tbuckley/cabot-search huggingface dataset:
Evaluation of efficacy of nivolumab by baseline factors from ATTRACTION-2.
Authors: Yoon-Koo Kang, Taroh Satoh, Yee Chao, Ken Kato, Hyun Cheol Chung, Jen-Shi Chen, Kei Muro, Won Ki Kang, Takaki Yoshikawa, Sang Cheul Oh, Takao Tamura, Keun-Wook Lee, Satoshi Morita, Li-Tzong Chen, Narikazu Boku
Journal: Journal of Clinical Oncology (2019)

8 Background: Nivolumab (Nivo) has shown superior efficacy with manageable safety for G/GEJ cancer refractory to, or intolerant of, standard chemotherapy in phase 3 study (ATTRACTION-2). Subgroup analysis of OS according to baseline demographics and disease characteristics favored Nivo over placebo in all subgroups. However, about half of patients had early disease progression even after administration of Nivo. Here, we explored factors of patients who had early progression after administration of Nivo. Methods: A statistical random forest method, a type of machine learning method, was used to explore clinical factors that could contribute to early progression after Nivo. In this analysis, the outcome variable was 56-day PD rate and covariates were patients’ clinical background factors. Factors were explored by comparing Nivo and placebo arms in all subgroups, constructed with 1) every single factor; 2) every pair of factors coming from the covariates. Results: In a single factor extraction, hyponatremia was identified as the most highly contributing factor to early progression. Of 330 patients in the Nivo arm, 59 patients showed hyponatremia at the baseline. Importantly, in a pair factor extraction, the patient population with hyponatremia and any of high NLR (N = 31, 9.4%, cut off; second tertile), high neutrophil (N = 28, 8.5%, cut off; second tertile), PS1 (N = 50, 15.2%) or no prior use of ramucirumab (N = 55, 16.7%), were found as risk factors of early progression in Nivo. PFS-KM curves were almost overlapped between Nivo and placebo arms in these patients with any pair of these risk factors. Conclusions: Our exploratory analysis suggested that a patient population with both ‘poor general condition’ represented by hyponatremia and PS 1, and ‘inflammatory conditions’ represented by high NLR and/or high neutrophil count, would be potential risk factors associated with early progression. This needs further validation with other potential biomarkers in tumor tissue and additional studies. Additional analysis with biomarkers such as PD-L1 will be presented at the meeting. Clinical trial information: NCT02267343.
Three different chemotherapeutic regimens as a postoperative adjuvant chemotherapy for curatively resected gastric cancer: A retrospective analysis.
Authors: Shen Zhao, SHEN ZHAO
Journal: Journal of Clinical Oncology (2019)

154 Background: Two double regimens, CAPEOX (CLASSIC trial) and docetaxel/S-1 (JACCRO GC-07), were standard treatment for curatively resected gastric cancer (GC) in Asia. However, the outcome of double regimens as postoperative adjuvant treatment remains unsatisfactory and the efficacy between oxaliplatin-based or taxane-based doublets is unknown. This study aimed to investigate if triplet improve survival compared with doublets and difference between oxaliplatin-based or taxane-based doublets. Methods: We found the patients with gastric cancer who received FOLFOX or POF or TF as adjuvant chemotherapy after curatively resection between 2002 and 2015 from our hospital. The POF consisted of a three-hour infusion of paclitaxel 135 mg/m 2 , followed by FOLFOX omitted 5-Fu bolus. The TF is a substitution of paclitaxel 135 mg/m 2 for oxaliplatin of FOLFOX. We checked the overall survival rate and the frequency of adverse reaction among the three groups. Results: We retrospectively studied 275 patients (POF 26, FOLFOX 172, TF 67). One, two, and three years OS rate were shown in table. POF was the worst survival among three regimens (p = 0.04). The patients with POF were shown more grade ¾ toxicity than two doublets. The patients with TF was more grade ¾ neutropenia, FOLFOX was more grade ¾ neuropathy. Conclusions: FOLFOX and TF which were similar in term of survival were recommended as adjuvant chemotherapy after curatively resection in the patients with gastric cancer. POF was less likely to improved survival than two doublets, which was not recommended. [Table: see text]
Case-control Study on Epidemiologic Factors Influencing The Occurrence of Immediate Wheat Allergy Among Thai Children
Authors: Nattiya Kitiphipat, Witchaya Srisuwatchari, Orathai Jirapongsananuruk, Nualanong Visitsunthorn, Pakit Vichyanond, Punchama Pacharn
Journal: Journal of Allergy and Clinical Immunology (2019)
Economic Outcomes Associated with Attainment of Healthcare Effectiveness and Data Information Set (HEDIS) Measures in Patients with Persistent Asthma (PA): Stratification by Attainment of Medication Management (MM) and/or Asthma Medication Ratio (AMR)
Authors: Huan Huang, Aimee Near, Rinat Ariely, Michael DePietro, Miao Jiang, Alberto Batista, Karthik Ramakrishnan, Giselle Mosnaim
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 186: Patient Positioning Improves Direct Laryngoscopy First-Attempt Success in Patients with Cardiac Arrest
Authors: Mark Escott, Guy Gleisberg, Kevin Traynor, Shane Jenks, Levon Vartanian, Casey Aaron-Wood, Jared Cosper, Brett Monroe
Journal: Circulation (2014)

Introduction: Multiple endotracheal intubation (ETI) attempts can facilitate complications and adversely affect patient outcomes. According to the AHA, in out-of-hospital urban and rural settings, patients intubated during resuscitation had a better survival rate than patients who were not intubated. Published literature on cardiac arrest (CA) patient positioning during ETI and its significance on first attempt success rate (FASR) are scarce. Objective: To compare direct laryngoscopy (DL) intubation FASR and glottic exposure with patient position during CA. Methods: An institutional review board approved, multi-agency prospective analysis was conducted comparing video laryngoscopy to DL from March 18, 2013 through March 17, 2014 performed by consented paramedics. Subsequently, a subgroup analysis was performed on CA patients, examining the effect of provider positioning on FASR during DL. Throughout this study, patient airways were managed in the following optional positions: (1) supine - floor (Floor), (2) supine stretcher - ambulance (Ambulance), and (3) supine stretcher - elevated (Elevated). We recorded the FASR, Cormack- Lehane and Percentage of Glottic Opening views within each intubation position. Results: A total of 190 first attempt DL intubations were recorded, of these 120 (63%) were successful. The DL intubation FASR by positions was: (1) Floor 37 (55%) compared to Ambulance 19 (58%) (95% CI: -0.179 - 0.216), (2) Ambulance 19 (58%) compared to Elevated 64 (71%) (95% CI: -0.047 - 0.323), (3) Floor 37 (55%) compared to Elevated 64 (71%)(95%: CI: 0.008 - 0.304). The Cormack- Lehane view grade mean was: Floor 2.6, Ambulance 2.4, and Elevated 2.0. The Percentage of Glottic Opening mean was: Floor 52%, Ambulance 53%, and Elevated 66%. Conclusions: This analysis demonstrated a 16% increase and superiority in DL intubation FASR from the Floor to the Elevated position on CA patients. The Elevated position offers an enhanced view of the airway anatomy and improved Cormack- Lehane and Percentage of Glottic Opening scores. The position of intubation should be considered when evaluating the appropriate stage in cardiac arrest to provide advanced airway management, particularly with anticipated difficult airways.
Updated results of the BEACON CRC safety lead-in: Encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) for BRAFV600E-mutant metastatic colorectal cancer (mCRC).
Authors: Scott Kopetz, Axel Grothey, Rona Yaeger, Pieter-Jan AR Cuyle, Sanne Huijberts, Jan H. M. Schellens, Elena Elez, Marwan Fakih, Clara Montagut Viladot, Marc Peeters, Jayesh Desai, Takayuki Yoshino, Fortunato Ciardiello, Harpreet Singh Wasan, Kati Maharry, Janna Christy-Bittel, Ashwin Gollerkeri, Eric Van Cutsem, Josep Tabernero
Journal: Journal of Clinical Oncology (2019)

688 Background: BRAF V600E mutation occurs in 10%-15% of patients (pts) with mCRC and confers a poor prognosis. After first-line therapy, standard second-line therapies provide limited benefit, with objective response rates (ORRs) &lt; 10%, and overall survival (OS) of 46 months (mo). BEACON CRC (NCT02928224) is a 3-arm phase 3 trial of triplet therapy with the BRAF inhibitor ENCO + MEK inhibitor BINI + antiEGFR antibody CETUX vs ENCO + CETUX vs a control arm (irinotecan/FOLFIRI + CETUX) in pts with BRAF V600E mCRC in the second or third-line setting. A safety lead-in (SLI) of the triplet therapy was conducted in 30 pts prior to initiation of the randomized part of the trial. Previously reported confirmed ORR in 29 pts with BRAF V600E mCRC was 48% and median progression-free survival (PFS) was 8.0 mo (Van Cutsem E, et al. Ann Oncol. 2018;29:O-027). Here we present updated safety and efficacy results including mature OS. Methods: All pts in the SLI received ENCO 300 mg once daily + BINI 45 mg twice daily + CETUX standard weekly dose. Assessments included efficacy (ORR, duration of response, time to response, PFS, and OS), safety, and tolerability. Results: Among 30 pts treated, 1 had a BRAF non-V600E mutation and is not included in the efficacy analyses. At data cutoff, the median follow-up time for survival was 18.2 mo and median exposure was 7.8 mo (range 0.521.4 mo). The confirmed ORR and median PFS remain unchanged from the previous report (ORR, 48% [95%CI, 29.467.5]; PFS, 8.0 mo [95% CI, 5.69.3 mo]). Mature median OS is 15.3 mo (95% CI, 9.6 monot reached). The triplet continues to be well-tolerated with no unexpected toxicities. The most common grade 3/4 toxicities were fatigue (13%), anemia, increases in creatine phosphokinase and/or aspartate aminotransferase, and urinary tract infections (each 10%). The rate of grade 3/4 skin toxicities continues to be lower than generally observed with CETUX in mCRC. Conclusions: With longer follow-up, triplet therapy with ENCO + BINI + CETUX continues to be well tolerated. Median PFS and now mature median OS are substantially improved over historical data for current standard-of-care options. Clinical trial information: NCT02928224.
Abstract O.71: Thrombosis and Thromboprophylaxis for Patients with Giant Coronary Artery Aneurysms after Kawasaki Disease: A Study from the North American Kawasaki Disease Registry
Authors: Cedric Manlhiot, William T Mahle, Kevin D Hill, Jennifer S Li, Dawn Tucker, Ashwini Kulkarni, Lillian S Lai, Brett Anderson, Aaron K Olson, Brian W McCrindle
Journal: Circulation (2015)

Background: Children with giant coronary artery aneurysms (CAA) after Kawasaki disease (KD) are at substantial risk of thrombosis. There are currently no evidence-based guidelines for optimal thromboprophylactic therapy in these children. Methods: The North American Kawasaki Disease Registry was queried to identify all patients with giant CAA (maximum coronary artery z-score &gt;10) and their antithrombotic therapy. Freedom from thrombosis was modelled using the Kaplan-Meier method; thrombotic complication rate was calculated per patient-year/month of follow-up. Results: n=202 patients with giant CAA were included, of whom 28 (14%) experienced either coronary artery thrombosis with or without myocardial infarction. Freedom from thrombotic complications was 92%, 85% and 79% at 3 months, 5 and 10 years after diagnosis, respectively. Non-pharmacological factors associated with increased risk of thrombotic complications included higher maximum coronary artery z-scores (HR: 1.7/+10 SD, p&lt;0.001), higher number of coronary artery branches with giant CAA (HR: 2.6/branch, p&lt;0.001), higher number of discrete CAA (HR: 1.4/aneurysm, p=0.001) and presence of complex CAA (involving the bifurcation or non-discrete; HR: 3.0, p=0.05). A total of 982 patient-years of follow-up were available for analysis (11% low molecular weight heparin (LMWH), 32% warfarin, 57% antiplatelet alone). All patients were maintained on ASA, with 47 patients (23%) also receiving clopidogrel. Patients while on LMWH had the highest event rate, at 1 event per 13 patient-years, compared to 1 per 39 on warfarin and 1 per 33 on no anticoagulant. However, LMWH was predominantly prescribed immediately after the acute phase, which is also the highest risk phase for thrombosis. When limiting analysis to events within 3 months of the acute phase, patients on LMWH had the lowest event rate at 1 per 46 patient-months, compared to 1 per 27 on warfarin and 1 per 33 on no anticoagulant (p=NS). Conclusions: Current thromboprophylaxis strategies in patients with giant CAA have suboptimal efficacy, and residual thrombosis risk persists. New anticoagulants/antiplatelet agents should be assessed in this population to determine if they provide better, safer and more tolerable thromboprophylaxis.
Outcomes of patients with borderline-resectable pancreatic cancer treated with FOLFIRINOX versus gemcitabine plus nab-paclitaxel.
Authors: Shaina D'Lee Templeton, Michael Moser, Haji I. Chalchal, John Shaw, Yigang Luo, Adnan Zaidi, Shahid Ahmed
Journal: Journal of Clinical Oncology (2019)

299 Background: Pancreatic cancer is a major cause of cancer-related death. Less than 20% of patients have resectable disease at diagnosis. Patients with borderline-resectable pancreatic cancer (BRPC) are at high risk of incomplete resection with upfront surgery. Currently there is no standard induction chemotherapy regimen exists for BRPC. Both FOLFIRINOX (5-FU, irinotecan, oxaliplatin) and gemcitabine/nab-paclitaxel (GnP) have shown better efficacy than gemcitabine in advanced pancreatic cancer. The current study aims to assess outcomes of real-world patients with BRCP who received induction FOLFIRINOX or GnP. Methods: In this population-based multicenter retrospective cohort study patients with biopsy proven BRPC as defined by the pancreatic surgical team diagnosed from 2011-2017, in the province of Saskatchewan, Canada, who received FOLFIRINOX or GnP were assessed. Kaplan Meier methods and log rank tests were performed for survival analyses. Results: Of 161 patients with pancreatic cancer who received FOLFIRINOX or GnP during the study period, 20 eligible patients with BRPC, with median age of 65 yrs (54-79) and M:F 14:6, were identified. 85% had pancreatic head tumours with a median CA19-9 of 470 u/mL. Of eligible patients, 10 each received FOLFIRINOX or GnP. No significant differences were found between the two groups, except more patients in FOLFIRINOX group had a WHO performance status of 0 (50% vs. 10%, p = 0.057) and had a higher body mass index (27.0 vs. 23.0, p = 0.027). Eleven patients showed partial response (5–FOLFIRINOX and 6–GnP), three progressed during treatment. Five patients (4–FOLFIRINOX, 1–GnP, p = NS) underwent curative surgery. Five patients (1–FOLFIRINOX, 4–Gnp) had radiation and four underwent Nanoknife procedure (3–FOLFIRINOX, 1–GnP). The median progression free survival was 17 months in FOLFIRINOX (95% CI: 5.3-28.6) versus nine months (3.0-15) in GnP group (p = 0.26). The median overall survival was 32 months in FOLFIRINOX (not reach) versus 16 months (9.3-22.7) in GnP group (p = 0.15). Conclusions: The current study suggests that patients with BRPC who received FOLFIRINOX tends to have better outcomes. Future study are warranted to establish a preferred systemic therapy for BRPC.
Characterization of Patients with Multiple Myeloma in Long- Term Remission
Authors: Raphael K. Lutz, Katharina Kriegsmann, Mohamed H.S. Awwad, Carsten Müller-Tidow, Gerlinde Egerer, Nicola Lehners, Marc S Raab, Brian GM Durie, Michael Hundemer, Hartmut Goldschmidt
Journal: Blood (2018)
Increase of bcr-abl chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression
Authors: Gaiger A, Henn T, Hörth E, Geissler K, Mitterbauer G, Maier-Dobersberger T, Greinix H, Mannhalter C, Haas Oa, Lechner K, Lion T
Journal: Blood (1995)
CEA response at four weeks as an early predictor for outcomes in patients (pts) with metastatic colorectal cancer (mCRC) treated with first-line cetuximab-based chemotherapy: A STEP-analysis in the JACCRO CC-05/06 trials.
Authors: Yu Sunakawa, Xuemin Fang, Masahito Kotaka, Hiroaki Tanioka, Akinori Takagane, Satoshi Tani, Tatsuro Yamaguchi, Takanori Watanabe, Toshiki Masuishi, Masahiro Tsuda, Tatsuya Okuno, Takao Tamura, Kaoru Furushima, Hidekazu Kuramochi, Junichi Koike, Yutaka Yonemura, Hisateru Yasui, Masahiro Takeuchi, Masashi Fujii, Wataru Ichikawa
Journal: Journal of Clinical Oncology (2019)

543 Background: We have reported that carcinoembryonic antigen (CEA) response correlated with clinical outcomes of 1st-line cet-based therapy (Target Oncol 2017). Early tumor shrinkage (ETS) is considered to be an on-treatment biomarker for outcomes of chemotherapy; however, clinical biomarkers to predict outcomes earlier are warranted. Methods: This study included 69 pts who were assessable for CEA at baseline and 4 wks, and with observed survival time from 2 phase II trials of 1st-line therapy for KRAS exon2 wild-type mCRC; JACCRO CC-05 of cet plus FOLFOX (UMIN000004197) and CC-06 of cet plus SOX (UMIN000007022). We investigated the influence of baseline age, gender, PS, primary tumor sidedness (PTS), number of tumor sites, as well as the CEA decrease at 4 wks to the patient’s OS and PFS. Results: PTS and the CEA decrease at 4 wks were found to be important predictors to OS and PFS. Baseline CEA and CEA decrease at 4 wks were median of 31.0 (range, 1.0-20920.0) and median of 35% (range, -259%-97%), respectively. The STEP-analysis indicated that CEA response was most significantly associated with OS when a cut-off value of 50% for CEA-responder (HR 0.49, log-rank test p = 0.03). Median OS in responders (n = 25) and non-responders (n = 44) were 36.2 m and 21.5 m, respectively. When the same cut-off value was used, median PFS in responders and non-responders were 11.6 m and 6.5 m, respectively (HR 0.64, log-rank test p = 0.08). In addition, a multivariate Cox Proportional-Hazards Model with both PTS and CEA response as risk factors showed that PTS correlated with both OS and PFS. In pts with left-sided tumors, non-responders (n = 33) had shorter OS and PFS compared to responders (n = 23). In the above 2-covariate Cox proportional hazard model, adjusted HR for CEA 50% decrease is 0.55, p = 0.1; adjusted HR for PTS is 2.66, p = 0.008. Conclusions: Our analysis suggests 50% CEA decrease at 4 wks as an early on-treatment biomarker for 1st-line cet-based therapy in mCRC. It may potentially predict outcomes earlier compared to ETS. Also, CEA response at 4 wks may differentiate pts who receive more benefit from cet treatment in left-sided tumors. Clinical trial information: UMIN000004197 and UMIN000007022.
PHF6 regulates hematopoietic stem and progenitor cells and its loss synergizes with expression of TLX3 to cause leukemia
Authors: Helen M. McRae, Alexandra L. Garnham, Yifang Hu, Matthew T. Witkowski, Mark A. Corbett, Mathew P. Dixon, Rose E. May, Bilal N. Sheikh, William Chiang, Andrew J. Kueh, Tan A. Nguyen, Kevin Man, Renee Gloury, Brandon J. Aubrey, Antonia Policheni, Ladina Di Rago, Warren S. Alexander, Daniel H. D. Gray, Andreas Strasser, Edwin D. Hawkins, Stephen Wilcox, Jozef Gécz, Axel Kallies, Matthew P. McCormack, Gordon K. Smyth, Anne K. Voss, Tim Thomas
Journal: Blood (2019)
Abstract IA19: MYC activation through enhancer hijacking or focal enhancer amplification drives a subset of high-risk pediatric neuroblastoma
Authors: Mark W. Zimmerman, Yu Liu, Shuning He, Adam D. Durbin, Brian J. Abraham, John Easton, Ying Shao, Beisi Xu, Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Richard A. Young, Jinghui Zhang, A. Thomas Look
Journal: Cancer Research (2018)

Abstract The amplified MYCN gene serves as an oncogenic driver in approximately 20% of high-risk pediatric neuroblastomas. Here we show that MYC itself is a potent transforming gene in a separate subset of high-risk neuroblastoma cases (~10%), based on (i) its upregulation by focal enhancer amplification or genomic rearrangements leading to enhancer hijacking, and (ii) its ability to transform neuroblastoma precursor cells in a transgenic animal model. The aberrant regulatory elements associated with oncogenic MYC activation include focally amplified distal enhancers or translocation of highly active enhancers from other genes to within topologically associating domains containing the MYC gene locus. The clinical outcome for patients with high levels of MYC expression is virtually identical to that of patients with amplification of the MYCN gene, a known high-risk feature of this disease. Together, these findings establish MYC as a bona fide oncogene in a clinically significant group of high-risk childhood neuroblastomas. Citation Format: Mark W. Zimmerman, Yu Liu, Shuning He, Adam D. Durbin, Brian J. Abraham, John Easton, Ying Shao, Beisi Xu, Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Richard A. Young, Jinghui Zhang, A. Thomas Look. MYC activation through enhancer hijacking or focal enhancer amplification drives a subset of high-risk pediatric neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA19.
Dialysis Access and Risk of Staphylococcus aureus Bacteremia – A Nationwide Study
Authors: Mavish Chaudry, Gunnar Gislason, Anne-Lise Kamper, Marianne Rix, Paal S Andersen, Henrik Westh, Henrik Carl Schønheyder, Christian Torp-Pedersen, Niels Eske Bruun
Journal: Journal of the American Society of Nephrology (2017)
Comparison of Efficacy and Safety of Biosimilar CT-P10 to Rituximab in Patients with Previously Untreated Low Tumor Burden Follicular Lymphoma (LTBFL): A Randomized Phase III Study
Authors: Michinori Ogura, Juan Manuel Sancho, Seok-Goo Cho, Hideyuki Nakazawa, Junji Suzumiya, Gayane Tumyan, Jin Seok Kim, Anne Lennard, Jose Mario Mariz, Nikolai Ilyin, Wojciech Jurczak, Aurelio Lopez Martinez, Olga Samoilova, Edvard Zhavrid, Eduardo Yanez Ruiz, Marek Trneny, Leslie Popplewell, Bertrand Coiffier, Christian Buske, Won Seog Kim, SangJoon Lee, Sungyoung Lee, YunJu Bae, Larry W Kwak
Journal: Blood (2018)
Comparison of Myeloablative Conditioning Regimes Based on Either Busulfan or Total Body Irradiation in Combination with Fludarabine for Patients with Acute Myeloid Leukemia. a Study on Behalf of the Polish Adult Leukemia Group
Authors: Malgorzata Maria Sobczyk Kruszelnicka, Anna Czyz, Anna Lojko-Dankowska, Magdalena Matuszak, Patrycja Mensah-Glanowska, Barbara Nasilowska-Adamska, Agnieszka Piekarska, Tomasz Czerw, Wlodzimierz Mendrek, Jacek Najda, Maria Sadus-Wojciechowska, Jerzy Holowiecki, Sebastian Giebel
Journal: Blood (2018)