barve, Devansu Tewari, John K. Chan, Elizabeth Grosen, Rodney Paul Rocconi, Erin Elizabeth Stevens, Leslie Robbins DeMars, Sharad A. Ghamande, Robert L. Coleman, Luisa Manning, Gladice Wallraven, Neil N. Senzer, Martin Birkhofer, John J. Nemunaitis
Journal: Journal of Clinical Oncology (2017)

TPS5604 Background: Vigil is an immuno-stimulatory autologous cellular therapy, which uses patient tumor cells transfected with a plasmid encoding genes for GM-CSF and furin (to down regulate TGFβ 1&amp;2). In Phase I, systemic immune activation was demonstrated in the majority of patients using an IFNƔ ELISPOT assay. A randomized Phase 2 assessment of Vigil maintenance therapy vs. observation in ovarian cancer demonstrated prolonged relapse free survival (RFS) (Oh J, Barve M, et al. Gynecologic Oncology, 2016; 143: 504–510.). Based on these observations, a Phase 3 study of maintenance Vigil therapy in patients with advanced ovarian cancer was initiated (NCT02346747). Methods: This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study of maintenance Vigil in women with Stage IIIb,c or IV high-grade papillary serous/clear cell/ endometrioid ovarian, fallopian tube or primary peritoneal cancer. Patients will have a minimum of 4 and a maximum of 12 Vigil doses manufactured from tumor obtained at primary debulking surgery. Patients must achieve a complete clinical remission following primary surgery and chemotherapy before being randomized 1:1 to receive either monthly intradermal Vigil or placebo. Randomization is stratified by extent of surgical cytoreduction (complete/microscopic vs. macroscopic residual disease) and neoadjuvant vs. adjuvant chemotherapy. The primary objective is to compare RFS of subjects randomized to Vigil vs. placebo, and the key secondary objective is overall survival (OS). The sample size calculation of 222 patients assumes 24 months for accrual and 36 months of follow-up with a median RFS of 19 months from randomization, in the control group. This provides 90% power to detect a hazard ratio (HR) of 0.6 favoring Vigil at the 0.05 level of significance. To date, 61 patients have been randomized and an additional 55 patients are receiving chemotherapy in anticipation of randomization. Tumor tissue is being obtained from approximately 20 patients per month at multiple sites across the U.S. At their last meeting in January, 2017 the independent DSMB recommended that the study continue without change. Clinical trial information: NCT02346747.