tbuckley/cabot-search huggingface dataset:
Ifosfamide or trofosfamide in patients with intraocular lymphoma: Final report
Authors: K. Jahnke, A. Korfel, N. E. Bechrakis, G. Willerding, D. F. Kraemer, L. Fischer, E. Thiel
Journal: Journal of Clinical Oncology (2008)

2030 Background: This abstract reports the long-term results of intraocular lymphoma (IOL) patients treated with ifosfamide (IFO) or trofosfamide (TRO). Methods: We previously reported the efficacy of intravenous IFO and oral TRO in a single center prospective study on 10 patients with IOL. IFO was given at a dose of 1,500 (≥65 years) or 2,000 (<65 years) mg/m²/day on days 1–3 and TRO at a dose of 150 and 400 mg/day (continuous or intermittent administration). Remission rate, progression-free survival (PFS), overall survival (OS) and long-term toxicity were evaluated in this follow-up analysis. Results: All patients responded to first treatment with IFO or TRO, including nine complete remissions and one partial remission. Median PFS from the first treatment with IFO or TRO was 18 (range, 7–36) months. Seven patients relapsed: five in the eye and two in the brain. Four patients were retreated with IFO or TRO on relapse, three of whom responded. Median OS was 32 (range, 7–37+) months. Acute toxicity was mainly hematologic. No long-term toxicity was observed in patients treated with IFO or TRO alone. Conclusions: Response rates to IFO and TRO are high with tolerable toxicity. Combination treatment of IFO/TRO with other cytostatics is warranted to improve long-term disease control. No significant financial relationships to disclose.
PDL1, PDL2, and CD8+ TIL expression in ovarian carcinosarcoma.
Authors: Wei Peng, Rong Jiang, Xiaohua WU, Ziting Li, Min Sun, Baohua Yu, Amita Patnaik, Rongyu Zang
Journal: Journal of Clinical Oncology (2015)

e16595 Background: Ovarian carcinosarcoma is a rare malignant gynecologic tumor and usually presented with progressive disease at initial diagnosis. Chemotherapy is the mainstay treatment for patients with inoperable or metastatic disease whereas the efficacy is limited. Immune checkpoint blockade inhibitors-anti-PD1/anti-PD-L1 mAbs have achieved remarkable success in treating various types of malignant tumors and PDL-1 was characterized as a valuable marker to predict the treatment outcome. We hypothesized that PD-L1 and other relevant markers expressed in ovarian carcinosarcoma may guide the Immune checkpoint blockade therapy for this disease, thus, we sought to investigate the expression of PD-L1, PD-L2 and CD8+ TIL in ovarian carcinosarcoma using IHC. Methods: Protein expression of PD-L1, PD-L2 and CD8+ TIL on tumor samples (primary or recurrent) obtained from 25 patients with ovarian carcinosarcoma were characterized by IHC. Staining was considered positive when staining was present in 5% or more of the tumor cells. Results: Each parameter was tested in 26 samples, 16 of which were of primary and 10 were of recurrent (one patient had both primary and recurrent samples). For PD-L1, 22 were positive (22/26, 84.6%) and 4 (4/26, 15.5%) were negative; For PD-L2, 20 (20/26, 76.9%) were positive and 6 (6/26, 23.1%) were negative; All the samples were CD8+ TIL positive. 15 (15/16) of the primary samples and 7 (7/10) of the recurrent samples were PD-L1 positive, respectively, (15/16 vs 7/10, p= 0.1025, Chi-square test). 11 (11/16) of the primary samples and 9 (9/10) of the recurrent samples were PD-L2 positive, respectively, (11/16 vs 9/10, p= 0.2109, Chi-square test). Conclusions: PD-L1, PD-L2 and CD8+ TIL were highly expressed in ovarian carcinosarcoma and may be indicative of applying anti-PD-1/PD-L1 mAbs for the treatment of this disease.
Preoperative imatinib for locally advanced gastrointestinal stromal tumors (GIST): CONVERT trial.
Authors: Bruno Dos Santos Vilhena Pereira
Journal: Journal of Clinical Oncology (2015)

130 Background: Primary GISTs are frequently diagnosed as large masses requiring wide resections. Our primary objective is to evaluate response rate of imatinib through RECIST and Choi criteria in these patients. Secondary endpoints were downstaging, resectability, safety and tolerability. Methods: This phase II Brazilian study was conducted in 7 centers between 2008 and 2012. To standardize elegibility, inclusion criteria took into account the primary site, size and multi-visceral resection need per surgeon evaluation. Thirty-nine non-metastatic GIST patients with measurable disease and no previous systemic or local treatment were assigned to daily imatinib 400mg for 16 weeks followed by surgery or until medical decision, progressive disease or toxicity. Imatinib could be continued whether adjuvant or palliative according to risk stratification and residual disease. Clinicaltrials.gov NCT01483014. Results: The objective response rate was 32,1% (IC95% 17,9% - 50,7%) on RECIST and 78,6% (IC95% 60,5% - 89.8%) on Choi. One patient (3,8%) had progressive disease, six patients (20%) had serious adverse events with two (6,7%) deaths, not related to the study drug. Treatment discontinuation due to intolerance was observed in 10% of patients caused by extremities pain, nausea, neutropenia, constipation and thrombocytopenia. Surgery was performed on 23 patients (82.1%), with 83,3% being R0. Median tumor size was 9,4cm (1,2 to 22,0cm) and 72,7% had &lt;5 mitosis/50HPF. Conclusions: Imatinib is active and safe in the preoperative setting. Although Choi criteria evaluates responses earlier, a longer course of imatinib, from 6 to 12 months, should be studied to evaluate if longer courses can increase tumor shrinkage and improve this strategy’s usefulness. Clinical trial information: NCT01483014.
A phase I study of CD40 agonist monoclonal antibody (CP-870,893) with gemcitabine in pancreatic cancer.
Authors: G. L. Beatty, E. G. Chiorean, D. A. Torigian, U. R. Teitelbaum, W. Sun, K. D. Fly, R. D. Huhn, R. H. Vonderheide, P. J. O'Dwyer
Journal: Journal of Clinical Oncology (2010)

2539 Background: CP-870,893 is a fully human CD40 agonist monoclonal antibody that activates antigen presenting cells, triggers the release of inflammatory cytokines, and enhances antitumor cellular immunity. In preclinical models chemotherapy enhances the antitumor effect of anti-CD40 immunotherapy by facilitating tumor antigen release. A phase I study was conducted to investigate the safety of CP-870,893 administered in combination with gemcitabine for patients with chemotherapy-naïve pancreatic adenocarcinoma. Methods: Patients with ECOG PS 0-1 were treated with gemcitabine (1000 mg/m2) i.v. on days 1, 8, and 15 of a 28-day cycle with escalating doses (0.1 or 0.2 mg/kg) of CP-870,893 given i.v. on day 3 of each cycle. Patients were monitored for toxicity, clinical response including FDG-PET/CT, and modulation of immune parameters. Results: DLTs were observed in 0 of 3 pts at 0.1 mg/kg and 0 of 6 pts at 0.2 mg/kg. The MTD/RP2D was defined as 0.2 mg/kg. The most common AE was transient cytokine release syndrome (grade 1-2). In the MTD expansion cohort (n=6) at 0.2 mg/kg, there was 1 DLT (nonfatal CVA). Analysis of plasma cytokines demonstrated increased IL-6, IL-10, TNF-alpha, and IL-12 after treatment consistent with immune activation. Changes in CA19-9 were evaluable in 13 patients, with 6 patients (46%) demonstrating a >50% decrease from baseline. There were 2 PRs (14%), 8 SDs (57%), and 4 PDs (29%). One pt with a PR remains on study after 13 months of treatment. Three patients with SD were evaluated with FDG-PET/CT imaging. Decreases in SUVmax were observed in the primary pancreatic lesion (decrease of 28-78%) as well as target metastatic lesions (decrease of 11-28%) of each patient, suggesting the utility of PET imaging for evaluating disease response to chemoimmunotherapy. Conclusions: Combined CP-870,893 and gemcitabine is well- tolerated and active in patients with pancreatic cancer. FDG-PET/CT identified metabolic responses both in the primary and in metastases in patients defined as having stable disease by RECIST. Further investigation of this combination in pancreatic cancer is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer
Randomized clinical trials in oncology stopped early for benefit (RCTSEB)
Authors: E. Segota, H. P. Soares, B. Djulbegovic, A. Kumar, D. Bassler, G. H. Guyatt
Journal: Journal of Clinical Oncology (2006)

6039 Background: Randomized clinical trials (RCT) that stop earlier than planned because of apparent benefit often receive great attention. However, how often these early results get confirmed by other subsequent meta-analysis/randomized studies, and how often results get included in clinical guidelines is not known. We conducted systematic review of oncologic RCTSEB to further determine if the results from RCTSEB are confirmed by the subsequent studies and/or included in guidelines. Methods: RCT of any intervention reported as having stopped early because of the results favoring the intervention were previously identified (JAMA.2005;294:2203).Trials with interventions in prevention and treatment of solid and hematologic malignancies were included for this review. Citation search was conducted by two reviewers to identify meta-analysis (MA), systematic reviews (SR) and RCTs that used similar trial design as the RCTSEB. National Comprehensive Cancer Guidelines were reviewed to identify the impact of the results on recommendations on clinical practice. Results: 33 trials were identified, and 5 were excluded because they did not fit the inclusion criteria. MA/SR were available for the assessment of interventions reported in 15/28 RCTSEB. Results of subsequent MA confirmed 12/15 findings, while 3 trials were contradicted. Of the remaining 13 trials, for 7 there was at least one subsequent RCT identified. 6/7 were confirmed as beneficial in the subsequent RCTs and 1 was contradicted. For 6/28 RCTSEB we did not find any subsequent MA/SR/RCTS. We also looked at the inclusion of interventions from RCTSEB in the clinical guidelines. 18/28 interventions from RCTSEB were mentioned in the formulation of clinical guidelines.16/18 were recommended as true positive recommendations. The other 2 interventions which were addressed in the guidelines were either not confirmed (n = 1) or incorrectly recommended (n = 1). Conclusions: In this set of oncology of RCTSEBs the findings were subsequently confirmed in 64% (18/28) cases. Guidelines developers used 2/28 (7%) of RCTSEB for which reliable confirmatory data were available. However, caution should be applied in the interpretation of our results because the same RCTSEB was also included in confirmatory MAs which possibly could have introduced bias. No significant financial relationships to disclose.
A practice-based, voluntary program for promoting excellence in cancer care: A pilot study of feasibility, cost and preliminary results
Authors: C. E. Desch, P. Eisenberg, D. Gesme, J. Jacobson, M. Jahanzeb, M. Neuss, J. Padberg, J. Rainey, J. Simone
Journal: Journal of Clinical Oncology (2004)

6029 Background: Many forces are pressing for the quality of cancer care to become more than a platitude. These include reports from the Institute of Medicine, employers seeking value, and managed care selecting “quality” practices. If oncologists do not take leadership in this arena, others will do so. The basic premise of this project is that a permanent quality improvement process must occur at the patient-caregiver interface. Methods: Seven practices of 5–35 oncologists from across the U.S. were invited to serve as the first (Alpha) group to devise the measures of quality. Quality measures were derived from ASCO guidelines, published treatment guidelines, and elements considered vital to excellent practice by experienced oncologists. Local data managers and nurses were involved in the design and planning. Each practice collected data from 50 consecutive charts and entered data online over a 2-week period. Data were analyzed for each practice and returned with mean and standard deviation scores for all 7 participants. HIPAA and IRB concerns were addressed. Four months later, a similar survey with revisions and operational enhancements were measured in 395 charts in the same practices. Each practice and the coordinating center estimated costs. Results: All 7 practices submitted the data on time. Participating physicians volunteered their time, and the cost of staff time per practice per chart review averaged $500. Data presented will show examples of concordance and variation in adherence to ASCO guidelines on growth factors and antiemetics, as well as measures related to practice operations (treatment consent, staging and pathology documentation) among others (Table). How practice changed after receiving their “report card” will also be shown. Conclusion: A practice-based quality improvement model is feasible, cost-effective, and scalable. No significant financial relationships to disclose.
Abstract 11197: Comparison of Long-Term Survival According to the Presence of Metabolic Syndrome in Patients With Acute Myocardial Infarction After Successful Percutaneous Coronary Intervention With Drug-Eluting Stents
Authors: K-Bum Won, Byeong-Keuk Kim, Hyuk-Jae Chang, Dong-Ho Shin, Jung-Sun Kim, Young-Guk Ko, Donghoon Choi, Jong-Won Ha, Myeong-Ki Hong, Yangsoo Jang
Journal: Circulation (2013)

Introduction: Despite the significance of coronary reperfusion in AMI, the prognostic impact of MS has been investigated under inconsistent reperfusion therapy in AMI patients. Hypothesis: We evalu...
Interim results from a dose-escalation study of the BCL-2 inhibitor venetoclax (ABT-199/GDC-0199) plus bendamustine (B) and rituximab (R) in patients (pts) with relapsed/refractory (R/R) Non-Hodgkin’s Lymphoma (NHL).
Authors: Sven De Vos, Christopher Flowers, Ding Wang, Lode J. Swinnen, Nathan Hale Fowler, Erin G. Reid, Jaclyn Cordero, Maryella Gifford, Diane D'Amico, Martin Dunbar, Ming Zhu, Ahmed H. Salem, Sari H. Enschede, Justin L. Ricker, David Chien, Rod Humerickhouse, Mark Kozloff
Journal: Journal of Clinical Oncology (2015)

8535 Background: Venetoclax (VEN) is a selective, potent, orally bioavailable BCL-2 inhibitor that has shown single agent activity in R/R NHL. The current study evaluates VEN with BR, an active regimen widely used for NHL. Methods: Objectives were safety, PK, preliminary efficacy, MTD, and recommended Phase 2 dose. Dose escalation (DE) used a 3+3 design on a 28 day (d) cycle (C) with 3 VEN (50–400 mg) schedules: 3, 7, and 28 d/C. The BR regimen was 6 C: B (2 d/C, 90mg/m2) and R (1 d/C, 375mg/m2). DLTs for DE were assessed during C1. Responses were first assessed on C3 d1. Pts who completed VEN + BR with continued tolerability and without disease progression could continue VEN monotherapy up to 2 yrs. Results: As of 1/9/15, 33 were treated: 20 (61%) FL, 10 (30%) DLBCL, and 3 (9%) MZL. Median age was 62 (29-90) yrs. All had prior R or R-combination, of which 32 (97%) had R-based chemotherapy and 8 (24%) had prior B or BR. 16 (48%) pts are active; 17 discontinued (12 PD, 2 AE, 1 each withdrew consent, non-compliance, pt decision). Median time on study was 90 d (1–876); 15 (45%) completed 6 C of the combination. The most common AEs (in >25%) were nausea (58%), anemia, neutropenia (each 42%), thrombocytopenia, diarrhea (each 39%), hyperglycemia (36%), and vomiting, hypokalemia, fatigue (each 27%). The most common gr 3/4 AEs (in >10%) were neutropenia (30%), leukopenia, thrombocytopenia, lymphopenia (each 21%), and anemia (18%). The most frequent SAE was febrile neutropenia (9%). There were no drug-related AEs that led to death. Co-administration of BR did not significantly impact VEN PK. 29 pts had ≥1 assessment: 6 (21%) CR and 13 (45%) PR. The ORR was 66% in all pts and 74% in pts with FL. Conclusions: Preliminary data demonstrate a tolerable safety profile of VEN + BR. Early responses were seen across all cohorts. Cohort 9 is enrolling at 600 mg 28 d/C. Clinical trial information: NCT01594229. Cohort 1 2 3 4 5 6 7a 8a Pts, n 4 4 4 3 3 4 5 6 VEN, mg 50 100 100 100 200 200 400 400 Schedule, d/C 3 3 7 28 28 7 7 28 DLTs, n Thrombocytopenia 1 Febrile neutropenia 1 Stevens-Johnson Syndromeb 1 aPost-amendment to G-CSF prophylaxis and DLT criteria; bPrimary reasonable possibility due to allopurinol; pt discontinued.
Calcium-regulated protein tyrosine phosphorylation is required for endothelin-1 to induce prostaglandin endoperoxide synthase-2 mRNA expression and protein synthesis in mesangial cells.
Authors: E J Coroneos, M Kester, J Maclouf, P Thomas, M J Dunn
Journal: Journal of the American Society of Nephrology (1997)

The role of endothelin (ET)-1-mediated cytosolic calcium ([Ca2+]i) elevation in regulating ET-1-induced prostaglandin endoperoxide synthase, prostaglandin G/H synthase (PGHS)-2 mRNA expression and protein synthesis was investigated in mesangial cells (MC). Ionomycin, a calcium ionophore, and thapsigargin, an inhibitor of calcium ATPase, mimicked the ET-1-stimulated PGHS-2 mRNA and protein induction. Inhibition of [Ca2+]i increases with (2-¿C2-bis-(carboxymethyl)-amino-5 methylphenoxy]methyl¿-6-methoxy-8-bis-(carboxymethyl)-aminoquinoline tetra-(acetoxymethyl)ester (Quin/AM), a calcium chelator, or with the combined presence of [8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate, HCl] (TMB), an inhibitor of intracellular calcium stores release, and ethyleneglycol-bis-(beta-aminoethyl)- N,N,N',N'-tetra-acetic acid (EGTA) suppressed ET-1, as well as ionomycin and thapsigargin-mediated PGHS-2 mRNA and protein formation. Also, the ET-1-, ionomycin-, and thapsigargin-induced PGHS-2 mRNA expression and protein formation was inhibited in MC pretreated with inhibitors of calcium calmodulin kinase. In contrast, these conditions did not inhibit interleukin (IL)-1-induced PGHS-2 mRNA expression and protein synthesis. Pretreatment with tyrosine kinase inhibitors abolished the ET-1-, ionomycin-, thapsigargin-, and IL-1-mediated PGHS-2 mRNA and protein induction. ET-1-, ionomycin-, and thapsigargin- induced protein tyrosine phosphorylation, but not IL-1-induced protein tyrosine phosphorylation, was suppressed by inhibiting either [Ca2+]i elevation or calcium calmodulin kinase activation. It was concluded that elevation of [Ca2+]i and activation of calcium calmodulin kinases are upstream mediators of ET-1-induced PGHS-2 gene expression through activation of non-receptor-linked protein tyrosine kinase in MC.
Commentary 2 "Metabolic equivalents during the 10-m shuttle walking test for post-myocardial infarction patients"
Authors: Sally Singh
Journal: British Journal of Sports Medicine (2008)

One of the key aims of a cardiac rehabilitation programme is to promote an active lifestyle. Walking is arguably the most convenient form of exercise for many, and within the context of a rehabilitation programme it is cheap and transferable to a home exercise programme. It is important to assess an individual’s exercise capacity before starting an exercise programme for a number of reasons—to identify peak exercise performance for appropriate exercise prescription, safety …
Abstract 13719: Incidence of Exercise Oscillatory Ventilation in a General Population at Cardiovascular Risk: Insights From the EURO(pean) EX(ercise) Population-Based Study
Authors: Marta Pellegrino, Greta Generati, Francesco Bandera, Eleonora Alfonzetti, Valentina Labate, Marco Guazzi
Journal: Circulation (2014)

Introduction: Among exercise-derived variables that define cardiovascular (CV) risk, oxygen consumption (VO2) is an established one. Gas exchange analysis allows to define ventilator and metabolic parameters that increase the amount of evidence for characterizing the levels of risk.

Hypothesis: We aimed at assessing the exercise gas exchange analysis phenotype in the general population at risk for CV disease enrolled in the EUROEX study.

Methods: 442 asymptomatic subjects enrolled in the EURO EX trial, (mean age 60±14 years; male 49.3%; BMI 28±5.5 kg/m2) with different CV risk factors (hypertension 66%, dyslipidemia 50.2%, smoking habit 19.2%, diabetes 15.4%) underwent a maximal cardiopulmonary exercise testing with personalized ramp protocol.

Results: In this population, 72 subjects (16.3%) exhibited an oscillatory gas exchange pattern as an unexpected finding. Subjects with exercise oscillatory ventilation (EOV) showed a reduced tolerance to exercise (lower peak VO2, % of predicted VO2, peak O2 pulse and delta VO2/delta WR), a worse ventilatory efficiency (steeper VE/VCO2, lower end tidal CO2) and an impaired response of heart rate to maximal exercise and recovery (reduced peak HR and HRR).

Conclusions: Our data show for the first time, that EOV, typical of heart failure populations, may also occur in healthy individuals in a meaningful percentage of cases. For the same rate of CV risk factors and demographic characteristics, these patients exhibit a lower performance, a worse ventilatory efficiency and an impaired HR reserve and recovery. These findings may provide the bases for a more in-depth definition of abnormal exercise phenotypes worth of consideration.

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QTIPs: Questionable theoretical and interpretive practices in social psychology
Authors: Mark J Brandt, Travis Proulx
Journal: Behavioral and Brain Sciences (2015)

One possible consequence of ideological homogeneity is the misinterpretation of data collected with otherwise solid methods. To help identify these issues outside of politically relevant research, we name and give broad descriptions to three questionable interpretive practices described by Duarte et al. and introduce three additional questionable theoretical practices that also reduce the theoretical power and paradigmatic scope of psychology.
Coevolution of the glucose dehydrogenase gene and the ejaculatory duct in the genus Drosophila.
Authors: D R Cavener
Journal: Molecular Biology and Evolution (1985)

The glucose dehydrogenase gene (Gld) in Drosophila melanogaster exhibits a unique spatial and temporal pattern of expression. GLD expression switches from a non-sex-limited state at the pupal stage to a male-limited state at the adult stage. At the adult stage, the enzyme is restricted to the ejaculatory duct. Within the genus Drosophila, the ejaculatory duct has undergone a simple morphological divergence. In order to determine whether correlated changes in GLD expression had occurred, GLD activity during the pupal and adult stages was determined for several Drosophila species. It was found that virtually all of the species exhibit pupal GLD activity, whereas only those species with an expanded ejaculatory duct express male-limited GLD. The results of interspecific genital imaginal disc transplantation experiments indicate that the expanded morphology and GLD expression do not require any species- or sex-specific diffusible factors. An apparent regulatory polymorphism exists within the D. takahashii species with respect to male-limited GLD expression.
Everolimus (Eve) Treatment for Advanced G1-G2 Neuroendocrine Tumours (Nets) in the Community Setting: Clinical Benefit Irrespective of Grade or Primary Tumour Site
Authors: None Custodio, P. Jimenez Fonseca, V. Alonso-Orduna, C. López, T. Alonso Gordoa, G. Crespo, A. Carmona-Bayonas, C. Álvarez-Escolá, E. Polo, M. Mangas, R.G. Herrera Gómez, M.D.P. Solís Hernández, R. Jimeno, P. Reguera, S. Ayuela, R. Madero, E. Burgos, E. Grande, J. Feliu, J. Barriuso
Journal: Annals of Oncology (2014)
Pleural Biopsy in Diagnosis of Thoracic Disease
Authors: G. Hanson, T. Phillips
Journal: BMJ (1962)

In the July issue of The Clhiropodist, the journal of the Society of Chiropodists, members are urged not to keep silent on the subject of their patients' footwear.The editorial says, " Should a chiropodist refuse to give more than a single treatment to corns which are produced by bad footwear?
Functional Activity of Ehrlich Carcinoma Cancer Stem Cells After Treatment By Orthovanadate-Based Nanoparticles
Authors: A.N. Goltsev, O.V. Chelombit'ko, N.N. Babenko, Y.A. Gayevskaya, T.G. Dubrava, N.A. Bondarovich, M.V. Ostankov, A.Y. Dimitrov, V.K. Klochkov, N.S. Kavok, Y.V. Malyukin
Journal: Annals of Oncology (2014)