tbuckley/cabot-search huggingface dataset:
Standardized symptom screening: Cancer Care Ontario's expanded prostate cancer index composite for clinical practice (EPIC-CP) provincial implementation approach.
Authors: Farzana Haji, Lisa Catherine Barbera, Colleen Bedford, Brett Nichols, Michael Donald Brundage
Journal: Journal of Clinical Oncology (2017)

100 Background: Cancer Care Ontario endorses patient reported outcome measures to improve outcomes and experience for nearly 14 million Ontarians. The EPIC-CP tool, validated to screen/monitor symptoms and side-effects in men with localized prostate cancer, was selected to improve patient and provider experience, and facilitate symptom management. Two pilots tested EPIC-CPs feasibility and acceptability. Subsequent recommendations include: province-wide implementation, improving technological privacy, patient and provider education and communication processes. This abstract will describe the provincial strategy for implementation of EPIC-CP. Methods: The implementation approach involved stakeholder-driven practices based on Kotter’s organizational process framework. Clinical, technical, administrative and patient stakeholder representatives from 14 cancer centres formed working groups to create a climate for change, to engage centres to strategize locally, to implement and sustain change and to address the challenges identified by the EPIC-CP pilot. Results: The final pilot ended in June 2015, and executive endorsement for EPIC-CP provincial implementation in March 2016. A schedule for multi-site phased implementation was informed by stakeholder consultations and began in Oct 2016. Technological privacy improvements were informed by 95 representatives creating a multidisciplinary team tasked with provincial oversight, development of EMR guidelines and IT solutions. Five patient and five clinical educational guides were designed to assist in symptom management, each focusing on one domain of EPIC-CP. Creation of the guides drew on the clinical and scientific expertise among 12 clinicians of varying disciplines in collaboration with four patients. This team assisted in enhancing communication processes by designing 21 training materials, including FAQs and narrated guides, accessible on a central communications hub. Conclusions: Results indicate that this framework-based, stakeholder-driven approach was successful and could be applied to other wide-scale implementations of symptom management tools.
Is oxaliplatin a good partner for EGFR monoclonal antibodies as first-line treatment in KRAS wild-type metastatic colorectal cancer? A meta-analysis.
Authors: Feng Wen, Qiu Li, Ruilei Tang, Yaxiong Sang, Meng Li, Qiancheng Hu, Zedong Du, Yi Zhou, Pengfei Zhang, Xiaofeng He
Journal: Journal of Clinical Oncology (2013)

e14645 Background: This meta-analysis was performed to determine whether the addition of monoclonal antibodies (mAbs) of epidermal growth factor receptor (EGFR) to oxaliplatin-based chemotherapy treatment improves efficacy in KRAS wild-type metastatic colorectal cancer (mCRC), and whether infusional 5-fluorouracil (5-FU) and oxaliplatin is a preferred combination for EGFR mAbs. Methods: Oxaliplatin (including treatment), EGFR mAbs, first-line treatment, KRAS wild-type, and mCRC were used as key words. The PRIME, OPUS, COIN, and NORDIC VII trials were identified by two independent authors. Time-to-event outcomes of overall survival (OS) and progression-free survival (PFS) were analyzed using HRs (Hazard Ratios) with fixed effect, and response rate (RR) using odd ratios (OR) with fixed effect. Results: A total of 1,767 patients who were KRAS wild-type were included in this meta-analysis, with 866 patients in the mAbs and chemotherapy combination group and 901 patients in the chemotherapy alone group. The addition of mAbs to oxaliplatin-based chemotherapy in patients with KRAS wild-type mCRC as first-line treatment resulted in significant improvements in PFS (HR=0.88; 95% confidence interval (CI), 0.79 to 0.99; P=0.03) and response rate (RR) (OR = 1.38; 95% CI, 1.14 to 1.66; P = 0.009) compared with chemotherapy alone, but the difference in OS was not significant (HR=0.96; 95% CI, 0.85 to 1.08; P=0.48). However, the differences neither in OS nor in PFS were not significant when mAbs were added to bolus 5-FU or capecitabine-based regimens compared with chemotherapy alone, whereas PFS improved with an infusional 5-FU and oxaliplatin combination (P=0.06; PFS, HR=0.76; 95% CI, 0.65 to 0.86; P=0.0002), and even OS was marginally significant. Conclusions: Oxaliplatin and infusional 5-FU regimen tends to be a better backbone combination with EGFR mAbs as first-line treatment in KRAS wild-type mCRC.
Automated Clustering Analysis of Immunoglobulin Sequences in Chronic Lymphocytic Leukemia Based on 3D Structural Descriptors
Authors: Paolo Marcatili, Konstantinos Mochament, Andreas Agathangelidis, Panagiotis Moschonas, Lesley-Ann Sutton, Xiao-Jie Yan, Vasilis Bikos, Anna Vardi, Anna Chailyan, Niki Stavroyianni, Kamilla Kjærgaard Jensen, Achilles Anagnostopoulos, Nicholas Chiorazzi, Chrysoula Belessi, Richard Rosenquist, Paolo Ghia, Kostas Stamatopoulos, Anastasia Hadzidimitriou, Dimitrios Tzovaras
Journal: Blood (2016)
Body-Weight Fluctuations and Outcomes in Coronary Disease
Authors: Sripal Bangalore, Rana Fayyad, Rachel Laskey, David A. DeMicco, Franz H. Messerli, David D. Waters
Journal: New England Journal of Medicine (2017)

Body-weight fluctuation is a risk factor for death and coronary events in patients without cardiovascular disease. It is not known whether variability in body weight affects outcomes in patients with coronary artery disease.We determined intraindividual fluctuations in body weight from baseline weight and follow-up visits and performed a post hoc analysis of the Treating to New Targets trial, which involved assessment of the efficacy and safety of lowering low-density lipoprotein cholesterol levels with atorvastatin. The primary outcome was any coronary event (a composite of death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, revascularization, or angina). Secondary outcomes were any cardiovascular event (a composite of any coronary event, a cerebrovascular event, peripheral vascular disease, or heart failure), death, myocardial infarction, or stroke.Among 9509 participants, after adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body-weight variability (measured according to average successive variability and used as a time-dependent covariate) was associated with an increase in the risk of any coronary event (2091 events; hazard ratio, 1.04; 95% confidence interval [CI], 1.01 to 1.07; P=0.01), any cardiovascular event (2727 events; hazard ratio, 1.04; 95% CI, 1.02 to 1.07; P<0.001), and death (487 events; hazard ratio,1.09; 95% CI, 1.07 to 1.12; P<0.001). Among patients in the quintile with the highest variation in body weight, the risk of a coronary event was 64% higher, the risk of a cardiovascular event 85% higher, death 124% higher, myocardial infarction 117% higher, and stroke 136% higher than it was among those in the quintile with the lowest variation in body weight in adjusted models.Among participants with coronary artery disease, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events independent of traditional cardiovascular risk factors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00327691 .).
Defining Functional Genic Regions in the Human Genome through Integration of Biochemical, Evolutionary, and Genetic Evidence
Authors: Zing Tsung-Yeh Tsai, John P. Lloyd, Shin-Han Shiu
Journal: Molecular Biology and Evolution (2017)

The human genome is dominated by large tracts of DNA with extensive biochemical activity but no known function. In particular, it is well established that transcriptional activities are not restricted to known genes. However, whether this intergenic transcription represents activity with functional significance or noise is under debate, highlighting the need for an effective method of defining functional genomic regions. Moreover, these discoveries raise the question whether genomic regions can be defined as functional based solely on the presence of biochemical activities, without considering evolutionary (conservation) and genetic (effects of mutations) evidence. Here, computational models integrating genetic, evolutionary, and biochemical evidence are established that provide reliable predictions of human protein-coding and RNA genes. Importantly, in addition to sequence conservation, biochemical features allow accurate predictions of genic sequences with phenotypic evidence under strong purifying selection, suggesting that they can be used as an alternative measure of selection. Moreover, 18.5% of annotated noncoding RNAs exhibit higher degrees of similarity to phenotype genes and, thus, are likely functional. However, 64.5% of noncoding RNAs appear to belong to a sequence class of their own, and the remaining 17% are more similar to pseudogenes and random intergenic sequences that may represent noisy transcription.
Abstract P327: Migraine and Cardiovascular Risk Profile in a Sample of Hong Kong Chinese Women
Authors: Yao Jie Xie, Suzanne C. Ho, Alice Yuen Loke
Journal: Circulation (2017)

Background: Migraine has been found to be a risk marker for several cardiovascular diseases (CVDs). Some studies have shown that migraineurs had unfavorable cardiovascular risk profile, which might partially explain the mechanisms that link migraine to CVD. But the results are still controversial. The relevant study in Chinese population was lacking. The aim of this study was to evaluate the cardiovascular risk profile in a sample of Hong Kong Chinese women with and without migraine. Methods: Three rounds of mail surveys were conducted among Chinese female nurses aged 35 to 65 years in Hong Kong. In total 1253 nurses were enrolled in analysis. Information on traditional CVD risk factors, including body mass index (BMI), blood pressure (BP), hypercholesterolemia, diabetes mellitus (DM), smoking, alcohol drinking, physical activity, and family history of CVD, together with the physician-diagnosed migraine, was collected by a self-administered questionnaire. The self-reported anthropometric variables and BP have been validated in a pilot study. Results: The overall prevalence of physician-diagnosed migraine was 7.9%. Women with migraine had higher systolic and diastolic BP than those without migraine (118.2 mmHg vs. 113.1 mmHg, 73.8 mmHg vs. 70.0 mmHg; both P&lt;0.001). More than half of the migraineurs (57.3%) had the family history of CVD, which was higher than non-migraineurs (33.0%, P&lt;0.001). Compared with non-migraineurs, the migraineurs were more likely to have hypertension (OR: 2.00, 95% CI: 1.14-3.51), high cholesterol (OR: 1.70, 95% CI: 1.02-2.85), and family history of CVD (OR: 2.72, 95% CI: 1.78-4.15). There were no statistically significant differences regarding obesity, smoking, alcohol drinking, physical activity, and DM between migraineurs and non-migraineurs (all P&gt;0.05). In the logistic regression analysis, after adjustment for age and BMI, the odds of having hypertension in migraineurs were 105% greater than in non-migraineurs (OR: 2.05, 95% CI: 1.08-3.91; P&lt;0.05), and strengthened in those with family history of CVD (OR: 2.81, 95% CI: 1.27-6.21; P&lt;0.05); however, the association between migraine and high cholesterol were eliminated (P&gt;0.05). Conclusion: We did not find an overall worse cardiovascular risk profile among Chinese women with migraine. While family history of CVD and hypertension were significantly associated with migraine. Further prospective studies with larger sample size are needed in Chinese population.
Safety and toxicity profile of high-dose IFN-α2b in 44 patients with malignant melanoma
Authors: E. Simoncini, F. Valcamonico, V. Amoroso, A. M. Manganoni, V. D. Ferrari, L. Vassalli, G. Rangoni, S. Grisanti, P. Marpicati, G. Marini
Journal: Journal of Clinical Oncology (2004)

7570 Background: High-dose IFN-α2b (HDI) is the only approved adjuvant therapy for high-risk melanoma, while lower dose IFN appears ineffective. Toxicity was substantial in patients (pts) enrolled in pivotal US randomised trials with HDI. Methods: Safety and toxicity of HDI were reviewed in 44 consecutive pts treated at a single Institution, from1997 to 2002. Results: Patients characteristics were as follows: M/F 25/19; median age 48 years (range: 15–68); ulcerated lesion in 14% of pts; AJCC stage IIB 5 pts, IIC 4 pts, IIIA 8 pts, IIIB 13 pts, IIIC 5 pts. Nine pts had metachronous lymph-node metastases. All pts were assessed for toxicity according to NCI-CTC (table 1). One pt developed a reversible thyroid storm. One pt died for myocardial infarction, possibly related to treatment. Dose-intensity was >75% in 31/44 pts (70%) during induction and in 20/44 pts (46%) during maintenance. 7/44 pts (16%) discontinued treatment for side effects, though dose modification. At a median follow-up of 46 months, 19/44 pts (43%) relapsed. Recurrence site was: soft tissue 11 pts, visceral 8 pts. Conclusions: HDI has an acceptable toxicity profile in the adjuvant setting; patient selection and careful toxicity management are mandatory. No significant financial relationships to disclose.
Randomized phase II trial of gemcitabine versus gemcitabine and imatinib mesylate in patients with previously treated metastatic breast cancer.
Authors: Pashna Neville Munshi, Deborah Toppmeyer, Serena Tsan-Lai Wong, Shridar Ganesan, Katherine Hanna Tkaczuk, Mary E. Cianfrocca, Virginia G. Kaklamani, William John Gradishar, Robert A. Somer, Kanu Sharan, Generosa Grana, Pauline Marie O. Lerma, Lillian F. Pliner, Robert Wieder, Michael P. Kane, Sinae Kim, Antoinette R. Tan
Journal: Journal of Clinical Oncology (2013)

1091 Background: Gemcitabine (GEM) as a standard 30-min infusion has activity as a single-agent in metastatic breast cancer (mbc). Prolonged infusion of GEM at a fixed dose rate (FDR) of 10 mg/m 2 /min is associated with greater formation of active metabolite and may result in improved antitumor activity. Imatinib mesylate (IM)-mediated inhibition of PDGFR reduces tumor interstitial fluid pressure allowing for improved chemotherapy penetration into tumors. We evaluated the addition of IM to FDR GEM in patients (pts) with previously treated mbc. Methods: This was a randomized phase II trial in mbc pts who progressed after 1 but no more than 2 prior cytotoxic regimens. Eligibility included measurable disease; no prior GEM or IM exposure. Group 1 received FDR GEM IV 1250 mg/m 2 at 10 mg/m 2 /min (over 120 min) on days 3 and 10 every 21 days; Group 2 received the same FDR GEM dose and schedule plus IM 400 mg orally daily on days 1-5 and 8-12 every 21 days. Primary endpoint was time to progression (TTP). Sample size of 40 pts per group was needed to detect an 8 mo increase in TTP with the combination (80% power, α = .05, 2-sided). Secondary endpoints included ORR and safety. Results: Between 5/2006-4/2011, 44 pts were randomized (22 per group). Study closed early due to slow accrual. Median age 54 (31-75); median ECOG PS 1 (0-2); 52% were hormone receptor-positive and HER2-negative; 27% triple-negative, and 20% HER2-positive. Median number of cycles was 2 in Group 1 (range 1-12) and 3.5 in Group 2 (range 1-13). Most common adverse events (%) of any grade, Group 1 vs Group 2 were neutropenia (68 vs. 78), anemia (48 vs. 65), thrombocytopenia (24 vs. 47), nausea (40 vs. 52) and vomiting (24 vs. 21). One gr 4 thrombotic thrombocytopenic purpura occurred in Group 2. Median TTP were 2 mo (95% CI: 1-5 mo) in Group 1 and 2.5 mo (95% CI: 1-5 mo) in Group 2 (p = 0.3 log rank test). ORR was 9.1% in each group (95% CI: 1.6-30.6%), with 2 PRs in each group. Stable disease (≥ 3 mo) was 32% in Group 1 and 41% in Group 2. Conclusions: This study was underpowered to draw any conclusion regarding a difference in TTP between the two groups at the time it was prematurely closed. Combination of IM and FDR GEM showed a trend to increased toxicity compared to FDR GEM alone. Clinical trial information: NCT00323063.
Telecolposcopy in a tertiary care women's clinic: A pilot study
Authors: A. M. Lopez, F. Garcia, K. Hatch, J. Byron, S. Kurker, J. Guillen, J. Major, S. Lazarus, D. Avery, R. Weinstein
Journal: Journal of Clinical Oncology (2004)

5119 Background: Invasive cervical cancer is the second most common cancer in women in the world. Because women with cervical carcinoma and it precursor lesion, cervical dysplasia, are asymptomatic, Pap smear screening and colposcopy are the best tools for early detection. Telecolposcopy involves the use of telemedicine technology to assess the cervix from a distance. The purpose of this pilot study was to evaluate the measure of agreement between telecolposcopy and in-person colposcopy in the diagnosis of cervical dysplasia. The setting for the study was a tertiary care cervical dysplasia clinic. Methods: Thirty-six participants underwent a clinical exam, an in-person exam, a store-forward telecolposcopy exam, and a cervical biopsy. Two examiners assessed the store-forward images. Analyses included comparison of the clinical and telemedicine diagnoses to each other and to the biopsy results. Confidence in diagnosis was also recorded. Results: Analyses reveal high sensitivity and positive predictive value of the colposcopy and telecolposcopy. Confidence in the diagnosis was high across reviewers, and exam results were significantly correlated with biopsy results (Spearman r = .55 p=.001, .53 p=.001, and .49 p<.01 for colposcopy, telecolposcopy A and telecolposcopy B respectively). Conclusions: Analyses of the data suggests moderate to high clinical efficacy of this intervention. Table 1. Diagnostic Value of Colposcopy and Telecolposcopy (n = 36) No significant financial relationships to disclose.
Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients (pts) with EGFR inhibitor–resistant non-small cell lung cancer (NSCLC).
Authors: Pasi A. Janne, Suresh S. Ramalingam, James Chih-Hsin Yang, Myung-Ju Ahn, Dong-Wan Kim, Sang-We Kim, David Planchard, Yuichiro Ohe, Enriqueta Felip, Claire Watkins, Mireille Cantarini, Serban Ghiorghiu, Malcolm Ranson
Journal: Journal of Clinical Oncology (2014)

8009^ Background: AZD9291 is a selective, third generation EGFR-TKI, effective against both EGFR-TKI sensitizing and resistance T790M mutations in preclinical models. We are conducting a phase I study of AZD9291 in EGFR mutant (EGFRm+) NSCLC pts. Methods: EGFRm+ NSCLC pts, with acquired resistance to EGFR-TKIs, were enrolled in a multicenter trial (NCT01802632) into dose escalation and expansion cohorts. AZD9291 was administered orally, at doses of 20–240 mg once daily. Stable brain metastases were allowed. All pts were assessed for pharmacokinetics (PK), response to therapy, and adverse events (AEs). Prospective mandatory central T790M testing was required in the expansion cohorts and was optional for dose escalation cohorts. Results: As of 16 January 2014, 199 pts (62% female, median age 60, Asian/Caucasian 65%/32%, immediate prior EGFR-TKI therapy: 57%) were enrolled including 31 across 5 dose levels in the dose escalation and 168 in 8 dose expansion cohorts. Median number of prior EGFR therapies: 1 (range, 1-5). PK was dose proportional, median t1/2 ~50 h. Plasma exposures achieved at all doses are predicted to be efficacious in preclinical models. Among all evaluable pts to date, the confirmed+unconfirmed overall response rate (c+uORR) was 51% (91/177). RECIST responses were observed at all dose levels and in brain metastases. In 132 pts with centrally confirmed T790M, the c+uORR in 89 EGFR T790M+ pts was 64% (95% CI; 53%, 74%) and in 43 EGFR T790M- pts was 23% (95% CI; 12%, 39%).The overall disease control rate (CR+PR+SD) in T790M+ pts was 96% (85/89). Among the 60 pts with a confirmed response, 97% (58/60) were ongoing at data cut-off; longest duration of response to date >8 months. No dose limiting toxicities were observed. Most common AEs (≥15%), mostly CTCAE Grade 1, were: diarrhea (30%), rash (24%), and nausea (17%). Grade 3/4 AEs occurred in 16% of pts. Six pts (3%) had dose reductions. Five reports of ILD-like events are under investigation. Conclusions: AZD9291 has robust efficacy and is well tolerated in EGFRm+ NSCLC pts with acquired resistance to EGFR-TKIs. Pts with EGFR T790M+ tumors have higher ORR with AZD9291 compared with those with EGFR T790M- tumors. Clinical trial information: NCT01802632.
Abstract P289: Cardiomyocyte-Specific, but Not Systemic, Rassf1A Deletion Is Protective Against Ischemia-Reperfusion Injury in the Heart
Authors: Dominic Del Re, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation Research (2011)

Our previous work demonstrated Rassf1A to be a critical mediator of Mst1 activation, the chief component of the mammalian Hippo pathway, in heart failure. In the setting of ischemia/reperfusion (I/R) injury, Mst1 is robustly activated in the heart; however, its regulation remains unclear. Further, the role of Rassf1A in I/R injury has not been investigated. Using genetically modified mice in which expression of Rassf1A is altered in a cell type-specific manner, we demonstrate that systemic deletion of rassf1a (KO) does not alter infarct size (36±4% vs 33±3%) or cardiac myocyte apoptosis (1.7±0.2% vs 2.1±0.4%) following I/R versus WT. Conversely, mice harboring deletion of rassf1a in cardiac myocytes (CKO) have smaller infarcts (38±3% vs 23±2%, p&lt;0.05) and less apoptosis (2.0±0.2% vs 0.9±0.2%) after I/R. Importantly, attenuation of Mst1 activation in ventricular homogenates was observed in both deletion models, implicating Rassf1A as a positive regulator of Mst1 during I/R. Langendorff global I/R injury yielded similar results - no protection in KO, yet significant protection in CKO hearts versus control mice, suggesting that native cardiac cells are sufficient to mediate this response. A candidate molecule screen found exaggerated TNF-α expression in KO hearts compared to WT (4.8±0.7% vs 1.0±0.3%), whereas TNF-α expression was attenuated in CKO hearts (0.9±0.2% vs 0.3±0.1%). Finally, WT and KO mice were administered TNF-α neutralizing or control IgG and subjected to I/R. KO hearts treated with TNF-α Ab, but not IgG, had reduced infarcts (19±4% vs 34±5%), but no significant reduction in infarct size was observed in WT mice given TNF-α Ab. Taken together these data suggest that TNF-α blockade prevents the deleterious consequences of Rassf1A deletion in non-myocytes while unmasking the protective effect of Rassf1A deletion in cardiac myocytes following I/R. Further, these results demonstrate the importance of non-myocytes in modulating cardiac myocyte survival and I/R injury.