tbuckley/cabot-search huggingface dataset:
Bendamustine/rituximab in relapsed or refractory diffuse large B-cell lymphoma.
Authors: J. L. Vacirca, P. I. Acs, B. J. Shimkus, P. J. Rosen
Journal: Journal of Clinical Oncology (2010)

8041 Background: Diffuse large B-cell lymphoma (DLBCL) accounts for 35% of all non-Hodgkins lymphomas in western society. Current front-line chemoimmunotherapies are highly effective, curing 50%-90% of patients based on stage and prognostic factors. Relapsed/refractory patients typically receive salvage chemotherapy and, if responsive and medically fit, autologous stem cell transplant. Patients ineligible for transplant or who relapse after transplant, generally have a poor prognosis. Many salvage regimens for DLBCL are poorly tolerated and may require hospitalization. Bendamustine has shown single-agent and combination activity in indolent lymphomas, however, data about its utility in aggressive lymphomas such as DLBCL are limited. The favorable toxicity profile of bendamustine and demonstrated synergy with rituximab make it worthy of investigation in DLBCL. Below are initial results of a phase II clinical trial of bendamustine rituximab (BR) for subjects with relapsed/refractory DLBCL. Methods: This open label, single arm trial will enroll up to 54, CD20+ patients whom have failed at least one prior therapy. Study treatment is given in six 28-day cycles, with bendamustine (120 mg/m2) given on days 1 and 2, rituximab (375 mg/m2) given on day 1. Safety is assessed weekly, and disease status is evaluated at completion of every two cycles by the Revised Response Criteria for Malignant Lymphoma. A two-stage Simon design is used to confirm interim response. Results: An ORR of 60%, required by the study design, was achieved in the first 15 subjects. Currently, the intent-to-treat population includes 25 subjects, (median age 75, range, 62-90) with baseline ECOG status of 0 (n=10, 40%), 1 (n=13, 52%), and 2 (n=2, 8%). In sum, 76 cycles were administered to the modified intent-to-treat population (23 subjects, median 3 cycles per subject). Current efficacy data received for 17 evaluable subjects results in ORR of 53% (CR 12%, PR 41%), with SD (18%) and PD (29%). Treatment related adverse events include one grade 4 neutropenia and nine additional grade 3 hematologic events. Conclusions: Thus far, the data suggests that BR is active and well-tolerated. This study is ongoing, data regarding response and toxicity will be updated upon completion. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Phamatech Cepahlon, Genentech
Costs, affordability, and feasibility of an essential package of cancer control interventions in low-income and middle-income countries: key messages from Disease Control Priorities, 3rd edition
Authors: Hellen Gelband, Rengaswamy Sankaranarayanan, Cindy L Gauvreau, Susan Horton, Benjamin O Anderson, Freddie Bray, James Cleary, Anna J Dare, Lynette Denny, Mary K Gospodarowicz, Sumit Gupta, Scott C Howard, David A Jaffray, Felicia Knaul, Carol Levin, Linda Rabeneck, Preetha Rajaraman, Terrence Sullivan, Edward L Trimble, Prabhat Jha
Journal: The Lancet (2015)
DeCIDE: A phase III randomized trial of docetaxel (D), cisplatin (P), 5-fluorouracil (F) (TPF) induction chemotherapy (IC) in patients with N2/N3 locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Authors: Ezra E. W. Cohen, Theodore Karrison, Masha Kocherginsky, Chao H Huang, Mark Agulnik, Bharat Bhushan Mittal, Furhan Yunus, Sandeep Samant, Bruce Brockstein, Luis E. Raez, Ranee Mehra, Priya Kumar, Frank G. Ondrey, Tanguy Y. Seiwert, Victoria Meucci Villaflor, Daniel J. Haraf, Everett E. Vokes
Journal: Journal of Clinical Oncology (2012)

5500 Background: IC is associated with lower distant failure (DF) rates in SCCHN but an improvement in overall survival (OS) has not been validated. The goal of this trial was to determine whether IC prior to chemoradiotherapy (CRT) improves survival compared to CRT alone. Methods: In this phase 3, open-label trial, subjects with pathologically confirmed SCCHN; N2/N3 disease without metastases; no prior therapy; KPS ³ 70%; and intact organ function were randomized to CRT alone (CRT arm) [5 days of D (25 mg/m 2 ), F (600 mg/m 2 ), hydroxyurea (500 mg BID), and RT (150 cGy BID) followed by a 9 day break] or to 2 cycles of IC [D (75 mg/m 2 ), P (75 mg/m 2 ), F (750 mg/m 2 day 1-5)] followed by the same CRT (IC arm). Primary endpoint was OS. Secondary endpoints included DF free survival, failure pattern, and recurrence-free survival (RFS). 280 subjects provided 80% power to detect a hazard ratio HR=0.5 for OS (a=0.05). Results: 280 subjects were accrued from 2004-09 with minimum follow-up 24 months. Of 142 patients randomized to IC, 91% received 2 cycles and 87% continued to CRT. Treatment adherence during CRT was high for docetaxel and hydroxyurea, but fewer than 75% of the patients received target dose of 5FU in both arms. RT was delivered without major deviations in 94% and 95% of patients on IC and CRT arms, respectively. The most common grade 3-4 toxicities during IC were febrile neutropenia (9%) and mucositis (8%), and during CRT (both arms combined) they were mucositis (45%), dermatitis (19%), and leukopenia (17%). Only grade 3-4 leukopenia and neutropenia rates were significantly higher in IC (p=0.002 and p=0.02, respectively). Table shows efficacy. Conclusions: High survival rates were observed in both arms. Further analysis and follow-up may provide insight into why the significant decrease in DF did not translate into improved OS. [Table: see text]
Abstract P2-14-06: Prediction of local recurrence following mastectomy
Authors: Sarah Al-Himdani, Simon Timbrell, Kian Tan, Julie Morris, Nigel Bundred
Journal: Cancer Research (2015)

Abstract Background: Rates of local recurrence following mastectomy vary considerably in the literature, ranging from 1.7% to 11.5%. Previous studies have attempted to identify risk factors for recurrence and whether these relate to aggressive disease or to inadequate local treatment. We aimed to identify local recurrence rates at our institution to determine risk factors associated with local recurrence. Methods and materials: A retrospective study of all women undergoing mastectomies for unilateral T1-T3 breast cancer between 2000-2005 was undertaken. Kaplan-Meier curves were created and the log-rank test calculated to assess for differences between groups. The incidence of local, regional and systemic recurrence was identified at 5 and 8 years post-mastectomy. Incomplete excision/margin involvement was defined as margins 1mm or less. Demographic, biological and treatment-related factors associated were used to identify predictors of local recurrence. Results: In total, 581 women were studied (mean age: 59; range: 22-96); 462 simple mastectomies (SM) and 106 skin-sparing mastectomies (SSM) which included 199 (34%) screen-detected and 382 (66%) symptomatic cancers. Mean follow up was 6.7 years (range: 5-12.4) and longest was 12.4 years. SSM patients had a lower mean age (p=&amp;lt;0.001), with a smaller tumour size (p=0.022), fewer positive lymph nodes (p=&amp;lt;0.001) and less co-existing ductal carcinoma in situ (DCIS) (p=&amp;lt;0.001) than SM patients. Recurrence rates for SM were 5.6% and 6.9% and for SSM, recurrence rates were 5.7% and 9.0% at 5 and 8 years respectively. Recurrence in node negative patients was 2.2% at 5 years. Predictors of local recurrence were node positivity (HR 8.03; 95% CI 3.2-20) and margin involvement/close margins (HR 3.34; 1.64-6.8). Conclusion: No significant difference between recurrence rates in SSM and SSM groups was identified. The presence of over four positive lymph nodes and incomplete excision margins indicates an increased risk of recurrence and in these patients, immediate SSM reconstruction should be considered prudently. Citation Format: Sarah Al-Himdani, Simon Timbrell, Kian Tan, Julie Morris, Nigel Bundred. Prediction of local recurrence following mastectomy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-14-06.
Abstract #LB-222: Dietary heme iron associated with colorectal cancer with G>A mutations in KRAS and APC genes; results from The Netherlands Cohort Study on diet and cancer.
Authors: Matty Weijenberg, Fiona Fransen, Anton de Goeij, Manon van Engeland, Adriaan de Bruine, Theo de Kok, Piet van den Brandt, Alexandra Goldbohm
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Dietary heme iron, mainly derived from red meat, has been associated with an increased risk of colon cancer in several studies. Heme iron is hypothesized to have cytotoxic and proliferative effects increasing overall mutation rates. Heme iron increases endogenous formation of N-nitroso compounds enhancing colonic formation of the DNA adduct O6-carboxymethyl guanine, which may result in G>A and G>T mutations. We investigated the association between heme iron and the risk of colorectal cancer with and without specific mutations in the KRAS and APC genes. The Netherlands Cohort Study was initiated in 1986 among 120,852 subjects aged 55 to 69 years who filled out a self-administered food frequency questionnaire. Heme iron content was calculated as a type-specific percentage of the total iron content of 19 items of fresh and processed meat. After 7.3 years of follow-up and excluding the first 2.3 years, 341 colon and 144 rectum cancer cases were available for data-analysis. Direct sequencing of DNA extracted from tumor samples was performed to assess mutations in codons 12 and 13 of KRAS and the mutation cluster region of APC . Multivariate adjusted RR and 95% CI were computed for cancer with or without (specific) mutations in KRAS and APC . Heme iron was significantly associated with increased risk of colon cancer with KRAS mutations (RR for highest versus lowest tertile of intake=1.86 (1.04-3.30)) but not of rectum cancer with KRAS mutations (RR=1.05 (0.42-2.63)), nor of colon or rectum cancer with APC mutations leading to a stop-codon (RR=1.44 (0.80-2.61), and 0.63 (0.24-1.68), respectively). Tertiles of heme iron intake showed a clear dose-response relationship with colon cancer with G>A mutations in KRAS and APC (RR=1.00, 1.44 (0.74-2.81), 2.39 (1.15-5.00), and 1.00, 1.23 (0.92-1.85), 1.70 (1.08-2.69), respectively). A similar association was observed for colon cancer with either a KRAS or APC G>A mutation. For rectum cancer with KRAS or APC G>A mutations the dose-response association was not statistically significant (RR=1.00, 1.74 (0.90-3.35), 1.91 (0.87-4.18)). For colon cancer with G>T mutations in either KRAS or APC increased RRs were observed for the second and third tertile of heme iron, but associations were not dose-response. No associations were observed for heme iron in relation to colon or rectal cancer without either G>A or G>T mutations in KRAS or APC (p-trend = 0.84 and 0.93, respectively). This is the first prospective observational study to report an association between heme iron and the risk of colon cancer with G>A mutations in KRAS and APC genes.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-222.
Phase I, dose-escalation study of BIIB022 (anti-IGF-1R antibody) in advanced solid tumors.
Authors: M. von Mehren, C. Britten, K. Lear, D. R. Camidge, Z. A. Wainberg, P. C. Pieslor, M. Darif, S. Harris, K. Balogh, S. Leong
Journal: Journal of Clinical Oncology (2010)

2612 Background: The IGF pathway is believed to play a key role in the pathogenesis of several tumors. BIIB022 is a human, nonglycosylated IgG4 monoclonal antibody that binds to IGF-1R and blocks IGF-1 and IGF-2 binding. Methods: A phase I study is ongoing to evaluate the safety of escalating doses of BIIB022 given IV q3wk until progression or unacceptable toxicity in patients (pts) with advanced solid tumors. Efficacy, PK, PET imaging, and biomarkers are also being evaluated. Results: 24 pts received BIIB022 at doses of 1.5-30 mg/kg. The median age was 59.5 yrs. All pts had an ECOG PS £1. Tumor types were sarcoma (10), colorectal (8), lung (3), pancreas (2), adrenal (1). All pts had at least 1 AE; 16 had related AEs. The most common (≥10% of pts) related AEs were headache, fatigue, and nausea. Most related AEs were ≤Grade 2. 4 pts had Grade 3 related AEs (hypertension, fatigue, dyspnea, QTc interval prolongation); 0 had Grade 4 related AEs. Two pts had AEs that met the DLT criteria (AEs ≥Grade 3 within the first 28 days and unlikely, possibly, or related to BIIB022). One pt (20 mg/kg) experienced Grade 2 T-wave inversion with transient apical hypokinesis and Grade 3 QTc interval prolongation possibly related to BIIB022. Another pt (30 mg/kg) had a Grade 3 GI bleed unlikely related to BIIB022, but probably related to bowel recurrence of sarcoma. Both pts were withdrawn from study and the events resolved. The 20 and 30 mg/kg cohorts were expanded to 6 pts. No further DLTs were seen. Sporadic fluctuations in glucose, fructosamine, and hemoglobin A1c occurred, but were not clinically significant. There were no objective responses, but 3 pts (1.5, 20, and 30 mg/kg cohorts) had FDG-PET metabolic responses, 1 of whom had SD for 7 months (sarcoma pt in 1.5 mg/kg cohort). PK data were available for cohorts 1.5-20 mg/kg. Cmax and AUC increased in a dose-proportional manner. Mean t1/2 ranged from 4.7-13.7 days. IGF-1R expression was downregulated on granulocytes within 2 hrs of BIIB022 treatment at all doses and remained downregulated for the treatment period. Conclusions: Preliminary results suggest that BIIB022 is tolerated at doses of 1.5-30 mg/kg q3wk. While there were no objective responses, metabolic responses were seen. Enrollment is continuing at 30 mg/kg. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen Idec Biogen Idec
GW26-e2308 Cystatin C is Associated with Cardiovascular Autonomic Neuropathy in Newly Diagnosed Type 2 Diabetic Patients
Authors: Xubin Yang, Shangyan Liang, Wen Xu, Yanhua Zhu, Bin Yao, Jianping Weng, Wen Xu
Journal: Journal of the American College of Cardiology (2015)
Death rates in patients during and after MDR-TB treatment in a semi rural area of South Africa
Authors: Karen Shean, Marissa Van Rensburg, Martie Van der Walt
Journal: European Respiratory Journal (2011)

Introduction: South Africa (SA) is ranked third amongst the 22 highest burden DR-TB countries in the world. The country also has an estimated HIV prevalence among incident TB cases of 73%. Very little data exists of death rates and causes of death both in patients on treatment and during post treatment follow up in these settings.

Methodology: Between 2000 and 2008, 753 drug resistant patients were registered at a dedicated MDR-TB service in the North West province of South Africa. Patients were hospitalised until culture conversion and after discharge return to the hospital outpatient clinic for follow-up and collection of medication.

Results: Of the 753 patients registered, 50.46% (380/753) were co-infected, of whom 37.6% (140/380) received HAART the majority from 2006 onwards. 5.4% (41/753) had primary resistance, and 1% (7/753) of patients had previous MDR-TB while the majority of patients, 90% (677/753) had been previously treated for sensitive TB. The overall cure rate was 67.2% (506/753) with default rates of 5% (37/753) and a failure rate of 2% (15/753). The death rate of patients on treatment was 20% (150/753); with 69.4% (68/98) having a known HIV-infected status. Death during the post treatment follow up phase was 6.4% (48/753) with a HIV-infection rate of 50% (24/48). These patients died despite a cure rate of 58.3%.

Conclusion: Successful treatment outcomes are possible in resource limited areas. It must be accepted, however, that despite these outcomes a proportion of patients are going to die post treatment, despite a good outcome, at least half of whom will be HIV-infected.
A simple and robust clinical manufacturing process for the ex-vivo expansion of autologous T cells genetically engineered to express an anti-BCMA chimeric antigen receptor (CAR) for the treatment of multiple myeloma
Authors: Alden Ladd, Graham Lilley, Mingli Li, Dan Cossette, Gregory W Hopkins, Dawn Maier, Michael Paglia, Richard A Morgan
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adoptive transfer of autologous T cells genetically engineered to express chimeric antigen receptors (CARs) has emerged as a promising approach for the treatment of cancer. To this end, we have been developing an anti-BMCA CAR T cell approach for the potential treatment of
Diagnostic and management modalities in early tubal ectopic pregnancy with focus on safety
Authors: Shashikant L. Sholapurkar
Journal: Human Reproduction Update (2015)

Sir, The paper by Kirk et al. (2014) on diagnostic modalities for ectopic pregnancy (EP) and management of pregnancy of unknown location (PUL) is a very succinct and balanced review covering a wide range of important issues. The discussion about the role of ultrasound scanning combined with serial human chorionic gonadotrophin (bhCG) estimation in diagnosis of tubal EP is particularly useful. This letter further debates a few particular aspects. Kirk et al. (2014) state that in their specialist early pregnancy unit (EPU) up to 73.9% of EP were visualized on transvaginal ultrasound scan (TVUS). The most common finding (60%) was a ‘nonhomogeneous mass’ in the adnexa separate from the ovary (a blob sign). However, other pathologies (e.g. broad ligament fibroids, ovarian cysts, fimbrial cysts or even faecoliths) can be mistaken for a blob sign as indeed pointed out by Kirk et al. (2014). For these reasons the ‘American consensus statement on nomenclature of PUL’ reserves the term ‘definite EP’ to those when an extra-uterine gestation sac containing a yolk sac or fetal pole is visualized (Barnhart et al., 2011) and ‘blob sign’ is called ‘probable ectopic’ pregnancy. Kirk et al. (2014) have pointed out how this distinction is crucial when treatment with methotrexate is considered. Hence it could be argued that it would be preferable to have one standard safe terminology (i.e. ‘probable ectopic’ for a blob sign), otherwise a potential risk of someone somewhere inadvertently administering methotrexate to an early viable intrauterine pregnancy is instigated.
Eradicating<i>H pylori</i>seems to reduce incidence of gastric cancer, review shows:
Authors: Jacqui Wise
Journal: BMJ (2015)

Eradicating Helicobacter pylori infection in otherwise healthy and asymptomatic people reduces the incidence of gastric cancer, a systematic review and meta-analysis published by the Cochrane Library has concluded.1

The researchers analysed all randomised controlled trials that compared at least one week of H pylori therapy with placebo or no treatment in healthy, asymptomatic people who had H pylori infection. The studies mainly used a combination of antibiotics with proton pump inhibitors. Only trials that followed …
Therapeutic Targets of Human AKI
Authors: Mark D. Okusa, Mitchell H. Rosner, John A. Kellum, Claudio Ronco
Journal: Journal of the American Society of Nephrology (2015)

The opportunity to make advances in the prevention and treatment of AKI has never been greater than it is today. Major advances have been made in the understanding of the biology of AKI, the design of clinical trials, and the use of diagnostic and prognostic biomarkers. These advances have been supplemented by the coordinated effort of societies, federal agencies, and industry, such that we are poised in the ensuing years to positively address the unrelenting harm that this disorder has created. Over the past decade, major advances have been made in understanding the pathophysiology of AKI, mainly through the study of small animal models. However, translating these findings to human AKI remains a barrier, which is typified by the absence of effective therapeutic agents. The purpose of the Acute Dialysis Quality Initiative (ADQI) XIII was to harmonize human and animal studies and determine what is known about potential therapeutic targets and what gaps in knowledge remain. A series of invited reviews will distill key concepts from this initiative that focus on different pathogenic features of AKI, including hemodynamics, immunity and inflammation, cellular and molecular pathways, progression, and regeneration and repair. This series will convey the status of our knowledge of the pathophysiology of human AKI and propose therapeutic targets for further investigation.
Patterns of differentiation and hybridization in North American wolflike canids, revealed by analysis of microsatellite loci.
Authors: M S Roy, E Geffen, D Smith, E A Ostrander, R K Wayne
Journal: Molecular Biology and Evolution (1994)

Genetic divergence and gene flow among closely related populations are difficult to measure because mutation rates of most nuclear loci are so low that new mutations have not had sufficient time to appear and become fixed. Microsatellite loci are repeat arrays of simple sequences that have high mutation rates and are abundant in the eukaryotic genome. Large population samples can be screened for variation by using the polymerase chain reaction and polyacrylamide gel electrophoresis to separate alleles. We analyzed 10 microsatellite loci to quantify genetic differentiation and hybridization in three species of North American wolflike canids. We expected to find a pattern of genetic differentiation by distance to exist among wolflike canid populations, because of the finite dispersal distances of individuals. Moreover, we predicted that, because wolflike canids are highly mobile, hybrid zones may be more extensive and show substantial changes in allele frequency, relative to nonhybridizing populations. We demonstrate that wolves and coyotes do not show a pattern of genetic differentiation by distance. Genetic subdivision in coyotes, as measured by theta and Gst, is not significantly different from zero, reflecting persistent gene flow among newly established populations. However, gray wolves show significant subdivision that may be either due to drift in past Ice Age refugia populations or a result of other causes. Finally, in areas where gray wolves and coyotes hybridize, allele frequencies of gray wolves are affected, but those of coyotes are not. Past hybridization between the two species in the south-central United States may account for the origin of the red wolf.