tbuckley/cabot-search huggingface dataset:
Fludarabine, Cyclophosphamide, and Alemtuzumab (FCC) In Relapsed/Refractory Patients with B-Cell Chronic Lymphocytic Leukemia (CLL): Final Report of the Italian Study
Authors: Marco Montillo, Alessandra Tedeschi, Francesca Ricci, Alfonso Zaccaria, Monica Crugnola, Mauro Spriano, PierAngelo Spedini, Fiorella Ilariucci, Lilj Uziel, Immacolata Attolico, Angelo De Blasio, Eleonora Vismara, Enrica Morra, Valeria Belsito Petrizzi
Journal: Blood (2010)
Pan-caspase peptide inhibitor to induce primary chronic lymphocytic leukemia (CLL) cell death through a non-apoptotic and non-necroptotic mechanism.
Authors: Daphne Ruth Friedman, Tiffany Stewart, Eross Guadalupe, Danielle M. Brander, David S. Pisetsky, J. Brice Weinberg
Journal: Journal of Clinical Oncology (2015)

e13536 Background: It is thought that CLL cells are poised on the brink of apoptosis. Recent advances in the understanding of the balance of BCL2 family proteins in CLL biology have led to the development and evaluation of specific BCL2 inhibitors. With this knowledge, we hypothesized that inhibition of CLL apoptosis in vitro with caspase inhibitors would improve cell viability. Methods: Primary CLL cells were purified by negative selection using RosetteSep. We incubated purified CLL cells with the pan-caspase inhibitor zVAD-fmk and/or TNFα, necrostatin-1, idelalisib, or TGR-1202 (gift of TG therapeutics) for three days at 37°C and 5% CO2. We assessed cell death using the colorimetric MTS reagent and apoptosis using flow cytometry with staining for Annexin V and 7AAD. Results: We observed a dose-dependent induction of CLL cell death with 0.78 to 50 μM of the pan-caspase inhibitor zVAD-fmk (n = 5, p = 0.005 comparing 0.78 μM to 50 μM). The estimated ED50 was 58 ± 34 μM. Apoptosis was not induced, as defined by the Annexin V+/7AAD- population (n = 3). Necroptosis is a mechanism of cell death mediated by receptor interacting protein (RIP) kinases, is potentiated by TNFα, and is inhibited by necrostatin-1. TNFα did not potentiate zVAD-fmk induced CLL cell death, but did significantly protect CLL cells from zVAD-fmk-induced cell death (n = 5, p = 0.009 comparing 12.5 μM zVAD-fmk ± 5 ng/mL TNFα). In addition, necrostatin-1 did not rescue CLL cells from zVAD-fmk induced cell death; in fact the addition of necrostatin-1 to zVAD-fmk potentiated CLL cell death (n = 7, p = 0.03 comparing 12.5 μM zVAD-fmk ± 100 μM necrostatin-1). In three of four CLL patients' cells tested, zVAD-fmk potentiated PI3K-delta inhibitor-induced CLL cell death (both idelalisib and TGR-1202). Conclusions: Contrary to our hypothesis, we noted that zVAD-fmk enhanced CLL cell death, though a mechanism that is not apoptosis or necroptosis. The results related to potentiation of CLL cell death with PI3K delta inhibitors and partial rescure by TNFα could indicate that zVAD-fmk affects pro-survival second messenger signaling. Lastly, understanding this new mechanism of cell death in CLL cells may have therapeutic importance.
Single-agent bevacizumab for recurrent high-grade glioma.
Authors: Megan Greally, Karen Anne Cadoo, Niamh Coleman, Michelle O'Brien, Lynda M. O'Riordan, William Grogan, Oscar S. Breathnach
Journal: Journal of Clinical Oncology (2013)

e13019 Background: High grade gliomas(HGG) are aggressive primary brain tumors. Most patients relapse following adjuvant therapy and treatment options are limited. Novel therapies have impacted little on overall survival (OS). Bevacizumab is approved for use following recurrence. We aimed to evaluate the extent of clinical benefit derived from this treatment, as defined by decreased steroid usage and median OS. Methods: We retrospectively reviewed medical records of consecutive patients with recurrent HGG treated with single agent Bevacizumab from May 2009 to Dec 2012 at our institution. We recorded patient demographics, histological features, therapeutic interventions, OS, steroid use and radiological response. Results: 29 patients with recurrent glioma were identified, 19 male and 10 female, with a median age at diagnosis of 47 years (16-72). All patients developed tumour recurrence following various combinations of multimodal therapies including 1-3 partial debulking surgeries, radiotherapy and chemotherapy. The median time from diagnosis of HGG to commencement of bevacizumab was 15 months (6-42). Patients received a median of 7 cycles (1-22) of therapy on a variable dosing schedule. 4 patients are alive, 2 continue on Bevacizumab. 19 patients were on steroid therapy when commencing therapy. There was a significant reduction in mean daily steroid use during therapy (7.65mg vs 3.97mg, p = 0.012). However, daily steroid use ultimately increased in some patients following treatment failure. Interval imaging appearances improved in 6 cases, deteriorated in 15, were stable in 4 and 1 patient had a mixed response. 1 patient was not re-imaged due to deterioration in performance status on therapy. The median OS was 5.5 months (0.5-16 months) from commencement of bevacizumab. Conclusions: The management of patients with recurrent HGG is challenging and prognosis remains dismal. In our unselected cohort, Bevacizumab therapy resulted in temporary or sustained steroid reduction in a majority. However, only a small number of patients demonstrated an objective radiological response and median OS was poor. Tumour response was variable and the addition of a predictive biomarker to establish which patients are likely to benefit from treatment may be helpful.
Restoring the Lost B-Cell Phenotype Renders Classical Hodgkin's Lymphoma Susceptible to B-Cell-Targeting Therapies
Authors: Nina Rosa Neuendorff, Jing Du, Yong Yu, Jens Peter von Kries, Stephan Mathas, Bernd Dörken, Soyoung Lee, Clemens A. Schmitt
Journal: Blood (2016)
New Rare Diseases Screening Test
Authors: Rebecca Voelker
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Deriving valid utilities for comparing treatments in clinical trials using standard quality-of-life (QoL) questionnaires
Authors: P. S. Grimison, R. J. Simes, M. R. Stockler
Journal: Journal of Clinical Oncology (2007)

6500 Background: Treatments for cancer have a myriad of beneficial and harmful effects. Benefits include prolonging survival and relieving cancer symptoms. Harms include side effects, inconvenience and costs. Assessing the overall impact of treatments requires a single, precise measure of net benefit, which combines information about health-related QoL, disease control and survival. Our aim is to develop a system for converting data from a QoL questionnaire into valid utilities, which allows comparison of treatments tested in clinical trials using utility measures and quality-adjusted survival analysis. Methods: 200 cancer patients previously completed the Utility-Based Questionnaire-Cancer (UBQ-C), a validated cancer-specific QoL measure which includes scales of health status (1 item), overall QoL (1 item), disabilities (12 items) and distresses (20 items); and were interviewed to elicit utilities using time trade-off (TTO) techniques. Scores were standardized to a scale bounded by 0 (worst outcome or death) and 1 (best possible health). A global QoL measure was derived from a weighted combination of the UBQ-C scales. Linear regression of overall health status on scales determined the weights. An equation to convert global QoL into utility was derived. Results: The global QoL measure as derived from the UBQ-C scales was more precise than the single- item scales. Median scores (IQR) were much lower for the global QoL measure: 0.77 (0.65–0.85) than for the direct measure of utility: TTO 0.98 (0.85 to 1.0). The best model to predict utility from derived global QoL was a power transformation: TTO=1-(1-global QoL) 2.1 . The mean absolute error in predicting utilities was 0.02. Conclusions: QoL measures underestimate utilities. A global QoL measure based on a weighted combination of the single item scales is more precise than single-item QoL scales. Our work enables QoL data obtained with a simple questionnaire to be converted into valid utilities that can be used in clinical trials to (i) describe the effects of cancer treatments on QoL (accounting for trade-offs between disparate aspects), (ii) evaluate trade-offs between quality and quantity of life, and (iii) do cost- effectiveness analysis. No significant financial relationships to disclose.
Stereotypes violate the postmodern construction of personal autonomy
Authors: Chris C. Martin
Journal: Behavioral and Brain Sciences (2017)

Abstract Individual autonomy, as constructed in the postmodern era, is violated by stereotypes, which makes stereotype accuracy morally unpalatable. Yet people are clustered and homogenized by social forces, entailing some accuracy in stereotypes. This tension can be ameliorated by unveiling the constructed nature of autonomous selfhood, and explaining why social clustering has occurred and been adaptive.
Abstract 20165: Laparoscopic Gastric Bypass Surgery and Adjustable Gastric Banding Significantly Improves Cardiometabolic Disease Risk Among Morbidly Obese Hispanic Adults
Authors: Nestor de la Cruz-Munoz, Gabriela Loez-Mitnik, Kristopher L Arheart, Alan Livingstone, Steven E Lipshultz, Sarah E Messiah
Journal: Circulation (2010)

Background: Morbid obesity, which continues to increase in the United States, is associated with serious health and social consequences, high medical costs and disproportionally affects ethnic minorities. Very little information is available on the long-term weight- and chronic disease risk reduction effectiveness of bariatric surgery among Hispanics, however.

Hypothesis: We hypothesized that morbidly obese Hispanic adults who underwent bariatric surgery would show significant improvements in weight and cardiometabolic disease risk factors one year post-surgery.

Methods: A retrospective medical chart analysis of 751 Hispanic adults (75% female, mean age at surgery 41.5 years, SD 12.4 years) residing predominantly from Central and South America and the Caribbean who met NIH criteria (body mass index [BMI] > 35 and ≥ 1 existing comorbidity) for, and underwent gastric bypass/ banding surgery in South Florida between 2002-2009 was conducted. Pre- and one year post surgery comparative means analysis of weight and cardiometabolic disease risk factors (systolic [SBP] and diastolic blood pressure [DBP], plasma glucose, glycated hemoglobin [HbA1c], HDL, LDL, total cholesterol, and triglyceride) was conducted.

Results: Mean BMI significantly decreased from 46.12 pre-surgery to 36.58 post surgery (P<0.0001). Similarly, weight significantly decreased from pre-to post surgery (125.45 to 95.21 kilograms, respectively, P<0.0001). All cardiometabolic disease risk factors significantly improved during the same time period as well; SBP decreased from 134.74 to 120.60 mmHG, DBP decreased from 85.22 to 76.68 mmHG, plasma glucose decreased from 101.03 to 88.50 mg/dL, HDL increased from 48.76 to 55.95 mg/dL, LDL cholesterol decreased from 110.05 to 85.78 mg/dL, total cholesterol decreased from 195.08 to 161.49 mg/dL, and triglyceride decreased from 170.21 to 93.85 mg/dL and HbA1c decreased from 6.50 to 5.57 % (P<0.0001 for all pre-post comparisons).

Conclusions: B ariatric surgery results in significant weight loss and cardiometabolic disease risk reduction among Hispanic adults one year post-surgery. Bariatric surgery has the potential to be an effective treatment option for weight loss and chronic disease risk improvements in this demographic.
The risk of second primary malignancy among male breast cancer patients: A population-based study.
Authors: Man-Hsin Hung, Chun-Yu Liu, Cheng-Hwai Tzeng, Yee Chao, Chia-Jen Liu
Journal: Journal of Clinical Oncology (2014)

1594 Background: Male breast cancers, thought rare, are in a trend of increasing in recent years. Owning to advances in diagnostic and therapeutic modalities, outcomes for breast cancer have been greatly improved. Therefore issues regarding second primary malignancy in these long-term breast cancer survivors become more important than before and should be further investigated. Methods: From the Taiwan National Health Insurance Program Database, patients with newly diagnosed breast cancer from January 1997 to December 2011 were recruited for analysis. The standardized incidence ratios (SIRs) of secondary non-breast primary cancer in male breast cancer patients were calculated and compared with the cancer incidence in the general male population. Results: Within a follow-up of 2,773 person-years, there were 73 primary non-breast cancers developed in 578 male breast cancer patients. Compared with the general population, the SIRs of second primary malignancy in male breast cancer patients were 2.17 [95% confidence interval (CI) 1.70- 2.73], which were particularly higher in patients with breast-cancer-diagnosis-age younger than 40 (SIR 29.70, 95% CI 6.12- 86.80; Table) furthermore, the SIRs of thyroid cancer (SIR 13.2, 95% CI 1.60- 47.69), skin cancer (SIR 8.24, 95% CI 3.02 – 17.94) and head and neck cancer (SIR 4.41, 95% CI 2.35 – 7.54) were the highest among all types of second primary malignant diseases observed. Conclusions: Compared with the general population, the SIRs of secondary non-breast-cancer malignant disease were significantly higher in male breast cancer patients, particularly in patients with breast cancer diagnosed younger than 40 years of age. Therefore, more intensive surveillance of second primary malignancy may be needed for male breast cancer survivors, particularly for those with high riskfeatures. Characteristics Observed Expected SIR (95% CI) All cancers 73 33.63 2.17 (1.70–2.73) Age at diagnosis, years 30 – 39 3 0.10 29.70 (6.12-86.80) 40 – 49 2 0.78 2.58 (0.31-9.31) 50 – 59 11 2.95 3.73 (1.86-6.68) 60 – 69 14 6.19 2.26 (1.24-3.79) 70 – 79 18 13.55 1.33 (0.79-2.10) >= 80 25 10.07 2.48 (1.61 - 3.67) Abbreviations: SIR, standardized incidence ratio; CI, confidence interval.
A phase Ib/II pilot trial with nab-paclitaxel plus gemcitabine plus cisplatin in patients (pts) with stage IV pancreatic cancer.
Authors: Gayle S. Jameson, Erkut Hasan Borazanci, Hani M. Babiker, Elizabeth Poplin, Anna A. Niewiarowska, Michael S. Gordon, Michael T Barrett, Karen Ansaldo, Leticia Lebron, Amy C. Stoll, Adam Rosenthal, Lynn R. Shemanski, Ronald Lee Korn, Ramesh K. Ramanathan, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2017)

341 Background: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations indicating DNA repair abnormalities associated with sensitivity to DNA damaging agents such as the platinums. Cisplatin was added to a nab-paclitaxel + gemcitabine regimen, which has been determined to improve survival over gemcitabine alone (NEJM 2013; 369:1691-1703). The objectives are to determine the efficacy and safety of nab-paclitaxel and gemcitabine plus cisplatin in patients with Stage IV pancreatic cancer. Methods: Eligibility criteria included Stage IV adenocarcinoma of the pancreas, no prior chemotherapy for systemic disease, KPS ≥ 70; life expectancy ≥ 12 weeks and measurable disease. Doses are nab-paclitaxel 125 mg/m 2 undiluted, gemcitabine 1000 mg/m 2 in 500 ml of normal saline (NS), each infused over 30 minutes on days 1 and 8 of a 21 day cycle, along with 3 different dose levels of cisplatin (25, 37.5 or 50 mg/m 2 ) in 500 ml of NS infused over 60 minutes, after the nab-paclitaxel infusion. Pre and post cisplatin hydration was given. The maximum tolerated dose and phase II dose of cisplatin is 25 mg/m 2 . Results: 25 pts were treated; 24 were evaluable (baseline and ≥ 1 follow up CT scan). The most common drug related grade (gr) 3 - 4 adverse events (AEs), n = 25, were thrombocytopenia 76% (gr 3 = 36%, gr 4 = 40%) with no serious bleeding events, anemia 32% (gr 3 = 32%, gr 4 = 0%), neutropenia 24% (gr 3 = 20%, gr 4 = 4%), infection 20% (gr 3 = 16%, gr 4 = 4%), and diarrhea 16% (gr 3 = 16%, gr 4 = 0%). Peripheral neuropathy ≥ gr 3 was seen in only 1 pt (gr 3 = 4%). Grade 5 AEs were infection (1), cardiac arrest (1), and stroke (1). Median time on therapy was 5.5 months, range (1 – 9.5). By RECIST 1.1 criteria, 2 pts had complete response (8.3%), 15 partial response (62.5%), 4 stable disease (16.7%), and 3 progressive disease (12.5%). Median overall survival to date as of 11/10/16 is 16.5 months. Conclusions: Although a small study, the high response rate and landmark evolving median survival are very encouraging. This regimen is being expanded in patients with stage IV pancreatic cancer, neoadjuvant and adjuvant settings. Clinical trial information: NCT01893801.
Epithelial ovarian carcinoma in very young patients.
Authors: Judith Michels, Olivier Caron, Annie Rey, Ariane Dunant, Pierre Duvillard, Sébastien Gouy, Alexandra Leary, Catherine Lhomme, Philippe Morice, Patricia Pautier
Journal: Journal of Clinical Oncology (2015)

e16546 Background: Epithelial ovarian carcinoma (EOC) is a rare disease in young women with an uncertain genetic and biological substrate. Our interest was to depict specific clinical and prognostic features in women aged ≤ 30 years. Methods: We conducted a single-centre retrospective matched cohort study at Gustave Roussy Institut. Young patients aged ≤ 30 years with a diagnosis of EOC between January 1990 and January 2009 were matched to randomly selected older patients aged ≥ 40 years according to four prognostic factors ((i) date of diagnosis, (ii) FIGO stage, (iii) tumour type and (iv) surgical residual disease). Results: EOC was diagnosed in 70 patients ≤ 30 years matched with 124 patients aged ≥ 40 years. In the younger population, early stage (54%, n = 38 FIGO I/II) and type I tumors (96%, n = 67) were predominant, and serous and mucinous histology types (43%, n = 30 and 37%, n = 26 respectively) were prevalent. Response rate (RR) to platinum based chemotherapy was inferior in young patients compared to matched older patients with an objective RR of 43 vs 83% (p = 0.0008). No difference in 5-year progression free survival (47% vs 56%, p = 0.6) and overall survival (68% vs 71%, p = 0.79) was found between younger and older patients respectively. Nor BRCA mutations nor Lynch syndromes were depicted among the younger patients. Conclusions: The most relevant clinical features of EOC in younger women are early FIGO stage and low grade serous or mucinous histology in an independent genetic context. The tumors were significantly more resistant to platinum based chemotherapy in patients aged ≤ 30 years compared to matched patients aged ≥ 40 years. Considering those results, a primary debulking surgery should be the strategy of choice in younger patients rather than after neoadjuvant chemotherapy. More efforts are warranted to explore the tumor biology and microenvironment and to detect more efficient treatments in this population.
Potent P2Y 12 Inhibitors in Men Versus Women
Authors: Emily S. Lau, Eugene Braunwald, Sabina A. Murphy, Stephen D. Wiviott, Marc P. Bonaca, Steen Husted, Stefan K. James, Lars Wallentin, Peter Clemmensen, Matthew T. Roe, E. Magnus Ohman, Robert A. Harrington, Jessica L. Mega, Deepak L. Bhatt, Marc S. Sabatine, Michelle L. O’Donoghue
Journal: Journal of the American College of Cardiology (2017)
The impact of technology diffusion on treatment for prostate cancer.
Authors: Florian Rudolf Schroeck, Samuel R Kaufman, Bruce L Jacobs, David Christopher Miller, Brent K. Hollenbeck
Journal: Journal of Clinical Oncology (2013)

5044 Background: Robotic prostatectomy and intensity modulated radiotherapy (IMRT) hold the promise of improving cancer control and minimizing side-effects for patients with prostate cancer, but are associated with significant upfront investments. Many worry that the perceived advantages of these new technologies and the need to recoup start-up costs could shift decision making in favor of local therapy in lieu of expectant management. In this context, we examined the association of market-level technology penetration with receipt of local therapy. Methods: We used the Surveillance Epidemiology and End Results (SEER) - Medicare linked database to identify all patients with loco-regional prostate cancer who were treated or managed expectantly from 2003 to 2007 (n=59,241). We measured technology penetration as the number of providers performing robotic prostatectomy or IMRT per population in a market (hospital referral region). We then performed multinomial logistic regression to examine the association of technology penetration with receipt of prostatectomy, radiotherapy, or no local therapy. Results: For each 1,000 patients diagnosed with prostate cancer, 171 underwent prostatectomy, 493 radiotherapy, and 336 had no local therapy. Markets with high robotic prostatectomy penetration had higher use of prostatectomy (175 vs. 141 per 1,000 men, p=0.004) but decreased use of radiotherapy (584 vs. 613 per 1,000 men, p=0.046), resulting in a stable rate of local therapy (Table). High versus low IMRT penetration did not significantly impact use of prostatectomy and radiotherapy (Table). Conclusions: Increased penetration of robotic surgical technology was associated with more use of prostatectomy and less use of radiotherapy. However, increased penetration of both robotic prostatectomy and IMRT did not change the overall rate of local therapy. Our findings allay concerns that new technology spurs additional local therapy of prostate cancer. [Table: see text]