tbuckley/cabot-search huggingface dataset:
Development of risk groups in metastatic castration-resistant prostate cancer (mCRPC) to facilitate the identification of active chemotherapy regimens
Authors: A. J. Armstrong, S. Halabi, I. F. Tannock, D. J. George, R. DeWit, M. Eisenberger
Journal: Journal of Clinical Oncology (2009)

5137 Background: Our aim was to develop and validate clinically applicable predictive factors for a &gt;30% PSA decline 3 months following chemotherapy initiation, and to assess the performance of a risk-group based classification in predicting PSA declines and overall survival (OS) in men receiving chemotherapy for mCRPC. Methods: In TAX327, 1006 men with mCRPC were randomized to receive docetaxel (D) in two schedules, or mitoxantrone (M), each with prednisone: 989 provided data on PSA decline at 3 months. Predictive factors for a &gt;30% 3-month decline in PSA levels were identified using multivariate logistic regression in D treated men (n = 656) and validated in M treated men (n = 333). Risk factors were combined to form risk groups to predict PSA declines, OS, tumor, and pain responses. Prostate Cancer Working Group (PCWG2) disease states were evaluated for these outcomes in docetaxel treated men. Results: In multivariate analysis, four independent risk factors predicted for absence of &gt;30% decline in 3-month PSA: significant baseline pain (OR 0.63 p = 0.02), visceral metastases (OR 0.66, p = 0.03), anemia (hemoglobin &lt;13 g/dl, OR 0.72 p = 0.07), and bone scan progression at baseline (OR 0.60 p = 0.009). Predictive accuracy was moderate with a concordance index (c-index) of 0.61. Risk groups (good, intermediate, poor) were developed with median OS of 25.7 (95% CI 23.3–28.6), 18.7 (17.3–19.7), and 12.8 (11.5–14.6) months, respectively (p &lt; 0.0001), and &gt;30% PSA decline in 78, 66, and 58 percent of men (p &lt; 0.001). In the validation M cohort, similar trends for PSA declines and OS were noted across risk groups (OS 22.5, 16.0, 11.8 mo, p &lt; 0.001). PCWG2 subtypes (node only, bone metastatic, and visceral disease), were also highly prognostic and predictive but did not predict OS as well as the TAX327 risk groups (c-index 0.56). Conclusions: Risk groups have been identified and internally validated that predict PSA decline and OS in men with mCRPC. This classification may facilitate evaluation of new regimens of systemic therapy that warrant definitive testing in comparison to docetaxel and prednisone in phase III trials. Prospective validation of these risk groups is needed. [Table: see text]
Hepatitis B Reactivation in the Chronic Myeloid Leukemia Patient Treated with Imatinib Mesylate
Authors: Kazutaka Ozeki, Yoshihisa Morishita, Tomohiko Suzuki, Koji Umemura, Yohei Yamaguchi, Shotaro Tatekawa, Koichi Watamoto, Keiji Ozeki, Akio Kohno
Journal: Annals of Oncology (2014)
Outcomes for patients with anaplastic astrocytomas treated with radiation and temozolomide (TMZ) and maintenance TMZ.
Authors: R. M. Sheth, S. A. Grimm, A. Rademaker, I. B. Helenowski, J. J. Raizer
Journal: Journal of Clinical Oncology (2011)

e12511 Background: The optimal treatment regimen for patients with anaplastic astrocytomas (AAs) is not defined. Patients are treated at diagnosis with Radiation Therapy, Chemotherapy or similar to GBM with chemoradiation. Studies are underway to determine the optimal treatment for AA. We did a retrospective review of our patients with AA treated with the Stupp regimen to assess TTP and OS. Methods: We reviewed our database for patients diagnosed with an anaplastic glioma between 8/1/2003-6/15/2010 who were treated with chemoradiation followed by maintenance chemotherapy. Inclusion criteria were age > 18 yrs, newly diagnosed with no prior treatment and sufficient data/follow up. Those without sufficient data were excluded. Data was analyzed to determine PFS, TTP and OS. Results: There were 28 pts identified (14 M and 14 W) with a median age of 45 yrs (24-76) and KPS of 90 (70-100). All patients were treated with chemoradiation, 2 received arsenic trioxide during RT and 1 received bevacizumab during the maintenance phase of TMZ. Pathology was 23 AA, 3 AOA, and 2 with anaplastic glioneuronal tumor. Resection was as follows: GTR 25%, STR 57% and Biopsy 18%. Median # of cycles was 10.5 (0-24). The median time to progression was 18. 5 m and PFS-6, 12 and 24 was 96.1%, 73.1%, and 51.6%. Median OS was 34.4 m with OS at 12, 24 and 60 m of 92%, 63% and 53.2%. Conclusions: There is no standard treatment for AA’s. Treating with the Stupp regimen is one option but how it compares to other regimens is unclear. Our data appear comparable to that of NOA-04 where pts were initially treated with chemotherapy or RT at diagnosis.
EGF105084, a phase II study of lapatinib for brain metastases in patients (pts) with HER2+ breast cancer following trastuzumab (H) based systemic therapy and cranial radiotherapy (RT)
Authors: N. U. Lin, V. Dieras, D. Paul, D. Lossignol, C. Christodoulou, D. Laessig, H. Roché, D. Zembryki, C. R. Oliva, E. P. Winer
Journal: Journal of Clinical Oncology (2007)

1012 Background: CNS disease is a major problem among pts treated with H for stage IV HER2+ breast cancer with a reported incidence of 28–43%. This study was designed to characterize further the activity reported with lapatinib in an initial phase II trial in women with HER2+ disease metastatic to brain (Lin et al ASCO ‘06). Methods: Eligible pts had HER2+ breast cancer, prior H therapy and cranial RT, ECOG PS 0–2, and radiographic evidence of progressive brain metastases with at least one measurable (LD = 10mm) brain lesion. Pts received lapatinib 750 mg PO BID. Brain MRIs were obtained at 3.0 mm slices without gaps in the axial dimension. The primary endpoint was CNS response as defined by a = 50% volumetric (vol) reduction of CNS lesions in the absence of: new lesions, need for increased dose of steroids, progressive neurological signs/symptoms (NSS), or progressive extra-CNS disease. CNS disease progression was defined as either a = 40% vol increase from nadir, increase in steroid requirements, or progression of NSS. Results: The study exceeded its accrual goal of 220 pts in &lt; 1 year; 238 pts were enrolled from Jan-Nov 06. Preliminary data from the initial 104 pts have undergone independent radiology review. 8 pts (7.7%) met vol criteria for partial response with a median absolute vol reduction of CNS disease of 3.6 cm3 (range 0.4 to 29.7 cm3). Exploratory analysis revealed that 17 of the initial 104 pts (16.3%) experienced a = 20% vol reduction of CNS disease with a median absolute vol reduction of 3.3cm3. The median time to vol progression in these 17 pts was 16 wks (range 12 -24 wks). Analysis of efficacy and tolerability based upon protocol defined criteria from all 238 pts will be presented. Conclusions: Preliminary data from this large multicenter trial provides evidence that lapatinib has activity based on vol reductions in pts with progressive HER2+ CNS disease following prior H-based systemic therapy and cranial RT. Definitive conclusions will be based on the entire database. Additional studies are warranted incorporating lapatinib in combination with other therapies and/or in a less refractory setting to optimize its use in HER2+ CNS disease. [Table: see text]
Treosulfan high dose therapy with autologous stem cell rescue in high-risk Ewing tumors
Authors: U. Dirksen, C. Lanvers-Kaminski, A. Ranft, A. Bremer, J. Boos, H. Jürgens
Journal: Journal of Clinical Oncology (2007)

10039 Background: High dose (HD) chemotherapy using a busulfan-containing regimen has been proven advantageous for some high risk Ewing tumor (ET) patients. HD busulfan is not compatible with radiotherapy to central axis sites. Treosulfan is a bifunctional alkylating agent, structurally related to busulfan, that has shown to be safe even in heavily pretreated patients and patients at risk to treatment related toxicity. Methods: In vitro: In order to compare the cytotoxicity of busulfan and treosulfan, growth inhibition was tested by a modified (4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium-bromide (MTT) assay. In vivo: 11 patients with primary disseminated ET and contraindication for busulfan HD treatment and 11 patients with relapsed ET were referred to HD treosulfan (36 g/m 2 ) and melphalan (140 mg/m 2 ) followed by autologous stem cell rescue. Results: In vitro: Busulfan and treosulfan were cytotoxic in a time and dose dependent manner. Treosulfan was 15-fold more cytotoxic compared to busulfan. In vivo: The median age in patients with disseminated ET was 14.3 years, in relapsed ET 22.7 years. Sex distribution was equal. Response status prior to HD treosulfan was: stable disease in 4, partial response in 6, complete remission in 8, progressive disease in 1, not documented in 3 patients. Median follow up time in patients with disseminated ET was 0.91 years. All patients are alive. Four patients have relapsed within 2 years after HD treatment. Median follow up time in relapsed ET was 1.35 years. Seven patients are in remission, one patient is under treatment and two patients have died after relapse. HD was well tolerated with mucositis °3 in seven, °4 in three, stomatitis °3 in four, °4 in three , neutropenic infection °3 in three and reversible myelitis in one patient. Conclusions: Treosulfan HD treatment is a feasible therapeutic option without overt acute toxicity for patients with advanced ET. Efficacy and late effects remain to be evaluated. No significant financial relationships to disclose.
Phase II study of docetaxel in combination with oxaliplatin in patients with metastatic or locally advanced esophagogastric cancer previously untreated with chemotherapy for advanced disease. Results of the CECOG-Study ESGAS.1.2.001
Authors: M. Hejna, J. Zacherl, A. Ba-Ssalamah, A. Püspök, U. Pluschnig, T. Brodowicz, C. C. Zielinski, M. Raderer
Journal: Journal of Clinical Oncology (2007)

4527 Background: A phase II trial was performed to determine the antitumor efficacy and tolerance of combined docetaxel and oxaliplatin in previously untreated, advanced patients with gastroesophageal adenocarcinoma. Methods: Thirty-six patients with histologically confirmed advanced gastroesophageal adenocarcinoma were entered in this trial. Treatment consisted of 3-weekly courses of docetaxel 80 mg/m 2 and oxaliplatin 100 mg/m 2 both given on day 1. A 5-day course of human granulocyte colony stimulating factor (G-CSF) 5 μg/kg/day was given subcutaneously to prevent neutropenia; in addition, if haemoglobin was &lt;12.0 mg/dl, erythropoietin 10,000 IU was administered subcutaneously 3 times per week. Primary objective was to evaluate the time to progression. Results: The confirmed overall response rate was 36%, including 3 complete responses (8.3%) and 10 partial responses (27.7%). Fifteen patients (41.7%) had stable disease and 8 (22.3%) progressed while on treatment. The median time to response was 2.5 months, the median time to progression was 5.3 (1- 33+) months and the median overall survival time was 9.8 (2.5–35+) months with 8 (22%) patients currently alive. Hematologic toxicity was common, though WHO grade 3/4 neutropenia occurred only in 6 (17%) patients and anaemia also in 6 (17%) patients, respectively. Nonhematologic adverse reactions were usually mild to moderate; grade 3 toxicities included emesis, diarrhoea and mucositis each in 1 patient (3%). Conclusion: Our data suggest that the combination of docetaxel and oxaliplatin with G-CSF and erythropoietin has a promising therapeutic index in patients with advanced gastroesophageal adenocarcinoma. No significant financial relationships to disclose.
Randomized Comparison of the Effects of Two Doses of Dabigatran Etexilate on Clinical Outcomes Over 4.3 Years : Results of the Rely-Able Double-Blind Randomized Trial
Authors: Stuart J. Connolly, Paul A. Reilly, Janice Pogue, John Eikelboom, Jonas Oldgren, Michael D. Ezekowitz, Lars Wallentin, Salim Yusuf
Journal: Circulation (2012)

Randomized Comparison of the Effects of Two Doses of Dabigatran Etexilate on Clinical Outcomes Over 4.3 Years : Results of the Rely-Able Double-Blind Randomized Trial
Hsp90 Is Critical for the Regulation of Phenotype and Functionality of Human Dendritic Cells.
Authors: Jooeun Bae, Constantine Mitsiades, Tai Yu-Tzu, Jeff Martinson, Ramesh Babu Batchu, Robert Bertheau, Cheng Li, Rao Prabhala, Shammas Masood, Teru Hideshima, Lawrence Catley, Kenneth Anderson, Nikhil Munshi
Journal: Blood (2005)
Abstract 14214: Severe Renal Disease Increases the Risk for Device Related Complications in Patients with an Implantable Cardioverter Defibrillator
Authors: Maurits S Buiten, M K de Bie, J Thijssen, J I Rotmans, M Groeneveld, T J Rabelink, J W Jukema, M J Schalij, L Van Erven
Journal: Circulation (2012)

Introduction ICD therapy has become a proven and well-accepted therapy for the prevention of sudden cardiac death. However, a major part of the present patient population has serious comorbidities,...
Boceprevir, peginterferon and ribavirin for acute hepatitis C in HIV infected patients
Authors: Sebastiaan J. Hullegie, Mark A.A. Claassen, Guido E.L. van den Berk, Jan T.M. van der Meer, Dirk Posthouwer, Fanny N. Lauw, Eliane M.S. Leyten, Peter P. Koopmans, Clemens Richter, Arne van Eeden, Wouter F.W. Bierman, Astrid M. Newsum, Joop E. Arends, Bart J.A. Rijnders
Journal: Journal of Hepatology (2015)
Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy after Radical Prostatectomy
Authors: Stephen J. Freedland, Voleak Choeurng, Lauren Howard, Amanda De Hoedt, Marguerite du Plessis, Kasra Yousefi, Lucia L. Lam, Christine Buerki, Seong Ra, Bruce Robbins, Edouard J. Trabulsi, Nikhil L. Shah, Firas Abdollah, Felix Y. Feng, Elai Davicioni, Adam P. Dicker, Robert J. Karnes, Robert B. Den
Journal: European Urology (2016)

Despite salvage radiation therapy (SRT) for recurrent prostate cancer (PCa) after radical prostatectomy (RP), some patients still progress to metastases. Identifying these men would allow them to undergo systemic therapy including testing novel therapies to reduce metastases risk. To test whether the genomic classifier (GC) predicts development of metastatic disease. Retrospective multi-center and multi-ethnic cohort study from two academic centers and one Veterans Affairs Medical Center in the United States involving 170 men receiving SRT for recurrent PCa post-RP. Time from SRT to development of metastatic disease tested using Cox regression, survival c-index, and decision curve analysis. Performance of GC was compared to the Cancer of the Prostate Risk Assessment Score and Briganti risk models based on these metrics. With a median 5.7 yr follow-up after SRT, 20 patients (12%) developed metastases. On multivariable analysis, for each 0.1 unit increase in GC (scaled from 0 to 1), the hazard ratio for metastasis was 1.58 (95% confidence interval 1.16–2.17; p = 0.002). Adjusting for androgen deprivation therapy did not materially change the results. The c-index for GC was 0.85 (95% confidence interval 0.73–0.88) versus 0.63–0.65 for published clinico-pathologic risk models. The 5-yr cumulative incidence of metastasis post-SRT in patients with low, intermediate, and high GC scores was 2.7%, 8.4%, and 33.1%, respectively (p < 0.001). While validation in larger, prospectively collected cohorts is required, these data suggest GC is a strong predictor of metastases among men receiving SRT for recurrent PCa post-RP, accurately identifying men who are excellent candidates for systemic therapy due to their very high-risk of metastases. Genomic classifier and two clinico-pathologic risk models were evaluated on their ability to predict metastases among men receiving salvage radiation therapy for recurrent prostate cancer. Genomic classifier was able to identify candidates for further therapies due to their very high-risk of metastases.
Blood Oxygenation Level-Dependent CMR-Derived Measures in Critical Limb Ischemia and Changes With Revascularization
Authors: Adnan Bajwa, Roman Wesolowski, Ashish Patel, Prakash Saha, Francesca Ludwinski, Mohammed Ikram, Mostafa Albayati, Alberto Smith, Eike Nagel, Bijan Modarai
Journal: Journal of the American College of Cardiology (2016)

Use of blood oxygenation level-dependent cardiovascular magnetic resonance (BOLD-CMR) to assess perfusion in the lower limb has been hampered by poor reproducibility and a failure to reliably detect post-revascularization improvements in patients with critical limb ischemia (CLI).This study sought to develop BOLD-CMR as an objective, reliable clinical tool for measuring calf muscle perfusion in patients with CLI.The calf was imaged at 3-T in young healthy control subjects (n = 12), age-matched control subjects (n = 10), and patients with CLI (n = 34). Signal intensity time curves were generated for each muscle group and curve parameters, including signal reduction during ischemia (SRi) and gradient during reactive hyperemia (Grad). BOLD-CMR was used to assess changes in perfusion following revascularization in 12 CLI patients. Muscle biopsies (n = 28), obtained at the level of BOLD-CMR measurement and from healthy proximal muscle of patients undergoing lower limb amputation (n = 3), were analyzed for capillary-fiber ratio.There was good interuser and interscan reproducibility for Grad and SRi (all p < 0.0001). The ischemic limb had lower Grad and SRi compared with the contralateral asymptomatic limb, age-matched control subjects, and young control subjects (p < 0.001 for all comparisons). Successful revascularization resulted in improvement in Grad (p < 0.0001) and SRi (p < 0.0005). There was a significant correlation between capillary-fiber ratio (p < 0.01) in muscle biopsies from amputated limbs and Grad measured pre-operatively at the corresponding level.BOLD-CMR showed promise as a reliable tool for assessing perfusion in the lower limb musculature and merits further investigation in a clinical trial.
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non–Small-Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis
Authors: Bin-Chi Liao, Jih-Hsiang Lee, Chia-Chi Lin, Ya-Fang Chen, Chin-Hao Chang, Chao-Chi Ho, Jin-Yuan Shih, Chong-Jen Yu, James Chih-Hsin Yang
Journal: Journal of Thoracic Oncology (2015)
Antithrombotic treatment for atrial fibrillation
Authors: G. Peterson, A. Howitt, D. Armstrong
Journal: BMJ (1999)

Editor—The findings of Howitt and Armstrong’s study of antithrombotic treatment for atrial fibrillation in general practice—in particular that patients were unwilling to take warfarin—have uncertain clinical relevance.1 They are in contrast to those of Sudlow et al, who reported that most elderly patients with atrial fibrillation would accept treatment to prevent stroke.2

The precise information provided to patients is critically important in influencing their beliefs. Lack of detail on the information provided about the drugs mars Howitt and Anderson’s study. The authors emphasised the value of a patient centred approach in determining antithrombotic treatment in chronic atrial fibrillation and presented to patients, in pictorial fashion, the benefits (derived from clinical trials) of warfarin and aspirin. An equally important methodological issue, however, is the presentation of the risks of the treatment.

The methods section states only that “detailed information about aspirin and warfarin treatment was given.” What exactly does this mean? If the material consisted of the typical prescribing information for warfarin or even the equally daunting consumer drug information developed by pharmaceutical companies, it is not surprising that many patients were frightened off treatment.

Adopting a patient centred approach to therapeutic decision making requires that the potential risks of the treatment are presented in as patient friendly a manner as the possible benefits.
Structural and functional differentiation of two clinally distributed glucosephosphate isomerase allelic isozymes from the teleost Fundulus heteroclitus.
Authors: R J Van Beneden, D A Powers
Journal: Molecular Biology and Evolution (1989)

The teleost Fundulus heteroclitus (L.) possesses two loci, Gpi-A and Gpi-B, for the glycolytic enzyme, glucose-phosphate isomerase (GPI; D-glucose-6-phosphate ketol-isomerase; E.C. 5.3.1.9). The Gpi-B locus is polymorphic in Fundulus, with two common alleles, Gpi-Bb and Gpi-Bc, distributed in a clinal manner in populations along the east coast of North America. Since this clinal distribution is strongly correlated with a temperature gradient, we asked whether the GPI-B2 allozymes were functionally adapted to the thermal environment in which a given phenotype predominated. The two major GPI-B2 allozymes were purified to homogeneity and were characterized as to molecular weight, isoelectric pH, thermal denaturation, and kinetic parameters. Both GPI-Bb2 and GPI-Bc2 allozymes have molecular masses of 110 kD, and they have isoelectric pHs of 6.4 and 6.6, respectively. The GPI-Bb2 allozyme was more stable to thermal denaturation than was the GPI-Bc2 enzyme. Kinetic properties of the allelic isozymes were investigated both as a function of pH and as a function of temperature. At 25 degrees C, over the pH range considered, there were no significant differences between allozymes, either in Km for fructose-6-phosphate or in Ki for 6-phosphogluconate, but apparent Vmax values differed between pH 7.5 and pH 8.5. All steady-state kinetic parameters showed strong temperature dependence, but the allozymes differed only in the Ki for 6-phosphogluconate at temperatures greater than 30 degrees C. On the basis of the observed structural and functional differences alluded to above, the hypothesis that the major allelic isozymes of the Gpi-B locus were functionally equivalent was rejected. However, it is not yet known whether these structural and functional differences have any significance at higher levels of biological organization.
TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL
Authors: Ilan R. Kirsch, Rei Watanabe, John T. O’Malley, David W. Williamson, Laura-Louise Scott, Christopher P. Elco, Jessica E. Teague, Ahmed Gehad, Elizabeth L. Lowry, Nicole R. LeBoeuf, James G. Krueger, Harlan S. Robins, Thomas S. Kupper, Rachael A. Clark
Journal: Science Translational Medicine (2015)

Early diagnosis of cutaneous T cell lymphoma (CTCL) is difficult and takes on average 6 years after presentation, in part because the clinical appearance and histopathology of CTCL can resemble that of benign inflammatory skin diseases. Detection of a malignant T cell clone is critical in making the diagnosis of CTCL, but the T cell receptor γ (TCRγ) polymerase chain reaction (PCR) analysis in current clinical use detects clones in only a subset of patients. High-throughput TCR sequencing (HTS) detected T cell clones in 46 of 46 CTCL patients, was more sensitive and specific than TCRγ PCR, and successfully discriminated CTCL from benign inflammatory diseases. HTS also accurately assessed responses to therapy and facilitated diagnosis of disease recurrence. In patients with new skin lesions and no involvement of blood by flow cytometry, HTS demonstrated hematogenous spread of small numbers of malignant T cells. Analysis of CTCL TCRγ genes demonstrated that CTCL is a malignancy derived from mature T cells. There was a maximal T cell density in skin in benign inflammatory diseases that was exceeded in CTCL, suggesting that a niche of finite size may exist for benign T cells in skin. Last, immunostaining demonstrated that the malignant T cell clones in mycosis fungoides and leukemic CTCL localized to different anatomic compartments in the skin. In summary, HTS accurately diagnosed CTCL in all stages, discriminated CTCL from benign inflammatory skin diseases, and provided insights into the cell of origin and location of malignant CTCL cells in skin.
Re: William C. Jackson, Matthew J. Schipper, Skyler B. Johnson, et al. Duration of Androgen Deprivation Therapy Influences Outcomes for Patients Receiving Radiation Therapy Following Radical Prostatectomy. Eur Urol 2016;69:50–7 Re: Ronald C. Chen. Postprostatectomy Radiotherapy: Whether and How Long to Give Concurrent Androgen Deprivation Therapy. Eur Urol 2016;69:58–9
Authors: Alan Dal Pra, Martin Spahn
Journal: European Urology (2015)