tbuckley/cabot-search huggingface dataset:
Abstract 16061: Effects of UNOS Policy Changes on Market Competition and Heart Transplant Outcomes
Authors: Raymond C Givens, Jennifer Lewey, Donna M Mancini, Paul C Schulze
Journal: Circulation (2015)

Introduction: Higher competition among transplant centers is associated with improved access of higher-risk patients to extrathoracic organ transplantation but worse outcomes. The effects of major United Network for Organ Sharing (UNOS) policies on competition for hearts are unknown. We studied associations of listing priority (1999) and organ allocation policy revisions (2006) with local organ procurement organization (OPO) competition and heart transplant (HT) outcomes. Methods: In the UNOS database we found 80 OPOs providing hearts to 45,727 adults from 1988-2013. We calculated for each OPO yearly a Herfindahl-Herschmann Index (HHI) that varies inversely with competition and used segmented regression analysis to assess trends. Results: Aggregate local competition was stable in era 1 (1988-2000) then increased until 2006 (era 2), after which there was an increase in competition but subsequent reversal of the previous trend (era 3; Figure). Across all eras, increasing competition was associated with higher proportions of recipients who were nonwhite, status 1 or 1A, and received IABP or LVAD bridging (all p &lt;0.0001 for era, competition and era*competition). Despite a progressive increase in center volume with level of competition (p &lt;0.0001), patients served by higher-competition OPOs in era 3 had higher post-HT death and graft failure rates (p &lt;0.0001). Conclusions: Policy revisions regarding listing criteria and organ allocation have been associated with specific changes in local competition. The most competitive OPOs appear to serve sicker patients but have lower post-HT survival. Understanding effects of market competition may inform future policy decisions.
Prospective study of the perceptions of oncology residents about learning from tumor boards.
Authors: Ramachandran Venkitaraman
Journal: Journal of Clinical Oncology (2018)

11018 Background: Tumor boards are a unique and integral component of oncology practice. Participation in the tumor board is an important aspect of education of oncology residents. This qualitative study based on phenomenological methodology, was conducted to assess the perception of residents and supervisors about how learning happens in tumor boards. Methods: Semi-structured interviews of ten oncology residents and five supervisors were conducted. The participants were requested to describe their experience of participating in and their perceptions of learning from tumor boards. The transcripts of the interviews were analysed by thematic analysis, to identify unifying themes which could explain how learning happens in tumor boards Results: All the residents and the supervisors perceived the tumor board meetings to be a good learning opportunity. The major underlying themes about learning from tumor boards that emerged from the interviews were: Educational gain (Positive experience vs Constraints), Involvement of the residents (Passive vs Active), Progression of residents (Junior vs Senior), Multi-Disciplinary Team dynamics (Integrated/Motivating vs Hierarchical/Intimidating), Background Reading and Learning (Pre-tumor board preparation vs Post- tumor board learning) and Feedback and Reflection (Formal vs Informal). Conclusions: Learning in tumor boards occur by active involvement of the residents. According to the residents, pre- tumor board preparation and post- tumor board reading are important for educational gain. The residents felt that their active involvement and learning from the tumor board meetings improved as they progress through their programme. Multi-disciplinary team dynamics was perceived to be an important determinant of resident learning in tumor boards
Exosomal circRNAs: biogenesis, effect and application in human diseases
Authors: Yangxia Wang, Jinbo Liu, Junfen Ma, Ting Sun, Quanbo Zhou, Weiwei Wang, Guixian Wang, Pingjun Wu, Haijiang Wang, Li Jiang, Weitang Yuan, Zhenqiang Sun, Liang Ming
Journal: Molecular Cancer (2019)

Exosomes have emerged as critical mediators of intercellular communication, both locally and systemically, by regulating a diverse range of biological processes between cells. Circular RNA (circRNA) is a novel member of endogenous noncoding RNAs with widespread distribution and diverse cellular functions. Recently, circular RNAs have been identified for their enrichment and stability in exosomes. In this review, we outline the origin, biogenesis and function of exosomal circRNAs as well as their roles in various diseases. Although their precise roles and mechanisms of gene regulation remain largely elusive, exosomal circRNAs have potential applications as disease biomarkers and novel therapeutic targets.
Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study
Authors: Sophie Glatt, Peter C Taylor, Iain B McInnes, Georg Schett, Robert Landewé, Dominique Baeten, Lucian Ionescu, Foteini Strimenopoulou, Mark I L Watling, Stevan Shaw
Journal: Annals of the Rheumatic Diseases (2019)

Evaluate the efficacy and safety of dual neutralisation of interleukin (IL)-17A and IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) and inadequate response (IR) to certolizumab pegol.During this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), patients with moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 and 4, and 200 mg at Week 6. Patients with IR at Week 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))>3.2) were randomised 2:1 to CZP (200 mg every 2 weeks (Q2W)) plus bimekizumab (240 mg loading dose then 120 mg Q2W) or CZP plus placebo. The primary efficacy and safety variables were change in DAS28(CRP) between Weeks 8 and 20 and incidence of treatment-emergent adverse events (TEAEs).Of 159 patients enrolled, 79 had IR at Week 8 and were randomised to CZP plus bimekizumab (n=52) or CZP plus placebo (n=27). At Week 20, there was a greater reduction in DAS28(CRP) in the CZP-IR plus bimekizumab group compared with the CZP-IR plus placebo group (99.4% posterior probability). The most frequent TEAEs were infections and infestations (CZP plus bimekizumab, 50.0% (26/52); CZP plus placebo, 22.2% (6/27)).PoC was confirmed based on the rapid decrease in disease activity achieved with 12 weeks of CZP plus bimekizumab. No unexpected or new safety signals were identified when neutralising IL-17A and IL-17F in patients with RA concomitantly treated with CZP, but the rate of TEAEs was higher with dual inhibition.
Abstract 3280: TTFields induces immunogenic cell death and STING pathway activation through cytoplasmic double-stranded DNA in glioblastoma cells
Authors: Dongjiang Chen, Nagheme Thomas, David D. Tran
Journal: Cancer Research (2019)

Abstract Glioblastoma (GBM) is the most common and deadliest malignant brain cancer in adults despite aggressive chemoradiotherapy. Tumor Treating Fields (TTFields) was recently approved in combination with adjuvant temozolomide chemotherapy for newly diagnosed GBM patients. The addition of TTFields resulted in a significant improvement in overall survival. TTFields are low-intensity alternating electric fields that are thought to disturb mitotic macromolecules’ assembly, leading to disrupted chromosomal segregation, integrity and stability. In many patients, a transient stage of increased peritumoral edema is often observed early in the course of TTFields treatment followed subsequently by objective radiographic responses, suggesting that a major component of therapeutic efficacy by TTFields may be an immune mediated process. However, the mechanism underlying these observations remains unclear. Here we report results on a panel of GBM cell lines treated with TTFields at the clinically approved frequency of 200 kHz using an in vitro TTFields system. Our data showed 24 hrs TTFields-treated GBM cells had a significantly higher rate (19.9% vs. 4.3%, p=0.0032) of micronuclei structures released into the cytoplasm as a result of TTFields-induced chromosomal instability. Nearly 40% of these micronuclei were co-localized with two upstream dsDNA sensors: absent in melanoma 2 (AIM2)andInterferon (IFN)-inducible proteinCyclic GMP-AMP synthase (cGAS), compared to absence of co-localization in untreated cells. TTFields-activated micronuclei-dsDNA sensor complexes led to i) induction of pyroptotic cell death, as measured by a specific LDH release assay, and through AIM2-recruited caspase1 and cleavage of pyroptosis-specific Gasdermin D; and ii) activation of STING pathway components including Type I IFNs and pro-inflammatory cytokines downstream of the NFκB pathway. GBM cell-specific shRNA depletion of either AIM2 or STING or both in a co-culture experiment of bone marrow cells or splenocytes with supernanants obtained from knockdown GBM cells was able to reverse the inducement of immune cells. These results provide compelling evidence that TTFields function as an activator of the immune system in GBM cells, and a strong rationale for combining TTFields with immunotherapy aimed at augmenting an anti-tumor immune response such as immune checkpoint inhibitors. Note: This abstract was not presented at the meeting. Citation Format: Dongjiang Chen, Nagheme Thomas, David D. Tran. TTFields induces immunogenic cell death and STING pathway activation through cytoplasmic double-stranded DNA in glioblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3280.
The prevalence of cardiac risk factors in men with localized prostate cancer undergoing androgren deprivation therapy in British Columbia, Canada.
Authors: Jennifer Rajala, Scott Tyldesley, Tom Pickles, Sean Virani
Journal: Journal of Clinical Oncology (2013)

e16086 Background: While androgen deprivation therapy (ADT) decreases the risk of prostate cancer specific mortality in high risk localized prostate cancer treated with radiotherapy, it worsens cardiovascular (CV) risk factor profiles in treated men. Patients with pre-existing traditional cardiac risk factors who are treated with ADT have a higher rate of CV mortality than patients without risk factors. Methods: We retrospectively reviewed the charts of the last 100 consecutive men with intermediate or high risk localized prostate cancer who were referred to the British Columbia Cancer Agency from October 1, 2011 to October 31, 2012 and treated with ADT. Inclusion criteria were referral to an oncologist within 3 months of diagnosis and a planned duration of ADT of 6 month or more. Patients with metastatic prostate cancer at diagnosis were excluded. Data on traditional cardiac risk factors were collected and a Framingham risk score was calculated on each patient to estimate their 10 year cardiac event risk. Results: The average age of the men referred for ADT was 71.7±7 years. Most, 70%, had poorly differentiated disease and the PSA was &gt;10ug/L in 62%. An updated Charlson score of 0 was calculated in 82% of patients; only 4% had a score ≥2. The Framingham risk of a cardiac event in the next 10 years was calculated to be high (more than 20% risk) in 69%, intermediate (a 10-20% risk) in 30%, and low (&lt;10% risk) in 1% of the patients. A history of coronary artery disease was present in 17 patients, 11 of whom had documented revascularization. Baseline type 2 diabetes or impaired glucose tolerance was present in 24 patients, and 58 patients had a history of hypertension. Lipid profiles had been measured within the past year in 38 patients, and 35 patients had a baseline ECG on the chart. Conclusions: Given the high prevalence of cardiac risk factors in men with prostate cancer referred for ADT, we recommend baseline cardiac risk screening of lipids, blood glucose, and blood pressure in these patients with subsequent close monitoring of these parameters while on ADT. Among those individuals with established or symptomatic CV disease, we recommend referral to a specialist with expertise in cardiology.
Effect of statin and metformin on survival in veterans (V) with B-cell lymphoproliferative disorders (BLD).
Authors: Shanthi Srinivas, Melanie L. Gonzalez, Sunniya Khan, Arpita Gandhi, Barbara Crump, Monica McPherson, Emma R Paz-Querubin, Victor T Chang, Basil Kasimis
Journal: Journal of Clinical Oncology (2013)

1602 Background: The incidence of BLD has been increasing in V. As many V are on statin and metformin for comorbid conditions, we evaluated the impact of their use on survival. Methods: In an IRB-approved protocol, we reviewed the records of 332 V diagnosed with BLD from January 1997 to Dec 2011 for demographics, height(H),weight(W), BMI,statin and metformin use, clinical and laboratory data and ECOG PS. Comorbidity was assessed using the Charlson Comorbidity Index (CCI),Kaplan-Feinstein Index (KFI) and Cumulative Illness Rating Scale (CIRS). Cox regression analysis was performed using SAS v 9.2. Results: There were 332 V with a median (M) age of 70 years (27-94). The M for H 70 inches (58-78), W 183lbs (99-356.5) and BMI 26.7 kg/m 2 (15.54 -48.45). The M for hemoglobin(Hgb) 12.8 g/dl (7.3-17.4), albumin 3.9(1.2-5.4), lactate dehydrogenase( LDH) 183 IU/L (85-1905), beta 2-microglobulin 2.6 mg/dl (0.8-39) . The M for CCI was 4.7 (0.8-12), KFI 2 (0-3), CIRS15 3 (0-6), CIRS16 6(0 -14), CIRS17 1.9(0-6), CIRS18 0(0-3), CIRS19 0(0-3). M survival was 1297days(4-7468).The number of V receiving statin was 167 (51%) and metformin 46 (14%). Statin use was a predictor of survival by both univariate and multivariate analysis but metformin was a predictor only by univariate analysis. Conclusions: Statin use was an independent and significant predictor of survival in this group of V with BLD and needs to be validated in a larger group of patients. [Table: see text]
Abstract 2987: Percutaneous Coronary Intervention for Management of CAD: Evidence-Based or Enthusiasm-Bound?
Authors: Sanjay Kaul, Jayanta R Das, Prediman K Shah, George A Diamond
Journal: Circulation (2007)

Background Revascularization by percutaneous coronary intervention (PCI) is widely used in the treatment of patients with CAD. The use of PCI has exploded in the last decade with recent estimates i...
The DIAL Study (Dual Immunomodulation in Aggressive Lymphoma): A randomized phase 2 study of CDX-1127 (varlilumab) in combination with nivolumab in patients with relapsed or refractory aggressive B-cell lymphomas (NCI 10089/NCT03038672).
Authors: Jose Caetano Villasboas, Craig B. Reeder, Han W. Tun, Nancy L. Bartlett, Elad Sharon, Betsy LaPlant, Alex A. Adjei, Stephen M. Ansell
Journal: Journal of Clinical Oncology (2019)

TPS7570 Background: The DIAL study is testing the efficacy of dual immunomodulation in patients with advanced B cell non-Hodgkin lymphoma (B-NHL). Developed by the Cancer Therapy Evaluation Program (CTEP), the trial combines the use of a programmed cell death protein 1 (PD-1) inhibitor (nivolumab) with an agonist of the CD27 receptor (varlilumab) in a randomized phase 2 design. CD27, a co-stimulatory receptor, regulates T cell activation through interaction with CD70. T cell exhaustion plays a major role in immune evasion in B-NHL. Varlilumab is an agonistic IgG1 monoclonal antibody that recognizes CD27 leading to prevention or reversal of exhaustion. Varlilumab also demonstrates direct anti-tumoral activity in xenograft models of human lymphoma cell lines via antibody-dependent cell-mediated cytotoxicity. Phase 1 data supports the safety and tolerability of single-agent varlilumab in advanced hematologic malignancies. We hypothesize that CD27 activation synergizes with PD-1 inhibition resulting in a superior anti-lymphoma effect compared to PD-1 blockade alone. The study will also evaluate the effect of these agents on tumor and immune cells using IHC, mass cytometry (CyTOF), multiplex ELISA, imaging mass cytometry, and whole exome sequencing. Methods: The trial is enrolling patients with advanced aggressive B-NHL. Standard inclusion criteria and prior treatment with at least 2 lines of standard therapy are required. Prior autologous stem cell transplant and/or chimeric antigen receptor (CAR) T cell therapy is allowed. Patients with active CNS disease are excluded. Eligible patients will be randomized to treatment with single-agent nivolumab (group 1) or dual immunotherapy with nivolumab and varlilumab. Group 1 is allowed to cross-over at the time of progression. Nivolumab will be administered intravenously (IV) every 2 weeks (240 mg) for 4 months followed by monthly dosing thereafter (480 mg). Varlilumab will be given IV every 4 weeks (3 mg/kg). Response assessment will be done by PET-CT scan every 12 weeks. Primary outcome is overall response rate (ORR) according to the LYRIC criteria. The trial will enroll 48 patients per arm, allowing 80% power to detect at least 20% increase in ORR in the experimental arm (group 2) assuming a 25% ORR in the control arm (group 1). The trial is registered and open to participation to members of ETCTN and EDDOP. Clinical trial information: NCT03038672.
Abstract P147: Statin Therapy is Associated With a Lower Risk of Death in Patients Post Myocardial Infarction
Authors: Jacqueline P Honerlaw, Yuk-Lam Ho, Bing Lu, Jason L Vassy, Luc Djousse, Christopher J O'Donnell, J M Gaziano, David R Gagnon, Kelly Cho, Peter W Wilson
Journal: Circulation (2018)

Introduction: The use of statins after acute myocardial infarction (MI) has been shown to reduce the risk of recurrent MI and mortality. We examined the association between statin therapy and the risk of 1 year mortality after MI hospitalization. Methods: Data from the Veterans Health Administration was used to create a national sample of Veterans hospitalized for their first MI event between 2002 and 2015. Veterans with prevalent heart failure, stroke, or cancer diagnoses at the time of discharge for the index MI and prolonged hospitalization (greater than 30 days) were excluded. The statin therapy group was defined as Veterans having any statin prescription at the time of discharge. The primary outcome was all-cause mortality obtained from the National Death Index. We fitted a Cox regression model adjusted for age, length of hospital stay, peak cardiac troponin I ratio (the ratio of the peak measurement to the reference upper limit of normal for the assay) during hospitalization, statin use before admission, beta blocker prescription at discharge, liver disease, peripheral arterial disease, estimated glomerular filtration rate, high-density lipoprotein and total cholesterol levels. Billing codes were used to define exclusion criteria and co-morbidities. Results: Among 16,263 Veterans hospitalized for MI, mean age was 62 years and 98% were men. During 350 days mean follow up, 966 deaths occurred. In the statin therapy group 709/13,334 (5.3%) of Veterans died compared to 257/2,929 (8.8%) of Veterans without statin therapy. In an age-adjusted model, 1-year mortality was 35% lower (HR 0.65, 95%CI 0.56 - 0.75) for patients that were prescribed a statin at discharge compared to Veterans who did not receive a statin at discharge. In a multivariable model we observed a 27% (HR 0.73, 95% CI 0.63 - 0.85) lower risk of death for users of statin therapy compared to non-users (Figure). Conclusions: Statin therapy prescribed after a first MI event may reduce the 1 year risk of all-cause mortality.
Abstract 575: Adaptive CD4 Th1 response against telomerase in blood counteracts T-cell exhaustion in non-small cell lung cancer
Authors: Caroline Laheurte, Magalie Dosset, Dewi Vernerey, Elodie Lauret Marie Joseph, Laura Boullerot, Vincent Kaulec, Marion Jacquin, Laurie Cuche, Guillaume Eberst, Pascale Jacoulet, Virginie Westeel, Olivier Adotevi
Journal: Cancer Research (2019)

Abstract Despite the critical roles played by IFN-γ+ CD4 Th1 response in tumor immunity, the translation of their potential in clinic remains challenging. Here, we evaluate the clinical significance of circulating anti-tumor CD4 Th1 response in non-small cell lung cancer (NSCLC) patients. 170 naïve-treatment patients were enrolled in this immune monitoring study. The antitumor adaptive Th1 response was assessed by IFN-γ ELISPOT assay in blood lymphocytes using a mixture of eight highly promiscuous and Th1-polarized HLA class II-restricted epitopes from telomerase (TERT). The presence of anti-TERT Th1 response was detected in 59/170 patients (35%). We found an opposite link between anti-TERT Th1 and hyper exhausted T cells co-expressing PD-1+ and TIM-3+ in NSCLC patients. In contrast to hyper exhausted CD8 T cells, the presence of anti-TERT Th1 response was associated with a low rate of hyper exhausted CD4 T cells. We showed that NSCLC stage dissemination is associated with a decrease of anti-TERT Th1 response but an increase of circulating hyper exhausted PD-1+/TIM-3+ CD4 T cells. Notably, anti-telomerase Th1 response and hyper exhausted CD4 T-cells displayed opposite prognosis value in NSCLC. While high level of anti-TERT Th1 cells play a protective role, hyper-exhausted PD-1+TIM-3+ CD4 T cells negatively affect patients’ survival. By using these two circulating immune factors, we stratified patients in distinct prognostic group. Patients with anti-TERT Th1high/CD4 PD-1 TIM-3low immune profile had better overall survival than anti-TERT Th1low/CD4 PD-1 TIM-3high group (median OS : not reached versus 4 months respectively p&amp;lt;0.0001). In conclusion, high circulating anti-TERT Th1 response plays a strong protective role in NSCLC by counteracting the deleterious effect associated with hyper exhausted T cells in blood. Our study provides a dynamic blood-based immunomonitoring tool allow patients stratification. Citation Format: Caroline Laheurte, Magalie Dosset, Dewi Vernerey, Elodie Lauret Marie Joseph, Laura Boullerot, Vincent Kaulec, Marion Jacquin, Laurie Cuche, Guillaume Eberst, Pascale Jacoulet, Virginie Westeel, Olivier Adotevi. Adaptive CD4 Th1 response against telomerase in blood counteracts T-cell exhaustion in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 575.