tbuckley/cabot-search huggingface dataset:
Further molecular profiling of tumors harboring therapeutic targets within non-small cell lung cancer.
Authors: Solange Peters, Andreas Voss, Kenneth Russell, Sherri Z. Millis, Elisabeth Brambilla
Journal: Journal of Clinical Oncology (2014)

8087 Background: Treatment of NSCLC has been revolutionized in recent years with the introduction of several targeted therapies for selected genetically altered subtypes of NSCLC. A better understanding of molecular characteristics of NSCLC, which features common drug targets, may identify new therapeutic options. Methods: Over 6,700 non-small cell lung cancer cases referred to Caris Life Sciences between 2009 and 2014. Diagnoses and history were collected from referring physicians. Specific testing was performed per physician request and included a combination of sequencing (Sanger, NGS or pyrosequencing), protein expression (IHC), gene amplification/rearrangement (CISH or FISH), and/or RNA fragment analysis. Results: Tumors profiles from patients with hormone receptor positive disease (HER2, ER, PR, or AR positive by IHC) (n=629), HER2 mutations (n=8) ALK rearrangements (n=55), ROS1 rearrangement (n=17), cMET amplification or mutation (n=126), and cKIT mutation (n=11) were included in this analysis and compared to the whole cohort. Tumors with ALK rearrangement overexpressed AR in 18% of cases, and 7% presented with concomitant KRAS mutation. Lower rates of PTEN loss, as assessed by IHC, were observed in ALK positive (20%), ROS1 positive (9%) and cKIT mutated tumors (25%) compared to the overall NSCLC population (58%). cMET was overexpressed in 66% of ROS1 translocated and 57% of HER2 mutated tumors. cKIT mutations were found co-existing with APC (20%) and EGFR (20%) mutations. Pathway analysis revealed that hormone receptor positive disease carried more mutations in the ERK pathway (32%) compared to 9% in the mTOR pathway. 25% of patients with HER2 mutations harbored a co-existing mutation in the mTOR pathway. Conclusions: Pathway profiling reveals that NSCLC tumors present more often than reported with several concomitant alterations affecting the ERK or AKT pathway. Additionally, they are also characterized by the expression of potential biological modifiers of the cell cycle like hormonal receptors, representing a rationale for dual inhibition strategies in selected patients. Further refining of the understanding of NSCLC biomarker profile will optimize research for new treatment strategies.
Impact of Eltrombopag on Clonal Evolution in Refractory Aplastic Anemia
Authors: Bhumika J. Patel, Shimoli Vipul Barot, Bartlomiej P. Przychodzen, Teodora Kuzmanovic, Michael Clemente, Cassandra M. Hirsch, Valeria Visconte, Roy Souaid, Marissa Versalle, Sarah S Lee, Tomas Radivoyevitch, Metis Haspiek, Swapna Thota, Aziz Nazha, Matt Kalaycio, Anjali S. Advani, Hetty E. Carraway, Mikkael A. Sekeres, Jaroslaw P. Maciejewski
Journal: Blood (2018)
Facility variation in clinical staging of rectal adenocarcinoma and its contribution to underutilization of neoadjuvant therapy.
Authors: Douglas S. Swords, David E. Skarda, Gregory J. Stoddard, H. Tae Kim, William T. Sause, Courtney L. Scaife
Journal: Journal of Clinical Oncology (2018)

810 Background: Studies of the National Cancer Database (NCDB) found that neoadjuvant therapy (NAT) for clinical stage II-III rectal adenocarcinoma is underutilized, but they reclassified patients without clinical staging by pathologic stage. Methods: Study of patients &lt; 80 with resected clinically non-metastatic rectal adenocarcinoma in the 2010-2014 NCDB. Reliability-adjusted (RA) facility rates of clinical staging were calculated. Then, patients with clinical stage I, unknown clinical/pathologic stage 0-1 and NAT contraindications/refusal were excluded. Multivariable Poisson regression was used to examine predictors of NAT. Multiple imputation was used to account for missing data. RA facility NAT rates were calculated. Variance partitioning was used to examine causes of omission of NAT. Results: Of 26220 patients with clinical stage II-III or unknown clinical/pathologic stage II-III, 3634 (14%) were not clinically staged. RA facility clinical staging rates ranged from 17%-99%. NAT was delivered to 20415/22586 (90%) patients who were clinical stage II-III vs. 1372/3634 (38%) of those without clinical staging. Of 4443 patients who did not receive NAT, 2262 (51%) did not have clinical staging. Treatment at facilities with higher volume and clinical staging rates was associated with delivery of NAT. RA facility NAT rates ranged from 33%-96%. Patient factors explained 15% of variance in facility NAT rates, type/volume 16%, and facility clinical staging rates 23%. Conclusions: A single process (omission of clinical staging) is present in half of cases omitted NAT (Pareto principle). Facility NAT rates vary 3-fold, and facility clinical staging rates explain much of the variation in use of NAT. Efforts to increase utilization of clinical staging are warranted. [Table: see text]
Clonal Suppression of TP53 Mutant MDS and Oligoblastic AML with Hypomethylating Agent Therapy Improves Overall Survival
Authors: David A Sallman, Najla Al Ali, Seongseok Yun, Eric Padron, Jinming Song, Mohammad Omar Hussaini, Chetasi Talati, Kendra L. Sweet, Jeffrey E. Lancet, Alan F. List, Rami S. Komrokji
Journal: Blood (2018)
儿科皮肤病专家和风湿病专家对 CLASI 的评估
Authors: C.J. Kushner, M. Tarazi, R.G. Gaffney, R. Feng, K. Ardalan, H.A. Brandling‐Bennett, L. Castelo‐Soccio, J.C. Chang, Y.E. Chiu, S. Gmuca, R.D. Hunt, P.J. Kahn, A.M. Knight, J. Mehta, D.R. Pearson, J.R. Treat, J. Wan, A.C. Yeguez, J.S.S. Concha, B. Patel, J. Okawa, L.M. Arkin, V.P. Werth
Journal: British Journal of Dermatology (2019)

术语“红斑狼疮”指的是一系列相关疾病。多达 70–80% 的狼疮患者将在他们疾病进程的一些时间点发生皮损(异常斑片)。影响皮肤的狼疮类型统称为皮肤红斑狼疮(CLE)。皮肤红斑狼疮疾病面积和严重程度指数 (CLASI) 是对 CLE 患者中皮肤症状严重程度进行分类的一种工具。能够准确可靠地测量皮损是监测某种疾病任何改善或恶化的一种重要方式,有助于在临床试验中观察某种治疗是否有效。已知 CLASI 在成人中是一种可靠(准确)的测量手段,但来自美国的研究者们进行了这项研究,以验证 CLASI 在儿科(儿童)人群中的可靠性,儿童人群中的 CLE 表现可能不同于成人。此验证将使临床试验能够可靠地评估 CLE 中的治疗疗效。研究者们招募了 11 名活动性 CLE 儿科患者,6 名皮肤科专家和 6 名风湿病专家在宾夕法尼亚大学参与了为期 1 天的事件。医师们被培训使用 CLASI 和另一种称为医师整体评估 (PGA) 的评分系统,以进行比较。医师(医生)们分别使用两种工具对所有患者进行评分。每名医师重新评估两名随机选择的患者。对于儿科 CLE,CLASI 被证实是一种可靠和有效的测量工具,优于 PGA,研究者们认为它可在未来的临床试验中使用。
An analysis of anxiety, depression, and quality of life in patients undergoing radiotherapy with curative intent.
Authors: Alison Ranger, Claire Mortimer, Afifa Hussain, Justin Shute, Lucinda Melcher
Journal: Journal of Clinical Oncology (2014)

e20581 Background: According to the Department of Health, there are 1.8 million people living with or beyond a diagnosis of cancer. In Improving Outcomes: a Strategy for Cancer 2011, the DOH states an important aim: to allow cancer survivors to live as healthily as possible. There is a significant body of evidence pointing to an increase in anxiety and depression levels in cancer patients (e.g. Linden W et al, J Affect Dis 2012 Dec 10; 141 (2-3):343-51) and some data suggesting that, for some patients, levels of anxiety and depression may stay high once treatment is completed (e.g. Mantegna et al, BMC Cancer 2013). The aim of this study is to analyse the levels of anxiety and depression and changes in quality of life in patients undergoing radiotherapy with curative intent at the North Middlesex Hospital during a specified time period. Methods: The study uses two validated questionnaires to assess anxiety and depression levels and effect on quality of life in patients undergoing radiotherapy: The Health Anxiety and Depression score (HADS – Zigmoid and Snaith 1983) and the EQ-SD-3L quality of life measure (The EuroQol group 1990, Health Policy 16 (3): 199-208) All eligible patients starting radiotherapy with curative intent during the project period were offered the opportunity to participate in the study and complete the questionnaires. Patients who agreed to participate were asked to complete the questionnaires at four time points; prior to starting treatment, at the end of radiotherapy, and again at 3 months and 6 months post treatment. If a significant degree of anxiety or depression is picked up during radiotherapy, patients will be offered referral for support or counselling. Results: A paired t test will be used to compare patients’ scores on the HADS and QoL questionnaire responses across the time points to determine whether patients are experiencing significant changes in anxiety and depression levels over time. Conclusions: The results will be used to assess the need for further psychological support for patients undergoing radiotherapy, and to analyse the trend of anxiety and depression over time, and the effect on quality of life, in order to assess where and when psychological intervention is likely to be needed.
18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography evaluation to predict postoperative outcomes for patient with luminal-type breast cancer.
Authors: Kenjiro Aogi, Sachiko Kiyoto, Yoshifumi Sugawara, Takayuki Kadoya, Hideo Shigematsu, Norio Masumoto, Morihito Okada
Journal: Journal of Clinical Oncology (2014)

e22207 Background: 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been reported as an useful tool for evaluating prognosis of cancer. Maximum standardized uptake value (maxSUV) and ER status were reported to be predictive factors for relapse-free survival (RFS) on breast cancer patients. In this study, 18F-FDG PET/CT was evaluated for predicting postoperative outcomes on hormonal receptor-positive breast cancer patients retrospectively. Methods: Three hundred forty four breast cancer patients with clinical Stage I-III who underwent preoperative 18F-FDG PET/CT were enrolled between January 2006 and December 2011 in two institutes. These patients were classified into 5 subtypes, Luminal A: Estrogen receptor (ER)(+) or Progesterone receptor (PR)(+), human epidermal growth factor receptor type 2 (HER2) (-), and nuclear grade (NG)1-2, Luminal B: ER(+) or PR(+), HER2(-), and NG3, Luminal HER2: ER(+) or PR(+), and HER2(+), HER2: ER(-), PR(-), and HER2(+), Triple negative: ER(-) , PR(-), and HER2(-) according to the subtype classification by hormonal receptors status, HER2 expression and nuclear grade. Patients diagnosed as luminal types were 262 in total (Luminal A 166; Luminal B 96 patients) and evaluated in this study. Statistical analyses were performed using Student t test, Cox regression model and log-rank test. Results: Patients were divided in two groups according to cut-off maxSUV on receiver operating characteristic (ROC) analysis (≤4.0 group vs >4.0 group, AUC=0.830). Significant correlations were shown between maxSUV and clinical T-factor, nuclear grade, vascular invasion and presence or absence of recurrence (p<0.0001, p<0.0001, p=0.0181, and p=0.0056, respectively). In uni- and multivariate analyses using Cox model for recurrence, only maxSUV was shown to be significant (p=0.021 and p=0.043, respectively). RFS curves showed the maxSUV≤4.0 group had significantly better prognosis compared to that of the maxSUV >4.0 group (p=0.003). Conclusions: Using 18F-FDG PET/CT is concluded to be useful for predicting prognosis on luminal types breast cancer patients.
THU0398 Unexplained iron deficiency is frequent in systemic sclerosis
Authors: A. Sari, A. Gill, S.I. Nihtyanova, V.H. Ong, C.P. Denton
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Prevalance of<b> i</b>ron deficiency (ID) in systemic sclerosis (SSc) is unclear and can occur related to several causes. <h3>Objectives</h3> This cross sectional study aims to analyse association between ID and disease characteristics in SSc patients who does not have an overt cause for ID. <h3>Methods</h3> We identified 227 consecutive SSc patients who had iron laboratory studies (serum iron, total iron binding capacity and ferritin) with concurrent full blood count and serum C-reactive protein (CRP) measurement between May 2015 and November 2017. Exclusion criteria were as follows: not having serum CRP levels within 1 month of iron studies, chronic kidney disease (eGFR &lt;60 ml/min), haemoglobinopathies, major surgery within one year, overt gastrointestinal (GI) or genitourinary blood loss, active GI cancer and vascular lesions of GI (GAVE, intestinal telengiectasia). Patients who have ferritin levels below cut-off values or were already on iron replacement were considered as iron deficient. To define iron deficient status, threshold levels of serum ferritin 30 ng/mL and 100 ng/mL were used to denote those with normal and high CRP levels (&gt;5 mg/L) respectively. WHO classification system was used to determine the presence and severity of anaemia. Relationship between demographic and disease characteristics and serum iron status was analysed using Fisher's exact and Mann-Whithey U test. <h3>Results</h3> 178 patients (76.4% female) were eligible for final analysis. Clinical characteristics are reported in table 1. Median age and disease duration (interquartile range, IQR) were 54.6 (44.8–66.1) and 4.9 (2.1–4.8) years, respectively. ID was present in 43.2% of the patients and 41.6% of these patients was not anaemic. Iron deficient patients were more frequently female and had longer disease duration. Among female patients, ID was significantly more prevalent before the age of 50 (77.6% vs 0%, p&lt;0.001). <h3>Conclusions</h3> Unexplained iron deficiency is frequent in scleroderma patients and a significant number of these patients do not have frank anaemia. Female sex and longer disease duration is associated with iron deficiency. Increased frequency in young female patients can be related to menstrual blood loss and further study to evaluate this association is required. <h3>Disclosure of Interest</h3> None declared
Follow-on rifaximin for the prevention of recurrence following standard treatment of infection with <i>Clostridium difficile</i>: a competing risks analysis provides a full picture of possible treatment effects
Authors: Maja Katharina von Cube, Martin Schumacher, Martin Wolkewitz
Journal: Gut (2018)

With interest we read the article by Major et al 1 on the effect of rifaximin ‘follow-on’ treatment to prevent recurrent Clostridium difficile infection (rCDI).

Major et al point out the advantage of their study sample being composed of elderly patients who represent the frailties and comorbidities of the target population. The frailty of the sample is reflected by the, compared with other trials on new agents, higher mortality rate, which is considered to increase the generalisability of the results to daily clinical practice.

A main statistical challenge when studying a frail patient population using a non-fatal endpoint is dealing with mortality.2 

Patients who died without rCDI are no longer at risk of a recurrent infection. Thus, death is a competing risk of rCDI.

In their analysis, Major et al first exclude patients who have died or have withdrawn from the study before end of follow-up by using generalised estimating equations to estimate the risk difference (RD) of rCDI. Second, they treat them equally as randomly censored by using a Kaplan-Meier estimator (K-M) to estimate the …
Fibrinogen Concentrate Vs Cryoprecipitate in Pseudomyxoma Peritonei Surgery: Interim Results from a Prospective, Randomized, Controlled Phase 2 Study
Authors: Ashok Roy, Nigel Sargant, Savita Rangarajan, Sue Alves, John Bell, Sophia Stanford, Cristina Solomon, Irina Kruzhkova, Sigurd Knaub, Faheez Mohamed
Journal: Blood (2018)
Final Analysis of the Front-Line Phase III Randomized ACT-1 Trial in Younger Patients with Systemic Peripheral T-Cell Lymphoma Treated with CHOP Chemotherapy with or without Alemtuzumab and Consolidated By Autologous Hematopoietic Stem Cell Transplant
Authors: Francesco d'Amore, Sirpa Leppä, Maria Gomes da Silva, Thomas Relander, Grete Fossum Lauritzsen, Peter De Nully Brown, Antonio Pezzutto, Jeanette K. Doorduijn, Eckhart Weidmann, Michel van Gelder, Achiel Van Hoof, Ilse Christiansen, Unn Merete Fagerli, Hans Hagberg, P.J. Lugtenburg, Jan Walewski, Ka Lung Wu, Hilde Maria Demuynck, Rob Fijnheer, Jacob H. Christensen, Milada Jankovská, Pär L. Josefsson, Hanneke Kluin-Nelemans, Jose Mario Mariz, Mats A. Merup, Thomas Noesslinger, Eric Van Den Neste, Josée M Zijlstra, Georg Hopfinger, VIT Prochazka, Esa Jantunen, Ludmila Boudova, Jose Cabecadas, Andreas Chott, Jan M.A. Delabie, Laurence de Leval, Arjan Diepstra, Marja-Liisa Karjalainen-Lindsberg, Peter Noergaard, Andreas Rosenwald, Grzegorz Rymkiewicz, Christer Sundström, Lorenz Truemper, Gerald Wulf, Lauren Chong, Alyssa Bouska, Lynette Smith, Christian Gisselbrecht, Marita Ziepert, Markus Loeffler, Knut Liestol, Christian Steidl, Randy D. Gascoyne, David W. Scott, Bettina Altmann, Javeed Iqbal, Wing C Chan, Helle Toldbod
Journal: Blood (2018)
Impact of acellular mucin pools on survival in patients with complete pathologic response to neoadjuvant treatment in rectal cancer.
Authors: Abu Bakar Hafeez Bhatti, Ali Akbar, Shahid Khattak, Syed Ather Saeed Kazmi, Aamir Ali Syed
Journal: Journal of Clinical Oncology (2014)

e14597 Background: Rarely, patients with pathological complete response (PCR) to neoadjuvant chemoradiotherapy demonstrate acellular mucin pools in resected rectal specimen. The clinical and prognostic significance of this finding is controversial. Current recommendation is to consider this as treatment response but the evidence is limited. The objective of this study was to determine impact of acellular mucin pools on disease free and overall survival in patients with complete pathological response to neoadjuvant chemoradiotherapy in rectal cancer. Methods: A total of 182 patients underwent surgery for rectal cancer from 2005 to 2011 at Shaukat Khanum Memorial Cancer Hospital. One hundred and sixty four patients received neoadjuvant treatment chemoradiotherapy. Presence of acellular mucin pools and PCR was identified in these patients from histopathology reports. Patients were divided into two groups based on presence of acellular mucin pools in resected specimen. Patient characteristics, surgical procedure, clinical stage and grade of tumor were noted. Locoregional failures, distant failures and deaths were compared. Expected five year disease free and overall survival was calculated. Results: Median follow-up was 36 (4-94) months. Complete pathological response was identified in 35 (21.3%) patients. Of these, 12(34.2%) had acellular mucin pools in resected specimen. Majority of mucin negative tumors were moderately differentiated (78% vs 25%) (P=0.005). Four patients relapsed in the follow up period (1 locoregional and 3 distant) with no significant difference between two groups. Median overall survival for mucin positive and mucin negative tumors was 4 (1.3-5.7) and 3.3(0.1-6.3) years respectively. Expected five year disease free and overall survival for mucin positive and mucin negative tumors was 73% and 89% (P=0.1) and 75% and 87% (P=0.4). Conclusions: Acellular mucin pools following complete pathological response to neoadjuvant treatment in rectal cancer do not have significant impact on disease free and overall survival.
Phase I/II study of vosaroxin and decitabine in older patients (pts) with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).
Authors: Naval Guastad Daver, Hagop M. Kantarjian, Sherry Pierce, Mark Brandt, Courtney Denton Dinardo, Naveen Pemmaraju, Kenneth Vaughan, Guillermo Garcia-Manero, Elias Jabbour, Gautam Borthakur, Tapan M. Kadia, Jorge E. Cortes, Adam Craig, Farhad Ravandi
Journal: Journal of Clinical Oncology (2014)

7098 Background: Vosaroxin is a first-in-class anticancer quinolone derivative (AQD) that intercalates DNA and inhibits topoisomerase II and has previously demonstrated activity in AML. We conducted this study to examine the efficacy and toxicity of the combination of vosaroxin and decitabine. Methods: Pts were eligible if they had AML or high-risk MDS (≥ 10% blasts in the bone marrow), were ≥ 60 years, had ECOG PS ≤ 2 and adequate organ function. Pts < 60 years who were unsuitable for standard chemotherapy were also eligible. The treatment regimen included vosaroxin 90 mg/m2 daily on days 1 and 4 with decitabine 20 mg/m2 daily for 5 days. Vosaroxin was reduced to 70 mg/m2 in consolidation cycles, for a total of up to 7 cycles. The primary endpoint is overall response rate (ORR) rate [ORR=CR + CRp + CRi]. Results: To date, 23 pts (21 AML, 2 high-risk MDS) with a median (med) age of 71 years (range, 41-78) have been enrolled. They included 11 (48%) with diploid cytogenetics, 7 (30%) with complex cytogenetics including chromosome 5 and/or 7 abnormalities, and 5 (22%) with other. 9 (39%) had antecedent hematological disorders (AHD). 5 pts with AHD had received prior therapy including azacitidine (n=1), ruxolitinib + azacitidine (n=1), lenalidomide (n=1) and hydroxyuea (n=2). Frequently identified mutations included: IDH1/2 in 8 (35%), RAS mutations in 6 (26%), TP53 in 6 (26%), and NPM1 in 4 (17%). Med bone marrow blast %, white blood cell, hemoglobin, & platelet counts were 36% (11-97), 4.6 x 109/L (1.0-25.1), 9.5 g/dL (6.8-11.5), and 42 x 109/L (7-333), respectively. 16 pts were evaluable for response; 9 (56%) achieved CR, 2 (13%) CRp, and 2 (13%) CRi, for an ORR of 81% with no evidence of minimal-residual disease in 11 of 13 responders (85%). 7 are too early for response assessment. Pts have received a med of 2 cycles (range, 1-5) with med number of cycles to response being 1 (range, 1-4). No pts have relapsed. 1 pt has proceeded to HSCT. Two pts died during induction. Additionally, 1 pt died on day 47 from sepsis and acute myocardial infarction. The main grade ≥ 3 toxicity was mucositis in 2 pts. Conclusions: Combination of vosaroxin and decitabine is effective and well tolerated. Enrollment is ongoing. Clinical trial information: NCT01893320.
Abstract 20: Cardiovascular Health Trends in Electronic Health Record Data (2010-2015): the Guideline Advantage
Authors: Randi Foraker, Sejal Patel, Yosef Khan, Mary Ann Bauman, Julie Bower
Journal: Circulation (2017)

Background: Electronic health records (EHRs) are an increasingly valuable data source for monitoring population health. However, EHR data are rarely shared across health system borders, limiting their utility to researchers and policymakers. The Guideline Advantage™ (TGA) program, a joint initiative by the American Heart Association (AHA), American Cancer Society, and American Diabetes Association, brings together data from EHRs across the country to support disease prevention and management efforts in the outpatient setting. Methods: We analyzed TGA EHR data from &gt;70 clinics comprising 281,837 adult patients from 2010 to 2015. We used the first available measure per patient for each calendar year to characterize trends in the proportion of patients in “ideal”, “intermediate”, and “poor” CVH categories for blood pressure (BP), body mass index (BMI) and smoking. Total cholesterol and fasting glucose values were not reported to TGA. Thus, we used low-density lipoprotein (LDL) and hemoglobin A1c (A1c) treatment guidelines to classify patients into CVH categories for the respective metrics. Results: Patients were an average of 50 years old, and 57.4% were female. Of records with complete data on race, 70.9% of patients were white. Over 6 years of observation, we documented increases in the proportion of patients at ideal levels for BP, smoking, LDL, and A1c, but decreases in the proportion of patients at an ideal level for BMI (Figure). Conclusions: TGA data provide a large-scale perspective of outpatient CVH, yet we acknowledge limitations associated with using EHR data to assess trends in CVH. Specifically, EHR data entry is clinically-driven - BP and BMI values are likely to be updated at each visit for each patient, while smoking status, LDL, and A1c are not. Our analysis lays the groundwork for EHR analyses as these data become less siloed and more accessible to stakeholders. Figure. Trends in CVH from 2010 to 2015: The Guideline Advantage™