tbuckley/cabot-search huggingface dataset:
Sunitinib in metastatic renal cell carcinoma (mRCC) patients (pts) with brain metastases (mets): data from an expanded access trial
Authors: S. Hariharan, C. Szczylik, C. Porta, S. Bracarda, R. Hawkins, G. A. Bjarnason, S. Oudard, S. Lee, G. Carteni, M. E. Gore
Journal: Journal of Clinical Oncology (2008)

5094 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs and PDGFRs that has demonstrated substantial antitumor activity in first- and second-line mRCC (JAMA 2006;295:2516; NEJM 2007;356:115). Brain mets are common from RCC and result in significant mortality (Curr Treat Options Oncol 2003;4:385; Med Oncol 2000;17:279). Safety and efficacy data for mRCC pts with brain mets on sunitinib in an ongoing, international, open-label expanded access trial are presented. Methods: The purpose was to provide sunitinib prior to regulatory approval to mRCC pts without access to study drug due to trial ineligibility or other reasons; as such, eligibility criteria were minimized to broaden enrollment, including allowance of pts with asymptomatic brain mets and any ECOG PS. Pts ≥18 yrs with histologically-confirmed mRCC received sunitinib 50 mg orally, once-daily in 6-wk cycles (4 wks on treatment [Tx], 2 wks off). Results: As of December 2007, 4,616 pts had been enrolled, with data available for 3,997 pts of whom 298 pts (7%) had baseline brain mets. Within this subgroup, 75% were male, median age was 58 yrs (range: 23–81), and prior Tx included nephrectomy (89%), cytokines (77%), and anti-angiogenic agents (7%). Median Tx duration was 4.3 mo. Dosing reductions (for any cause) occurred in 102 pts (34%); 196 pts (66%) discontinued, 81 pts (27%) due to lack of efficacy and 19 pts (6%) adverse events (AEs), rates similar to those for all clinical trial mRCC pts treated with sunitinib. The most common grade 3/4 Tx-related AEs were fatigue (6%), asthenia (5%), and vomiting, hypertension, thrombocytopenia, neutropenia, and anemia (all 3%). One pt experienced grade 1/2 Tx-related cerebral hemorrhage. Of 192 brain mets pts with efficacy data, 22 (11%) had a partial response and 98 (51%) had stable disease ≥3 mo. For brain mets pts with (n=217) and without (n=58) prior cytokine Tx, median progression-free survival was 5.6 and 5.3 months, respectively. Median overall survival had not yet been reached. Conclusions: The safety of sunitinib in mRCC pts with brain mets mirrored that for the overall trial population, as previously reported. Sunitinib showed antitumor activity in this subgroup of pts with limited treatment options. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Bayer, GlaxoSmithKline, Pfizer, Roche, Schering-Plough, Wyeth Pfizer Pfizer Bayer, Pfizer Pfizer
Abstract 17858: Aortic Dissection and Survival in the Angiotensin II Infused ApoE Deficient Mouse- the Influence of Transforming Growth Factor Beta
Authors: Maria Nataatmadja, Malcolm West, Sulistiana Pradowo, Andrew Dettrick, Fraser Russell
Journal: Circulation (2012)

The role of transforming growth factor-beta (TGFB) in the development of aortic aneurysm (AA) in the angiotensin (Ang)II infused ApoE-/- mouse is uncertain with induction of AA complicated by aorti...
Organ sparing by conformal avoidance intensity modulated radiation therapy for anal cancer: Dosimetric evaluation of coverage of pelvis and inguinal/femoral nodes
Authors: Y.-J. Chen, A. Liu, P. T. Tsai, N. L. Vora, R. D. Pezner, T. E. Schultheiss, J. Y. C. Wong
Journal: Journal of Clinical Oncology (2005)

4257 Background: To describe a novel and straightforward conformal avoidance IMRT technique for coverage of pelvis and inguinal/femoral nodes and to compare the dosimetry of the new method with that of other methods of radiation treatment. Methods: Data of 2 patients with anal cancer were used as example cases to illustrate details and advantages of conformal avoidance IMRT technique. Conventional photons with enface electrons design was created first, thereby providing “outermost boundaries” defined as planning target volume (PTV) for subsequent conformal avoidance IMRT design. Organs at risk (OARs) including femoral head and neck and external genitalia were contoured as conformal avoidance structures. A step-and-shoot inverse IMRT planning was generated. For dosimetric comparison, technique by modified segmental boost was also generated. These treatment techniques were evaluated by dose volume histogram (DVH) of PTV and OARs. Dose profiles at 4 different depths from each treatment planning were generated. Results: DVH of PTV shows that coverage of the PTV is comparable among 3 treatment techniques. Volume of PTV receiving more than 90% prescription dose are in the range of 94 to 98% for the 3 treatment techniques and all have only 0 to 2% of PTV receiving more than 110% prescription dose. DVH of OARs confirms that both femoral head and neck and external genitalia could be spared well by conformal avoidance IMRT. Although greater inhomogeneity of dose distribution within the PTV is noted by conformal avoidance IMRT as shown by dose profiles at 4 depths, the maximum doses at different depths are less than 115% which are comparable to the planning by modified segmental boost technique. Planning by photons and enface electrons technique however shows a greater dose variation up to 134% of the prescription dose at 1.5 cm depth along photon-electron match-line. Conclusions: To cover pelvis and inguinal/femoral nodes conformal avoidance IMRT is technically simple to simulate, plan and execute. Dosimetric study demonstrated that it achieves comparable PTV coverage compared with other approaches while at the same time significantly spares the surrounding OARs. No significant financial relationships to disclose.
Overhead costs (OC) associated with quality oncology care (QOC) monitoring to ensure compliance with national treatment guidelines (TG)
Authors: R. Vakil, L. D. Bosserman, C. Presant, W. McNatt, A. Der, A. Greenburg, A. Estrella, G. Upadhyaya, M. Vakil
Journal: Journal of Clinical Oncology (2007)

6637 Background: QOC is a goal of all oncology practices (op), healthcare insurance plans (hip), HMOs, and payers for health insurance. In order to ensure compliance with TG and maintain QOC in a multi-site op, we adapted an electronic medical record (EMR) to evaluate tumor and stage specific compliance in oncology treatments. This report evaluates the OC associated with development and operation of that monitoring system and its application to an HMO patient population of 75,000 covered lives. Methods: OC included 25% (proportion of HMO to total patients )of the emr system developmental costs (DC) and operational costs (OpC). Personnel time included entering data and treatments, training, data coordination, and data analysis. Salaries were based on regional averages for physicians, administrators, clerks, and nurses. Time estimates were made for monitoring quality data only, excluding standard patient care. Compliance data is reported separately. Results: 1,250 patients over 18 months were treated by 5 of the op physicians. DC for this program included computer hardware $25,000, personnel training $10,900, and EMR licensing $12,500. Annualized operational costs (OpC) included emr maintenance fees $1000, IT consultants $4500, physician time to enter individual patient data at first consultation and follow up visits $58,000, nursing time to enter treatment data and continued training $7650, physician continued training $11,250, senior administrator coordination $30,000, administrative supervision $17,900, clerical data analysis $22,500, and senior physician supervision $50,000. Costs per covered life for DC were $0.645 and for OC were $2.704 per year. Conclusions: The costs to maintain QOC and ensure TG compliance are substantial and must be reimbursed by hips and HMOs. Understanding these costs is essential to negotiating care contracts with hips that will monitor care appropriately. Investing in EMR methods to ensure QOC will be important to patients and op, as well as hips. Monitoring continuing OC to determine if they decrease with additional experience is essential. Standardizing EMR data sets aad op methodologies for compliance monitoring will further improve efficiencies and cost efficacy in documenting delivered QOC. No significant financial relationships to disclose.
IMPAIRED JAK-STAT SIGNALING OF INTERFERON-alpha IN CHRONICALLY HCV INFECTED LIVER TISSUE
Authors: Bret Poat, Sidhartha Hazari, Feyza Gunduz, Partha K. Chandra, Lili Bao, Jonathan Stone, Tong Wu, David Bruce, Ari J. Cohen, Humberto E. Bohorquez, George E. Loss, Srikanta Dash
Journal: Hepatology (2010)
A Novel Mouse Model for RPS19-Deficient Diamond-Blackfan Anemia Locates the Erythroid Defect at CFU-E / Proerythroblast Transition.
Authors: Pekka Jaako, Johan Flygare, Karin Olsson, Axel Schambach, Christopher Baum, Jonas Larsson, David Bryder, Stefan Karlsson
Journal: Blood (2009)
Chemotherapy (CT) with or without carboplatin as neoadjuvant treatment in patients with basal-like breast cancer: GEICAM 2006-03—A multicenter, randomized phase II study.
Authors: E. Alba, J. I. Chacon, A. Lluch, L. García-Estevez, A. Anton, B. Cirauqui, J. A. Lopez Garcia-Asenjo, E. M. Carrasco, C. Rodriguez, M. J. Escudero, A. Sanchez, N. Ribelles, C. Romero, J. Alvarez, J. Albanell
Journal: Journal of Clinical Oncology (2011)

1015 Background: Platinum salts are active in basal-like breast cancer in preclinical models and has been widely used in clinical trials in this subtype. However its utility added to conventional drugs has never been tested in a randomized trial. This study investigates the benefit of the addition of carboplatin to conventional neoadjuvant CT in basal-like breast cancer patients. Methods: Patients (Pt) with tumors ≥ 2 cm (or less with positive axilla) and immunophenotypically defined basal-like disease (ER-/PR-/HER2-/Cytokeratin 5/6+ and/or EGFR+) assessed in a central laboratory were recruited. Pts were randomized to receive epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 x 4 cycles (cy) followed by either docetaxel 100 mg/m2 x 4 cy (EC-T) or docetaxel 75 mg/m2 plus carboplatin AUC 6 x 4 cy (EC-TCb). The primary end-point was pathological complete response (pCR) in the breast measured by the Miller and Payne criteria. Secondary end-points were clinical response, toxicity, type of surgery and axillary status at surgery. Results: From April-07 to January-10, 94 pts were randomized (46 EC-T, 48 EC-TCb). Pts characteristics were well balanced between arms. Median age was 47 years (27−74), 65% of pts were premenopausal, 3% grade I, 73% grade III, 10/69/19/2% were T1/T2/T3/T4 and 53% N+. One patient (in the EC-TCb arm) never received treatment and was not considered evaluable. pCR rate in the breast was 35% for EC-T and 30% for EC-TCb (p-value=0.6064 ). pCR+pN0 was 30% in both arms. Mastectomy rate was similar in both arms (EC-T: 33%, EC-TCb 28%; p-value=0.6029) Patients with any grade III-IV toxicity (excluding amenorrhea) was similar in both arms (54% and 53%), with more neutropenia and febrile neutropenia with EC-T and more anemia and trombocytopenia with EC-TCb. Conclusions: The addition of carboplatin to conventional chemotherapy with EC-T though did not increase the toxicity neither produced a better efficacy in basal-like breast cancer patients, probably because all of them had received already an alkylating agent. The findings from this trial should be taken into account in the future development of PARP inhibitors.
Caring for Older People: Community care and social services
Authors: D Renwick
Journal: BMJ (1996)

The aim of community care is to enable people with various types of disability to live in their own homes, rather than in institutions. This involves the provision of support and services at home by various agencies. After a critical report in 1986 identified problems with coordination and flexibility of community care services, the white paper Caring for People (1989) stated the government's aim to provide a "needs led," responsive range of services, promoting maximum independence of those wishing to live at home rather than enter institutional care. New arrangements were introduced in 1993, involving a formal assessment procedure and the production of a personalized care plan for each individual, incorporating services provided by private and voluntary agencies as well as by social services departments. This article describes the components of community care services supplied by local social services authorities, including housing adaptations, equipment, telephones and alarms, home care, meals, and respite care.
Using Behavioral Economics to Design Physician Incentives That Deliver High-Value Care
Authors: Ezekiel J. Emanuel, Peter A. Ubel, Judd B. Kessler, Gregg Meyer, Ralph W. Muller, Amol S. Navathe, Pankaj Patel, Robert Pearl, Meredith B. Rosenthal, Lee Sacks, Aditi P. Sen, Paul Sherman, Kevin G. Volpp
Journal: Annals of Internal Medicine (2015)

Behavioral economics provides insights about the development of effective incentives for physicians to deliver high-value care. It suggests that the structure and delivery of incentives can shape behavior, as can thoughtful design of the decision-making environment. This article discusses several principles of behavioral economics, including inertia, loss aversion, choice overload, and relative social ranking. Whereas these principles have been applied to motivate personal health decisions, retirement planning, and savings behavior, they have been largely ignored in the design of physician incentive programs. Applying these principles to physician incentives can improve their effectiveness through better alignment with performance goals. Anecdotal examples of successful incentive programs that apply behavioral economics principles are provided, even as the authors recognize that its application to the design of physician incentives is largely untested, and many outstanding questions exist. Application and rigorous evaluation of infrastructure changes and incentives are needed to design payment systems that incentivize high-quality, cost-conscious care.
Oppositional defiant disorder
Authors: J M Rey
Journal: American Journal of Psychiatry (1993)

Oppositional defiant disorder is a common clinical diagnosis that has attracted little research interest, and doubts about its validity as a distinct category remain. However, it underwent substantial changes from DSM-III to DSM-III-R, and more are proposed for DSM-IV. The objective of this study was to review the literature on this condition to establish its place in the psychiatric nosology.The terms used in computerized searches of the literature included "oppositional disorder," "oppositional defiant disorder," and "oppositional behavior." Publications found by these searches were supplemented with references in articles, searches in the epidemiological literature, and noncomputerized searches.Findings of studies in which multivariate analyses were used support a distinction between oppositional defiant disorder and conduct disorder. In these studies, one-third of all community-based children with any psychiatric condition had a diagnosis of oppositional defiant disorder and used mental health services often. Symptoms of oppositional defiant disorder appear to be stable over time and to have a developmental profile and sex distribution different from those of conduct disorder. The reliability of the diagnosis is low.There is some support for oppositional defiant disorder as a category that reflects an oppositional-aggressive psychological dimension, which is different from a delinquent dimension. There is little evidence for making oppositional defiant disorder a part of the construct of conduct disorder and for making "lying" a criterion for it. Considerable impairment should be required for the diagnosis. A more detailed description of symptoms, including a threshold for considering them present, may increase reliability of the diagnosis.
Non-castrate status at the end of chemotherapy for metastatic hormone-resistant prostate cancer (HRPC) correlates with a better overall survival
Authors: M. Gerlinger, P. Wilson, T. Powles, J. Shamash
Journal: Journal of Clinical Oncology (2008)

16102 Background: In our institution patients with HRPC (defined as resistance to androgen ablation and to subsequent dexamethasone + diethylstilbestrol) are given chemotherapy without concurrent hormone manipulation. On progression of disease, patients are rechallenged with hormone therapy (maximum androgen blockade followed by dexamethasone and diethylstilbestrol when this fails). In this study we analysed the influence of castration status at the end of chemotherapy on survival outcome. Methods: The overall survival of 102 patients with HRPC who had been treated with chemotherapy (chlorambucil and lomustin or docetaxel) between July 2000 and July 2007 was analysed by castration status. The response rates to chemotherapy and further hormone therapy were assessed. Results: The median overall survival for the whole group was 11.4 months (95% CI 9.4–15.0). Forty two (41%) patients were non- castrate at the end of chemotherapy, which was associated with a prolonged survival (15.6 months vs. 10.8 months p=.08). Median patient age (70 years vs. 74 years), PSA (149.5 vs. 159) alkaline phosphatase (167 vs. 111) of the non-castrate and the castrate group were similar at the time of starting chemotherapy. Non-castrate patients had a higher PSA response rate to chemotherapy (21% vs. 13%, p=.41), maximum androgen blockade (38.5% vs. 8.5%, p=.015) and further dexamethasone and diethylstilbestrol (23% vs. 17%, p=.56). Conclusions: Individuals who are not castrate at the end of chemotherapy have a prolonged survival compared to patients who remain castrate. There is no evidence that being non-castrate at the end of chemotherapy has an adverse effect on response to further hormone therapy or survival. This challenges the current practice of continuing hormone therapy during chemotherapy in HRPC. No significant financial relationships to disclose.
The incidence of prostate cancer in patients under the age of 60 from an urban setting
Authors: M. Shum, E. Bodofsky, Z. Skaff, M. El-Khoury, S. Kankipati, C. Dalsania, V. Khemka, R. Parra, S. Dibiase, R. Somer
Journal: Journal of Clinical Oncology (2006)

14622 Background: Although the risk for developing prostate cancer increases with age, few studies have reported the incidence of prostate cancer in men younger than 60 from an urban setting. Methods: All patients diagnosed and treated for prostate cancer at The Cancer Institute of New Jersey at Cooper University Hospital in Camden County, New Jersey from January 1, 2004 to December 31, 2004 were retrospectively identified from our tumor registry. Age comparison at diagnosis was made utilizing the Cooper registry and the National Cancer Database (NCDB), 2001. Results: A total of 141 men (88 Caucasians, 37 African Americans, 14 Hispanic, and 6 unknown) with a median age of 64 years (range, 44–88 years) were diagnosed with prostate cancer in 2004. Staging revealed Stage II (118), Stage III (3), Stage IV (4), Stage unknown (16) cases. Median Gleason score was 6. 74 patients underwent radical prostatectomy, 50 had radiation, 30 received hormone therapy and 2 received chemotherapy. At diagnosis, 19.95% of the men were under 50 and 41.84% were under 60 years of age. Our dataset from these two age groups compared to NJ and US figures are noted below. Conclusions: When comparing the respective data sets from CINJ at Cooper to NJ and US utilizing the NCDB, there are striking differences with a higher incidence of prostate cancer in younger men. These incidences parallel those seen in other urban university teaching hospitals from the Healthcare Utilization Project (2005), where more patients under the age of 60 are being diagnosed with prostate cancer when compared to community centers. Subset analysis shows that our institution had a disproportionately larger number of African American men with prostate cancer which may relate to our culturally directed screening program, accounting for the higher incidence. These data support that hospital characteristics may impact age at diagnosis of prostate cancer, and further investigation is warranted. [Table: see text] No significant financial relationships to disclose.
Phase II trial of the epidermal growth factor receptor (EGFR) inhibitor erlotinib (E) in patients (pts) with advanced papillary renal cell carcinoma (pRCC)—SWOG S0317
Authors: C. Pan, M. Hussey, P. Lara, P. C. Mack, R. B. Nagle, J. Dutcher, W. Samlowski, J. Clark, E. D. Crawford, M. S. Gordon
Journal: Journal of Clinical Oncology (2007)

15516 Background: Clear cell RCC often has mutations of the von Hippel-Lindau (vHL) gene and over expression of vascular endothelial growth factor (VEGF). pRCC has mutations of c-met and not vHL. Pre-clinically, normal vHL expression is associated with greater activity of EGFR inhibitors in clear cell RCC (Clin Can Res 6:1518, 2000). PRCC has no effective treatment. Given the absence of vHL mutations we undertook a study of E in pts with pRCC. Methods: Pts with histologically confirmed advanced or metastatic pRCC with measurable disease received E 150 mg PO QD from day 1 to disease progression, pt refusal, unacceptable toxicity, or a delay of therapy &gt;3 wks. Central path review and tissue submission for vHL gene analysis were required. The primary endpoint was response. Further study of this regimen would be considered if the observed response rate (RR) was =20% (i.e. 5+ observed responses). Results: 52 pts from 27 SWOG and 2 ECOG institutions were registered. 7 pts were ineligible (no path submission-3; incorrect histology-1; no measurable disease-2; scans outside timeframe-1). Central path review is ongoing for 7 pts, leaving 39 pts evaluable for response including 30M/9F with a median age of 60.2 y (range 27.9 to 82.3). Median follow-up was 12.8 months (range 1.5 to 35.4 m). 4 pts had confirmed PRs for a RR of 10% (95% CI: 3 - 24%). Five evaluable patients with inadequate response assessment were assumed to be non-responders. Median OS was 26.9 months (95% CI lower limit 12.8 m, upper limit not yet estimable). Probability of freedom from treatment failure at 6 m is 30% (95% CI: 15–45%). There was one Grade 5 adverse event (AE) of pneumonitis thought to be possibly drug-related and one Grade 4 thrombotic AE. 8 pts experienced Grade 3 AEs common to E including rash, anorexia, diarrhea and fatigue. vHL mutation was observed in two patients with stable disease. Conclusions: Though the observed RR in pts with pRCC receiving E is similar to pts with clear cell RCC we did not see enough responses to warrant further study. As this is the first phase II trial reported (to our knowledge) for the subset of pts with pRCC we have demonstrated that less common and distinct histological subtypes can be independently studied in the cooperative group setting. [Table: see text]
HLA and Aplastic Anemia: associations In Large Brazilian Cohorts
Authors: Marco Aurelio Salvino, Larissa A Medeiros, Alessandro Moura, Marianna Batista, Marilda Souza Goncalves, Eliane Mezes, Luciano Santos, Gloria Bomfim Arruda, Noemi Farah Pereira, Bruno A. V. Cerqueira, Anelisa Schittini, Monica Botura, Ana Luzia Fernandes Schriefer, Michel M Oliveira, Vaneuza A M Funke, Ricardo Pasquini, Phillip Scheinberg, Roberto Meyer
Journal: Blood (2013)