tbuckley/cabot-search huggingface dataset:
A randomized phase II study of paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer.
Authors: J. D. Hainsworth, T. M. Numnum, G. G. Rao
Journal: Journal of Clinical Oncology (2010)

TPS257 Background: The majority of patients diagnosed with ovarian cancer have advanced disease at the time of diagnosis, and are incurable with surgical therapy. Systemic chemotherapy, following initial cytoreductive surgery, has markedly improved the treatment of patients with advanced ovarian cancer. Standard first-line combination chemotherapy includes a taxane and a platinum agent. Further improvement in the first-line treatment of ovarian cancer will likely depend on the successful incorporation of novel, targeted agents into therapy. Several angiogenesis inhibitors have shown activity against refractory ovarian cancer. Sorafenib efficiently blocks the VEGF receptor and demonstrates antitumor activity in murine xenografts using a human ovarian cancer line (SKOV3). This randomized phase II study compares the efficacy and toxicity of a standard paclitaxel/carboplatin regimen, either alone or with the addition of sorafenib, in the first-line treatment of patients with stage III/IV ovarian cancer following cytoreductive surgery. Randomization of 120 patients will allow detection of an improvement in 2 yr PFS from 45% to 67% (α=.10). Methods: Eligibility: All patients must have previously untreated, histologically confirmed, stage III or IV epithelial ovarian carcinoma, with no residual tumor nodule > 3 cm, no involvement of the bowel (i.e. invasion into bowel wall) and no intestinal obstruction after surgical cytoreduction. Trial Design: Following recovery from cytoreductive surgery patients are randomized (1:1) to receive treatment with paclitaxel/carboplatin ± sorafenib. Regimen A: paclitaxel 175mg/m2, 1-3 hr infusion, day 1; carboplatin AUC=6.0 IV day 1; sorafenib 400 mg bid orally, days 1-21. Regimen B: paclitaxel/carboplatin (same doses as Regimen A). Cycles are repeated every 21 days. Patients are reevaluated every 6 weeks; responding/stable patients continue treatment for 6 cycles. After 6 cycles, responding patients on Regimen B continue single agent sorafenib to complete a 12 month course. Current Enrollment: 55 of 120 patients are currently enrolled. No significant financial relationships to disclose.
A comparative study of circulating endothelial cells (CECs) and circulating progenitor cells (CPCs) kinetics in four multidisciplinary phase II studies of antiangiogenic agents
Authors: D. G. Duda, K. S. Cohen, M. Ancukiewicz, E. di Tomaso, A. X. Zhu, R. T. Penson, N. S. Horowitz, T. T. Batchelor, C. G. Willett, R. K. Jain
Journal: Journal of Clinical Oncology (2008)

3544 Background: CECs and CPCs are being evaluated as generic biomarkers of antiangiogenic therapy in cancer patients (pts). We hypothesized that: 1. CEC and CPC kinetics depend on the antiangiogenic agent used; and 2. CECs and CPCs have differential biomarker value. Methods: Using a standard flow cytometry protocol, we measured the fraction of cells with CEC and CPC phenotype among blood mononuclear cells at multiple time-points during treatment in 4 phase 2 studies of anti-VEGF agents: 1. sunitinib in hepatocellular carcinoma (HCC); 2. cediranib in glioblastoma (GBM); 3. bevacizumab (BV) with chemoradiation in rectal cancer (RC); and 4. BV with chemotherapy in ovarian cancer (OC). The changes posttreatment were evaluated using the Wilcoxon test. Correlations between CECs and CPCs with measures of tumor response (imaging, histology, RECIST) were analyzed with a Spearman’s correlation test in a mixed effects model or using the Wald test in a proportional hazards model. Results: Sunitinib induced a sustained decrease in CPCs (p<0.05), but not CECs in HCC pts. Cediranib did not significantly change the CECs or CPCs over time in GBM pts. BV decreased the CECs and CPCs on day 3 (p<0.05) but not on day 12 when given alone, and not when combined with chemoradiation in RC pts. BV with chemotherapy induced a sustained increase in CPCs (p<0.01), but not CECs in OC pts. The number of CECs correlated with RC response to BV/chemoradiation when evaluated at pre- surgery (p<0.05) and tended to correlate with GBM radiographic relapse on cediranib (p=0.06). In contrast to results from preclinical studies, best tumor responses to BV/chemotherapy in OC correlated with higher pretreatment CPCs (p<0.05). In HCC pts, the time-dependent CPC changes positively correlated with mortality risk on sunitinib (p<0.05). Conclusions: CEC and CPC kinetics depend on the type of antiangiogenic agent. Similarly, their biomarker value is differential. Further characterization of the CECs and CPCs in an agent-specific manner might provide ways to use them to optimize antiangiogenic therapies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, Bayer, Dyax, Eli Lilly and Company, Genentech, GlaxoSmithKline, Pfizer, Takeda Pharmaceuticals Genentech AstraZeneca, Bayer HealthCare Pharmaceuticals, CuraGen Corporation, DARA Biosciences, Genentech, Inc., MGI Pharma, Inc.
Analysis of the p53/BAX Pathway in Colorectal Cancer: Low BAX Is a Negative Prognostic Factor in Patients With Resected Liver Metastases
Authors: Isrid Sturm, Claus-Henning Köhne, Gerhard Wolff, Henrik Petrowsky, Timo Hillebrand, Steffen Hauptmann, Matthias Lorenz, Bernd Dörken, Peter T. Daniel
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the prognostic value of the central downstream apoptosis effector BAX in relation to its upstream regulator p53 in R0-resected hepatic metastases of colorectal cancer. PATIENTS AND METHODS: Retrospective analysis of 41 patients who underwent potentially curative resection of liver metastases from colorectal cancer was performed. Tumor DNA was screened for p53 mutations by single-stranded conformational polymorphism polymerase chain reaction and for BAX frameshift mutations by fragment length analysis. Protein expression of BAX, p21, and p53 was investigated by immunohistochemistry. RESULTS: Overall median survival was 40.2 months. Tumors with BAX frameshift mutations were considered microsatellite mutator phenotype–positive and were excluded from further prognostic analyses. Patients with high BAX protein expression had a median survival of 53.6 months compared with 35.4 months for patients with low BAX expression (P &lt; .05). The negative prognostic value of low BAX expression was more evident in those patients with wild-type p53 (median survival, 54.0 v 23.3 months for BAX-negative tumors; P &lt; .01). Low BAX expression was an independent negative prognostic marker in multivariate regression analysis for all patients independent of the p53 status (relative risk, 3.03, P = .03), especially for p53 wild-type tumors (relative risk, 8.21; P = .0095). CONCLUSION: We conclude that low BAX expression is an independent negative prognostic marker in patients with hepatic metastases of colorectal cancer. The best survival was seen in patients with an intact p53-to-BAX pathway; ie, wild-type p53- and BAX-positive tumors. Thus, analysis of apoptosis signaling pathways (here, p53 in concert with its downstream death effector, BAX) might yield more prognostic power in future studies as compared with analysis of single genes such as p53 alone.
"Worse than death": psychodynamics of rape victims and the need for psychotherapy
Authors: D S Rose
Journal: American Journal of Psychiatry (1986)

Victims of rape routinely are acknowledged to need counseling but not psychotherapy; if psychotherapy is provided, the major focus is on preexisting psychopathology. The author examines these assumptions and presents a different formulation based solely on an in-depth examination of the many levels of the trauma. Case material reveals the typical symptoms, conflicts, and defenses found in rape victims. The author makes recommendations for psychotherapeutic technique, especially in regard to difficulties in forming a therapeutic alliance.
PWE-025 Quality improvement in the colorectal cancer multi-disciplinary team (mdt): a prospective evaluation of team factors
Authors: MK Matharoo, R Baldwin, J Jenkins, D Burling, A Haycock, N Sevdalis, S Thomas-Gibson
Journal: Gut (2015)

<h3>Introduction</h3> Significant improvements in the quality assurance of endoscopy have occurred driven partly by Bowel Cancer Screening. The same focus on quality however, has not been applied to the Colorectal Cancer (CRC) MDT process where key management decisions are made for patients diagnosed with CRC. Objectives: 1. Quantify quality of clinical information at MDT 2. Quantify core specialty contribution to MDT. <h3>Method</h3> Two independent clinical evaluators prospectively rated CRC MDTs. A previously validated MDT team evaluation tool<sup>1</sup>was adapted following tiered focus groups with core members. This tool objectively measures quality of clinical data, relative contribution and quality of discussion by core specialities and case note availability for each patient. <h3>Results</h3> 412 MDT patient discussions over 27 meetings were prospectively analysed (216 pre and 196 post-treatment). 217 (53%) patients were double-rated. Inter-rater reliability was acceptable with weighted kappa coefficients of 0.52 for information and 0.37 for specialty input scores. The mean scores are presented in Table 1for information and Table 2 for specialty input. Patient-focussed information (i.e. patient preferences and background) was poorly presented whilst clinical data (e.g. Radiology) scored higher. The quality of MDT discussion and decision-making from core members was highly variable with surgeons scoring highly compared to specialist nurses. Mean time per patient discussion was 4.46 min (range 1–18 min). Medical notes were unavailable for 73 (21%) of patients. <h3>Conclusion</h3> This study demonstrated variability in information provision and discussion from contributing team members. However, a limitation of the rating tool is that a low score is assigned (no contribution) even when no specialty specific contribution is required. This may explain the low scores for Endoscopists and Liver Surgeons, as their expertise was not required for all cases. The MDT tends to focus on 9clinical9 discussions and may neglect relevant patient-focussed information. Optimal MDT decision-making requires attention to technical factors (e.g. availability of key information) and non-technical factors such as inclusive discussion, leadership and teamwork skills. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Lamb BW, <i>et al</i>. Teamwork and team performance in multidisciplinary cancer teams: development and evaluation of an observational assessment tool. <i>BMJ Qual Saf</i>.<i>June </i>2011
A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma.
Authors: C Erlichman, S Fine, A Wong, T Elhakim
Journal: Journal of Clinical Oncology (1988)

We determined the therapeutic effect of fluorouracil (5-FU) in combination with folinic acid (FA) in patients with measurable recurrent or metastatic carcinoma of the colon or rectum by comparing it to standard 5-FU therapy in a prospective randomized controlled trial. Patients were randomized to receive either FA, 200 mg/m2/d for five consecutive days, or nothing. All patients received 5-FU, 370 mg/m2/d for five days on the first course, with subsequent dose modifications to maintain equal toxicity in the two arms. One hundred thirty patients were entered on trial and only five were excluded from the analysis because they did not meet the eligibility criteria or they refused therapy after randomization. The two treatment arms were balanced for 11 clinical characteristics. Patients were evaluated for response at the end of every two treatment courses and toxicity after every course of therapy. Median follow-up was 1.45 years. Dose-limiting toxicity was mucositis and diarrhea on this treatment schedule, although neutropenia was apparent. The response rate was 33% (21 of 63 patients) in the 5-FU and FA arm and was 7% (four of 61 patients) in the 5-FU arm (P less than .0005). Time to disease progression was significantly different in the combination arm as compared with the single-agent arm (P = .023). Overall survival was significantly longer for patients treated with 5-FU and FA as compared with those receiving 5-FU alone (P = .05). The median survival was 12.6 months for patients receiving the combination, and 9.6 months for those receiving 5-FU alone. Our results indicate that the combination of 5-FU and FA is effective treatment for patients with metastatic or recurrent carcinoma of the rectum and colon who have not received prior chemotherapy.
Abstract 9943: Aged Garlic Extract Plus Coenzyme Q10 Significantly Reduce Perceived Mental Stress, Inflammaion and Subclinical Atherosclerosis in Firefighters ‰the FAITH Randomized Clinical Trial
Authors: Vahid Nabavi Larijani, Fereshteh Hajsadeghi, Ferdinand flores, Matthew budoff, Naser Ahmadi
Journal: Circulation (2012)

Background: We previously reported that Aged Garlic Extract (AGE) is associated with significant reduction of subclinical atherosclerosis measured by coronary artery calcium (CAC) in asymptomatic individuals. Stressful lifestyle is a well-known risk factor of atherosclerosis. In the current study, we evaluate the effect of AGE plus CoQ10 on perceived mental stress score (PMSS), inflammation and CAC in Firefighters with highly stressful lifestyle. Methods: In this placebo-controlled, double blinded, randomized trial, 65 firefighters, age 55±6 years, 100% male, with intermediate risk for coronary artery disease (CAD) subjects were randomized to AGE and CoQ10 vs. placebo for 1-year. Subjects’ mental stress was assessed as perceived mental stress score (PMSS) using validated perceived mental stress questionnaire (PSQ). PMSS, high sensitive C reactive protein (CRP) and CAC were measured at baseline and follow up. Results: There was no significant difference between PMSS, CRP, CAC and other risk factors at baseline (p&gt;0.5). At-year follow-up, PMSS reduction was significantly higher in AGE plus CoQ10 as compared to placebo (-10.6% vs. 14.7%, p=0.001). After adjustment for risk factors, AGE plus CoQ10 was independently associated with significant reduction in PMSS, CRP and CAC (p&lt;0.05) (Table). In which, the likelihood of decrease in PMSS was 84% higher with AGE plus CoQ10. Decrease in PMSS in response to AGE plus CoQ10 was significantly associated with decrease in CRP and CAC (p&lt;0.05). Conclusion: This study reported the beneficial effect of AGE-CoQ10 on mental stress in subjects with highly stressful lifestyle independent of risk factors. Furthermore, it highlights the association between decrease in mental stress , inflammation and atherosclerosis in response to such therapy.
Clinical pharmacodynamics of continuous infusion topotecan in children: systemic exposure predicts hematologic toxicity.
Authors: C F Stewart, S D Baker, R L Heideman, D Jones, W R Crom, C B Pratt
Journal: Journal of Clinical Oncology (1994)

PURPOSE Topotecan pharmacokinetics and pharmacodynamics were studied following a 72-hour continuous infusion in 20 children with cancer (median age, 8 years; range, 3.5 to 18). METHODS Serial plasma and urine samples were collected during the infusion and for up to 6 hours following the end of infusion. Topotecan (lactone) and total (lactone plus hydroxy acid) concentrations were determined by a sensitive and specific high-performance liquid chromatography (HPLC) assay with fluorescence detection. Using maximum a posteriori-Bayesian modeling, lactone and total plasma concentrations were described separately by a two-compartment model. Hematologic toxicity was expressed as the percent decrease in absolute neutrophil count (ANC) and platelet count. The relation between systemic exposure (SE) and hematologic toxicity was modeled using a sigmoid maximum-effect model. RESULTS Systemic clearance rates for lactone and total topotecan were (mean +/- SD) 18.5 +/- 7.0 and 6.5 +/- 2.4 L/h/m2, respectively. Urinary recovery of total topotecan was (mean +/- SD) 67.5% +/- 25.2% (n = 12 patients). SE (area under the concentration-time curve from zero to infinity [AUC] or steady-state plasma concentration [Cpss]) to either topotecan lactone or total topotecan was significantly correlated to hematologic toxicity (P &lt; .05). Overall, patients with a higher SE to topotecan experienced greater hematologic toxicity. CONCLUSION These data demonstrate a relation between systemic exposure to topotecan and clinical effect (myelosuppression). Moreover, these data provide the basis for development of individualized topotecan administration schedules.
Impact of surgical treatment on survival in patients with primary rectal melanoma
Authors: J. C. Yap, G. Yang
Journal: Journal of Clinical Oncology (2007)

19001 Background: Reports of melanoma of the lower GI tract, especially in the rectal area, were often grouped with diseases from the anal canal region. Outcome and pattern of care regarding primary melanoma of the rectum only were not well described in the literature. This review examined the utilization of surgery, radiotherapy (RT), and the potential impact on survival outcome in this subgroup of patients. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (1973 to 2003) was searched. Only patients with primary melanoma of the rectum (excluding anal lesions) with recordable pathology reports were included. 79 patients were identified. 61 of them had melanoma of the rectum as the sole primary disease, and these patients were the focus of this study. Kaplan Meier estimation and Cox-Mantel test were used to calculate and compare survival rates. Results: Among the 61 patients, 20 patients did not have further surgery after biopsy. Another 20 patients had surgery, but the types of procedure were unknown. Of the remaining 21 patients eligible for analysis, eight patients had abdominoperineal resection (APR), and one of them received postoperative RT. Thirteen patients had partial proctectomy (PP), and none had RT. In univariate analysis, the 5-year overall survival rates for APR and PP groups were 12.5% and 7.7% respectively (p=0.63). There were one survivor in each group at the last follow up period with crude survival time of 15 years and 13.5 years respectively. More patients in APR group had locoregional disease (extramural and nodal) than in PP group (63% versus 0% respectively) at diagnosis. Comparing the time intervals by decade between 1973 to 1982, 1983 to 1992, and 1993 to 2003 in all 61 patients, use of postoperative RT was relatively limited at 1 in 14 cases, 1 in 19 cases, 2 in 28 cases respectively. RT was used mostly in patients who were not candidate for surgery and in patients with metastatic disease at diagnosis presumably for palliation. Conclusions: Primary melanoma of the rectum is a rare disease. Data for analysis were limited. There was no significant difference in overall survival between patients who had APR versus PP although APR group had higher tumor burden at diagnosis than PP group. Use of adjuvant RT is rare, and its role has yet to be further defined. No significant financial relationships to disclose.
Keratins are novel markers of renal epithelial cell injury
Authors: Sonja Djudjaj, Marios Papasotiriou, Roman D. Bülow, Alexandra Wagnerova, Maja T. Lindenmeyer, Clemens D. Cohen, Pavel Strnad, Dimitrios S. Goumenos, Jürgen Floege, Peter Boor
Journal: Kidney International (2016)
Cutaneous rash as a surrogate marker of time to tumor progression (TTP) with erlotinib in previously treated advanced non- small cell lung cancer (NSCLC)
Authors: S. Cedrés Pérez, A. Prat, E. Felip, S. Peralta, J. Perez, J. del Campo, G. Sala, J. Andreu, E. Pallisa, J. Baselga
Journal: Journal of Clinical Oncology (2008)

19125 Background: Inhibition of the EGFR pathway has become an established strategy in NSCLC patients (pts) treatment. The aim of this study is to assess the value of predictive clinical variables associated with outcome in advanced NSCLC pts treated with erlotinib. Methods: Pts (n = 62) from a phase II trial with advanced NSCLC were treated with erlotinib (150 mg/day) upon chemotherapy (CT) progression. Pts characteristics were: performance status (PS), 0–1, 100%; median age, 58 years; males, 73%; adenocarcinoma, 45%; smoking history, 83%. Cutaneos rash during erlotinib: grade 0, 22 pts (35%); grade 1, 20 pts (32%); grade 2, 16 pts (26%); grade 3, 4 pts (7%). Standard Kaplan-Meier methods were used to plot the TTP of members of each group. The relative contribution of the different potential correlates of prognosis was assessed by the Cox proportional hazards method. Results: Partial response was noted in 6 pts (9.6%) and stable disease in 16 (26%). The median TTP was 43 days (95% confidence interval 19–326 days). The predictive factors analyzed were rash (0–1 vs 2–3), smoking history (yes vs no), PS (0 vs 1), age (≤ 65 vs > 65), and histology (adenocarcinoma vs others). Pts who developed rash grade 2–3 had TTP of 92.5 days vs 41 days for those without rash or rash grade 1 (P = 0.04, log-rank test). Pts with and without smoking history had TTP of 42 days vs 116.5 days, respectively (P = 0.002, log-rank test). Female and male had TTP of 85 days vs 42 days, respectively (P = 0.085, log-rank test). Pts with adenocarcinoma and other histologies had TTP of 76 days vs 42 days, respectively (P = 0.98, log-rank test). In a simple correlation analysis, a significant association was found between rash (grades 0, 1, 2 and 3) and TTP (Spearman rank correlation coefficient; Rs 0.34, P = 0.006). The Cox model showed a significant impact of rash grade (grade 2–3 vs 0–1; hazard ratio (HR) = 0.72, P = 0.045) on TTP and smoking history (no vs yes; HR = 0.31, P = 0.025). Conclusions: The appearance of rash grade 2 or higher is associated with improved TTP with erlotinib for advanced NSCLC pts previously treated with CT. In addition, a significant positive correlation has been found between rash grade and TTP. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche
Abstract 17059: Closing the Gap of Increased Mortality between Diabetic and Non-diabetic Patients with STEMI. Data from the USIK 1995, USIC 2000, FAST-MI 2005 and 2010 French Nationwide Registries
Authors: Etienne Puymirat, Roxane Ducloux, Veronique Lucke, Yann Valy, Gerald Vanzetto, Gilles Grollier, Vincent Bataille, Elodie Drouet, Tabassome Simon, Nicolas Danchin
Journal: Circulation (2012)

Background and aim: Early mortality in diabetic patients with STEMI is known to be worse than in non-diabetic subjects. Whether this worse outcome persists with the decline in mortality observed fo...