tbuckley/cabot-search huggingface dataset:
Obstetric Outcomes in West Cumberland Hospital: Is There a Risk from Sellafield?
Authors: K P Jones, A W Wheater
Journal: Journal of the Royal Society of Medicine (1989)

A retrospective study was made of the obstetric outcome of 18,252 babies born in West Cumberland Hospital in the years 1975 to 1985. There were 934 premature births (before 37 weeks), 555 small for dates births (under 2.5 kg but not before 37 weeks), 167 stillbirths, 125 neonatal deaths and 236 reported congenital malformations. The 212 babies born to mothers from Seascale during that time were compared with the births to mothers from other areas in West Cumbria Health District in order to assess any adverse effect from possible radioactive discharge at nearby Sellafield. There was no evidence of any increased incidence of these outcomes in Seascale births. Adequate retrospective data on miscarriage rates were not available, but using indirect information on hospital inpatients, no statistically significant increased incidence was found, although the absolute numbers of miscarriage in Seascale were slightly higher than expected. From this evidence, no adverse effects on completed pregnancies can be attributed to the Sellafield plant of British Nuclear Fuels. However, a prospective study of miscarriage incidence in West Cumbria and near other nuclear installations is urgently needed.
Vaccination with epidermal growth factor (EGF) for non small cell lung cancer (NSCLC) therapy: Preliminary results from a randomized phase II clinical trial
Authors: T. Crombet, E. Neninger, M. Osorio, M. Catala, A. Torre, I. Leonard, B. Garcia, G. Gonzalez, R. Perez, A. Lage
Journal: Journal of Clinical Oncology (2004)

2514 Background: Epidermal growth factor (EGF) plays an important role in the regulation of tumor growth. Our approach consists of active immunization with human recombinant EGF coupled to a carrier protein and adjuvanted in Montanide to induce EGF deprivation. Here we report the preliminary results of a randomized Phase II trial designed to test the efficacy of the EGF cancer vaccine in stage IIIb/IV NSCLC patients. Methods: Two groups of 40 unresectable NSCLC patients were compared. All patients received first line chemotherapy and then were randomized to receive the EGF cancer vaccine (group 1) or best supportive care (group 2). Patients were vaccinated on days 0, 7, 14, 21, 51 and then monthly. Anti-EGF antibody titers and EGF concentration ([EGF]) in sera were measured. Results: Fifty patients have been included in the trial (25 vaccinated and 25 controls). Seventy (70) % of the vaccinated patients have shown seroconversion, defined as at least 2X the original antibody titer while 40 % of controls have shown a 2X increase of the natural anti-EGF antibody titers in the follow-up time. However, 50% of the vaccinated subjects developed a good antibody response (GAR), defined at least 4 times above baseline and 1:4000 titer while none of the controls did. The geometric mean of maximal antibody titers was 1: 3500 for group 1 and 1:462 for Group 2. Mean minimal [EGF] was 20 pg/ml for group 1 and 60 pg/ml for group 2. A significant increase in survival was obtained for GAR patients as compared with poor responders. A trend to increase in survival was observed for group 1 (median 8.47 months) as compared with group 2 (median 5.47 months). Conclusions: Preliminary results from a randomized Phase II trial corroborate the immunogenicity and safety of EGF cancer vaccine and the relationship between anti-EGF response and survival of advanced NSCLC patients. No significant financial relationships to disclose.
Oxidative metabolism dysfunction and morphological damage in breast cancer cell mitochondria
Authors: L. Putignani, S. Raffa, R. Pescosolido, F. Signore, D. Menichella, R. Boldrini, M. R. Torrisi, P. Grammatico
Journal: Journal of Clinical Oncology (2008)

22200 Background: Mitochondria are cell energy and signalling source, generating ATP and regulating apoptosis. Altered mitochondrial functions have been identified as causative or contributing factors in many diseases and mitochondriopathy has been recently rekindled as new cancer theory. We report on reduced expression levels of the oxidative phosphorylation system (OXPHOS), structural damage and membrane abnormality of breast-infiltrating ductal carcinoma (IDC) mitochondria. Methods: Mitochondria isolated from HMC-1 (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures were assayed for OXPHOS expression levels, using Western blot and quantitative densitometry; cryo-immunoelectron microscopy (CIEM) quantitative labelling was performed on unfractionated HMC and HEMC cells and compared to MitoTracker Red and fluorescence immunolabelling merging. Convolution degeneration and ultrastructural abnormalities of mitochondria phenotype were quantitatively established by transmission electron microscopy (TEM). MitoTracker Red and Green co-staining was exploited to assess mitochondria membrane defects. Results: Depressed expression levels were detected for all HMC OXPHOS complexes by both densitometry and CIEM. Drastic reduction was observed for the succinate-dehydrogenase complex II SDH-B protein, while decreasing was reported for the NADH-ubiquinone oxidoreductase complex I NDUFS3 and the ubiquinol cytochrome c reductase complex III UQCRC2 subunits. A significant dropping was detected for the ATP-synthase complex V F1β protein. For the cytochrome-oxidase complex IV (CO) near-depletion of the mitochondrial-encoded COI and no apparent variation of the COIV subunits were observed. Fluorescence immunolabelling overlapped quantitative data. TEM assessed morphology deterioration of HMC cell mitochondria. MitoTracker's co-staining showed modification of mitochondria inner membrane potential and permeability. Conclusions: The relevance of mitochondrial pathobiology in breast cancer therapy has not been adequately explored or clinically exploited. Insights on bioenergetic dysfunction and phenotypic injury of IDC cell mitochondria might thereby provide new cancer hallmarks in breast cancer onset and progression. No significant financial relationships to disclose.
A new methodology to compare clinical strategies with application in screening and diagnosis for cervical intraepithelial neoplasia (CIN)
Authors: R. J. Swartz, D. D. Cox, S. B. Cantor, K. Davies, M. Follen
Journal: Journal of Clinical Oncology (2004)

6105 Background: Medical decision making seeks to help clinicians identify optimal clinical strategies. For example, one might want to identify conditions when “see and treat based on colposcopy” would be a better option than the current standard of care (SOC) for screening, diagnosing and detecting CIN. Comparing strategies requires quantifying the outcomes (expressed as losses) associated with different strategies. However, in many medical settings determining losses is difficult especially when considering both clinical and economic outcomes. Methods: We modeled the screening, diagnosis and detection of CIN as a Bayesian sequential decision problem. We compared the current SOC to several alternative clinical strategies involving the same sequence of tests (Papanicolaou smear, colposcopic exam, and biopsy). Results: We found that several alternative strategies for screening and diagnosis of CIN were always dominated. To consider our example, we used a dataset of 624 women to determine operating characteristics and found “see and treat based on colposcopy” is better than the SOC when the net loss for treating non-diseased individuals is less than 1.4 times the incremental loss associated with the biopsy (i.e. the loss associated with a colposcopically directed biopsy that is additional to the loss associated with colposcopy alone.) We also found that the strategy in which all patients receive a biopsy is better than the SOC whenever the loss associated with not treating diseased individuals is greater than 1.7 times the incremental cost of biopsy. Conclusions: Our method provides an efficient means to compare clinical strategies based on both clinical and economic outcomes. No significant financial relationships to disclose.
Synthetic tubulin inhibitor HTI-286 and hepatocellular carcinoma: an in-vitro and and in-vivo study
Authors: C. Redaelli, Y. Vashist, C. Tiffon, M. Wagner, C. Stoupis
Journal: Journal of Clinical Oncology (2005)

4201 Background: HTI-286 (HTI) is a synthetic tubulin inhibitor and a hemiasterlin analogue. It is a potent inhibitor of cell growth with an additional advantage of circumventing the P-glycoprotein-mediated resistance, which hampers efficacy of several antimicrotubule agents. Aim of our study was to investigate in-vitro antiproliferative effect of HTI in several hepatic cancer cell lines (Morris hepatoma (MH), Hep G2 and Hep 3B) and on primary human hepatocytes. Furthermore tumor growth inhibition was analyzed in a rat in-vivo study. Methods: MTT assay was done to determine the doubling time of each cell line. Exponentially growing cells were seeded with different concentrations of HTI for several doubling times. We determined the cytotoxicity and IC(50) by the MTT method. Microtubule structure was visualized by alpha-tubulin-immunofluoresence (aTIF). All animal experiments were approved by the local ethic commission. MH were implanted into American cancer institute rats (ACI) and tumor growth was pursued with MR-imaging (MR). HTI was administered via tail injection at several time points. The tumor growth was followed for over a period of one month. Results: In MH, HepG2 and Hep3B cells HTI has shown an antiproliferative effect already after one doubling time (22, 48 and 55 hours). IC(50) in MH cells was around 1 nM. Cytotoxic effect of HTI rose with increasing concentration. Proliferation of primary human hepatocytes was not affected by the HTI-treatment. aTIF showed a significant difference in HTI-treated compared to non-treated cells. The in-vivo study revealed significant growth inhibition in HTI treated group compared to a saline solution treated group. Conclusions: Our in-vitro data show that HTI inhibits proliferation of hepatic tumor cells in-vitro and tumor growth in-vivo. aTIF confirmed disrupture of microtubule organization. Furthermore primary human hepatocytes do not seem to be affected by the HTI treatment. The data suggest HTI to be considered as a potent promising cytotoxic and antiproliferative drug in liver oncology especially as it circumvents the P-glycoprotein-mediated drug resistance, being responsible for resistance to taxanes and vinca alkaloids. No significant financial relationships to disclose.
Prostate cancer screening practice among men age 75 and older: Results from a national survey
Authors: K. E. Hoffman, A. V. D'Amico
Journal: Journal of Clinical Oncology (2009)

e16034 Background: The U.S. Preventative Services Task Force recently recommended not to screen men aged 75 and older for prostate cancer. This study evaluated the use of prostate specific antigen (PSA) screening among men age 75 and older prior to this declaration. Methods: The study cohort comprised 718 men age 75 or older without a history of prostate cancer who responded to the 2005 National Health Interview Survey, representing an estimated 4.47 million non-institutionalized men annually. Univariable and multivariable logistic regression was used to determine factors associated with PSA screening. Results: Of the 718 men, 19.2 % were age 85 or older, 42.2% reported fair or poor health, 24% had two or more significant diseases and 10.9% were dependent in at least one instrumental activity of daily living (IADL). More than half (51.6%) underwent PSA screening within the previous two years. Men who reported poor health status (42.2 vs. 55.2%, p=0.005) and men who had difficulty with at least one IADL (37.4 vs. 53.3%, p=0.010) were less likely to have a screening PSA. After adjustment for age, race, education status, and physician access, poor health status (adjusted odds (AOR): 0.70, 95% CI (CI): 0.45 to 1.10; p = 0.119), two or more significant diseases (AOR: 0.78, CI: 0.48 to 1.27; p = 0.333) and difficulty with at least one IADL (AOR: 0.71, CI: 0.42, 1.20; p = 0.202) were not associated with the use of PSA screening. Of the 104 men likely to live for five years or less because of poor health, 35.0% underwent PSA screening. Conclusions: Health status, a predictor of life expectancy, should be considered when determining which men receive PSA screening. This would reduce the use of PSA screening in men unlikely to benefit. No significant financial relationships to disclose.
Trajectories of performance status decline in advanced cancer.
Authors: Christine Ritchie, Amy Pickar Abernethy, Jean Kutner, Cari Levy, Sean O'Mahony, Ramona Rhodes, Anna Roshal, Lauren Allison Wiebe, Patrick Jud Blatchford
Journal: Journal of Clinical Oncology (2014)

100 Background: Historically, functional decline is considered to occur steadily and inexorably in the last months of life, with a relatively steep trajectory compared to non-cancer patients (pts). As part of a trial evaluating the safety and clinical impact of discontinuing statin medications for patients in the palliative care setting, we recorded the performance status (PS) in 186 cancer patients regularly during their time on study and compared changes among those with differing baseline PS levels and between those with and without cancer. Methods: This was a multi-center, parallel-group, unblinded pragmatic trial. Eligibility included: age &gt; 18; life expectancy between 1 month and 1 year, on a statin for ≥ 3 months for primary or secondary prevention, recent deterioration in PS and no recent active cardiovascular disease. Participants, randomized to either discontinue or continue statins, were followed monthly for up to 1 year. Outcomes included survival, cardiovascular events, and PS. PS was measured using the Australia-modified Karnofsky Performance Status (AKPS) scale and grouped into 4 categories: AKPS=70, 60; 50 and 0-40. The trajectory of PS decline for each group was modeled using a piecewise-linear function allowing for knots at 4, 8, and 12 weeks and separated out between those participants who died and did not die during their time on study. A mixed model was used allowing for a random intercept for each participant. Results: Among the 186 subjects whose primary diagnosis was cancer, 111 died; among 195 without cancer, 75 died. Those who did not die maintained a relatively flat trajectory of AKPS across 20 weeks; for those who did die, AKPS scores declined somewhat over 20 weeks but this decline was most remarkable among those with a starting AKPS of 0-40. Compared to noncancer patients who died during the study period, PS levels were higher at baseline and had initially greater rates of decline. Conclusions: For advanced cancer patients, PS declines are less dramatic than previous estimates have suggested except for those with AKPS 0-40, suggesting precipitous declines at the very end of life for those with higher initial AKPS. Compared to noncancer patients, PS decline is slightly steeper among cancer pts.
Inflmation Regulates Tmprss6 Expression Via Stat5 in Human Cells and Mice
Authors: Delphine Meynard, Chia Chi Sun, Wenjie Chen, Qifang Wu, Shanzhuo Chen, Caroline. N. Nelson, Michael. J. Waters, Jodie. L. Babitt, Herbert Y. Lin
Journal: American Journal of Hematology (2013)
Metastatic Colorectal Cancer Treatment to progression or Not?
Authors: B. Melosky, C. Lohrisch, C. Kollmansberger, S. Gill, H. Kennecke, A. Shah, A. Coldman, N. Phillips, H. Lim
Journal: Journal of Clinical Oncology (2006)

13511 Background: Treatment until progression or planned interruption of first line chemotherapy is common in the therapy for metastatic colorectal cancer and are upon the discretion of the oncologist. A retrospective analysis was performed to determine the impact of these differing therapeutic strategies on overall survival. Methods: Eligible patients were treated between 2002 to 2004 in British Columbia. All patients received chemotherapy with both FOLFOX and FOLFIRI, either first or second line. Records were retrospectively reviewed for treatment interruption, efficacy and toxicity. Overall survival was the primary endpoint. Results: 101 patients were identified. Twenty-three patients who progressed before receiving 8 cycles of chemotherapy and 9 patients who stopped their chemotherapy due to toxicity were excluded. The remaining patients were analyzed for survival. Twenty-three patients were treated to progression of whom 6 received first line FOLFIRI and 17 received first line FOLFOX. The mean number of cycles of first line therapy was was 11.5. Forty six patients received a planned break. Of these, 21pateints received first line FOLFIRI and 25 patients received first line FOLFOX. Mean number of cycles of first line therapy was 9.7. Median survival of patients treated to progression was 16 months compared to 22 months for patients with planned break of therapy (p=0.003). The Hazard ratio was 2.3 (p=0.01) in favor of patients who had a planned break. Uni-variate and multivariate analysis showed no significance of sex, age, site (colon versus rectal), sequence and ECOG status as predictive factors. Conclusion: In this study, patients who were treated until progression with first line chemotherapy with either FOLFOX or FOLFIRI had an inferior survival. Possible explanations for the detrimental hazard ratio for patients treated to progression are decreasing reserve for second line therapy when first line therapy is prolonged and increasing resistance to 5-FU based therapy with prolonged exposure. As this is a retrospective, observational study, other variables not captured by the modeled covariates that may have influenced results. This data suggests that treating to best response and then allowing a break does not detrimentally affect survival. No significant financial relationships to disclose.
Phase II trial of docetaxel and carboplatin in patients with newly diagnosed, extensive-stage, small cell carcinoma of the lung (SCLC)
Authors: D. V. Jones, F. Klementich, R. Logrono, M. Eltorky, M. Bhutani, E. Walser, J. Zwischenberger, I. Kessel
Journal: Journal of Clinical Oncology (2005)

7346 Background: The platinum-based agents form the backbone of most regimens for SCLC. For patients with extensive stage disease (stage IIIb-IV), doses and schedules used in current programs, such as etoposide with a platinum, yield overall response rates of 70%–85% and complete response rates of 20%–30%. However, virtually all of these patients (pts) will relapse within 6 months. Due to the aggressive nature of this disease, new combinations must be evaluated. Docetaxel has been evaluated in the setting of previously treated, as well as chemo-naive SCLC, and has demonstrated activity. Docetaxel has replaced etoposide (both with a platinum) as an accepted frontline treatment regimen for non-SCLC, but has not been reported in SCLC. Here, we report the interim results of docetaxel in combination with carboplatin as frontline therapy for SCLC. Methods: Eligibility criteria included previously untreated measurable stage III-B or stage IV SCLC, Karnofsky PS 70–100%, and adequate renal, hepatic and bone marrow functions. All pts provide written informed consent. Carboplatin, AUC = 6 (Calvert method) is administered with docetaxel, 75 mg/m2, on day 1 of a 21-day cycle, without prophylactic neutrophil CSFs. Tumor assessments are obtained every other cycle. Results: 11 pts have enrolled thus far, 10 of which are evaluable for toxicity, and 7 are evaluable for activity; 1 pt was found to have a poorly differentiated NSCLC upon further pathology review after provision of informed consent, but prior to initiation of therapy; he is not included in further analysis. One pt is too early for response evaluation. There are 4 males and 6 females; all have stage IV disease; the median age is 59 years (range 45–66 years). Of those evaluable for response, there are 2 CR (both after 4 cycles), 2 PR (2 and 4 cycles), and one SD (57.1% response rate, 71.4% clinical benefit rate). One PR progressed at cycle 6. Of the responders, median times to progression and survival have not been reached. 2 pts were removed for toxicity (anaphylaxis and pancreatitis). There has been no febrile neutropenia or grade 3–4 toxicities. Conclusions: This regimen is active and well tolerated. Pt accrual is continuing to further define activity. No significant financial relationships to disclose.
Phase I study of vandetanib with radiation therapy and temozolomide for newly diagnosed glioblastoma
Authors: J. Drappatz, A. D. Norden, E. T. Wong, A. B. Lassman, L. Doherty, D. LaFrankie, M. Gerard, P. Phan, D. Schiff, P. Y. Wen
Journal: Journal of Clinical Oncology (2009)

2031 Background: There is increasing evidence that angiogenesis inhibition may potentiate the effects of radiation therapy (RT) and chemotherapy in patients with glioblastoma (GBM). In addition, inhibition of the epidermal growth factor receptor (EGFR) may be of therapeutic benefit, as EGFR is often upregulated in GBM and contributes to radiation resistance. We conducted a phase I study of vandetanib, an inhibitor of VEGFR2 and EGFR, in patients with newly-diagnosed GBM in combination with RT and temozolomide (TMZ). Methods: Using a standard 3 + 3 dose escalation design, 13 newly-diagnosed GBM patients received vandetanib with RT (60 Gy) and concurrent TMZ 75 mg/m 2 daily, followed by adjuvant TMZ for up to 12 cycles (150–200 mg/m 2 on days 1–5 of each 28 day cycle). The maximum tolerated dose (MTD) was defined as the dose with ≤1/6 dose-limiting toxicities (DLT). Eligible patients were adults with newly-diagnosed GBM or gliosarcoma, Karnofsky performance status of ≥60%, normal organ function, and not taking enzyme-inducing anti-epileptic drugs. MTD was determined by evaluation of DLTs during the first 12 weeks of therapy. Results: Six patients were treated with vandetanib at 200 mg daily. 2/6 patients developed DLTs (grade 5 gastrointestinal hemorrhage and grade 3 thrombocytopenia in one patient and grade 4 neutropenia in one patient). Seven patients were treated at 100 mg daily with no DLTs observed, establishing 100 mg daily as the MTD. Of 10 evaluable patients, one had a minor response (10%), defined as 25% to &lt;50% reduction in enhancing area for 8 weeks; eight had stable disease (80%), defined as &lt;25% increase or decrease; and one had progressive disease (10%). Conclusions: These data suggest that vandetanib may be combined with RT and TMZ in GBM patients. A randomized phase II study in which patients receive RT and TMZ with or without vandetanib 100 mg daily is underway. [Table: see text]
Predictors of Death and Life-threatening Ventricular Tachyarrhythmias in Patients With Previous Myocardial Infarction by Left Ventricular Longitudinal Strain Analysis
Authors: Arnold C. Ng, Matteo Bertini, Jan Willem Borleffs, Victoria Delgado, Gaetano Nucifora, Miriam Shanks, Giuseppe Boriani, Dominic Y. Leung, Martin J. Schalij, Jeroen J. Bax
Journal: Circulation (2009)