tbuckley/cabot-search huggingface dataset:
Predictors of prostate cancer in men undergoing serial prostate biopsies: results from 371 patients
Authors: M. Garzotto, S. Mongoue-Tchokote, J. Bledsoe, R. O. Parra, L. Peters, Y. Park, T. M. Beer, M. Mori
Journal: Journal of Clinical Oncology (2004)

4589 Background: Due to a high rate of false negative prostate biopsies, a repeat biopsy is often recommended to men if there is a suspicion of occult carcinoma. We sought to determine the rate of prostate cancer (PC) detection and identify risk factors for cancer detection in men who despite suspicion of PC had a negative biopsy initially and then underwent serial prostate biopsies. Methods: Records of all men undergoing at least one repeat biopsy of the prostate from 1992 to 2003 were reviewed. Variables recorded were: age, race, family history of PC (FH), body mass index, biopsy indication, all PSA values, digital rectal exam (DRE), PSA density (PSAD; i.e. PSA/prostate volume), ultrasound findings, total number of cores obtained at all procedures, and the presence of high-grade PIN on initial biopsy. Outcome was defined as time from the initial biopsy to cancer detection or last follow-up. The data were analyzed by Kaplan-Meier method, log-rank test (univariate analysis), stepwise Cox regression (multivariate analysis) and binary recursive partitioning for censored data (survival tree). Results: 373 patients underwent 977 biopsy procedures. Median FU was 3.1 years for all patients and 3.6 years for patients without PC. PC was detected in 105 of 373 (28.7%) patients during follow-up. The estimated median time to PC detection for the entire cohort was 10.3 years. Factors significantly associated (p < 0.05) with a positive biopsy in the univariate analysis were PSADT, PSAD, biopsy indication, and PIN. The survival tree analysis identified 4 distinct risk groups with estimated 5-year PC detection rates (±S.E.) of 21 ± 4%, 40 ± 7%, 58 ± 8% and 100%. The Cox regression analysis showed: Conclusions: Patients who are referred for suspicion of PC but have a negative biopsy can be stratified into clinically meaningful risk groups. Prospective validation of this model is warranted. No significant financial relationships to disclose.
An integrative and comprehensive approach to evaluate lung mechanics in seated and upright positions
Authors: Andre Albuquerque, Pedro Caruso, Renata Pletsch, Pauliane Santana, Leticia Cardenas, Andre Apanavicius, Gabriel Rozin, Marcelo Macchione, Joao Marcos Salge, Carlos Carvalho
Journal: European Respiratory Journal (2012)

Ventilatory and sensorial differences have been found between treadmill and cycle in respiratory diseases. However, there are still many doubts about lung mechanics in these two body positions.  Methods: 5 male healthies were evaluated at quite breathing (QB) and voluntary hyperventilation (VH) in seated (ST) and upright (UR) with: transdiafragmatic pressure (Pdi) - oesophageal and gastric sensors, electromyography (RMS) of sternocleidomastoid, Intercostal, Rectus abdominis and External Abdominal Oblique (OblEMG), ribcage (RC) and abdominal (Ab) bi-dimensional movement by inductotrace (Volt), and flow measurement (L.min-1).  Results: At QB in ST with similar flows, we found: the chest wall movement was mainly the Ab, with similar Pdi than UR (20.9 vs 28.1 cmH2O) but with a lower gastric pressure (12.3 vs 21.9cmH2O, NS). Inspiratory muscles accessory were poorly recruited in both positions, but UR lead to higher activity of abdominal muscles (p=0.08).  During (VH): the chest wall increase was mainly dependent of RC in ST, while in UR the contribution of RC and Ab was the same. Despite the incPes was equivalent (305 vs 295%) in both positions during VH, gastric pressure augmented more in ST than UR (169 vs 109%, NS). Finally, VH in ST resulted in similar recruitment of insp accessory muscles but superior of exp muscle (incOblEMG 118% vs 83%, NS) than UR.  Conclusion: Seated is characterized by greater contribution of Ab to chest wall movement despite the lower gastric pressure and also lower exp muscle recruitment than UR. During hyperventilation, the increase of Ab contribution was also greater in ST. Ab compartment is more recruited and less contributing to chest wall mechanics in UR.
A feasibility study of gefitinib in association with capecitabine (CAP) and oxaliplatin (OXA) as first-line treatment in patients with advanced colorectal cancer (ACRC)
Authors: M. Zeuli, A. Gelibter, C. Nardoni, T. Gamucci, A. Gabriele, C. F. Pollera, F. Di Costanzo, C. Signorelli, V. Ferraresi, F. Cognetti
Journal: Journal of Clinical Oncology (2004)

3748 Background: EGF-receptor (EGF-R) is commonly overexpressed in epithelial tumors including ACRC and has thus become the target of various molecular therapeutic approaches. Gefitinib (Iressa), an EGF-R tyrosine kinase inhibitor, demonstrated activity in lung and head and neck cancer, but its clinical activity in ACRC is still unknown. We designed this trial to assess the safety and efficacy of Iressa in association with CAP-OXA regimen as first-line treatment in pts affected by metastatic colorectal cancer Methods: From October 2002 21 pts were included in a two steps trial (m:f:12/9, median age 66 yrs (54–73). Actually the twelve pts planned for first safety analysis are evaluable for toxicity and response. CAP was orally administered (1000 mg/m2) twice a day continuously for 15 days and OXA was administered (120 mg/m2) as a 2-hour infusion on day 1, repeated every 3 weeks for six courses. Gefitinib has been given orally, once daily, at 250 mg, continuously from day 1.Pts on response at the end of the treatment continued to receive gefitinib until progression or unacceptable toxicity. Results: 40 cycles were totally administered. The most common side-effect was Diarrhea (14/40 cycles: one G4, two G3 and five G2).Acneiform skin lesion (NCI-CTC grade 1–2 in four and one pts respectively) was frequent, but often disappeared or decreased under continued therapy with Iressa. Further major side-effects included Nausea/Vomiting G1–2 in 12/40 cycles, thrombocytopenia G1–2 6/40 cycles, neutropenia G2–3 4/40 cycles. 82,5% of cycles were given at full dose, while 17,5 were given at full dose but delayed; no reduction of dose was performed. 12 pts are evaluable for efficacy according to an intent-to-treat analysis: 1 CR, 5 PR, 1 SD, 3 PD and 2 withdrawn for SAE (asthenia, diarrhea, and vomiting). Conclusions: Iressa in combination with Cape and Oxa is a feasible regimen in ACRC with an acceptable toxicity profile and an interesting, although preliminary, activity. Further studies are required to assess the potential of Iressa as treatment option in ACRC. Accrual will continue up to 35 patients as planned. No significant financial relationships to disclose.
The anatomic localization of circulating tumor cells and the immediate impact of surgery and radiofrequency ablation
Authors: L. Jiao, C. Apostolopoulos, J. Jacob, N. Johnson, N. Tsim, N. Habib, R. Coombes, J. Stebbing
Journal: Journal of Clinical Oncology (2009)

e22004 Background: There are few data on the impact of immediate and differing surgical interventions on circulating tumor cells (CTCs), nor their compartmentalization or localization in different anatomic vascular sites. Methods: CTCs from consecutive patients with colorectal liver metastases were quantitated prior to and immediately after open surgery, laparoscopic resection, open radiofrequency ablation (RFA) or percutaneous RFA. For individuals undergoing open surgery, either hepatic resections or open RFA, CTCs were examined in both systemic and portal circulation by measuring CTCs in samples derived from the peripheral vein, an artery, the portal vein and hepatic vein. Results: A total of 29 consecutive patients with colorectal liver metastases were included with a median age of 55 (range 30 - 88 years). CTCs were localized to the hepatic portosystemic macrocirculation with significantly greater numbers than in the systemic vasculature. Surgical procedures led to a statistically significant fall in CTCs at all sites measured (p&lt;0.05). Conversely, RFA, either open or percutaneous was associated with an increase in CTCs. Conclusions: Surgical resection of metastases but not RFA decreases CTC levels. In patients with colorectal liver metastases, CTCs are localized to the hepatic (and probably pulmonary) macrocirculations. This may explain why metastases in sites other than the liver and lungs, are infrequently observed in cancer. No significant financial relationships to disclose.
Prospective study comparing hospital costs and DRG reimbursement of inpatient treatment of febrile neutropenia during adjuvant anthracycline-based CTX for primary breast cancer
Authors: V. R. Jacobs, S. C. Mayer, B. Paessens, G. Anker, U. Schwarz-Boeger, S. Paepke, N. Harbeck, R. Bernard, M. Kiechle, A. Ihbe-Heffinger
Journal: Journal of Clinical Oncology (2009)

e11570 Background: Febrile neutropenia (FN) is an undesired effect of myelosuppressive chemotherapy (CTX). To date limited data on costs of FN management is available. We compared costs and reimbursement of FN in a study of BC patients during adjuvant anthracycline (AC)-based CTX. Methods: Prospective, observational, longitudinal study in primary BC patients, enrolled 1–12/2006 consecutively before start of CTX in a German university clinic. FN was defined as fever &gt;38ºC + ANC &lt;1x10 9 /L. Clinical and resource use data + DRG reimbursement were analyzed from medical charts. Costs for inpatient therapy of FN were compared to DRG reimbursement and results are presented from provider's perspective. Results: Of all patients approached (n=61), n=54 signed informed consent (88.5%), n=2 withdraw (3.3%) and n=2 were excluded from evaluation because of non-AC-based CTX. Patients were on avg. 57.4 (32–74) years and otherwise healthy ECOG 1 (n=50; 100%). Tumor classification was T1 n=25, T2 n=19, ≥T3 n=5 and pTx n=1. Chemo regimen was either AC-based n=29 (58.0%) or AC+taxane-based n=21 (42.0%). 12 episodes of FN occurred (24.0%) in 11 patients, one patient had 2 episodes; n=11 were treated as inpatients, n=1 as outpatient. Hospital stay for inpatients was on avg. 5.4 days (4–8), 0.7 days below average according to G-DRG catalog. Mean cost per FN episode requiring hospital treatment was 1.827 €, SD ±795 € (95%CI: 1293, 2361). Basic hospital costs were 83%, drug treatment 9% and diagnostics 8% of total direct costs. DRG reimbursement for inpatient FN was 2.145 € per episode, thus cost covering for the provider. Avg. reimbursement rate/day was 417 € (253–665 €). Inadequately DRG coding (n=4) resulted in a loss of 1.069 €/case (-42.2%). Conclusions: Costs for FN treatment vary among patients and DRG reimbursement does not necessarily reflect providers’ costs. Main cost drivers are hospitalization, length of stay, diagnostics and antibiotics. Surprisingly, inpatient treatment of FN under current therapy regimen is cost covering if adequately coded. This prospective evaluation and calculation of provider's costs and reimbursement helps understanding the allocation of resources for rational and cost-covering therapy. [Table: see text]
Epithelial ovarian cancer (EOC) without macroscopic residual tumour: Long-term, population-based outcomes
Authors: K. D. Swenerton, B. Gilks, N. Le
Journal: Journal of Clinical Oncology (2004)

5053 Background: Outcomes in “early” EOC have been uncertain, given inconsistent definitions, low incidence, fair prognosis, and few trials (of potentially unrepresentative populations). For 2 decades multi-modal treatment policies have been advocated for women with EOC in our province. All new pts were stratified into 4 risk groups using FIGO stage (S), grade (gr) and post-operative residual (invisible = R-, visible = R+): 3 groups are R- (Low, Moderate, High - see table for definitions); the 4th comprises the R+ and stage IV (Extreme). Methods: In the 17y including 1984 through 2000, 3501 pts were recorded to have “ovarian cancer”. On review, 82% (2886) of these were found to have EOC, 89% (2558) being invasive. The 1659 E pts are not subjects of this analysis. The records of the 895 R- pts were reviewed in detail. L pts normally received surgery alone. M and H pts were offered platinum-based chemotherapy (CT) and abdomino-pelvic radiotherapy (APR wasn't used in H pts from 1989 - 1994). Results:When CT and APR were advised, acceptance was usual, 97 and 90% respectively. The completion rate of APR was 89%, with 34% mild-moderate late diarrhea/colic and 3.5% needing surgery. Death from M and H EOC continues to be seen more than15y from diagnosis. Conclusions: This risk classification is useful; further analysis may allow refinement. With a durable disease-specific survival (DSS) of 94%, surgery alone is confirmed as sufficient for L; better therapy is needed for others as ∼1/3 and 1/2 of M and H pts respectively die of EOC by 15y. Ongoing analysis may indicate if APR has a positive therapeutic ratio. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lerner David Littenberg Krumholz & Mentlik
Evidence that suicide terrorists are suicidal: Challenges and empirical predictions
Authors: Adam Lankford
Journal: Behavioral and Brain Sciences (2014)

Abstract The Myth of Martyrdom: What Really Drives Suicide Bombers, Rampage Shooters, and Other Self-Destructive Killers proposes that suicide terrorists are psychologically and behaviorally similar to other people who commit suicide, due to a range of individual, social, and situational factors. Some commentators agree, while others are skeptical, given the lack of information about many attackers' lives. However, the book's position is not simply based on individual case studies; it is also supported by other independent assessments, the confirmation of empirical predictions, the paucity of contradictory evidence, and new applications of evolutionary theory. It is undisputed that human beings behave as the author suggests; it is unknown if they behave as the conventional wisdom suggests. Those who argue that suicide terrorists are psychologically normal and altruistically sacrificing their lives for an ideological cause should bear the burden of proof for those claims.
Plasma IL-6 level and survival of pancreatic cancer patients treated with a VEGFR inhibitor, vatalanib (PTK/ZK)
Authors: A. F. Baker, T. Dragovich, A. Cui, D. Laheru, C. Campen, D. D. Von Hoff, M. Hidalgo
Journal: Journal of Clinical Oncology (2009)

e15514 Background: Use of anti-angiogenesis drugs in pancreatic cancer has not yet resulted in significant clinical improvements and it is unknown if there are subsets of patients with pancreatic cancer that may benefit from this therapeutic approach. We have reported on a phase II trial of PTK/ZK (VEGFR inhibitor) in patients (n=65) who have failed or progressed on gemcitabine. The 6- month OS met the primary endpoint of 29 % and there were 2 partial responses. We investigated some of the plasma proteins relevant for angiogenesis in correlation with clinical outcomes on this trial. Methods: Plasma samples were obtained prior to and after 4 weeks of therapy with PTK/ZK, aliquoted and frozen until assayed. Patient plasma was assayed for: VEGFA, VEGFC, VEGFR1, VEGFR2, FGFb, PDGFBB, OPN, ANG2, IL-6, and sIL-6R (SearchLight, Pierce Biotechnology Multiplex ELISA and IL-6 and sIL-6R using R&amp;D Systems).The Spearmen correlation was utilized to look for correlations and changes from baseline compared to post-treatment levels. The correlation of baseline levels with survival were analyzed using the Cox proportional hazard model. Results: Thirty eight paired patient samples were assayed. A significant correlation of baseline values was found between VEGF-C and VEGFR1 (p=0.0496), VEGF-C and VEGF (0.0092), PDGFB and ANG2 (p=0.0003), IL-6 and ANG2 (p=0.0089), and FGFb and OPN (p=0.0281). A correlation in post-treatment change was observed between VEGF-C and PDGFB (p=0.0008), FGFb and OPN (p=0.0374), PDGFB and ANG2 (p=0.0005), IL-6 and ANG-2 (p=0.0464), and VEGF and IL-6 (p=0.0546). Lower baseline IL-6 levels correlated with longer survival (p=0.0227). A post-treatment decrease in plasma IL-6 levels was significantly associated with improvement in survival (p=0.0457). IL-6 mediates multiple effects including angiogenic and pro-survival signaling and has been proposed as a potential prognostic factor in different malignancies. Conclusions: Of all angiogenesis markers analyzed only a post-treatment decrease in plasma IL-6 correlated with improved survival on study. IL-6 warrants further investigation as a potential marker of sensitivity to anti-angiogenesis therapy, especially in patients with pancreatic cancer. Supported by: 1P50 CA95060; 1PO1CA109552–01A1 [Table: see text]
A phase II study of imatinib mesylate in prostate cancer patients with evidence of biochemical relapse following definitive radical retropubic prostatectomy or radiation therapy
Authors: G. K. Bajaj, E. Garrett-Mayer, R. Drew, V. J. Sinibaldi, M. Gaver, R. Pili, S. Denmeade, M. A. Carducci, M. Eisenberger, T. L. Deweese
Journal: Journal of Clinical Oncology (2005)

3092 Background: Biochemical recurrence of prostate cancer after definitive or salvage local therapy in the absence of metastatic disease represents a group of men well suited for a novel therapeutic intervention. Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor which has previously been tested in men with androgen-independent and metastatic prostate cancer. This phase II study was undertaken to determine the safety and efficacy of imatinib mesylate in men with biochemical relapse of non-metastatic, androgen-sensitive prostate cancer following local therapy. Patients and Methods: Twenty-seven patients were treated with imatinib mesylate 400mg twice daily for 12 months or until evidence of disease progression or dose limiting toxicity. All patients had evidence of biochemical progression with a rising PSA after definitive radiation therapy, prostatectomy, or prostatectomy and salvage radiation therapy. Three patients (11%) completed less than 4 weeks of therapy and were not evaluable. Results: Of the 24 patients evaluated for a biochemical response, six patients (22%) demonstrated a stable PSA over the course of treatment; two patients (7%) experienced a partial response to treatment as defined by a PSA decline of greater than 50% for at least 4 weeks duration. Duration of response in these two patients was 5 months and 12 months. Sixteen patients (59%) demonstrated progressive disease as defined by a 25% or greater increase in PSA above the baseline value at study entry. There was no association between overall PSA response and changes in serum testosterone level. The proportion of patients achieving a partial response in PSA while on therapy did not significantly differ from the null rate of 5% using a two-sided exact binomial test (P=0.394; 95% CI 0.9% - 24.3%). There was no irreversible NIH-CTC Grade 3 or 4 toxicities. Grade 3 and 4 toxicity included leukopenia (3.7%), elevation in SGOT (7.4%) and SGPT (7.4%), and rash (18.5%). Conclusions: Imatinib mesylate delivered at a dose of 400mg twice daily is associated with acceptable toxicity and limited ability to confer a PSA response in this patient population. No significant financial relationships to disclose.
Use of metabolic profiling by metabolomic technology to distinguish between localized and metastatic breast cancer patients.
Authors: O. Tredan, B. Blaise, C. Pontoizeau, M. E. Dumas, B. Elena, T. D. Bachelot, P. Toulhoat
Journal: Journal of Clinical Oncology (2010)

e21005 Background: Tumor pathophysiological conditions depending on tumor cell metabolism and tumor microenvironment offer an opportunity to better characterize tumors by providing metabolic signature. Metabolomics is the combination of analytical techniques such as Nuclear Magnetic Resonance (NMR) spectroscopy with statistical data analysis methods aimed to evaluate the metabolic status of biofluids. This technology may be relevant for breast cancer prognosis. Therefore, the first objective of this study was to provide evidence that metabolomics from patients' (pts) blood sample is able to distinguish between metastatic and localized breast cancer. Methods: Serum samples from 2 cohorts of pts were analyzed using 1H NMR spectroscopy on a Bruker Avance III spectrometer operating at 800 MHz and equipped with a triple resonances automated TXI probe. Fasting blood sample were drawn from 30 pts with localized breast cancer (before surgery), and from 25 pts with metastatic breast cancer (before the first chemotherapy injection). For each sample, a 1D NMR spectrum was acquired, showing a large number of resonances corresponding to protons belonging to different classes of metabolites. A spectral database was generated, and bioinformatic tools were used to analyze the results using supervised multivariate analysis (Partial Least Square Regression). Results: The use of very high-field NMR allows the acquisition of resolved spectra with a reliable assignment of resonances based on multidimensional homo- and heteronuclear experiments. We identify metabolic signature of metastatic breast cancer, which is statistically different from the metabolic signature of localized breast cancer. Target analysis is on going to have further quantitative analysis of a class of metabolites that are related to the metastatic condition. Conclusions: Metabolomics may become a novel biomarker for cancer prognosis. Prospective studies to validate metabolomics as a prognostic/predictive tool are planed. No significant financial relationships to disclose.