tbuckley/cabot-search huggingface dataset:
A SU2C catalyst randomized phase II trial of pembrolizumab with or without paricalcitol in patients with stage IV pancreatic cancer who have been placed in best possible response.
Authors: Vincent M. Chung, Erkut Hasan Borazanci, Gayle S. Jameson, Ronald Evans, Michael Downes, Morgan L Truitt, Hitendra Patel, Andrew M. Lowy, Denise Roe, Karen Ansaldo, Michael T. Barrett, Ronald Lee Korn, Lana Caldwell, Gavin Slethaug, Rolf Hultsch, Haiyong Han, David Engelthaler, Talima Pearson, Elizabeth Lenkiewics, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2018)

TPS4154 Background: Pancreatic cancer remains a deadly disease and despite advances in chemotherapy treatment, survival for most patients is still less than one year. Refractory pancreatic cancer has not been responsive to checkpoint inhibitors and only in the small population of MSI high pancreatic cancers have we seen activity. The microenvironment plays an important role in limiting the immune response and researchers from the Salk Institute demonstrated that vitamin D receptor agonists sensitize both primary and metastatic pancreatic cancer lesions to checkpoint blockade. Our trial evaluates the role of maintenance immunotherapy and paricalcitol after best response to cytotoxic chemotherapy. Methods: This SU2C Catalyst trial will be conducted at Honor Health Research Institute, City of Hope National Medical Center and University of California San Diego Moores Cancer Center. Patients with metastatic pancreatic cancer receiving standard first line chemotherapy are eligible to be randomized after achieving best response defined as stable disease or partial response for 2 months with no further shrinkage of ≥ 20% on scan and no further decrease of ≥ 10% in the tumor markers while on chemotherapy. Patients with a serum vitamin D level ≥ 50 ng/mL are excluded. The primary endpoint of this study is to estimate the percentage of patients progressing at 6 months while on maintenance therapy. Secondary objectives evaluate the toxicity of the combination, overall survival and tumor mutational landscape. Twenty-four patients are planned to be randomized 1:1 to either pembrolizumab 200 mg every 3 weeks plus paricalcitol 25 mcg 3 times per week or pembrolizumab plus placebo. Archival tumor tissue is required and optional biopsies are allowed to further explore biomarkers of response to therapy. ClinicalTrials.gov Identifier: NCT03331562 Support: Stand Up To Cancer (SU2C) Catalyst Merck Grant Clinical trial information: NCT03331562.
Glutathione system to characterize the biological aggressiveness of the gastric cancer.
Authors: Elena V. Shalashnaya, Irina A. Goroshinskaya, Ekaterina Igorevna Surikova, Dar'ja E. Medvedeva, Polina S. Kachesova, Ludmila A. Nemashkalova, Irina Valerevna Neskubina, Andrey A. Maslov, Oleg I. Kit
Journal: Journal of Clinical Oncology (2017)

e15512 Background: The aim was a comparative study of glutathione system of tumor and its peritumoral tissues at gastric signet ring cell carcinoma (SRCC) and gastric adenocarcinoma (AC) to identify pathogenetic features of malignancy. Methods: Content of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST) were determined in the samples of tumor and peritumoral tissues, obtained during the surgery in 21 primary patients: 13 patients with SRCC, 8 patients with AC (G2-G3) without preoperative therapy. Tissue of intact stomach was studied in 12 randomly bereaved. Results: In the AC tumor tissue the GSH level was decreased by 43% and the activity of GPx and the GST was increased by 121.7% and 44.3% (p &lt; 0.05–p &lt; 0.001) compared with intact stomach. In peritumoral tissue both the level of GSH and GPX activity were less than in the tumor tissue at 40-45% (p &lt; 0.05–p &lt; 0.01). In SRCC both the GSH level and the activity of GPx and GST were increased in tumor tissue by 78%, 93.6% and 49.5% (p &lt; 0.05–p &lt; 0.001) compared with the intact stomach. In peritumoral tissue the GSH level was lower than in the tumor tissue by 60.2% (p &lt; 0.01), the enzymes activity was unchanged remaining higher than in the intact stomach. The GSH level both in tumor and in peritumoral tissues was 2-3 folds higher in gastric SRCC than in AC. No significant differences in the activity of glutathione-dependent enzymes in tumors of different histotype were revealed. Conclusions: The results show the differences in the functioning of the glutathione system, depending on the histological type of gastric tumors. It is possible that greater activity of glutathione-dependent system in tissue of SRCC is needed to maintain its increased proliferative activity and determines the features of the biological behavior of this tumor histotype.
Anaesthetist suspended after GMC appeal to High Court
Authors: Clare Dyer
Journal: BMJ (2018)

A medical practitioners’ tribunal has suspended an anaesthetist for four months after the General Medical Council successfully appealed to the High Court against a tribunal decision in 2017 to take no action against him.

Anoop Patel was found to have billed for three days’ locum on-call cover at the private unit of Charing Cross Hospital, London, when in fact he had been off sick one of those days and rostered to work for the NHS at the hospital on the others. The 2017 medical practitioners’ tribunal that found these GMC charges proved also decided that his actions had been dishonest.

It found that he had placed patients at risk and …
Use of next-generation sequencing tests to guide cancer treatment: Results from a survey of U.S. oncologists.
Authors: Andrew N. Freedman, Carrie N. Klabunde, Kristine Wiant, Lindsey Enewold, Stacy W. Gray, Kelly Kristin Filipski, Nancy Lynn Keating, Debra Leonard, Tracy G. Lively, Timothy S. McNeel, Lori M. Minasian, Arnold L. Potosky, Donna Rivera, Richard L. Schilsky, Deborah Schrag, Naoko Ishibe Simonds, Helmneh M. Sineshaw, Gordon Willis, Janet de Moor
Journal: Journal of Clinical Oncology (2018)

6529 Background: The proliferation of next-generation sequencing (NGS) tests provides an opportunity to advance oncology care. However, there are limited data about when and how NGS tests are used and the extent to which test results inform clinical care. Methods: Between February and May 2017, a survey developed by the National Cancer Institute and American Cancer Society was mailed to a nationally-representative sample of oncologists; 1281 responded, reflecting a 38% participation rate. Oncologists reported their use of NGS tests over the past year, including their use in different clinical scenarios. We restricted our analysis to the 1123 respondents who treated patients with solid tumors. Weighted percentages were used to describe NGS test use and its association with oncologists’ demographic and practice characteristics. Results: Overall, 63% of oncologists reported using NGS tests to guide treatment decisions. Among these oncologists, 36% used them “often” to guide treatment decisions for patients with advanced refractory disease, 29% to determine eligibility for clinical trials and 19% to decide whether to use FDA-approved drugs off-label. For 28% of oncologists, NGS test results informed treatment recommendations “often,” 53% reported “sometimes,” and 19% of oncologists reported that results “never” or “rarely” informed treatment recommendations. Oncologists < 50 years of age, practicing in an urban or suburban setting, treating patients at an academic center, holding a faculty appointment or receiving genomics training were more likely to use NGS tests. Over 50% of all oncologists reported that one or more patients presented with NGS test results from a commercially-available company they had not ordered. Conclusions: Most U.S. oncologists use NGS tests for their patients with solid tumors to inform treatment options for those with advanced cancer, and to identify clinical trials and/or approved drugs for off-label use. Among oncologist using NGS tests, over 80% reported that results informed their treatment recommendations either sometimes or often. Research is needed to more clearly establish the clinical utility of NGS tests and to inform clinical guidelines for their use in practice.
Endoscopic molecular imaging of early gastric cancer targeting transferrin receptor 1.
Authors: Jie Tian, Yang Du
Journal: Journal of Clinical Oncology (2017)

e23093 Background: Gastric cancer is primarily managed endoscopically by white light gastroscope with suboptimal diagnostic accuracy. Emerging optical imaging technologies possess great potential for improving diagnostic accuracy but currently lack imaging agents for molecular specificity. In this study, a novel ligand of transferrin receptor 1 (TfR1), human H-ferritin (HFn), was labeled with fluorescent agents to enable in vivo real-time imaging by confocal laser endomicroscopy (CLE). Methods: In vivo fluorescence imaging was performed in tumor-bearing mice from human gastric cancer cell lines using fluorescently labeled HFn nanoprobe. The HFn-FITC as molecular imaging agent was applied to the gastric cancer with confocal laser endomicroscopy (CLE) in fresh endoscopic submucosal dissection (ESD) of early gastric cancer. Results: Intravital imaging of gastric xenograft tumors revealed a specific tumor targeting effects of HFn-IRDye800CW, whereas no specific signal was observed in mice injected with free dye. An ex vivo experiment on human specimens using a rigid confocal probe showed positive fluorescent staining in ESD samples diagnosed as early gastric cancers. Our CLE evaluation correlated well with immunohistochemical findings. Conclusions: CLE can be used for in vivo, molecular analysis of early gastric cancer and to identify TfR1 expression in xenografts and human tissue samples. HFn-targeted molecular imaging could improve early detection of gastric cancer.
P01.097 Subclassification of low-grade gliomas considering TERT promoter mutation and ATRX loss: beyond the 2016 WHO classification
Authors: T Roh, S Kang, E Kim, J Moon, C Hong, J Chang
Journal: Neuro-Oncology (2018)

Grade II glioma is a heterogeneous group of various pathologies. 2016 WHO classification defined subgroups of Grade II gliomas based on isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status. However, implications of telomerase reverse transcriptase promoter (TERTp) mutation and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) loss are not considered in the classification. Patients (n = 191) who underwent surgery and pathologically proven for supratentorial newly diagnosed low-grade glioma (WHO grade II) were included this study. Molecular diagnoses including IDH1/2 mutation, 1p/19q codeletion, TERTp mutation, ATRX expression, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was evaluated. The overall survival according to TERTp mutation and ATRX loss in each 2016 WHO class were compared. There were 34 (17.8%) IDH-wildtype astrocytomas, 81 (42.4%) IDH-mutant astrocytomas, and 76 (39.8%) IDH-mutant and 1p/19q-codeleted oligodendrogliomas. The median overall survival (OS) of each group were 3.9, 10.4, and 18.7 years, respectively. TERTp mutation had negative impact for survival in IDH-wildtype astrocytomas (HR = 5.458, 95% confidence interval [CI] 1.771–16.826), while no significant differences were observed regarding TERTp mutation in IDH-mutant astrocytomas and oligodendrogliomas. Among IDH-wildtype/TERTp-mutant astrocytomas, ATRX loss was significantly correlated with poor outcome (2.1 vs 3.0 years, p=0.033). Molecular status of TERTp mutation and ATRX expression can be integrated into the 2016 WHO classification of low-grade gliomas. TERTp mutation has the reciprocal implication depending on the presence of IDH mutation in astrocytomas. IDH-wildtype astrocytomas which harbor TERTp mutation only without ATRX loss showed the worst prognosis which is comparable to glioblastomas. Low-grade glioma is a collection of heterogeneous tumors and needs more segmentation.
P07 Preliminary Orthogonal Analysis of EML4-ALK Gene Fusion Detection Methods in Chilean Patients with Lung Adenocarcinoma
Authors: M. Freire, R. Lizana, L. Ramos, G. Sepúlveda-Hermosilla, A. Blanco, P. Perez, O. Aren, S. Chernilo, C. Fernández, R. Armisen
Journal: Journal of Thoracic Oncology (2018)
TCT-197 Early Vascular Healing after Implantation of a Biolimus-Coated BioFreedom stent or a Sirolimus Eluting Orsiro stent in Patients with ST-segment Elevation Myocardial Infarction
Authors: Kirstine Hansen, Lisette Okkels Jensen, Michael Maeng, Lisbeth Antonsen, Akiko Maehara, Lars Jakobsen, Julia Ellert, Christian Terkelsen, Ole Ahlehoff, Troels Thim, None christian oliver fallesen, Steen Carstensen, Knud Nørregaard Hansen, Karsten Veien, Evald Christiansen
Journal: Journal of the American College of Cardiology (2018)
Hubert Greenslade Britton
Authors: Chris Mathias, Thomas Britton
Journal: BMJ (2018)

Hubert Greenslade Britton initially followed in his father’s footsteps and obtained a degree in chemistry from Exeter (where his father was professor of chemistry). Subsequently, however, he qualified in medicine from Trinity College Cambridge and University College Hospital. He then completed a PhD in chemistry and found a research position in the physiology department of St Mary’s Hospital Medical School, London, where he stayed until retirement. His academic work was broad and …
Retrospective study of treatment outcomes among metastatic castration-resistant prostate cancer patients receiving cabazitaxel and/or enzalutamide in later lines of therapy.
Authors: Bradford R Hirsch, Raymond Miao, Louis Hudspeth, Hong Wang, Debra Payne, John McCormick
Journal: Journal of Clinical Oncology (2016)

e16542 Background: Optimal treatment sequences, and the associated outcomes, for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) are not clearly defined. The objective of this study was to assess the experience of pts receiving third-line cabazitaxel (C) or enzalutamide (E) after treatment with both abiraterone (A) and docetaxel (D). Methods: Pts ≥18 years of age receiving C and/or E between September 2012 and March 2014 after D and A were identified in US Oncology iKnowMed (iKM) Electronic Health Records, an oncology-specific database that captures outpatient encounter history. Demographic, clinical and treatment data were obtained by chart review, supplemented by the iKM database. Results: Of 173 identified pts, 24.3% and 75.7% received third-line C or E, respectively. Among these, 59.0% received DAE/ADE, 16.8% DAEC/ADEC, 12.7% DACE/ADCE, and 11.6% DAC/ADC. Select baseline characteristics of identified pts are shown in the table. With initiation of third-line C or E, a prostate-specific antigen (PSA) decline of >50% was seen in 35.9% vs 27.9% of pts, respectively. Mean time to treatment discontinuation was 2.03 mos with C vs 2.35 mos with E. Conclusions: Despite the limitations of retrospective studies and a relatively small sample size, outcomes appeared to be similar between the two agents, with a trend toward greater PSA decline among those receiving third-line C. Data may be consistent with emerging clinical sensitivity patterns. Real world observational studies could help further define optimal treatment sequencing and inform clinical decision making for pts with mCRPC. Funding: Sanofi. Baseline characteristics (ini tiation of first-line therapy) Third-line C (DAC, ADC, DACE, ADCE) N = 42 Third-line E (DAE, ADE, DAEC, ADEC) N = 131 Median age, yrs (range) 66.5 (49–87) 72 (50–91) Mean PSA level, ng/mL, mean (median [Q1, Q3]) 166.3 (63.5 [29.7, 198.6]) 121.4 (51.2 [17.4, 119.0]) Gleason score >7, %* 51.4 59.8 Charlson comorbidity index ≥1, %** 28.6 35.9 Narcotic use, %* 35.0 49.2 *Excluding unknown. **Based on Deyo-adapted Charlson Comorbidity Index. Malignant tumor not included in assessment of overall score.
Role of non-myeloablative allogeneic stem cell transplant in chronic lymphocytic leukemia and its implications in current era: A systematic review.
Authors: Francisco Andres Socola, Belal Firwana, Sheila Louise Thomas, Appalanaidu Sasapu, Yogesh Jethava
Journal: Journal of Clinical Oncology (2016)

e18536 Background: TP53 mutated or del(17p) chronic lymphocytic leukemia (CLL) has high incidence of transformation to high-grade lymphoma. Ibrutinib is approved as first line agent for these high risk CLL patients and is not a curative treatment. Ibrutinib is associated with 18% to 36% discontinuation rates and 1-year cumulative incidence of Richter’s transformation of 4.5%. Median survival after Richter’s transformation is 3.5 months. We performed systematic review of Stem cell transplant (SCT) studies for CLL and measured overall survival (OS), progression-free survival (PFS), relapse rate (RR), treatment-related mortality (TRM), graft-versus-host-disease, acute (aGVHD) or chronic (cGVHD). Methods: A systematic literature review of Medline and EMBASE databases, from April 1991 to October 2015, was undertaken to identify prospective and retrospective studies that evaluated the role of allogeneic stem cell transplant in CLL. Random-effects meta-analysis of proportions was used to pool results across single-arm studies. Results: 43 studies with 1880 patients were identified. 1697 patients received non-myeloablative (NMA) SCT and 167 patients received myeloablative SCT. In the NMA group, 54.5% were males and the median age ranged from 44 to 58 years. The incidence of fludarabine refractory disease was 53.5% (CI 44.6% to 62.4%), del(17p) was 21.9% (CI 15.7% to 28.1%), and unmutated immunoglobulin variable heavy-chain gene was 68.7% (CI 53.6% to 83.8%). The estimated 5-years OS and PFS rates were 50.2% (CI 44.1% to 56.3%) and 37.2% (CI 30.7% to 43.7%) respectively. The RR was 26.9% (CI 20.7 to 33.0 %) and TRM was 12.5% (CI 8.8 to 16.1%). The incidence of grade II-IV aGVHD and cGVHD were 42.7% (CI 34.4% to 51.0%) and 48.1% (CI 43.0% to 53.2%) respectively. Conclusions: Allogeneic SCT is the only curative treatment for high risk CLL. 17p deleted CLL has high incidence of transformation and although Ibrutinib might delay progression, it will not prevent it. This analysis shows that NMA SCT outcomes have improved significantly and suggests the incorporation of allogeneic SCT early during the treatment of high risk CLL as an effective treatment strategy.
Association of activated B-cell infiltration in the tumor microenvironment with regulatory T-cell (Treg) infiltration, but not macrophages polarization in immunogenic human cancers.
Authors: Young Kwang Chae, William Han Bae, Young Suk Kim, Jonathan Forrest Anker, Maria Matsangou, Francis J. Giles
Journal: Journal of Clinical Oncology (2017)

e23174 Background: We reported an inverse association between tumor-infiltrating B and CD8 T cells in human cancers. Preclinical studies suggested that B cells regulate T cell activities via activation of Treg cells and alternative polarization of macrophages. In this study, we investigated the relationship between B cell infiltration, Treg cell infiltration, and macrophage polarization in five human cancers approved for the use of immune checkpoint inhibitors by the FDA. Methods: mRNA expression scores of 812 immune-related genes from the TCGA database were analyzed to calculate tumor infiltrating cells in 2951 patients with bladder urothelial carcinoma, renal cell carcinoma, skin melanoma, non-small cell lung cancer, and head and neck squamous cell carcinoma (Angelova et al., 2015). Expression patterns of Treg markers and M1/M2 phenotypic macrophage polarization markers were compared in relation to the presence of activated B cells (ActB) in human tumor tissues. Odds ratios (OR) of the numbers of tumors with versus without Treg cell infiltration by the presence of ActB cells were calculated. Results: Infiltration by ActB cells was significantly correlated with Treg cell infiltration in human cancers (OR=10.86, p&lt;0.001). In lung adenocarcinoma, ActB cells also demonstrated a significant association with myeloid derived suppressor cells (MDSCs, p&lt;0.05). Tumors infiltrated by ActB cells had significantly elevated expressions of Treg markers and suppressive cytokines (Table), but not macrophage polarization markers. No significant changes in survival outcomes were noted. Conclusions: We report for the first time an association between B cells and Treg cells in human immunogenic cancer tissues. ActB cell infiltration in the tumor microenvironment was positively correlated to Treg cell infiltration, but not macrophages polarization in immunogenic human cancers. [Table: see text]
Barriers in time to initiation of therapy for newly prescribed novel oral oncolytics.
Authors: Christopher Tapia, Ann Andee Wang, Yasin Bhanji, Christopher Campbell, Daniel Larsen, Seema Ganatra, Derick Gross, Regina Michelle Stein, Claudia Tellez, Shikha Jain
Journal: Journal of Clinical Oncology (2017)

e18005 Background: Novel oral oncolytics have been incorporated into standard of care for many malignancies. With increasing utility of these medications, accessibility issues have emerged. The purpose of this study is to examine the time-to-therapy initiation of novel oral oncolytics and to identify barriers that result in delays and access issues. Methods: A retrospective review of our electronic data warehouse was performed of adults newly prescribed a novel oral oncolytic for FDA approved indications from 04/01/16 to 12/31/16. Exclusion criteria: traditional chemotherapy or previous treatment with the same agent. Primary outcome: time from date prescribed to date filled. Record of pharmacy transfer, manufacturer assistance, and delays in treatment were also extracted. Kruskall-Wallis and Mann Whitney U tests of association were performed to identify whether pharmacy transfers or manufacturer assistance were associated with delays in time to treatment filled. Fisher’s Exact tests were performed to identify drug or insurance related associations with delays. Results: Of our interim analysis of 92 patients who met inclusion criteria, 9 (9.8%) were insured by Medicaid, 32 (34.8%) by Medicare, 51 (55.0%) by private insurance or other. The median time between date prescribed and date filled was 6 days (range 0-109 days). The most frequently prescribed drug was palbociclib (n = 22, 23.9%). 25 (27.2%) of patients had a pharmacy transfer prior to receiving their drug, 15 (16.3%) patients received manufacturer assistance, and 17 (19%) of patients’ records indicated a delay. Transfers, manufacturer assistance, and delays each had a statistically significant relation with time-to-fill (p &lt; 0.05), though none were significantly associated with drug or insurance type. Time-to-fill was not significantly associated with a particular drug or insurance type. Conclusions: As the landscape of oncology changes, barriers to treatment will be discovered as new novel agents are approved. Our study shows that potential exists to prevent treatment delays and improve access to care. By studying the factors affecting time-to-treatment, quality improvement initiatives can be developed to better streamline the process.