tbuckley/cabot-search huggingface dataset:
Extent and nature of advertising in leading hematology-oncology journals
Authors: D. Sieber, J. A. Lee, J. K. Keller, M. A. Mathiason, R. S. Go
Journal: Journal of Clinical Oncology (2007)

6634 Background: Advertising in most medical journals is dominated by pharmaceuticals in part due to journal policy. This is primarily a fiscal consideration. Because advertising clearly influence physicians’ prescribing pattern, an indirect conflict of interest exists and may potentially affect patient care. The objectives of this study were to evaluate the extent of advertising in leading hematology-oncology (HO) journals published in the U.S. and to compare the findings to those of multi-specialty journals. Methods: We evaluated the following high impact journals that publish original research and included all issues issued in 2006: Journal of National Cancer Institute (JNCI), Journal of Clinical Oncology (JCO), Blood, New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), and Annals of Internal Medicine (AIM). Of these, only JNCI (currently not affiliated with U.S. NCI) is not owned by a medical society. The number and nature of advertising for each journal were collected. Results: There was an average of 84, 283, and 459 pages for each issue of JNCI, JCO, and Blood, respectively. Overall, HO journals allocated 20% (range, 8–32) of their pages for advertising. JCO had the most, while JNCI the least, advertising, both classified (6% vs 1% vs 1%; P = 0.001) and non-classified (26% vs 10% vs 7%; P = 0.001). Among non- classified advertising, the major categories were drugs (48.5%), journal information (14.1%), conference announcements (10.1%), research/clinical trial (7%), disease information (6.4%), continuing medical education (3.6%), and others (10.3%). Among journals, JCO had the most drug advertising (72.5%), followed by Blood (65.6%), while JNCI did not have any (0%). Compared to multi-specialty journals, HO journals had less amount of classified (3% [range, 1–6] vs 15% [range, 10–19]; P = 0.001) and non-classified (17% [range, 7–26] vs 21% [range, 18–25]; P = 0.001) advertising. Conclusions: While less than their multi-specialty counterparts, HO journals allocated a substantial proportion of their pages to advertising, the overwhelming majority of which were sponsored by pharmaceutical companies. The extent of advertising varied by journal, but was most prominent with JCO. Notably, JNCI did not have any drug advertising. No significant financial relationships to disclose.
Original association of chemo and radiotherapy for locally advanced non-small cell lung cancer (NSCLC): LIEGE experience
Authors: L. Bosquee, F. Bustin, M. Gustin
Journal: Journal of Clinical Oncology (2004)

7330 Background: Locally advanced Non Small Cell Lung Cancer has a poor prognosis when treated by either surgery or radiotherapy or chemotherapy. Since 2000, we have developed, for these patients, an association of chemotherapy and radiotherapy, eventually followed by surgery. We report the results of this approach.Material and methods: From oct 16th 2000 to oct 20th 2003, 48 patients (12 ♀, 36 ♂; 7 IIB, 10 IIIA, 26 IIIB, 5 IV : cyto- or histological proof of extension) have been enrolled in a local protocol of CT and RT. Median age was 59 y (37 to 77) and median Karnofsky 90 (70 to 100). Chemotherapy consisted of three cycles of 28 days, with Platinum, Ifosfamide and Vinorelbine (Pt 100 mg/m2 divided among D1,2 and 8 for cycles 1–2 and among D1 to5 for the 3rd cycle, Ifo 4500–6000 mg/m2 divided among D1,2 and 8 for cycles 1–2 and 3000 mg/m2 divided among D1 to 5 for the 3rd cycle, VRL 25 mg/m2 D1,8,15 for cycles 1–2 and 25 mg/m2 divided among D1 to 5 for the 3rd one). Radiotherapy begins on Day 8 of the 2nd cycle and 40 gys are delivered between D8 of cycle 2 and D5 of cycle 3. After these 3 cycles and 40 gy of radiotherapy, all the patients benefit of pulmonary function tests and a chest CT Scan. The eligible patients go to surgery. The others receive 20 gys more, with a new cycle of the same chemotherapy during the last week (like cycle 3). Results: OR rate after cycle 3 and 4 is 85%. 17 patients (35%) were operated on (5 IIB, 5 IIIA, 7 IIIB). Downstaging was seen in all but one patient (unexpected stage IV, despite good response). Pathological CR is 45% among these patients. Tolerance was good, but during cycle 3, we observed esophagitis : 16% gr≥ 3, vomiting : 16% gr≥ 3 and neutropenic fever : 11% gr≥ 3 in spite of antibiotic prophylaxis during each cycle. One patient died after cycle 1 of unknown reason.Median survival is 31 months for the global and also for the IIIB group.Conclusions: This approach has deeply modified the management of these patients in our institution. The median survival as well as the OR rate and the pathological CR give us tremendous reasons to follow this way. No significant financial relationships to disclose.
Preliminary results of a Cancer Research UK phase I trial combining the dinitrobenzamide prodrug CB1954 (tretazicar) and the NQO2 substrate EP-0152R (caricotamide) intravenously (IV) every 3 weeks
Authors: D. Sarker, D. Anderson, V. J. Spanswick, S. Davies, R. Agarwal, G. Aitken, D. J. Kerr, J. A. Hartley, I. Judson, M. R. Middleton
Journal: Journal of Clinical Oncology (2008)

2505 Background: CB1954 (CB) is a dinitrobenzamide prodrug that is converted in the presence of the enzyme NQO2 and co-substrate EP-0152R (EP) into a potent cytotoxic bifunctional alkylating agent. Methods: Patients (pts) with histologically confirmed advanced solid tumours and WHO Performance Status 0 - 2 were treated with CB and EP. CB was administered IV over 15 minutes midway through a 4 hour IV infusion of EP. Objectives were to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination, evaluate pharmacokinetics (PK) and pharmacodynamic (PD) effects and describe antitumour activity. PD effects were assessed in lymphocytes and tumour biopsies by the Single Cell Gel Electrophoresis (Comet) assay. Early PK data indicated that 200 mg/m2 EP maximally activated NQO2. Subsequent patients were treated at this dose whilst dose escalating CB in cohorts of 3–6 patients. Results: 29 pts (median age 57 yrs; 15 Male/14 Female) were treated in 5 cohorts (escalating doses of CB: 12, 16, 20, 26.6, 35 mg/m2). DLTs were seen at 26.6 mg/m2 (1 pt, grade 3 transaminitis), and in 2 pts at 35 mg/m2 (1 pt grade 3 transaminitis and 1 pt grade 3 diarrhoea). Other drug-related toxicities at these dose levels included grade 1 - 3 nausea and vomiting, and grade 2 anorexia, dehydration and abdominal pain. Exposure to CB increased in a supra-proportional manner with increasing dose. CB elimination was very rapid when co-administered with EP, with mean clearance being up to 970-fold higher than when administered alone, resulting in a plasma t1/2 of 2 - 5 minutes. The consequent decrease in CB area under curve was consistent with EP activating NQO2 conversion of CB. PD analysis showed evidence of DNA interstrand cross-linking in lymphocytes, and in 1 melanoma pt where tumour was obtained. 1 pt with ocular melanoma had evidence of stable disease for over 4 months. Conclusions: The combination of CB and EP was well tolerated with MTD defined as CB 26.6 mg/m2 with EP 200 mg/m2. This cohort is being expanded to define PD effects in tumour. No significant financial relationships to disclose.
Optimal chemotherapy utilisation rate in breast cancer: setting an evidence-based benchmark for the best-quality cancer care
Authors: W. L. Ng, G. Delaney, S. Jacob, M. Barton
Journal: Journal of Clinical Oncology (2008)

6613 Background: The proportion of patients with breast cancer receiving chemotherapy varies from 21% to 42% in high-income countries. The utility and accountability of the quality measures developed by The National Initiative for Cancer Care Quality and National Quality Forum are limited by the lack of benchmarks that can be applied to the entire breast cancer population. The aim of this study was to estimate the optimal proportion of patients with breast cancer who should receive chemotherapy at 1) first course of treatment and 2) at least once during the course of their illness. Methods: Indications for chemotherapy were identified from all nationally endorsed guidelines. Epidemiological data on the proportion of patient (age, performance status, patient preference) and tumour (stage, size, grade, nodal status, hormone receptor and HER2 status) attributes for each indication were sourced and ranked. Treatment indications and epidemiological data were merged using the decision analysis software (TreeAge Pro 2007) to construct an optimal chemotherapy utilisation model. Sensitivity analyses were performed to assess the impact of controversial indications and major variations in the epidemiological data on the overall utilisation rate. The model was externally reviewed by independent experts. Results: Chemotherapy is indicated in 58% of patients as part of their initial management of breast cancer. Chemotherapy is indicated at least once during the course of their disease in 68% of breast cancer patients. Sensitivity analyses indicate a range of 51%-59% for first course of treatment and 60–69% for at least once during the course of their illness. The available data on actual first course treatment rates in Australia (32%), United States (36%), United Kingdom (29%) and Canada (40%-42%) showed underutilisation of chemotherapy for breast cancer. Conclusions: The evidence-based model sets an optimal chemotherapy utilisation rate for breast cancer. Available data from high-income countries showed significant underutilisation of chemotherapy for breast cancer. No significant financial relationships to disclose.
Stage and grade of colorectal cancer at presentation in the West of Ireland
Authors: D. McKeown, M. G. Waldron-Lynch, M. Keane
Journal: Journal of Clinical Oncology (2008)

15095 Background: Colorectal Cancer is the most common non-cutaneous cancer and the most common cause of death from cancer in Ireland. Early diagnosis is essential to improved survival and advanced stage at presentation has been a limiting factor in improving survival rates. Methods: This was a retrospective observational cohort study, to generate a dataset of patients presenting with colorectal cancer to hospitals in the West of Ireland from January 2000-December 2006. Data was gathered by note search, and recorded on a standardised questionnaire. Details included demographic and clinical characteristics, pathological features and survival outcomes for patients presenting to hospitals in the West of Ireland. Univariate categorical data were analysed using Epi Info 2002 and the Chi-square test with Fisher's exact correction, and stratified Mantel-Haenszel chi-square as appropriate. Quantitative data were analysed using Student's t-test/ANOVA, or Mann-Whitney test for non-parametric data. Results: In this pilot sample of 62 patients with colorectal cancer, mean follow-up was 34 months (median 29 months). During the study period, 27 (43%) died and there were 10 recurrences. Mean time to relapse was 18 months and to death was 12 months. The majority of tumours were Grade 2 at presentation, however, 77% presented at T3 or higher and almost one third of patients had metastatic disease at diagnosis. Those taking part in a clinical trial were likely to have a better prognosis, although this was not significant. Smoking was not a significant risk factor. Mean age at diagnosis was 66 years. Those presenting younger had a poorer prognosis (p=0.06), and were more likely to recur (p=0.0077) Those privately insured did not have better outcomes; however males had a poorer outcome than females (p=0.06). Conclusions: In this series, it appears that colorectal cancer presents late and at an advanced stage in this demographic area and younger patients tended to have more advanced disease at diagnosis and poorer outcomes overall. The final series will include a range of other variables, and these will be analysed using logistic and Cox regression to determine the relative part each variable plays in the overall outcome. No significant financial relationships to disclose.
Initiation of controller medication in newly diagnosed asthma patients: Impact on economic resource utilization
Authors: Pierrick Bedouch, Mohsen Sadatsafavi, J. Mark FitzGerald, Carlo Marra, Larry Lynd
Journal: European Respiratory Journal (2011)

Introduction:  To better understand the economic burden of asthma, we compared asthma-related direct costs among adults prescribed controller regimens.   Methods:  A cohort of newly diagnosed asthma patients (14-65 y/o), initiating a controller therapy for the first time between 1997 to 2007, was created from the health administrative database of British Columbia, Canada. Five cohorts of patients were created according to the way controller therapy was initiated: inhaled corticosteroid (ICS group), ICS/long-acting beta-agonist combination (ICS/LABA group), ICS+LABA in separate formulations (ICS+LABA group), leukotriene receptor antagonist (LRA group) or ICS+LRA in separate formulations (ICS+LRA group). Index Date (ID) was defined as the date controller medication prescribed. Direct cost of asthma in the post-ID year (2008 Canadian dollars) was calculated from the hospital, physician visits, and prescription records, adjusted for multiple covariates estimated from the pre-ID year.   Results:  153,224 patients were included: 109,601 ICS; 34,184 ICS/LABA; 2,249 ICS+LABA; 6,289 LRA; 901 ICS+LRA. The average age was 37.7 and 61.0% were female. The average direct costs of asthma for the post-ID year for the ICS group was 265.2$. All other groups had higher incremental costs: ICS/LABA +$125.9, ICS+LABA +$218.2, LRA +$198.4, and ICS+LRA +$322.4 (all p   Conclusions:  Initiation of ICS, as recommended by guidelines, was associated with the lowest costs than initiation of other controller or combination therapies.
How Many Ontogenetic Roads to Mantle-Cell Lymphoma? Immunogenetic and Immunohistochemical Evidence
Authors: Evi Pouliou, Aliki Xochelli, Evangelia Stalika, Lesley-Ann Sutton, Alba Navarro, Andreas Agathangelidis, Kypros Dimosthenous, George Kanellis, Achilles Anagnostopoulos, Efstratios Patsouris, Penelope Korkolopoulou, Christer Sundstrom, Paolo Ghia, Maurilio Ponzoni, Birgitta Sander, Elias Campo, Richard Rosenquist, Anastasia Hadzidimitriou, Kostas Stamatopoulos, Theodora Papadaki
Journal: Blood (2014)
Glioblastoma stem cells mediate immune suppression that can be inhibited with Jak2/Stat3 blockade
Authors: A. B. Heimberger, W. Sun, L. Kong, M. Abou-Ghazal, J. Wei, J. Gumin, H. Colman, W. Priebe, F. F. Lang
Journal: Journal of Clinical Oncology (2008)

2012 Background: We have recently isolated as distinct subsets from glioblastoma tumors mesenchymal stem cells (gMSC) that are adherent, pleuripotent, CD73+, CD90+ and CD105+-expressing but non-tumorgenic and cancer stem cells (gCSC) that grow as neurospheres, CD133+-expressing and are tumorgenic in vivo. Mesenchymal stem cells have been shown to be immunosuppressive; however, the immune function and phenotype of gMSC and gCSC are unknown and the purpose of this study. Methods and Results: ELISA assays were used to determine the elaboration of immunosuppressive cytokines such as TGF- β (impairs antigen presentation and maintains Treg suppressor function), IL-6 (inhibits B cells, NKT, and T cells), IL-10 (inhibits Th1 function), VEGF (prevents dendritic cell maturation), and the Treg chemokine CCL-2 by gMSC and gCSC. Only gMSC (n=7) secrete CCL-2, TGF-β, VEGF, and IL-6, whereas gCSC (n=4) do not. In order to characterize the immunological phenotype of gMSC and gCSC, immune marker surface expression was evaluated by FACscan. The gMSC and gCSC express MHC I, but not MHC II, or the T cell co-stimulatory molecules. CTLA-4 (inhibitor molecule of T cell activation typically expressed on activated T cells) could be observed on a minority population of gCSC. Western blot analysis was utilized to determine differences between operational pathways and the gMSC frequently over-expressed the transcriptional factor p-STAT3. The gMSC were treated with WP1066, a potent inhibitor of the JAK2/STAT3 pathway, at physiological doses and there was inhibition of TGF-β, VEGF, and CCL-2 indicating these immunosuppressive properties could be down modulated. Conclusions: The presence of only MHC I and the lack of MHC II and co-stimulatory molecule expression on gMSC and gCSC would trigger T cell anergy/unresponsiveness. The expression of CTLA-4 on gCSC would further inhibit T cell activation. However, the gMSC are the primary mediators of cytokine mediated immunosuppression and are the key source of the Treg chemotactic factor CCL2 within glioblastomas. These immunosuppressive cytokines can be down-modulated with an inhibitor to the JAK2/STAT3 pathway. No significant financial relationships to disclose.
Clinical course of advanced non-small cell lung cancer (NSCLC) patients (pts) experiencing hypertension (HTN) during treatment (TX) with bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P) on E4599
Authors: S. E. Dahlberg, A. B. Sandler, J. R. Brahmer, J. H. Schiller, D. H. Johnson
Journal: Journal of Clinical Oncology (2009)

8042 Background: B is a monoclonal antibody that targets VEGF with demonstrated efficacy in combination with PC for the TX of advanced NSCLC. Administration of B is thought to decrease nitrous oxide synthesis and lead to HTN, one of the known toxicities associated with PCB on E4599. This side effect may be a physiological sign that the VEGF pathway is more actively being blocked and indicate differential outcomes between hypertensive and non-hypertensive pts. Methods: Pts randomized to PCB constituted the cohort. Hypertensive pts (HTN of any grade or TX relation reported via a toxicity form, CTCAE v2) were compared to nonhypertensive pts with respect to baseline pt characteristics, overall survival (OS) and progression-free survival (PFS). Blood pressure (BP) data were also collected at each TX cycle; similar comparisons were made for high BP (&gt;150/100). Results: In E4599, 33/417 (7.9%) eligible pts experienced HTN; 30/33 (90.9%) were grade 3 events. Baseline characteristics of the HTN cohort were similar to those in the non-HTN cohort except for a higher proportion of PS 0 pts (70% vs. 38%, p=0.001) and females (67% vs. 48%, p=0.05). Median follow-up was 54.8 mos. The 6-month cumulative incidence of HTN adjusting for death as a competing risk was 6.2% (95% CI: 3.9–8.6%). Landmark analyses measured from the median time to onset of HTN (1.9 mo) suggested higher OS for the HTN pts (14.0 vs. 11.3 mo) as well as higher PFS (8.0 vs. 4.5 mo) although these comparisons did not reach statistical significance. Proportional hazards models for OS and PFS adjusting for HTN as a time-varying covariate resulted in an OS HR=0.64 (0.43–0.96, p=0.03) and PFS HR=0.83 (0.57–1.20, p=0.32). The same modeling adjusting for high BP (&gt;150/100) as a time-varying covariate resulted in OS HR=0.60 (0.44–0.82, p=0.002) and PFS HR=0.71 (0.54–0.95, p=0.02). Results for high BP remained statistically significant after adjusting for sex, PS, histology, adrenal, liver and bone mets. Conclusions: Data from E4599 suggest that onset of HTN during TX with PCB may be associated with improved OS and PFS. Further studies of the downstream effects of VEGF suppression and HTN are needed. [Table: see text]
Initiating epoetin alfa (EPO) 120,000 U every three weeks (Q3W) in pts with chemotherapy (CT)-induced anemia (CIA)
Authors: J. Glaspy, V. Charu, V. Moyo, M. Kamin, F. E. Wilhelm
Journal: Journal of Clinical Oncology (2007)

19564 Background: Emerging data suggest that initiating EPO therapy earlier (at a higher hemoglobin [Hb] trigger) in the setting of active CT may provide better maintenance of Hb within a target range with no adverse safety consequence. Reported here are the final results of the first study to explore the efficacy and safety of early vs standard intervention with EPO initiated Q3W at 120,000 U. Methods: This 16-wk open-label randomized study enrolled pts with non-myeloid malignancy, baseline (BL) Hb =11.0 and =12.0 g/dL, and CT planned for =9 wks. Pts were randomized (1:1) to receive EPO 120,000 U subcutaneously Q3W immediately (early intervention group, EIG) or when their Hb fell to &lt;11.0 g/dL (standard intervention group, SIG). If, at any dosing visit after the first EPO dose, Hb decreased to &lt;10.0 g/dL, pts were switched to EPO 40,000 U weekly (QW). Dose was withheld for Hb &gt;13.0 g/dL at any dosing visit; dose was reduced for Hb &gt;12.0 g/dL or Hb increase &gt;1.5 g/dL in a 3-wk period (current prescribing information recommends target Hb not to exceed 12 g/dL). Hb response was defined as Percent Values in Range (PVR; the mean proportion of weekly Hb levels that were =11.0 and =13.0 g/dL) and by mean Hb change from BL. Hb data following switch to 40,000 U QW were censored. Results: A total of 136 pts were randomized (68 per group). Demographics were similar; BL Hb was 11.5 g/dL in both groups. PVR was 60% in the EIG and SIG. Mean Hb change from BL to final value on Q3W dosing was -0.1 g/dL in both groups. Among the 51 pts whose Hb fell below 11 g/dL in the SIG, their Hb decreased to a mean of 10.4 g/dL before initiation of EPO. Their subsequent mean Hb increase was 0.7 g/dL at the final visit on Q3W therapy. PRBC transfusion rates after the first 4 wks of EPO treatment were 8.8% (6/68) and 7.8% (4/51) for the EIG and SIG, respectively. In the EIG vs SIG, EPO was withheld in 38% vs 22% of pts and reduced in 43% vs 26% of pts. Two deaths and 6 clinically relevant TVEs while on EPO treatment were reported in each group. Conclusions: This is the first study to show EPO may be initiated at 120,000 U every 3 wks. Hb outcomes in the EIG and SIG were similar. These data provide further evidence that half-life of erythropoietins may not correlate with their effectiveness when used at extended dosing intervals. Future research is warranted. No significant financial relationships to disclose.
Treatment of Macroglobulinaemia
Authors: N. Conway, J. M. Walker
Journal: BMJ (1963)

with his whole body in the lateral position), and with the attendant's four fingers of the more convenient hand slightly cupped, and applied to the under surface of the chin, pulling it gently forward in such a way that each breath can be felt on the palm of the hand.Very little pressure is needed, and the method is easily learned in a few minutes even by a beginner.Immediate warning is given should respiration cease or even become shallow, and only one hand is used.I always demonstrate to each new group of nurses how chest movement per se means only that the patient is attempting respiration, not necessarily breathing-a fact known to all anaesthetists but usually kept a carefully guarded secret.-I am, etc.,