tbuckley/cabot-search huggingface dataset:
Abstract P277: The Influence of Interval Training on Physical Capacity and Exercise-induced Ischemia in Patients with Coronary Artery Disease
Authors: Iwona Korzeniowska-Kubacka, Maria Bilinska, Ewa Rydzewska, Barbara Dobraszkiewicz-Wasilewska, Ryszard Piotrowicz
Journal: Circulation (2012)

Introduction: Patients(pts) with CAD referred for cardiac rehabilitation on the out-patient basis include those whose exercise stress test(EST) has been positive. The limit of the training heart rate(HR) is set below the ischemic threshold (IT), which result from angina and/or ischemic ST segment depression by ≥1 mm during an exercise test. The literature provides few original studies of this issue, and the answers to the question if ischemia during exercise should be avoided are inconsistent. Objectives: The aim of the study was to compare the safety and effectiveness of interval training at and below IT, and its influence on physical capacity and exercise-induced ischemia in pts with CAD and positive exercise stress test. Methods: The study comprised 30 clinically stable pts with positive EST, aged 55.22±10.29 years, after myocardial infarction and/or surgically treated ischemic heart disease, who were included in a cardiac rehabilitation program one month following MI or CABG. All subjects were divided into two groups: Group A-training at IT i.e. HR at which 1-mm ST depression appeared during the initial EST ( n=10),group B -training below IT i.e. HR10 bpm lower than the one at which 1-mm ST appeared ( n=20).All of them underwent a two-month interval training on cycloergometer three times a week. EST was performed before and after the completion of the training program(TP). The following variables were assessed: walking distance, WD (m), EST duration (min), metabolic equivalent (METs), time to 1 mm ST depression (min), max ST depression (mm).Also adverse events that occurred during training were analyzed. Results: After TP, following analyzed variables improved significantly in Group A: WD- 706.90±101.02 vs 770.90±139.78, p&lt;0.05; EST duration - 10.15±3.89 vs 11.11±3.94, p&lt;0.01; METs- 8.19±1.33 vs 9.27±1.89, p&lt;0.05; time to 1mm ST depression- 9.08±4.27 vs 10.33±3.74,p&lt; 0.01. The analyzed variables of Group B pts also improved: WD- 541.50±204.48 vs 646.30±175.72, p&lt;0.01; EST duration- 8.49±3.01 vs 10.44±3.33, p&lt;0.01; METs- 6.54±2.00 vs 7.83±1.2, p&lt; 0.01; time to 1 mm ST depression- 7.89±3.30 vs 9.03±2.82,p &lt;0.05 .Yet no significant decreasing of max ST depression in EST after TP in either group was observed. The assessment also included comparing the outcome of both forms of training finding no significant differences in the percentage changes in all parameters studied between the groups. No severe adverse events were reported during trainings. Conclusions 1.Both forms of interval training below and at ischemic threshold enhanced the physical capacity and had an anti-ischemic effect. 2.Interval training at ischemic threshold was an equally effective and safe form of rehabilitation as the training according to the current standards.
Response to Letter Regarding Article, “Facility Level Variation in Hospitalization, Mortality, and Costs in the 30 Days After Percutaneous Coronary Intervention: Insights on Short-Term Healthcare Value From the Veterans Affairs Clinical Assessment, Reporting, and Tracking System (VA CART) Program”
Authors: Steven M. Bradley, Colin I. O’Donnell, Gary K. Grunwald, Chuan-Fen Liu, Paul L. Hebert, Thomas M. Maddox, Robert L. Jesse, Stephan D. Fihn, John S. Rumsfeld, P. Michael Ho
Journal: Circulation (2016)
A phase II study of gemcitabine (G) and capecitabine (C) in advanced cholangiocarcinoma (CC) and gall bladder carcinoma (GBC)
Authors: R. V. Iyer, J. Gibbs, D. Lawrence, N. Soehnlein, B. Kuvshinoff, M. M. Javle
Journal: Journal of Clinical Oncology (2005)

4230 Background: CC and GBC are rare but lethal cancers. Although surgery can be curative, most patients are inoperable at diagnosis. Median survival with standard chemotherapy (CT) is 6 months. The goal of therapy is palliative, aimed at improving quality of life, pain and symptoms of biliary obstruction. The impact of CT on quality of life (QOL) in these patients is not reported. We performed a phase II study to determine the clinical benefit response [CBR= partial response (PR) + stable disease (SD)], time to tumor progression (TTP) and overall survival (OS) in patients with advanced CC and GBC treated with a combination of G +C as first line therapy and assessed the effect of CT on QOL, using the EORTC QLQ-C30-PAN 26. Methods: G (1000mg/m2) IV over 30-minutes was administered on days 1 and 8 and C was given orally (650mg/m2) twice a day for 14 days, both repeated every 21 days. Tumor response was measured using standard RECIST criteria. All patients filled QOL questionnaires on day 1 of each cycle. Cumulative QOL scores were calculated. The design was 2-stage for 17 patients to evaluate confirmed CR/PR (CRR) rate at 9 weeks. Results: Total of 12 patients with the following characteristics were enrolled: 11 CC and 1 GBC; median age 54 years (range 46–85 years), 5 males (42%) and 7 females (58%); ECOG PS 0 (n=4) or 1 (n=8). Median 8 cycles per patient (range 0 to 19 cycles) were completed. The 90% 1-sided confidence interval on the CRR was (0, 17%). The CBR based on best response [2PR (17%) + 5SD (42%)] was 59%. With median follow up of 8.6 months, median TTP was not reached. Due to limited number of deaths (4/12 patients), median OS was not reached. Median time to treatment failure (TTF) was 5.4 months with 3 patients still on treatment. 8/12 patients had either grade 3 or 4 toxicities. There were no treatment related deaths. Using a threshold of 5% above baseline to indicate decreased QOL, all patients with PR and 2/5 patients with SD had improved or stable QOL scores with G+C. Conclusions: G + C given in this dose and schedule is well-tolerated, effective and leads to QOL benefit for some patients with advanced CC and GBC. CBR may be a better endpoint to assess response in this disease. No significant financial relationships to disclose.
Why Michael Couldn't Hit, by Harold Klawans
Authors: O. Sacks
Journal: BMJ (1997)

Harold Klawans Macmillan, £17.95, pp 308 ISBN 0 716 73001 4

Harold Klawans is among the most versatile of contemporary neurologists–not only an eminent “straight” neurologist, author of scores of technical articles, and an editor of The Handbook of Clinical Neurology , he is also a graceful and witty writer who has given us several books of delightful clinical tales ( Toscanini's Fumble and Newton's Madness perhaps the best known) as well as a number of mystery novels and plays. In addition, as we see from his latest book, he is an ardent and keenly analytical sports fan as well (a trait he shares with another grand biologist-writer contemporary, Stephen Jay Gould).

The range of “true stories” in this new book is wide–baseballers, basketballers, boxers, runners, and golfers leap out of the pages, some his own patients, some weekend athletes, and some famous professional players–and the range of neurological or neuromedical conditions presented through them is equally great. Some of the conditions Klawans describes preceded an athletic career–acromegaly, Marfan's syndrome, and Tourette's syndrome among …
Treatment Outcomes in Stage I Lung Cancer
Authors: Varun Puri, Traves D. Crabtree, Jennifer M. Bell, Stephen R Broderick, Daniel Morgensztern, Graham A. Colditz, Daniel Kreisel, A. Sasha Krupnick, G. Alexander Patterson, Bryan F. Meyers, Aalok Patel, Clifford G. Robinson
Journal: Journal of Thoracic Oncology (2015)

The relative roles of surgery and stereotactic body radiation therapy in stage I non-small-cell lung cancer (NSCLC) are evolving particularly for marginally operable patients. Because there is limited prospective comparative data for these treatment modalities, we evaluated their relative use and outcomes at the population level using a national database.Patient variables and treatment-related outcomes were abstracted for patients with clinical stage I NSCLC from the National Cancer Database. Patients receiving surgery were compared with those undergoing stereotactic body radiation therapy (SBRT) in exploratory unmatched and subsequent propensity matched analyses.Between 1998 and 2010, 117,618 patients underwent surgery or SBRT for clinical stage I NSCLC. Of these, 111,731 (95%) received surgery, whereas 5887 (5%) underwent SBRT. Patients in the surgery group were younger, more likely to be males, and had higher Charlson comorbidity scores. SBRT patients were more likely to have T1 (versus T2) tumors and receive treatment at academic centers. Thirty-day surgical mortality was 2596 of 109,485 (2.4%). Median overall survival favored the surgery group in both unmatched (68.4 versus 33.3 months, p < 0.001) and matched analysis based on patient characteristics (62.3 versus 33.1 months, p < 0.001). Disease-specific survival was unavailable from the data set.In a propensity matched comparison, patients selected for surgery have improved survival compared with SBRT. In the absence of information on cause of death and with limited variables to characterize comorbidity, it is not possible to assess the relative contribution of patient selection or better cancer control toward the improved survival. Rigorous prospective studies are needed to optimize patient selection for SBRT in the high-risk surgical population.
Human Mena (hMena), estrogen receptor-β (ER-β), and epidermal growth factor receptor (EGFR) expression as prognostic factors in node-negative non-small-cell lung cancer (NSCLC)
Authors: E. Bria, M. Mottolese, I. Sperduti, P. Visca, B. Antoniani, F. Facciolo, E. Terzoli, F. Cognetti, P. Nisticò, M. Milella
Journal: Journal of Clinical Oncology (2009)

e22105 Background: hMena is a cytoskeleton regulatory protein involved in adhesion and cell motility, particularly in response to EGFR activation. In addition, a possible correlation between ER-β and EGFR expression has been recently suggested in NSCLC. We therefore investigated the potential relationship and prognostic value of hMena, ER-β, and EGFR expression in node-negative NSCLC patients (pts) who underwent surgery at our institution. Methods: hMena, ER-β (isoforms 1, 2), and EGFR expression, analyzed on Tissue Micro Array, were correlated to disease-free, cancer-specific, and overall survival (DFS/CSS/OS) using a Cox model including sex, stage, age, grading, histology, number of resected nodes (RN). Logistic and generalized linear models were used to evaluate predictors of significant Cox-model variables. Receiver Operative Curve (ROC) analysis identified optimal cutoff values. Internal cross-validation (100 simulations with 80% of the dataset) was accomplished. Results: 248 pts were gathered (median follow-up 26 months, range 1–75; male/female 71/29%; adeno/other 43/57%; grading G1–2/G3 45/55%; Stage I/II 82/8%; RN ≤10/&gt;10 34/66%). Multivariate analysis, highlighting the prognostic role of RN and hMena, is shown in the table . ER-β/2 and EGFR strongly predicted hMena overexpression (p=0.009, p=0.01); indeed, when hMena was removed from the multivariate model, both factors were independent predictors of DFS/CSS. Cross-validation analysis confirmed the prognostic role of hMena with a replication rate of 43/66% for DFS/CSS. Conclusions: hMena expression is prognostic in early NSCLC undergoing curative surgery. ER-β/2 and EGFR strongly correlate with hMena status and their prognostic role deserves further investigation. [Table: see text] No significant financial relationships to disclose.
SWOG S0709: Randomized Phase II Trial of Erlotinib versus Erlotinib Plus Carboplatin/Paclitaxel in Patients with Advanced Non–Small Cell Lung Cancer and Impaired Performance Status as Selected by a Serum Proteomics Assay
Authors: Primo N. Lara, James Moon, Paul J. Hesketh, Mary W. Redman, Stephen K. Williamson, Wallace L. Akerley, Fred R. Hirsch, Philip C. Mack, David R. Gandara
Journal: Journal of Thoracic Oncology (2015)
Quality-of-life assessment: performance status upstaged?
Authors: J Weeks
Journal: Journal of Clinical Oncology (1992)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1992.10.12.1827 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1453195 Quality-of-life assessment: performance status upstaged? J WeeksxJ WeeksSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.12.1827 First Page PDF © 1992 by American Society of Clinical Oncology
A phase I dose escalation and pharmacokinetic (PK) study of intravenous (iv) aflibercept (VEGF Trap) plus FOLFOX4 in patients (pts) with advanced solid tumors: Preliminary results
Authors: S. Limentani, R. Just, A. Purdham, M. Mulay, A. Bair, J. F. Tamby, L. I. Chap, L. S. Rosen
Journal: Journal of Clinical Oncology (2008)

3556 Background: Aflibercept (AF) is a recombinant fusion protein that is a potent inhibitor of vascular endothelial growth factor (VEGF). This study was designed to assess the safety/tolerability, dose-limiting toxicities (DLTs), recommended Phase II dose, and PK of AF + FOLFOX4. Methods: This combination trial explored escalating iv doses of AF followed by standard fixed FOLFOX4 regimen, every 2 weeks. Results: 32 pts (M/F 9/23, median age 59 [25–79], ECOG-PS 0/1: 11/21) were enrolled in 3 AF dose levels: 2.0 (n = 4), 4.0 (n = 18) and 5.0 (n = 10) mg/kg. Primary tumors were mostly gastro-intestinal (16, including 8 pancreas, 3 cholangiocarcinoma and 3 gastric), breast (5), ovarian (4), and others (7). Most (75%) pts were heavily pre-treated, with a median number of prior lines of 3[1–9]. Pts received a median number of 4.5 [1–20] treatment cycles (cy). During the dose escalation phase, no AF-related DLT (first 2 cy) was observed. Gr > 3 NCI-CTCAE v3.0 toxicity observed included: neutropenia (69%), thrombocytopenia (13%), hypertension (13%), proteinuria (13%), hemorrhagic events (9%, including one G5 hemorrhagic stroke at 4 mg/kg), febrile neutropenia (3%), deep vein thrombosis (3%). A G5 posterior leukoencephalopathy syndrome was reported at 5 mg/kg. Five partial responses were noted (pancreas, cholangiocarcinoma, colo-rectal; all at doses > 4 mg/kg) and 10 pts had stable disease. Free and bound AF drug concentrations in combination with FOLFOX4 are comparable to those observed with AF as monotherapy. At doses > 4 mg/kg, free AF exceeds bound AF over the dosing interval, suggesting sustained effective trapping of VEGF. Conclusions: AF 4 mg/kg combined with FOLFOX4 was selected for further investigations, based on activity, overall safety profile (consistent with that of other agents from the same class), and PK. Updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis
Phase II trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma
Authors: D. G. Perez, V. Suman, T. Amatruda, M. Gornet, R. Morton, S. Jilani, C. Constantinou, J. Egner, S. Markovic
Journal: Journal of Clinical Oncology (2007)

8560 Background: In patients with metastatic melanoma, the combination of chemotherapy with an agent that specifically targets vascular endothelial growth factor (VEGF) might be able to control tumor growth and progression much more effectively than chemotherapy alone. Methods: A two-stage phase II clinical trial was conducted in patients with unresectable stage IV melanoma to assess the anti-tumor activity and toxicity profile of the combination of paclitaxel (80 mg/m 2 IV on days 1, 8 and 15 of a 28-day cycle), carboplatin (AUC = 6 IV on day 1) and bevacizumab (10 mg/kg IV on days 1 and 15). The primary end point of the study was the 8-week progression-free survival rate (PFS). Enrollment to the second stage of the study was opened if 8 or more of the first 20 patients enrolled remained progression-free at 8 weeks. Eligible patients had measurable disease by RECIST criteria, a performance status (PS) of 0–2 and acceptable pre-registration organ function. Exclusion criteria included: brain metastases, significant recent bleeding, uncontrolled hypertension and ongoing anticoagulation. The study opened in February 2006 and completed full study accrual in August 2006. Data from the 20 patients enrolled in the first stage are presented here. Results: Patients (60% male) had a median age of 63 and had a good performance status (85% had PS of 0). M1c disease was present in 45% of patients and 35% had undergone previous chemotherapy for stage IV melanoma (50% prior immunotherapy). Only 6 patients did not complete more than 2 cycles of chemotherapy due to refusal (3), desire for alternative treatment (1) or progression (2). Median follow-up among the 15 patients still alive was 5.5 months (range: 6 weeks - 9 months). The 8-week PFS rate was 70% (14/20). The median time to progression was 163 days. One partial response was observed. There were 3 disease-related deaths at 65, 120 and 190 days post-registration. The most common toxicities were neutropenia (95%; 45% = grade 3), anemia (95%; 15% = grade 3), fatigue (90%; 5% = grade 3), leukopenia (85%; 25% = grade 3), and thrombocytopenia (75%; 5% = grade 3). Conclusions: The combination of paclitaxel, carboplatin and bevacizumab appears to be well tolerated and clinically active in patients with stage IV melanoma. No significant financial relationships to disclose.
Inferring the Effects of Cancer Treatment: Divergent Results From Early Breast Cancer Trialists’ Collaborative Group Meta-Analyses of Randomized Trials and Observational Data From SEER Registries
Authors: Katherine E. Henson, Reshma Jagsi, David Cutter, Paul McGale, Carolyn Taylor, Sarah C. Darby
Journal: Journal of Clinical Oncology (2016)

Purpose To compare the effect of breast cancer radiotherapy as estimated from observational data with findings from randomized trials. Materials and Methods Rate ratios were obtained for selected end points among 13,932 women randomly assigned to receive radiotherapy or not in trials contributing to recent meta-analyses by the Early Breast Cancer Trialists’ Collaborative Group. Estimates of the same quantities were derived for 393,840 women registered with breast cancer in the US SEER registries between 1973 and 2008. Results In the randomized trials, radiotherapy after breast-conserving surgery reduced mortality from both breast cancer (rate ratio, 0.82; 95% CI, 0.75 to 0.90) and all causes (rate ratio, 0.92; 95% CI, 0.86 to 0.99). Reductions of similar magnitude were seen in the trials of radiotherapy after mastectomy in node-positive disease (rate ratios, breast cancer 0.84; 95% CI, 0.76 to 0.94; all causes, 0.89; 95% CI, 0.81 to 0.97). In the observational data, radiotherapy after breast-conserving surgery was associated with much larger mortality reductions (rate ratios, breast cancer, 0.64; 95% CI, 0.62 to 0.66; all causes, 0.63; 95% CI, 0.62 to 0.65), whereas radiotherapy after mastectomy in node-positive disease was associated with substantial increases in mortality (rate ratios, breast cancer, 1.34; 95% CI, 1.31 to 1.37; all causes, 1.23; 95% CI, 1.22 to 1.25). Detailed adjustment of the observational data for potential confounders did not reduce the divergence from the randomized data. Conclusion This study of mortality after radiotherapy for breast cancer found strikingly divergent results between the Early Breast Cancer Trialists’ Collaborative Group meta-analyses of randomized data and the SEER observational data, even when efforts had been made to remove confounding and selection biases. Nonrandomized comparisons are liable to provide misleading estimates of treatment effects. Therefore, they need careful justification every time they are used.
A new mechanism of estrogen action in prostate cancer: Inhibition of tissue androgen production and prostate cancer growth by Estradiol in androgen independent prostate cancer xenografts
Authors: B. Montgomery, P. Nelson, D. L. Hess, R. Vessella, E. Corey
Journal: Journal of Clinical Oncology (2007)

15509 Background: Estrogens are effective agents in treating prostate cancer in patients in which serum androgens are already at ‘castrate‘ or anorchid levels. The mechanisms whereby estrogens inhibit ‘androgen-independent‘ prostate cancer are unclear. Methods: The androgen-independent human prostate cancer xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo pellets, 17β-estradiol (E2) slow-release pellets or E2 with the estrogen receptor antagonist ICI 182,780 as previously described (Clin Cancer Res 8:1003). Effects of E2 on tumor growth and tissue testosterone (T) and dihydrotestosterone (DHT) levels were evaluated by radioimmunoassay. Results: E2 significantly inhibited growth of androgen-independent LuCaP35V ( ∼35% inhibition at 4 weeks, p=0.0047, and increased survival of tumor bearing animals, (p trend =0.03) . The estrogen receptor antagonist ICI 182,780 did not block E2 inhibition of tumor growth, suggesting a receptor independent mechanism of tumor suppression. We then examined the effect of E2 on tissue T and DHT. E2 suppressed levels of tumor T and DHT in treated tumors. Tissue androgens in placebo treated LuCaP35V xenografts were; T=1.21 (± 0.18) pg/mg and DHT=3.54 (±1.07) pg/mg, and in E2-treated LuCaP35V T=0.23 (±0.09) pg/mg and DHT =0.44 (±0.14) pg/mg, (p&lt;0.001). Levels of T and DHT in control liver tissue from both placebo and E2-treated animals were equivalent, at less than 0.2 pg/mg. Conclusions: We have shown that E2 inhibits growth of the androgen- independent human prostate cancer xenograft LuCaP35V, and that this inhibition is estrogen receptor independent. E2 significantly suppressed tumor tissue T and DHT suggesting a new mechanism of E2 mediated growth inhibition of androgen independent prostate cancer, potentially through inhibition of tumoral steroidogenesis. This model of ‘intracrine‘ tumor androgen production can be used to evaluate other inhibitors of tissue steroidogenesis. No significant financial relationships to disclose.