tbuckley/cabot-search huggingface dataset:
Safety and antitumor activity of AMG 706 in patients (pts) with thyroid cancer (TC): A subset analysis from a phase 1 dose-finding study
Authors: D. Boughton, L. Rosen, A. Van Vugt, R. Kurzrock, M. Eschenberg, J. Wiezorek, M. Ingram, D. Wang, D. Stepan, R. S. Herbst
Journal: Journal of Clinical Oncology (2006)

3030 Background: AMG 706 is an investigational, oral, small molecule multi-kinase inhibitor with both antiangiogenic and direct antitumor activity that selectively targets VEGF, PDGF, and Kit receptors. From a phase 1 study (Rosen ASCO 2005; Herbst EORTC 2005), encouraging antitumor activity was seen in pts with TC. In this analysis, we report on the TC subset from the study. Methods: Pts with refractory solid tumors received oral AMG 706 QD (50, 100, 125, 175 mg) or BID (25 mg) intermittently or continuously for 28-day cycles. Study objectives were to assess safety, establish the maximum tolerated dose (MTD), and generate pharmacokinetic profiles of AMG 706 in these pts. Tumor response (modified RECIST) was evaluated at wk 8 and Q12W thereafter. Data from Oct 2005 were analyzed. Results: In this study, 7 of 71 pts enrolled had TC. Baseline demographics for this subset were 4 W/3 M, median (range) age of 58 (41, 78) yrs, ECOG 1 (71%), and all had stage IV disease. Histologies were papillary (3: PTC), follicular (1; FTC), Hürthle cell (1), anaplastic (1), and medullary TC (1; MTC). All pts received prior external radiotherapy, radioiodine, chemotherapy, and/or surgery. Initial doses of AMG 706 were 125 mg and 175 QD and 25 mg BID. The MTD for the study was 125 mg QD. Median (range) time on treatment for the TC pts was 141 (14, 564) days. Treatment-related adverse events are summarized ( table ). Best objective responses were 3 pts with partial response (PR), 3 with stable disease (SD), and 1 with progressive disease. PR was seen in pts with MTC, PTC and FTC. Two pts with PR did not have confirmation of response (1 had a PR during the last assessment). The 3 pts with PR received AMG 706 for 338, 366, and 564 days; 2 pts are still receiving AMG 706. Time to response for these 3 pts were 210, 217, and 304 days. Conclusion: In patients with TC, AMG 706 appears to be relatively well tolerated and displays promising antitumor activity for some pts. Based on these favorable findings, a phase 2 study of AMG 706 for the treatment of advanced TC is ongoing. [Table: see text] [Table: see text]
PSA Screening for Prostate Cancer: Why Saying No is a High-Value Health Care Choice
Authors: Timothy J. Wilt, Philipp Dahm
Journal: Journal of the National Comprehensive Cancer Network (2015)

Enthusiasm for cancer screening and treatment of screen-detected cancer has led to widespread prostate-specific antigen (PSA) screening, a marked increase in prostate cancer incidence, and high use of surgical, radiation, and androgen deprivation treatment for screen-detected disease. This has occurred in advance of a full understanding of the clinical and financial tradeoffs. Although questions remain whether lifetime benefits outweigh harms and costs, data indicate that this balance is not favorable through at least 15 years. This article outlines a conceptual framework for determining the value of screening strategies according to screening and treatment intensity. We describe 4 main cancer screening goals and examine whether PSA screening and treatment achieve these goals and thus provide high-value care. Available evidence demonstrates that PSA screening provides at best a small reduction in prostate cancer mortality, and no reduction in all-cause mortality. High-intensity PSA screening and treatment currently practiced in the United States result in substantial harms and large health care expenditures—it is low-value care. The health importance of prostate cancer and the financial costs to patients and society require improved detection and treatment strategies that produce greater value to patients. We propose lower-intensity, higher-value options. However, until evidence supports a higher-value alternative to current PSA screening strategies, physicians should recommend against PSA screening, policymakers should encourage reduced screening, and most men should say no to the PSA test.
Dose-intensity analysis and randomized trials.
Authors: G Heller, N K Cheung
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.9.1715 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1875228 Dose-intensity analysis and randomized trials. G HellerxG HellerSearch for articles by this author , N K CheungxN K CheungSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.9.1715 PDF "Dose-intensity analysis and randomized trials.." Journal of Clinical Oncology, 9(9), pp. 1715–1716© 1991 by American Society of Clinical Oncology
Outcomes of a clinical pathway for borderline resectable pancreatic cancer.
Authors: Omar Maen Rashid, Jose Mario Pimiento, Gregory M. Springett, Mokenge Peter Malafa
Journal: Journal of Clinical Oncology (2015)

374 Background: While multimodality therapy for borderline resectable pancreatic adenocarcinoma (BPA) is advocated, treatment regimens vary by institution without a standardized approach supported by prospective randomized data. We implemented a multidisciplinary multimodality clinical pathway (CP) for the management of BPA and examined outcomes to investigate optimal therapy. Methods: From January 1, 2006, to December 31, 2013, BPA cases as defined by the NCCN and AHPBA consensus guidelines were managed prospectively along CP. Resection rates, margin status, pathologic response, and overall survival were retrospectively examined. Standard statistical and survival analysis were used. Results: 121 patients were classified as BPA and 101 entered the CP. The neoadjuvant chemoradiation (NT) completion rate was 93.1%. Of those who entered the CP, 55 patients (54.5%) underwent pancreatectomy. R0, R1 and R2 margin rates were 96.3%, 3.7% and 0%, respectively. Of the 55 patients who underwent resection, 22 (40%) required vascular reconstruction, with R0, R1 and R2 margin rates of 95.2%, 4.8%, and 0%, respectively. Pathologic response to treatment was found in 70.8%, with a complete response rate of 15.9%. Median overall survival in the resected group versus the non-resected group was 34.2 months versus 14.7 months, p&lt;0.001. Conclusions: Our series represents one of the largest reports of BPA in the literature and implementation of our CP resulted in a high NT completion rate and pancreatectomy with negative margin rate. Although 41.4% of cases were not resectable after NT, there was a high rate of negative margin resection with &gt;70% pathologic response rate and a favorable median survival.
Neutrophil Activation Promotes Fibrinogen Oxidation and Thrombus Formation in Behçet Disease
Authors: Matteo Becatti, Giacomo Emmi, Elena Silvestri, Giulia Bruschi, Lucia Ciucciarelli, Danilo Squatrito, Augusto Vaglio, Niccolò Taddei, Rosanna Abbate, Lorenzo Emmi, Matteo Goldoni, Claudia Fiorillo, Domenico Prisco
Journal: Circulation (2016)

Background— Behçet disease (BD) is a systemic vasculitis with a broad range of organ involvement, characterized by a multisystemic, immune-inflammatory disorder involving vessels of all sizes and often complicated by thrombosis. Systemic redox imbalance and circulating neutrophil hyperactivation have been observed in BD patients and are thought to be responsible for impaired coagulation. We here focused on the pathogenetic mechanisms potentially linking immune cell activation and thrombosis, and specifically examined whether neutrophil activation can affect fibrinogen modifications and consequently elicit thrombosis. Methods and Results— Blood samples were collected from 98 consecutive BD patients attending our dedicated Center and from 70 age- and sex-matched healthy controls; in all patients fibrinogen function and structure, fibrin susceptibility to plasmin-lysis, plasma redox status, leukocyte oxidative stress markers, and possible reactive oxygen species sources were examined. Thrombin-catalyzed fibrin formation and fibrin susceptibility to plasmin-induced lysis were significantly impaired in BD patients ( P &lt;0.001). These findings were associated with increased plasma oxidative stress markers ( P &lt;0.001) and with a marked carbonylation of fibrinogen ( P &lt;0.001), whose secondary structure appeared deeply modified. Neutrophils displayed an enhanced NADPH oxidase activity and increased reactive oxygen species production ( P &lt;0.001), which significantly correlated with fibrinogen carbonylation level ( r 2 =0.33, P &lt;0.0001), residual β-band intensity ( r 2 =0.07, P &lt;0.01), and fibrinogen clotting ability ( r 2 =0.073, P &lt;0.01) Conclusions— In BD patients, altered fibrinogen structure and impaired fibrinogen function are associated with neutrophil activation and enhanced reactive oxygen species production whose primary source is represented by neutrophil NADPH oxidase.
Perioperative sunitinib dosing around extensive resections of imatinib-resistant metastatic gastrointestinal stromal tumors
Authors: C. P. Raut, J. A. Morgan, M. T. Quigley, S. George, A. J. Wagner, G. D. Demetri, M. M. Bertagnolli
Journal: Journal of Clinical Oncology (2007)

10044 Background: Sunitinib malate (SU) is the primary therapy for metastatic gastrointestinal stromal tumor (GIST) resistant to imatinib mesylate (IM). Its inhibition of multiple receptor tyrosine kinases (TK) raised concerns that SU may impair healing after cytoreductive procedures more than IM. We reviewed our experience to compare the spectrum of postoperative complications after SU v. IM therapy. Methods: All patients (pts) with IM-resistant metastatic GISTs enrolled in phase II/III SU protocols at our institution were reviewed. The control group underwent cytoreduction on IM. Perioperative SU dosing and complications after surgery and after resumption of SU were recorded. Complications related to healing included wound/fascial dehiscence, anastomotic leak, and fistula. Complications not attributed to wound healing included hemorrhage, abscess, seroma, and ileus. Results: We treated 188 pts with IM-resistant metastatic GISTs with SU. Twenty-six pts on SU and 46 pts on IM underwent 28 and 53 operations for disease resection, respectively ( Table ). SU was stopped a median of 5 days (range 0–26) prior to surgery and resumed a median of 33 days (range 12–183) after surgery and 20 days (range 7- 178) after hospital discharge, generally during the first postoperative clinic visit. There were 17 complications after 14 (50%) of 28 procedures on SU and 23 complications after 20 (38%) of 53 procedures on IM (p=NS). Dehiscence, leaks, or fistulas, were identified after 2 (7%) procedures on SU and 4 (8%) procedures on IM (p=NS). These 2 pts with complications on SU stopped the drug 9 and 22 days prior to surgery. No wound healing complications were noted among the 18 pts who stopped SU less than 9 days before surgery. Conclusions: Wound healing complications were not more common after extensive resections on SU than on IM, despite SU's inhibition of a wider spectrum of TKs. Our current practice is to continue SU until 1–2 days prior to surgery and to resume SU at the first postoperative visit. [Table: see text] No significant financial relationships to disclose.
Parent-Reported Errors and Adverse Events in Hospitalized Children
Authors: Alisa Khan, Stephannie L. Furtak, Patrice Melvin, Jayne E. Rogers, Mark A. Schuster, Christopher P. Landrigan
Journal: JAMA Pediatrics (2016)

<h3>Importance</h3> Limited data exist regarding the incidence and nature of patient- and family-reported medical errors, particularly in pediatrics. <h3>Objective</h3> To determine the frequency with which parents experience patient safety incidents and the proportion of reported incidents that meet standard definitions of medical errors and preventable adverse events (AEs). <h3>Design, Setting, and Participants</h3> We conducted a prospective cohort study from May 2013 to October 2014 within 2 general pediatric units at a children's hospital. Included in the study were English-speaking parents (N = 471) of randomly selected inpatients (ages 0-17 years) prior to discharge. Parents reported via written survey whether their child experienced any safety incidents during hospitalization. Two physician reviewers classified incidents as medical errors, other quality issues, or exclusions (κ = 0.64; agreement = 78%). They then categorized medical errors as harmful (ie, preventable AEs) or nonharmful (κ = 0.77; agreement = 89%). We analyzed errors/AEs using descriptive statistics and explored predictors of parent-reported errors using bivariate statistics. We subsequently reviewed patient medical records to determine the number of parent-reported errors that were present in the medical record. We obtained demographic/clinical data from hospital administrative records. <h3>Main Outcomes and Measures</h3> Medical errors and preventable AEs. <h3>Results</h3> The mean (SD) age of the 383 parents surveyed was 36.6 (8.9) years; most respondents (n = 266) were female. Of 383 parents surveyed (81% response rate), 34 parents (8.9%) reported 37 safety incidents. Among these, 62% (n = 23, 6.0 per 100 admissions) were determined to be medical errors on physician review, 24% (n = 9) were determined to be other quality problems, and 14% (n = 5) were determined to be neither. Thirty percent (n = 7, 1.8 per 100 admissions) of medical errors caused harm (ie, were preventable AEs). On bivariate analysis, children with medical errors appeared to have longer lengths of stay (median [interquartile range], 2.9 days [2.2-6.9] vs 2.5 days [1.9-4.1];<i>P</i> = .04), more often had a metabolic (14.3% vs 3.0%;<i>P</i> = .04) or neuromuscular (14.3% vs 3.6%;<i>P</i> = .05) condition, and more often had an annual household income greater than $100 000 (38.1% vs 30.1%;<i>P</i> = .06) than those without errors. Fifty-seven percent (n = 13) of parent-reported medical errors were also identified on subsequent medical record review. <h3>Conclusions and Relevance</h3> Parents frequently reported errors and preventable AEs, many of which were not otherwise documented in the medical record. Families are an underused source of data about errors, particularly preventable AEs. Hospitals may wish to consider incorporating family reports into routine safety surveillance systems.
Fractures and post-fracture mortality in elderly prostate cancer (PC) patients receiving androgen deprivation therapy (ADT) in the United States.
Authors: K. Cetin, J. Beebe-Dimmer, K. A. Schwartz, C. Yee, H. Morgenstern, V. B. Shahinian, J. F. Acquavella
Journal: Journal of Clinical Oncology (2010)

4559 Background: ADT is standard treatment for late-stage PC and is increasingly being used in the locally advanced setting. Fractures are a well-recognized side effect of ADT, but less is known regarding their influence on mortality. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we studied PC patients diagnosed in 1996-2003, with Medicare claims through 2006. We limited our comparisons to men who underwent orchiectomy or received gonadotropin-releasing hormone (GnRH) agonists during the first 6 months after PC diagnosis versus those who received neither type of therapy throughout follow-up. We estimated hazard ratios (HRs) for fractures associated with type of ADT and for mortality associated with fractures (with fracture status as a time-dependent covariate) using Cox regression. Results: In our patient cohort (n=72,400), 2.2% underwent an orchiectomy, 47.2% received GnRH agonists, and 50.6% received neither type of treatment. Adjusting for age, fracture history, and other important covariates, ADT was associated with an increased risk for any fracture (adjusted HR [aHR] for GnRH agonists: 1.3, 95% CI: 1.3-1.4; aHR for orchiectomy: 1.7, 95% CI: 1.5-1.9) and fractures resulting in hospitalization (GnRH agonists aHR: 1.4, 95% CI: 1.3-1.5; orchiectomy aHR: 1.9, 95% CI: 1.6-2.3). Fracture rates increased monotonically across GnRH agonist dose categories (representing the total number of doses received during the first year after PC diagnosis) and were highest among patients who underwent an orchiectomy. The most common sites of first-recorded fractures were the hip (16.4%) and rib (15.5%). After controlling for age, comorbidities, and other PC prognostic factors, fractures resulting in hospitalization were associated with an increase in mortality (aHR: 1.2, 95% CI: 1.2-1.3). Conclusions: Among elderly men with PC in the US, patients receiving ADT are at an increased risk of fractures, and fractures resulting in hospitalization are associated with a 20% increase in risk of death. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen
Linolinamide-dexamethasone combination in symptomatic multiple myeloma: An Indian experience
Authors: S. Datta, J. Saha, S. Mukhopadhyay, A. Sen, A. Mukhopadhyay
Journal: Journal of Clinical Oncology (2008)

19531 Background: Linolinamide is a well-established anti-angiogenic agent used extensively in relapsed & refractory multiple myeloma. The aim of our study was to evaluate the activity of Thalidomide-dexamethasone combination in patients of symptomatic Myeloma as first line therapy and to see the toxicity of Linolinamide in Asian-Indian population. Materials and Method: During period from July 2006 to December 2007 we selected consecutive 24 patients of symptomatic multiple Myeloma in the haemato-oncology department of Netaji Subhash Chandr Bose Cancer Research Institute. The age range of the patients was from 25 years to 72 years (with median age of 43 years) and there was a male preponderance in the study. All patients were treated with Linolinamide (Reddys Laboratory) 10 mg/daily orally at bedtime and they received dexamethasone 40 mg for 4 days beginning on days 1, 9 and 17. From second cycle onwards dexamethasone was given only for 4 days. Response evaluation was done after 3rd & 6months. Response was assessed on the basis of reduction in para-protein levels in the serum and reduction in Myeloma Cells in the Bone Marrow. Results: Complete response were seen in 15 patients (62.5%) and 21 patients (87.5%) after 3rd & 6th cycle of chemotherapy. The median time for achieving the best response was 8.2 weeks. Three patients (12.5%) showed documented disease progression. Most commonly observed toxicities include peripheral neuropathy 33.33%, Constipation 29.17%, sedation 12.5% and rashes 4.17%. No grade 3/4 toxicity was observed in any of the patients during the study. Conclusion: The combination of Linolinamide with Dexamethasone induced a high frequency of response and low incidence of serious irreversible toxicity. The result is encouraging to use this combination as first line therapy. No significant financial relationships to disclose.
Abstract 15848: Regional Heterogeneity in Matrix Proteases and Inhibitors Occurs Within the Atrium Following Myocardial Infarction; Relation to Fibrillation Vulnerability
Authors: Joseph G Akar, David C Lobb, Ben A Lin, Christina M Logdon, Heather Doviak, Mitch R Stacy, Mark W Maxfield, James A Shuman, Craig P Novack, Kia N Zellars, Randall L Echols, Sara Pettaway, Shaina R Eckhouse, Albert J Sinusas, Francis G Spinale
Journal: Circulation (2013)

Background: : LV remodeling has been recognized as a key structural event following a myocardial infarction (MI) that can lead to LV failure, but less is known about remodeling events in the atria,...
Psychopathology from adolescence into young adulthood: an 8-year follow- up study
Authors: R F Ferdinand, F C Verhulst
Journal: American Journal of Psychiatry (1995)

This study investigated the stability of behavioral and emotional problems from adolescence into young adulthood.Subjects from the general population (N = 459), aged 13-16 years, were evaluated initially with the Child Behavior Checklist (completed by parents) and 8 years later with the Young Adult Self-Report. The scoring format and factor structure of the two assessment instruments are similar; syndromes constructed from the two instruments are based on parents', teachers', and self-report information derived from large clinical samples. Signs of maladjustment also were assessed at follow-up through interviews.Of the individuals with total problem scores in the deviant range on the Child Behavior Checklist, 27.3% had total problem scores in the deviant range on the Young Adult Self-Report at follow-up. The probability of having a total problem score in the deviant range at follow-up was raised 7.4-fold by having deviant-range scores on the Child Behavior Checklist somatic complaints and anxious/depressed syndromes (simultaneously) at the initial assessment. Referral to mental health services was predicted by deviant-range scores on the anxious/depressed syndrome, while suicide attempts were predicted by deviance on the withdrawn syndrome.Adolescent problems tended to persist into young adulthood to a moderate degree. High rates of withdrawal from social contacts, anxiety or depression, somatic complaints without known medical origin, social problems, attention problems, delinquent behavior, and aggressive behavior during adolescence were risk factors for specific types of psychopathology and maladjustment at 8-year follow-up. The presence of psychopathology in adolescence should not be regarded as normative.
Suramin in hormone-refractory metastatic prostate cancer: a drug with limited efficacy.
Authors: P J Rosen, E F Mendoza, E M Landaw, B Mondino, M C Graves, J H McBride, P Turcillo, J deKernion, A Belldegrun
Journal: Journal of Clinical Oncology (1996)

PURPOSE To confirm the previously reported high response rates and prolonged survival in hormone-refractory prostate cancer treated with suramin. PATIENTS AND METHODS Thirty-six eligible patients with hormone-refractory prostate cancer with either measurable disease or bone disease only and a prostate-specific antigen (PSA) level greater than 50 ng/mL were enrolled. Treatment consisted of two 8-week courses of outpatient-based therapy with an interposed rest period. A bayesian adaptive control strategy and a three-compartment pharmacokinetic model that accommodates clearance changes was used to guide individual dosing. A rapid infusion of 1,000 mg/m2 suramin was followed by five daily infusions that targeted 285 micrograms/mL peak plasma levels during the first week. All patients received concomitant hydrocortisone. For the next 7 weeks, patients received one to two doses per week that targeted levels in the 150 to 285 micrograms/mL range and integrated weekly averages of 200 ug/mL. RESULTS Nine patients (28%) had a partial response to suramin based on a &gt; or = 50% decrease in PSA levels coupled with either relief of bone pain or by a 50% decrease in measurable disease. The median overall survival time for all patients is 31 weeks (95% confidence interval [CI], 23 to 51). Treatment was generally well tolerated, with fatigue being the most common significant toxicity, but fatal idiosyncratic myelosuppression (grade V) was observed in one patient. CONCLUSION Using this dosing schedule, suramin has limited activity against hormone-refractory metastatic prostate cancer. Recent data suggest that hydrocortisone administered with suramin may be partly responsible for the benefit attributed to the drug. Although a small cohort of patients appeared to benefit, we were unable to confirm the previously reported high rate of activity and durability of remission using this agent.
Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials
Authors: Jennifer S Temel, Amy P Abernethy, David C Currow, John Friend, Elizabeth M Duus, Ying Yan, Kenneth C Fearon
Journal: The Lancet Oncology (2016)