tbuckley/cabot-search huggingface dataset:
A phase III, randomized trial of docetaxel plus carboplatin (TP) versus epirubicin plus cyclophosphamide followed by docetaxel (EC-T) as adjuvant treatment for triple-negative, early-stage breast cancer in Chinese patients.
Authors: Peng Yuan, Binghe Xu
Journal: Journal of Clinical Oncology (2012)

TPS1135 Background: Triple-negative [estrogen receptor (ER)-/progesterone receptor (PR)-/HER2-] breast cancer (TNBC) accounts for about 15% of all breast cancers and is associated with very poor prognosis. A combination of anthracycline and taxanes represents the most commonly used adjuvant chemotherapy for TNBC patients. BRCA1, a protein responsible for repair upon DNA damage, is often dysfunctional in TNBC. As a result, TNBC is often sensitive to DNA-damaging agents (e.g., cisplatin and carboplatin). A phase II study of docetaxel plus carboplatin as neoadjuvant treatment for TNBC achieved promising response rate (Chang, CANCER, 2010). Encouraged by this important finding, we are currently conducting a phase III trial to examine docetaxel plus carboplatin as adjuvant chemotherapy in patients with early-stage TNBC (registration number at www.ClinicalTrials.gov: NCT 01150513). Methods: All participants received radical mastectomy or breast-conserving surgery for pT1-3N0-2 breast cancer. All cancers were negative for ER, PR, HER2/Neu. All participants had adequate organ function and performance status. The age ranged from 18 to 70 years. Patients randomly received a TP regimen (docetaxel 100 mg/m 2 plus carboplatin AUC=6 on day 1, 21 days a cycle for 6 cycles) or a EC-T regimen (epirubicin 90 mg/m 2 plus cyclophosphamide 600 mg/m 2 on d1, 21 days a cycle for 4 cycles; followed by docetaxel 100 mg/m 2 on d1, 21 days a cycle for 4 cycles). Adjuvant radiotherapy was permitted in both arms. The primary endpoint is disease-free survival (DFS). Secondary endpoints included adverse event and quality of life (QoL). The study planned to recruit 500 subjects over a period of 5 years, with 5-year follow-up (once every 6 months). Target hazard ratio is 0.86 (5 year DFS of 74.0% vs. 71.0%). The estimated power is 0.80; 1-sided type 1 error was set at 0.05). The study was activated in June 2010 with enrollment of 110 subjects.
Utilizing patient reported outcomes for patients recieving oral chemotherapy.
Authors: Emily R. Mackler, Kathleen W. Beekman, Laura Bushey, Anne Gentz, Kathleen Davis, Carol Yarrington, Karen B Farris, Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2017)

190 Background: Management of oral chemotherapy presents many challenges to oncology practitioners. The purpose of this study is to describe how incorporation of patient reported outcomes (PRO) for patients receiving oral chemotherapy can identify those patients who are experiencing moderate to severe symptom burden and nonadherence. Methods: As part of a statewide quality collaborative, we wished to improve our monitoring of patients receiving oral chemotherapy. The quality collaborative created a PRO assessment that includes a revised Edmonton Symptom Assessment Scale (ESAS), a single-item adherence question, reasons for nonadherence, the patient’s most bothersome symptom and questions related to patient confidence. Our medical assistants provide the assessment to the patient before each appointment. Results: Patients completing the PRO during the first 3 months (7/7/16 – 9/27/16) were evaluated. We had 32 assessments completed by 23 patients. The oral chemotherapy prescribed were capecitabine (48%), erlotinib (13%), temozolomide (13%), and not recorded (26%). Of the 29 completed ESAS assessments, 72% included at least 1 moderate side effect, and 48% included at least 1 severe side effect. 29% of patients reported low-moderate confidence to self-manage their symptoms. Less than excellent adherence (&lt;80% adherence) was reported in 30% of patients with the most commonly reported reason being related to side effects or concerns about side effects. Conclusions: Use of PROs in our oral chemotherapy population identified a large proportion of patients experiencing moderate to severe side effects. Further assessment of how this compares to what patients report to their oncologist during their visits will be reviewed. In addition, we found that approximately 30% of our patients are nonadherent to their oral chemotherapy. This is consistent with recent publications. We plan to continue assessing patient outcomes and utilizing the data we collect to improve patient self-management support.
Rapid induction of colonic neoplasms in ICR mice treated with azoxymethane followed by dextran sodium sulfate
Authors: Takuji Tanaka, Hiroyuki Kohno, Rikako Suzuki, Shigeyuki Sugie
Journal: Cancer Research (2004)

1523  Male Crj: CD-1 (ICR) mice were given a single and low dose of a genotoxic colonic carcinogen azoxymethane (AOM, 10 mg/kg bw, i.p. injection) followed by one-week oral exposure (2% in drinking water) of a non-genotoxic carcinogen dextran sodium sulfate (DSS) to develop an efficient and rapid animal model for colon carcinogenesis. Animals were sequentially sacrificed at Wks 2, 3, 4, 5, 6, 9, 12 and 20 for macroscopic and histopathological examinations. At Wk 3, colonic adenomas developed in 2 of 5 mice (40% incidence with 0.4 ± 0.5 multiplicity). Colonic adenocarcinomas were seen in 2 of 5 mice (40% incidence with 2.0 ± 3.5 multiplicity) at Wk 4. After this time point, the incidence and multiplicity of colonic neoplasms gradually increased with time and reached to 100% incidence at Wk 6. At Wk 20, the multiplicities of adenocarcinoma and adenoma were 5.60 ± 2.42 (100% incidence) and 0.20 ± 0.40 (38% incidence), respectively. Besides these neoplasms, dysplastic lesions and aberrabt crypt foci (ACF) developed in the colonic mucosa and the frequency of the latter was well correlated with the multiplicity of the colonic malignancy. Immunohistochemical investigation of such dysplasias and neoplasms revealed that all lesions expressed positive reactivities against β-catenin, cyclooxygenase-2, and inducible nitric oxide synthase, but did not show p53 immunoreactivity. Thus, we could develop a novel and rapid mouse model for investigating the genesis of colon carcinogenesis and for identifying xenobiotics with modifying effects.
Activity and safety of biweekly docetaxel plus capecitabine as first-line treatment for patients with metastatic breast cancer
Authors: C. Llorca, J. Mayordomo, E. Adrover, I. Alvarez, C. Madroñal, M. Burillo, J. Sanz, A. Lorenzo, H. Palombo, J. Janariz
Journal: Journal of Clinical Oncology (2004)

788 Background: The combination of docetaxel (D) plus capecitabine (CAP) administered every three weeks significantly improves survival over D alone in anthracycline- pretreated patients (p) with metastatic breast cancer. Biweekly administration of these agents may result in better activity/toxicity ratios. We have tested the activity and safety of D plus CAP as first-line treatment in p with metastatic breast cancer. Methods: P with histologically confirmed metastatic breast cancer, age older than 18 years, measurable disease, performance status 2 or better (ECOG) and adequate bone marrow, renal, hepatic and cardiac functions were eligible. Previous adjuvant or neoadjuvant chemotherapy was allowed. No prior chemotherapy for metastatic disease was allowed. Treatment consisted of D 50 mg/m2 i.v. on day 1 and CAP 750 mg bid po days 1–10 of a 14-day cycle. Vitamin B6 300 mg bid day 1–14 was also given. In the absence of progression or unacceptable toxicity, treatment was to be continued for 12 courses. Primary endpoint was response. Results: To date 37 p have been included. Median age was 55 years (range: 35–82). Performance status was 0–1 in 33 p (89%). Estrogen receptors were positive in 16 p, negative in 16 and unknown in 5. Previous treatment included surgery in 28 p (75%), (neo)adjuvant chemotherapy in 24 (65%) (22 with anthracyclines), hormonal therapy in 13 (35%) and radiotherapy in 17 (46%). Median number of metastatic sites was 3. In total, 249 treatment courses were given (median: 7 per p, range 2–12). Median received dose intensity was 90% for CAP and 98% for D. All p were evaluable for safety. Grade 3–4 toxicities per p included neutropenia (3 p, 8%), thrombocytopenia (2 p, 5%), febrile neutropenia (1 p, 3%), nail disorders (5 p, 13%), stomatitis (3 p, 8%) and hand-foot syndrome (2 p, 5%). Response was evaluated in 26 p (11 too early): 4 (15%) achieved complete response, 12 (46%) partial response, 4 (15%) stable disease and 6 (23%) progressive disease. Median time to progression and survival have not yet been reached. Conclusions: Biweekly D plus CAP is an active and well tolerated first-line first-line treatment for metastatic breast cancer. No significant financial relationships to disclose.
Monitoring and developing volunteer patient navigation intervention to improve mammography compliance in a safety net hospital.
Authors: Anitha Srinivasan, Judith Zwillenberg, Anisha Chadda, Hannah Gissel, Michael Lettera, Sarah Bender, Marc K. Wallack, Ilana Greene Margulies
Journal: Journal of Clinical Oncology (2017)

62 Background: Mammography screening is crucial for cancer detection. Screening rates have been declining in patients of low socioeconomic status and minorities, supporting the need for intervention at our safety-net hospital. Methods: Patients with a primary care provider order for screening mammograms over a one month period were monitored for 90 day compliance. This analysis determined compliance rate and optimal intervention period. A prospective randomized trial was done to improve compliance using a volunteer patient navigator. All patients received educational material and were randomly assigned to the control or intervention group. The latter were further educated on breast cancer and mammograms and, if amenable, were escorted to a walk-in mammogram. The study period was 3 weeks with 49 participants-24 patients in the control and 25 patients in the intervention group. The principal outcome was the 14 day mammography compliance rate. Secondary analysis examined efficacy of the study with respect to patient demographics, prior mammography compliance, family history of cancer, beliefs on mammography and past medical history and analyzed using GraphPad Prism 7. Results: Analysis revealed a noncompliance rate of 52% with majority compliance occurring within two weeks of order placement. The patient navigation intervention significantly improved compliance by 34% (42% in the control group, 76% in the intervention group, p &lt; 0.05 Fisher exact test). Intervention significantly improved compliance in patients with low susceptibility to cancer belief, who understood benefits of mammography and early diagnosis (p &lt; 0.05 Fisher exact test), had a prior mammogram (p &lt; 0.05 Fisher exact test), a family history of cancer (p &lt; 0.01 Fisher exact test), hyperlipidemia (p &lt; 0.05 Fisher exact test), and those employed (p &lt; 0.05 Fisher exact test). Conclusions: A system to monitor compliance and intervene using patient navigation significantly improved mammography compliance of patients in a safety net urban hospital. The relatively straightforward design of the volunteer based intervention makes it affordable, easily replicable and perhaps beneficial at other institutions.
Out of system (OOS) costs for oncology clinics treating patients with breast, colorectal, and non-small cell lung cancer in Washington state.
Authors: Catherine R. Fedorenko, Karma L. Kreizenbeck, Laura Panattoni, Julia Rose Walker, Mikael Anne Greenwood-Hickman, Gary H. Lyman, Ted Conklin, Bruce Smith, Sarah Barger, Scott David Ramsey
Journal: Journal of Clinical Oncology (2017)

5 Background: As payers move from fee-for-service to episode-based reimbursement, there is a need for oncology providers to accurately measure in- and out-of-system resource use and cost for patients under their care. Medicare assigns management of a patient to only one provider, yet delivery systems may assume contractual responsibility for a patient with cancer’s entire episode costs, including care received outside of their system. Accordingly, the goal of this study was to estimate OOS care for patients with breast, colorectal (CRC), and non-small cell lung cancer (NSCLC). Methods: Cancer registry records for patients with breast, CRC, or NSCLC diagnosed in Western Washington State from January 2007 to June 2016 were linked with claims from two regional commercial insurers. The analysis focused on initial treatment phase: first day of treatment (surgery, radiation, chemotherapy) through the first 4-month gap in treatment. Patients were assigned an oncology provider group by identifying the clinic Tax ID Number (TIN) with the most Evaluation &amp; Management (E&amp;M) claims with a cancer diagnosis. Claims were considered in system if the TIN matched the assigned clinic. Costs included claims paid to all providers (adjusted to 2016 dollars). Results: The study included 7,686 newly diagnosed patients with breast, CRC, or NSCLC. The average cost for the initial treatment phase was $61,147/patient (SD $75,432, median $35,750). Nearly 31% of claims paid (mean $18,684, SD $32,649) were out of system. Among OOS costs, 24% were for inpatient care, 68% were for outpatient care, and 8% were for outpatient pharmacy. Conclusions: Among newly diagnosed patients with breast, CRC, or NSCLC, approximately 1/3 of costs for the initial treatment period stemmed from OOS care. Developing best practices for the reporting and management of OOS will be critical for organizations to succeed under episode-based reimbursement plans.[Table: see text]
Effect of Baseline Nutritional Status on Long-term Multivitamin Use and Cardiovascular Disease Risk
Authors: Susanne Rautiainen, J. Michael Gaziano, William G. Christen, Vadim Bubes, Gregory Kotler, Robert J. Glynn, JoAnn E. Manson, Julie E. Buring, Howard D. Sesso
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> Long-term multivitamin use had no effect on risk of cardiovascular disease (CVD) in the Physicians' Health Study II. Baseline nutritional status may have modified the lack of effect. <h3>Objective</h3> To investigate effect modification by various baseline dietary factors on CVD risk in the Physicians' Health Study II. <h3>Design, Setting, and Participants</h3> The Physicians' Health Study II was a randomized, double-blind, placebo-controlled trial testing multivitamin use (multivitamin [Centrum Silver] or placebo daily) among US male physicians. The Physicians' Health Study II included 14 641 male physicians 50 years or older, 13 316 of whom (91.0%) completed a baseline 116-item semiquantitative food frequency questionnaire and were included in the analyses. This study examined effect modification by baseline intake of key foods, individual nutrients, dietary patterns (Alternate Healthy Eating Index and Alternate Mediterranean Diet Score), and dietary supplement use. The study began in 1997, with continued treatment and follow-up through June 1, 2011. <h3>Interventions</h3> Multivitamin or placebo daily. <h3>Main Outcomes and Measures</h3> Major cardiovascular events, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Secondary outcomes included myocardial infarction, total stroke, CVD mortality, and total mortality individually. <h3>Results</h3> In total, 13 316 male physicians (mean [SD] age at randomization, 64.0 [9.0] years in those receiving the active multivitamin and 64.0 [9.1] years in those receiving the placebo) were observed for a mean (SD) follow-up of 11.4 (2.3) years. There was no consistent evidence of effect modification by various foods, nutrients, dietary patterns, or baseline supplement use on the effect of multivitamin use on CVD end points. Statistically significant interaction effects were observed between multivitamin use and vitamin B<sub>6</sub>intake on myocardial infarction, between multivitamin use and vitamin D intake on CVD mortality, and between multivitamin use and vitamin B<sub>12</sub>intake on CVD mortality and total mortality. However, there were inconsistent patterns in hazard ratios across tertiles of each dietary factor that are likely explained by multiple testing. <h3>Conclusions and Relevance</h3> The results suggest that baseline nutritional status does not influence the effect of randomized long-term multivitamin use on major CVD events. Future studies are needed to investigate the role of baseline nutritional biomarkers on the effect of multivitamin use on CVD and other outcomes. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00270647
Loss of heterozygosity in benign breast epithelium in relation to breast cancer risk
Authors: D. Yamamoto, K. Tanaka
Journal: Journal of Clinical Oncology (2004)

9671 Background: The multistage model of breast carcinogenesis suggests that errors in DNA replication and repair generate diversity in the breast epiethlium (the mutant phenotype), resulting in selection and expansion of premalingant clones with an acquired survival advantage. Methods: We measured Loss of heterozygosity (LOH) in breast epithelial cells obtained by ductal lavage from 35 asymptomatic women whose risk of breast cancer had been defined by the Gail model. Polymorphic microsatellite markers were selected on the basis of their relevance to breast cancer. Results: Breast epithelium of 17 (48 %) of 35 women had normal cytology, and that of 18 (52 %) had proliferative cytology. LOH was detected in 18 women with normal cytology and in 12 women (five with atypia and seven without atypia) with proliferative cytology. The frequency of LOH was associated with cytological diagnosis, as well. The mean ratio of positive markers demonstrating LOH was 1.2 for the 11 women with normal cytology, as compared with 3.5 for the 19 women with proliferative cytology. These results suggest that multistage model of breast carcinogenesis where the initiating events are those that result in genomic instability. Conclusions: Accurate individualized breast cancer risk assessment may be possible based on molecular analysis of breast epithelial cells obtained by ductal lavage. No significant financial relationships to disclose.
The semiotic dynamics of colour: authors' response
Authors: L Steels, Tony Belpaeme
Journal: Behavioral and Brain Sciences (2005)

The interesting and deep commentaries on our target article reflect the continued high interest in the problem of colour categorisation and naming. Clearly, colour remains for many cognitive science related disciplines a fascinating microworld in which some of the most fundamental issues for cognition and culture can be studied. Although our target article took the stance of practically oriented engineers who are trying to find the best solution for orchestrating the self-organisation of communication systems in artificial agents, most commentators focus on the implications for cognitive science and we will do the same in our reply.
Exploration of a plucked hair gene signature as a potential pharmacodynamic marker for the dual PI3K/mTOR inhibitor VS-5584.
Authors: David T. Weaver, Daniel Paterson, Gino Miele
Journal: Journal of Clinical Oncology (2013)

11064 Background: The PI 3-kinase/mTOR pathway plays a central role in cancer cell proliferation, survival, and cancer stem cell mechanisms. Depending on the mode of pathway activation, different PI3K isoforms and mTOR complexes have been shown to play essential roles in oncogenesis. VS-5584 inhibits PI3K/mTOR signaling with equipotency against all four human Class I PI3K isoforms and the mTOR kinase. VS-5584 has been shown to induce broad and robust antitumor activity with corresponding inhibition of PI3K/mTOR downstream targets in human xenograft models. Considering the inhibitory activity of VS-5584 against multiple targets within the PI3K/mTOR pathway, multiple clinical pharmacodynamic biomarkers need to be assessed. Methods: Due to its vascularization, ease of sampling and epithelial origin, anagen hair represents a practical surrogate tissue for monitoring drug effects in patients. Human anagen hair from volunteer donors were treated ex vivo with VS-5584 and another PI3K/mTOR dual inhibitor, BEZ235. Following 6, or 24 hour exposure to various drug concentrations, RNA was extracted, amplified and analyzed on Affymetrix PrimeView microarrays. Results: Transcriptomic profiles indicated a robust and dose-dependent response to VS-5584. A VS-5584-specific 91 gene signature was identified by 3-way ANOVA, and a Connectivity map evaluation indicated a strong positive correlation with other agents targeting the PI3K/mTOR pathway (wortmannin, LY-294002 and sirolimus). Likewise, VS-5584 exposure ex vivo in human anagen hair follicles resulted in a dose responsive suppression at both 6 and 24 hrs with an alternative PI3K/mTOR dual inhibitor 115 gene signature trained on BEZ235. A seven gene subset was consistently reduced by both VS-5584 and BEZ235 at 6 hrs and 24 hrs. Conclusions: Gene signatures from plucked anagen hair may provide a non-invasive approach to assess pharmacodynamic effects of VS-5584 in cancer patients.
Spatiotemporal patterns and drivers of landscape change in a semi-arid, southern African savanna: a satellite imaging and intensity analysis
Authors: John Tyler Fox, Kathleen Alexander
Journal: The Lancet Global Health (2017)

BackgroundThe savannas of southern Africa are a highly variable and globally important biome that supports rapidly expanding human populations. They also have one of the greatest concentrations of wildlife on the continent. Savannas occupy a fifth of the earth's land surface, yet despite their ecological and economic significance, little is understood about the complex couplings and feedbacks that drive long-term spatiotemporal patterns of change. Here, we aimed to describe land-cover change in Chobe District, Botswana, and address questions about the complex drivers of patterns of land cover change, with a particular focus on climate, fire, herbivory, and anthropogenic disturbance.MethodsWe used Landsat Thematic Mapper (TM), Enhanced Thematic Mapper Plus (ETM+), and Operational Land Imager (OLI) satellite imagery from 1990 to 2013 to explore land-cover change across the 21 000 km2 Chobe District. Net and gross land cover change were assessed for the Chobe National Park, six protected forest reserves, areas surrounding towns and villages, and the riparian corridor of the Chobe River. We also used intensity analysis methods developed by Aldwaik and Pontius to compare observed changes to a hypothetical uniform change to examine how the size and intensity of land cover losses and gains vary between time periods and across different land-cover classes.FindingsPatterns of land-cover change in the Chobe District were not strictly linear in nature, a characteristic noted for other dryland systems, with gross land-cover change and intensity analysis showing extensive, active bidirectional exchange between woodland, shrubland, and grassland. Changes in land cover over the study period were characterised by a loss of woodlands, accompanied by an expansion of shrubland. Woodland losses were greatest along the Chobe River, which provides a large proportion of the drinking water, and other essential resources, for human and wildlife populations.InterpretationThe multi-decadal monitoring of land-cover changes in southern Africa using remote-sensing provides essential information for societies to manage ecosystem resources locally, so that they might increase resilience to future climate change. Our identification of spatial and temporal patterns of land-cover changes supports the need to develop an early warning framework to identify existing and emergent threats to forest resources and services, and reduce potential adverse effects on the livelihoods and health of local communities.FundingForest Conservation Botswana (FCB); National Science Foundation.