tbuckley/cabot-search huggingface dataset:
Abstract 15931: Risk of Post Procedural Atrial Fibrillation in Patients Undergoing Transcatheter Aortic Valvular Replacement - A Meta-Analysis
Authors: Waqas Qureshi, Usama b Nasir, Elsayed Z Soliman, Peter M Belford, Sanjay K Gandhi, Robert J Applegate, David X Zhao
Journal: Circulation (2015)

Introduction: Atrial fibrillation is a common postoperative complication of surgical aortic valve replacement (SAVR). However, it is not known if the incidence of post procedure AF is impacted by performing Transcatheter Aortic Valvular Replacement (TAVR) instead of SAVR. Hypothesis: There is no difference in risk of post procedure incident AF in patients undergoing TAVR vs. SAVR. Methods: We systematically reviewed studies evaluating TAVR vs. SAVR and risk of post procedure AF. We searched MEDLINE, EMBASE, CINAHL, Web of Science, meeting abstracts, presentations and Cochrane central databases from inception through May 2015. For a study to be selected, it had to report the rates of incident AF in individuals undergoing TAVR. Data were extracted by 2 independent authors (WTQ and UBN). Forrest plot was created to show the effect sizes (Figure 1). Results: A total of 8 studies including 2483 patients (mean age 81.4 years, 70.3% male) were analyzed. There were 1293 patients that underwent TAVR and 1190 patients that underwent SAVR. The 1- year incidence of AF was 231 (17.9%) in TAVR group vs. 377 (31.6%) in SAVR group. In a random effects model, patients treated with TAVR had a 48% decreased risk of post procedural 1 year risk of AF [pooled Risk Ratio (95% confidence interval) 0.52 (0.37-0.73), p &lt;0.001]. There was moderate heterogeneity in the results (I2 = 80%). The risk of AF was higher in studies with older patients and was lower in studies with higher proportion of patients that underwent transfemoral TAVR vs. transapical TAVR. Conclusions: In this meta-analysis, the post procedure risk of AF was lower in TAVR group as compared to SAVR group. The risk of post procedure AF should be considered while making decision for TAVR vs. SAVR.
TCT-193 The Effect of Plaque Type on Strut Embedment/Protrusion and Shear Stress in Bioresorbable Scaffold: Is There a New Horizon For Bioresorbable Scaffolds?
Authors: Erhan Tenekecioglu, Ryo Torii, Yuki Katagiri, Ply Chichareon, Taku Asano, Jouke Dijkstra, Rodrigo Modolo, Yoshinobu Onuma, Christos Bourantas, Patrick Serruys
Journal: Journal of the American College of Cardiology (2018)
TRIBE; Tyrosine kinase inhibitor therapy in renal-cell carcinoma: Immune biomarker evaluation
Authors: S. Villa, M. Pillai, D. Graham, E. Kilgour, N. Overton, N. Vasudev, A. Hughes, A. Walker, S. Dransfield, F. Thistlethwaite
Journal: Annals of Oncology (2018)
Ivosidenib (IVO; AG-120) in mutant IDH1 relapsed/refractory acute myeloid leukemia (R/R AML): Results of a phase 1 study.
Authors: Daniel Aaron Pollyea, Courtney Denton Dinardo, Stéphane de Botton, Eytan Stein, Gail J. Roboz, Alice S. Mims, Ronan T. Swords, Jessica K Altman, Robert Collins, Gabriel N. Mannis, Geoffrey L. Uy, William Bruce Donnellan, Arnaud Pigneux, Amir Tahmasb Fathi, Hua Liu, Bin Wu, Eyal C. Attar, Martin S. Tallman, Richard M. Stone, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2018)

7000 Background: IVO is an oral, targeted inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1) that is being evaluated in a phase 1 dose escalation and expansion study of mIDH1 advanced hematologic malignancies (NCT02074839). Here we report updated efficacy and safety data from all patients with R/R AML receiving IVO 500 mg once daily (QD). Methods: The primary efficacy endpoint was the CR+CRh rate (complete remission [CR] according to modified IWG 2003 criteria plus CR with partial hematologic recovery [CRh]). CRh was defined as absolute neutrophil count > 0.5 × 109/L and platelet count > 50 × 109/L. The overall response rate (ORR) comprised CR, CR with incomplete hematologic or platelet recovery, partial response, and morphologic leukemia-free state. The data cutoff date for this analysis was Nov 10, 2017. Results: A total of 258 patients were treated with IVO. Among 179 R/R AML patients who received IVO 500 mg QD, 17 (9.5%) remained on treatment at data cutoff. In R/R AML patients, the CR+CRh rate was 31.8% (95% CI: 25.1%, 39.2%), including CR in 24.0% (95% CI: 18.0%, 31.0%). Median duration of CR+CRh was 8.2 months (95% CI: 5.6, 12.0), and median duration of CR was 10.1 months (95% CI: 6.5, 22.2). The ORR was 41.9% (95% CI: 34.6%, 49.5%). Treatment was well tolerated; the most common adverse events (AEs) of any grade, irrespective of causality and occurring in ≥25% of 179 R/R AML patients were diarrhea (33.5%), leukocytosis (31.3%), nausea (31.3%), febrile neutropenia (29.1%), fatigue (28.5%), and electrocardiogram QT prolonged (25.7%). The majority of these AEs were grades 1–2 and unrelated to treatment. IDH differentiation syndrome (IDH-DS) was reported in 19 of 179 (10.6%) patients, including grade ≥3 IDH-DS in 9 (5.0%); study drug was held owing to IDH-DS in 6 patients (3.4%), and no instances of IDH-DS led to dose reduction, permanent treatment discontinuation, or death. Updated mutation clearance results will be provided. Conclusions: In a high-risk, molecularly defined R/R AML patient population, IVO induced durable remissions and was well tolerated. Studies in previously untreated AML populations are ongoing. Clinical trial information: NCT02074839.
Frequency of overexpression of HER3 and prognostic consequences in European patients with early gastric cancer.
Authors: Nieves Martinez Lago, Ihab Abdulkader Nallib, Maria Vieito, Juan Jose Carrera, Sonia Candamio Folgar, Yolanda Vidal Insua, Francisca Vazquez Rivera, Jose Ramón Antunez Lopez, Rafael López López, Maria Elena Padin Iruegas
Journal: Journal of Clinical Oncology (2018)

4068 Background: HER2 status is a predictive biomarker to response to trastuzumab in metastatic gastric adenocarcinomas. However, relatively little is known about the role of HER2 and HER3 in the non-metastatic disease in European population. Methods: Immunohistochemical expression of HER2 was analyzed using DAKO-HercepTest™ and gene amplification using DAKO-DuoCISH kit; both were scored according to published criteria. HER3 expressión was analyzed using HER3 clon DAK-H3-ICHER3 HER2 patients with 0-1+ were classified as HER2 negative, patients with 2+ and negative DuoCISH as equivocal and 3+ or 2+ with positive DuoCISH as positive. HER3 pts were classified as negative if 0-1+ or positive 2-3+ by two independent observers. Six subtypes according to HER2 and HER3 status were defined. Relationship between this classification and the clinicopathological characteristics and survival was analyzed retrospectively. Results: 106 pts diagnosed between Jan-2007 and Jun-2014 were analyzed. Subtype distribution was: HER2-HER3 (-) (56.6%), HER2 equivocal/HER3 (–) 9 pts (8.5%), HER2 (-) HER3 (+) (15.1%), HER2 equivocal HER3 (+) (6.6%), HER2 (+) HER3 (-) (7.5%) and HER2 (+) HER3 (+) (5.7%). HER2 had a significant association with HER3 (p = 0.018). Strong or moderate HER2 expression was associated with intestinal differentiation (p = 0.020) while tumors with strong or moderate HER2 expression or high HER3 expression were associated with lower grade (p = 0.050). Patients with low expression of HER2 and HER3 had a better specific overall survival ( > 85%) than those with HER3 overexpression (66.7-68.6%). Patients with strong or moderate HER2 expression without HER3 expression tumors had the worse survival (50%). Conclusions: Our algorithm based in HER2 and HER3 status proposes a classification in 6 groups with clinicopathologic and prognostic correlates. Overexpression of HER3 is a frequent phenomenon in early gastric cancer that modulates the adverse prognosis associated with HER2 overexpression. Patients with HER3 overexpression have an intermediate prognosis between patients with isolated HER2 overexpression and those who lack both drivers.
A randomized multicenter phase II study of FOLFIRI plus either panitumumab (Pmab) or bevacizumab (Bmab) as second-line treatment for wild-type <i>KRAS</i> exon 2 metastatic colorectal cancer (mCRC) with exploratory biomarker analysis by liquid biopsy: WJOG6210G.
Authors: Kohei Shitara, Kimio Yonesaka, Tadamichi Denda, Kentaro Yamazaki, Toshikazu Moriwaki, Masahiro Tsuda, Toshimi Takano, Hiroyuki Okuda, Tomohiro Nishina, Kazuko Sakai, Kazuto Nishio, Shoji Tokunaga, Takeharu Yamanaka, Narikazu Boku, Ichinosuke Hyodo, Kei Muro
Journal: Journal of Clinical Oncology (2016)

3567 Background: The objective of this phase II trial wasto compare efficacy of Pmab plus FOLFIRI and Bmab plus FOLFIRI as second-line chemotherapy for patients (pts) with wild-type (WT) KRAS exon 2 mCRC, associated with comprehensive biomarker analysis. Methods: Pts with WT KRAS exon 2 mCRC refractory to first-line chemotherapy containing oxaliplatin and Bmab were randomly assigned to Pmab plus FOLFIRI or Bmab plus FOLFIRI. The primary endpoint was OS; secondary end points included PFS, ORR, safety and translational research. Results: Of 121 randomly assigned pts, 117 pts were eligible for analysis. OS was almost similar between two arms (HR, 1.16; 95% CI, 0.76 to 1.77) with median OS of 16.2 months in Pmab and 13.4 months in Bmab (Stratified Log-rank P=0.499). Median PFS was 6.0 months in Pmab and 5.9 months in Bmab (HR, 1.14; 95% CI, 0.78 to 1.66). ORR was 46.2% in Pmab and 5.7% in Bmab. KRAS, NRAS or BRAF mutations in circulating tumor DNA were identified in 19 (17.4%) of 109 pts whose baseline plasma samples were available for biomarker analysis. For pts with any of these mutations, Pmab showed worse OS than Bmab (HR, 0.42) meanwhile better trend was observed in Pmab for all WT (HR, 1.21; P for interaction =0.026). Pmab showed better OS than Bmab in patients with low serum VEGF-A (≤ median) level, (HR 1.92) while Bmab showed better OS among those with high level (HR 0.67; P for interaction=0.016, table). High serum levels of HGF, amphiregulin, EGF and Tenascin C were associated with worse OS among all pts. Conclusions: OS was almost similar with second-line FOLFIRI plus either Pmab or Bmab in pts with WT KRAS exon 2 mCRC. Oncogenic mutation in circulating tumor DNA and serum VEGF-A may be candidate biomarkers to stratify pts, which warrants further evaluation. Clinical trial information: UMIN000005216. Mutation in circulating tumor DNA Serum VEGF-A All Wild RAS or BRAF mutant Low (≤ median) High (>median) Pmab Bmab Pmab Bmab Pmab Bmab Pmab Bmab N of patients 46 44 8 11 30 24 24 31 Median OS (month) 18.9 16.1 5.4 8.2 22.4 13.4 10.7 13.7 HR 1.21 0.42 1.92 0.67 95% CI 0.74 - 1.99 0.15 - 1.12 0.98 - 3.76 0.37 - 1.21 P for interaction 0.026 0.016
Epidemiological trends of head and neck cancer survivors in Alberta: Towards improved understanding of the burden of disease.
Authors: Patrick Vallance, Caroline Jeffery
Journal: Journal of Clinical Oncology (2018)

e18052 Background: Head and neck cancer is a devastating disease that impacts every aspect of a patient’s life, but has particular effects on communication, voice, swallowing, and body image. The incidence of head and neck cancer has increased dramatically in the last two decades due to Human papillomavirus-related oropharyngeal cancer. While survival outcomes have traditionally been very poor for some head and neck cancer sub-sites, favorable oncologic outcomes are increasingly achievable with current treatment paradigms. This has created a population of head and neck cancer survivors that are different from preceding decades. This study was undertaken to determine the changing incidence and epidemiological trends of head and neck cancer survivors in Alberta. Methods: Retrospective cohort study of head and neck cancer patients from the Alberta Cancer Registry. This Registry was queried for head and neck cancer patients who were at least 1-year post-treatment that initiated between 1997 to 2016. Cutaneous head and neck and thyroid cancer patients were excluded. Extracted data was then used to calculate the incidence and prevalence for early ( < 5 years from treatment), intermediate (5 to < 10 years from treatment), and late ( > 10 years from treatment) survivors of head and neck cancer. Analysis of demographic changes over time and sub-stratification by gender, sub-site, and age were also performed. Results: Head and neck cancer survivors tend to be younger (64.0 vs. 62.1, p = 0.046) and male (M:F 2.45:1 vs 2.54:1). Sub-site distribution of patients have also changed. In 1997 the majority of cases arose from the oral cavity (45.8%) and the larynx (30.9%) whereas in 2015 the bulk of cases arose from the oral cavity (33.0%) and oropharynx (29.4%). The prevalence of late head and neck cancer survivors increased to 13.3 per 100,000 people in 2015. Conclusions: Head and neck cancer survivors are now younger with a slight male predominance. Oral cavity cancers have decreased and oropharyngeal cancers have become a major subsite. In addition, there is an increasing population of long-term survivors.
P04.72 Using Mendelian randomization to find potential novel drug targets for the treatment of glioma
Authors: J W Robinson, J Zheng, S Tsavachidis, P Haycock, M Bondy, C Relton, R Martin, G D Smtih, K M Kurian
Journal: Neuro-Oncology (2018)

There are about 12,000 new brain tumours each year in the UK. Around 50% of these are gliomas, of which the majority are the highly aggressive glioblastoma multiforme (GBM) subtype. The median survival rate of GBM is 15 months. The treatment regime for glioma has remained relatively static since the introduction of temozolomide; the median survival rate for patients has increased relatively little since, despite advances in potentially helpful fields such as genomics and bioinformatics. Current methods of drug discovery are unsustainable and inefficient. Costs for development of a new drug can run up to around US$802 million per drug, taking around 12 years before approval for marketing. It is not always guaranteed a drug will make it to market; many fail in stage III trials due to insufficient safety or efficacy. A paradigm shift in the industry is necessary for innovation to remain high. We propose the use of Mendelian randomization (MR) - a statistical method that uses genetic anchors to infer causal relationships between exposure (e.g. phenotype) and outcome (e.g. disease) - as a potential tool to find novel drug targets for glioma. MR produces more reliable results compared to standard observational epidemiological studies, as MR is less susceptible to many bias, e.g. reverse causation and confounding. Specifically, we propose that results from MR analyses may prioritise which drug targets are most likely to pass efficacy tests. We used protein quantitative trait locus (pQTL) data on plasma proteins as genetic instruments and glioma data from the recent genome wide association study as the outcome (12,497 cases, 18,190 controls from six studies). To increase reliability of the instruments, we focused on 2,346 significant pQTLs (Bonferroni-corrected P threshold of 5x10-8) with no heterogeneity across studies and performed two-sample MR. For MR results that reached statistical significance, we further evaluated the findings by performing Steiger filtering to assess the directionality of effects (e.g. whether the proximal pQTL effect is on the protein which then influences glioma, or vice versa). All analyses were performed in the TwoSampleMR R package. The MR analysis identified three proteins strongly associated (1,398 tests, P threshold of 3.58x10-5) with glioma: CD36, SEMA6A and CDH5. The top hit, CD36, is known to play a part in angiogenesis and its expression has been found to affect prognosis for patients with GBM. These associations are necessary but not sufficient to prove causality, as potential horizontal pleiotropy remains an alternative explanation. The results provide three potential new targets for the prevention of GBM progression, provided the causes of incidence are the same as progression. Upon further research, this could be evidence that MR may be a useful tool in the drug discovery process and have translational uses.
Impact of obesity on survival and recurrence of high grade serous carcinoma of the ovary.
Authors: Carolina Ibañez, Elisa Orlandini, Mauricio Cuello, Jorge Brañes, Nicanor Barrena, Francisco Acevedo, Nicolas Yanez, Alejandra Perez, Sebastian Mondaca, Bruno Nervi
Journal: Journal of Clinical Oncology (2016)

e17081 Background: Obesity is a public health problem in most developed countries, with growing incidence in the last decades. Epidemiologic studies associate obesity with increased risk of developing ovarian cancer, however, its impact on survival and recurrence is not well established. High grade serous ovarian carcinoma (HGSC) is the most common histology and has a high mortality rate. The aim of this study was to determine if a high Body Mass Index (BMI) before platinum based chemotherapy in advanced stage HGSC is associated with poor progression free (PFS) or overall survival (OS). Methods: A prospective chart review of clinicopathological data was done of patients with HGSC treated at Pontificia Universidad Catolica de Chile between 2011 and 2015. We included patients wih stage III/IV treated with primary cytoreduction, combined platinum based adjuvant chemotherapy and complete follow-up. Data collected included height/weight, age, tumor stage, plasma Ca-125 levels, type of chemotherapy, and optimal/suboptimal cytoreduction. The diagnosis of recurrence was made by positive radiological findings, Ca-125 levels, clinical symptoms or a combination of them. Following WHO guidelines patients were stratified by BMI (normal range: < 25, and overweight/obese: > 25). Time to recurrence and OS was registered in months. Survival analysis was made by Kaplan Meier method and compared with log-rank test. Results: We included 46 patients with stage III/IV HGSC.Complete cytoreduction was achieved in 20/21 of overweight/obese patients versus 20/25 of normal weight patients. Recurrence rate was 52% on overweight/obese patients versus 50% of patients with normal BMI. Progression free survival at 36 months was similar in both groups, 21% versus 19%, respectively (p = 0.52). Median OS of the whole group (46 patients) was 118 months. At 36 months, OS was 62% on the overweight/obese patients versus 89% of normal weight, this difference was not significant (p = 0.108). Conclusions: BMI did not correlate with the ability to perform optimal cytoreduction. Overweight and obesity does not impact on recurrence. Although there was a trend towards an increased overall survival in the normal weight group, this difference was not statiscally significant.
A phase IV study using multi-omics to identify mechanisms of response and resistance to crizotinib in ALK+ advanced non-small cell lung cancer (NSCLC) patients with distinct progression free survival outcomes.
Authors: Mathilde Couetoux du Tertre, Lise Tremblay, Nicole Bouchard, Razvan Diaconescu, Normand Blais, Errol Camlioglu, Andre Constantin, Cyrla Hoffert, Karen Gambaro, Archana Srivastava, Celia Greenwood, Christian Couture, Suzan McNamara, Gerald Batist, Victor Cohen, Jason Scott Agulnik
Journal: Journal of Clinical Oncology (2017)

e20588 Background: Crizotinib is the current first-line standard of care for ALK+ NSCLC with response rates reaching 65% [1] . However, most patients progress within 1 or 2 years and mechanisms of resistance remain unknown for approximately 30% of patients [2] . [1] Shaw et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. NEJM 368: 2385-2394, 2013. [2] Doebele et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res 2012; 18:1472-1482 Methods: Eligible patients had locally advanced or metastatic ALK+ NSCLC. Patients were asked to undergo a repeat tumor biopsy at time of progression and serial bloods and archived primary tumor were collected. Responses were assessed by RECIST 1.1. ctDNA and protein expression on serial blood will be evaluated over the course of treatment. Tumors were profiled using exome sequencing and targeted genomic analysis to identify novel mutations associated with response. Results: 24 patients with stage IV adenocarcinoma received crizotinib as first-line (n = 22) and second-line (n = 2) treatment. Mean age was 60 y (range 41-80). 4% were smokers, 33.5% were former and 62.5% were never-smokers. At data cutoff (Jan 26, 2017), 16 patients have discontinued treatment (14 due to progression and 2 withdrew). The median PFS markedly differed in non-responders (patients with immediate progression) vs responders (patients with initial response or stable disease) (1.8 vs. 27 months). Profiling was performed to identify the genomic traits in tissue and blood that correlate to treatment response. Conclusions: We identified a previously unrecognized subset of patients treated with crizotinib with an exceptionally long PFS. We also observed a subset of patients intrinsically resistant to crizotinib despite harboring ALK+. There are no known predictive biomarkers which can identify patients that will have a long-lasting response or who may not derive benefit from crizotinib. The multi-omics profiling applied to these groups may provide novel insights into mechanisms of response and resistance to crizotinib. Clinical trial information: NCT02041468.
Regional lymph node metastases oncogenic mutations compared to primary tumors in HPV+ oropharynx patients.
Authors: John F. Deeken, Dzung Thach, Patty Lee, Gopal Krishna Bajaj, Moin Ahmad, Ramaswamy K Iyer
Journal: Journal of Clinical Oncology (2018)

6078 Background: Residual disease after concurrent chemoradiation in locally advanced Head and Neck cancer is typically contained in involved lymph nodes (LNs), with primary tumors (PTs) showing complete response to treatment. This resistant phenotype in LNs is not well characterized. Clonal genomic evolution in node metastases may explain this phenotype. Methods: PTs and matched LNs from consecutive patients who underwent trans-oral robotic surgery with modified neck dissections as primary therapy were tested using NextGen sequencing using the Oncomine Comprehensive Assay run on the Ion Torrent S5 system. This platform detects genetic mutations in 143 known cancer related genes. Tumors from patients treated with primary surgery were used given the need for sufficient tumor content to run the assay. Results were interpreted using the Ion Reporter Software. Results: A total of 21 patients had sufficient tumor content in FFPE samples that passed QC testing. Eight (38%) matched sets of PTs and LNs displayed the same mutation profile. LNs from four patients (19%) showed loss of mutations detected in primary tumors. Nine patients (43%) showed gain of mutations in neck LNs compared to PTs. Genes showing gain of mutation in LNs included: TP53 (4), PIK3CA (3), FBXW7 (3), VHL (1), PTEN (1), JAK3 (1), and MAPK1 (1). Conclusions: Gain of mutations in regional LNs was detected in almost half of all HPV-positive oropharynx patients. Gain of mutations in genes such as TP53 and PIK3CA may define a resistant genotype when such patients are treated with primary chemoradiation.
TCT-599 The GlucagOn-like peptide 1 Loading During PCI (GOLD PCI) trial: 12-month clinical outcomes
Authors: Joel Giblett, Sophie Clarke, Liam McCormick, Tian Zhao, Sofia Villar, Sarah Fielding, Denise Braganza, Cameron Densem, Nick West, Stephen Hoole
Journal: Journal of the American College of Cardiology (2018)