tbuckley/cabot-search huggingface dataset:
A Pivotal Phase 2 Trial of Ponatinib in Patients with Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Resistant or Intolerant to Dasatinib or Nilotinib, or with the T315I BCR-ABL Mutation: 12-Month Follow-up of the PACE Trial
Authors: Jorge E. Cortes, Dong-Wook Kim, Javier Pinilla-Ibarz, Philipp le Coutre, Ron Paquette, Charles Chuah, Franck E Nicolini, Jane Apperley, H. Jean Khoury, Moshe Talpaz, John F. DiPersio, Daniel J. DeAngelo, Elisabetta Abruzzese, Delphine Rea, Michele Baccarani, Martin C Muller, Carlo Gambacorti-Passerini, Stephane Wong, Stephanie Lustgarten, Victor M. Rivera, Tim Clackson, Christopher D. Turner, Frank G Haluska, Francois Guilhot, Michael W. Deininger, Andreas Hochhaus, Timothy Hughes, John M Goldman, Neil Shah, Hagop M Kantarjian
Journal: Blood (2012)
Prognostic relevance of circulating tumor cells (CTC) before adjuvant chemotherapy in patients with breast cancer: Results of the German SUCCESS trial.
Authors: J. K. Jueckstock, B. K. Rack, T. Zwingers, P. G. M. Hepp, A. Schneeweiss, M. W. Beckmann, W. Lichtenegger, H. L. Sommer, K. Pantel, H. Tesch, H. Forstbauer, R. Lorenz, M. Rezai, J. K. Neugebauer, U. Andergassen, K. Friese, W. Janni
Journal: Journal of Clinical Oncology (2011)

1033 Background: The prognostic significance of CTC in primary breast cancer has been demonstrated for 2,026 patients (pts) of the German SUCCESS-study (Rack et al, in press). In this analysis the prognostic relevance of CTC in peripheral blood at primary diagnosis in a different cohort of pts of the same trial regarding disease free (DFS) and overall survival (OAS) was investigated. Methods: As part of the translational research project we analyzed 23ml of peripheral blood from 1247 breast cancer pts before adjuvant taxane based chemotherapy. Cells were separated by Oncoquick (greiner bio-one, Frickenhausen, Germany) followed by labelling of epithelial cells with the anti-cytokeratine-antibody A45-B/B3 (Micromet, Munich, Germany) directed against cytokeratines 8, 18 and 19 and immunohistochemically staining with neu-fuchsin. All cytospins were screened by two independent persons. Results: In 21.1% of all pts (n=263) at least 1 CTC was detected (median 1.8, range 1−28) while 78.9% of the pts (n=984) were negative for CTC before adjuvant chemotherapy. 38.3% of the pts had a pT1 tumor, 4.7% G1 grading and 27.4% of the pts were node negative. None of these factors were statistically significant. Survival data analyses showed a disease recurrence rate of 7.6% and a mortality rate of 3.8% (n=48). With a median follow-up (FU) of 32 mon 9.9% of the pts (n=26) showing CTC relapsed compared to 7.0% of the pts (n=69) who were CTC negative (p=.124). There was no statistically significant difference seen in OAS: 15 deaths (5.7%) occurred in pts with CTC vs. 33 deaths (3.4%) in pts without CTC (p=.11). In multivariate analyses only larger tumor size, detection of lymph node metastases and negative hormone receptor status were associated with reduced DFS and OAS (p<.05, respectively). Conclusions: In contrast to our previous findings, in this cohort detection of CTC in peripheral blood of early breast cancer pts before chemotherapy was not statistically associated with DFS or OAS maybe due to the small number of events and short FU in this cohort. Further follow up will show, if this method can be used for risk stratification and monitoring of treatment efficacy in adjuvant breast cancer.
Accuracy and upgrade rates of stereotactic vacuum-assisted breast biopsy: Impact of number of core samples taken on malignancy underestimation rates.
Authors: J. A. Vossen, S. D. Edwards, M. Pronovost, P. Reeser
Journal: Journal of Clinical Oncology (2011)

20 Background: There are multiple options for the diagnostic evaluation of mammographic suspicious breast abnormalities. The therapeutic strategy is often based on lesion histopathological information obtained from stereotactic vacuum-assisted biopsy (VAB). Therefore, accurate information obtained by VAB is very important. This study was performed to evaluate the impact of the number of core samples obtain during VAB on malignancy underestimation rates for mammographically detected breast lesions. Methods: The pathologic results of 128 consecutive stereotactic biopsies (January 2010-December 2010) were retrospectively reviewed. All biopsies were performed using a 9-gauge needle. Pathologic results of core biopsies and surgical excision were compared. Underestimation rates of malignancy were calculated and correlation was made with the number of core samples obtained. Results: Surgical excision was performed on 41% (52/128) lesions; 4 benign, 19 indeterminate and 29 malignant. Overall malignancy underestimation rate was 19%. There were 8 cases of ductal carcinoma in situ (DCIS) on core biopsy that were proven to be invasive ductal carcinoma (IDC) on surgical excision. There was one case of benign microcalcifications that was proven to be lobular neoplasia (LN). There was one case of an atypical papillary lesion that was proven to be DCIS. There was a significant difference (p=0.02) between the mean number of core samples taken in the underdiagnosed lesions (8, range 6-12) and the concordant lesions (10, range 6-20). Conclusions: In the case of stereotactic VAB diagnosis of breast lesions, the underestimation rate of malignancy is more likely with a lower number of core samples obtained.
Disease variants alter transcription factor levels and methylation of their binding sites
Authors: Marc Jan Bonder, René Luijk, Daria V Zhernakova, Matthijs Moed, Patrick Deelen, Martijn Vermaat, Maarten van Iterson, Freerk van Dijk, Michiel van Galen, Jan Bot, Roderick C Slieker, P Mila Jhamai, Michael Verbiest, H Eka D Suchiman, Marijn Verkerk, Ruud van der Breggen, Jeroen van Rooij, Nico Lakenberg, Wibowo Arindrarto, Szymon M Kielbasa, Iris Jonkers, Peter van 't Hof, Irene Nooren, Marian Beekman, Joris Deelen, Diana van Heemst, Alexandra Zhernakova, Ettje F Tigchelaar, Morris A Swertz, Albert Hofman, André G Uitterlinden, René Pool, Jenny van Dongen, Jouke J Hottenga, Coen D A Stehouwer, Carla J H van der Kallen, Casper G Schalkwijk, Leonard H van den Berg, Erik W van Zwet, Hailiang Mei, Yang Li, Mathieu Lemire, Thomas J Hudson, P Eline Slagboom, Cisca Wijmenga, Jan H Veldink, Marleen M J van Greevenbroek, Cornelia M van Duijn, Dorret I Boomsma, Aaron Isaacs, Rick Jansen, Joyce B J van Meurs, Peter A C 't Hoen, Lude Franke, Bastiaan T Heijmans
Journal: Nature Genetics (2016)
Racial disparities in stage IV prostate cancer outcomes in the Veterans Affairs hospital system.
Authors: I. Al-Howaidi, L. Shatat, T. Tashi, W. Gonsalves, P. T. Silberstein, S. Subbiah
Journal: Journal of Clinical Oncology (2011)

199 Background: Epidemiological studies have demonstrated that African-American (AA) men with prostate cancer have lower overall survival and cancer-specific survival rates than Caucasian (CA) men with prostate cancer. We aim to assess whether racial disparities exist for prostate cancer within an equal access health care system like the Veterans Affairs (VA) hospitals. Methods: A retrospective analysis of AA and CA with metastatic prostate adenocarcinoma diagnosed between 1995 to 2007 via the Veterans Affairs Central Cancer Registry was conducted. Age, Race and type of treatment received were studied with respect to overall survival by using log-rank and Kaplan-Meier analysis. Results: A total of 8,195 patients with advanced prostate cancer were analyzed, majority of them where CA (66.32%), 30.8% were AA and 2.8% belonged to other races. The median survival for AA was 2.71 years, 2.88 years in CA and 4.02 years in other races (P value &lt;0.0001). Subgroup analysis based on treatment modality used showed the following median survival rates in years: No treatment (CA: 1.73, AA: 1.39, other races: 3.79, P&lt;0.816), Hormonal therapy alone (CA: 2.51,AA: 2.45, Others:3.72, P&lt;0.022), Radiation therapy alone (CA: 2.2, AA: 2.7, Others: 2.26, P&lt;0.832), combined hormone and radiation therapy (CA: 2.71, AA: 2.31, Others: 6.64, P&lt;0.029). However when CA and AA survival were compared excluding other races there was no statistically significant difference in survival irrespective of type of therapy received. Conclusions: In advanced prostate cancer, AA and CA have uniformly poor prognosis. Type of therapy received did not influence the survival of both races. The numbers for other races is too small to make a definitive conclusion regarding their prognosis. No significant financial relationships to disclose.
Symptom changes that predict disease control by systemic chemotherapy in patients with advanced pancreatic cancer.
Authors: Akiko Kuwahara, Shuichi Mitsunaga, Izumi Ohno, Satoshi Shimizu, Hideaki Takahashi, Hiroyuki Okuyama, Takuji Okusaka, Hideki Ueno, Chigusa Morizane, Shunsuke Kondo, Masafumi Ikeda
Journal: Journal of Clinical Oncology (2012)

195 Background: Alleviation of symptoms is related to good tumor control in patients undergoing systemic chemotherapy for pancreatic cancer (PC). The predictive value of symptom change has not been fully understood. The aim of this study was to identify symptom changes that predicted disease control by systemic chemotherapy in PC patients. Methods: Patients with unresectable PC who had not received any anti-cancer therapy for PC were eligible for inclusion in this study. Patients with obvious infectious conditions were excluded. Symptoms were scored from 0 to 10 using the Japanese version of the MD Anderson Symptom Inventory before the start of chemotherapy and one month later. The response of the tumor was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) vs. 1.0. Disease control was defined as CR, PR, or SD. An attempt was made to identify symptom changes that predicted disease control, and their impact on progression-free survival (PFS) was assessed. Results: The symptoms of 87 patients (male/female: 46/41, Karnofsky performance status (KPS): 100/90/80/70-50: 32/29/17/9, median age: 66 years) were prospectively assessed. Gemcitabine monotherapy (GEM), a GEM-based regimen, and S-1 monotherapy were performed in 42, 41, and 4 patients, respectively. Disease control was observed in 31 patients. The pain scores (P=0.047) and sleep disturbance scores (P=0.052) one month later were lower than before treatment in patients with disease control. Patients without deterioration of pain or sleep disturbance had a higher frequency of disease control (P=0.098 and P=0.004, respectively) and a longer PFS (P=0.021 and P&lt;0.001, respectively) than patients whose pain or sleep disturbance became more severe. Conclusions: Improvements in pain and sleep disturbance scores at one month predict disease control by systemic chemotherapy in patients with advanced PC.
Loss of the Y Chromosome Predicts Lower Complete Cytogenetic Remission Rate in Patients (pts) with Chronic Myeloid Leukemia (CML)
Authors: Mohamed Abdelfatah, Adel Al-Alwan, Zeyad Kanaan, Mark R Litzow, Alexandra Wolanskyj, Kebede Begna, William Hogan, Daniel L. Van Dyke, Aref Al-Kali
Journal: Blood (2012)
Combined Schedule of Fludarabine and Alemtuzumab Followed by Maintenance with Low-Dose Alemtuzumab Is Effective for Patients with Progressive B-Cell Chronic Lymphocytic Leukemia.
Authors: Malgorzata Kowal, Wieslaw Nowak, Aleksandra Nowaczynska, Anna Dmoszynska, Aleksander B. Skotnicki
Journal: Blood (2005)
ORAL01.04: Phase II Trial of Atezolizumab for Patients with PD-L1–Selected Advanced NSCLC (BIRCH): Updated Efficacy and Exploratory Biomarker Results
Authors: Heather Wakelee, Jyoti D. Patel, Rebecca Heist, Ani Balmanoukian, Benjamin Besse, Enriqueta Felip, Enric Carcereny Costa, Laura Q. Chow, Marianna Koczywas, Marina C. Garassino, Daniel Christoph, Chee Keong Toh, Melissa L. Johnson, Jamie Chaft, Takayasu Kurata, Jiaheng Qiu, Marcin Kowanetz, Shelley Coleman, Simonetta Mocci, Alan Sandler, Scott N. Gettinger, Solange Peters
Journal: Journal of Thoracic Oncology (2016)
Abstract 18619: All Advanced Lipid Tests are Not Equal: Prospective Analysis of Discordance Between LDL-P, Small Dense LDL (or Subfractions), and HDL-P (or Subfractions) as Determined by NMR, Ion Mobility, and VAP in Treated Patients
Authors: Kanae Mukai, Kellie Rolph, Julie C McCauley, Douglas W Triffon
Journal: Circulation (2015)

Introduction: LDL-P has been shown to be a better predictor of cardiovascular risk than LDL-C (Framingham Offspring, Jupiter, and MESA). HDL-P has been reported as a better predictor than HDL-C (Jupiter and MESA) and small dense LDL measurements have been reported as more predictive of cardiovascular disease progression than LDL-C (HATS). Clinicians rely on these markers to assess residual risk in treated patients. Hypothesis: NMR, ion mobility (IM), and VAP tests will report discordant results for LDL-P, HDL-P (or subfraction), and small dense LDL (or subfraction) in treated patients. Methods: This is a prospective study (#SCIML001 on ClinicalTrials.gov), approved by the Scripps Clinic (#IRB-14-6458). We aimed to determine the discordance between Liposcience NMR, Quest CardioIQ, and Atherotech VAP Plus. 102 patients older than 18 years on therapy for at least 30 days were included. A one-time fasting lab draw was obtained with all 3 lipid tests performed simultaneously on fresh samples. Concordance and discordance analysis was performed with the cut-off between normal and abnormal ranges. Results: Pearson correlations between LDL-P by VAP and NMR, NMR and IM, and VAP and IM were 0.886, 0.785, and 0.762, respectively. All 3 tests were concordant 63% and discordant 37% of the time. IM reported an abnormal LDL-P more commonly (28% of time vs NMR and 20% of the time vs VAP) when using the same cutoff value of 1000 as NMR. When using the cutoff of 1260 for LDL-P for IM, NMR was abnormal 15.6% of the time vs IM and VAP was abnormal 24% of the time vs IM. VAP more frequently reported an abnormal LDL-P vs NMR (27% of the time) and vs IM (32% of the time). VAP small LDL sub-fractions were more commonly reported as abnormal vs NMR and IM (27% and 32% respectively). Ion mobility more consistently reported a lower large HDL-P (48% of the time vs VAP and vs NMR). Conclusions: Correlations between advanced markers of residual risk were low and would give discordant signals on decisions to intensify therapy.
P0325 : Every 3-month surveillance is superior to semiannual surveillance for the survival of patients with hepatocellular carcinoma after hepatectomy: A 10-year observational study
Authors: M. Lee, S. Oh, Y.Y. Cho, J.-J. Yoo, Y. Cho, D.H. Lee, E.J. Cho, J.-H. Lee, S.J. Yu, N.-J. Yi, K.-W. Lee, J.-H. Yoon, K.-S. Suh, H.-S. Lee, Y.J. Kim
Journal: Journal of Hepatology (2015)
A Comparison of Stem Cell Source in Recipients of T-Cell Depleted Myeloablative Transplants for Leukaemia: No Difference in Mortality Using BM or PBSC.
Authors: B.E. Shaw, Nigel H. Russell, A. Pagliuca, J. Apperley, G. Cook, S. Mackinnon, J.A. Madrigal, D. Marks, G.J. Morgan, K. Peggs, M.N. Potter, K. Towlson, J.L. Byrne
Journal: Blood (2007)
Effect of post-operative intra-abdominal infectious complications on overall and relapse-free survival following curative gastrectomy in patients with gastric cancer.
Authors: Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Masanori Terashima
Journal: Journal of Clinical Oncology (2012)

86 Background: The number of reports investigating the impact of postoperative complications on long-term outcome following curative gastrectomy is limited and still remains unclear. The aim of this study is to clarify the effect of postoperative intra-abdominal infectious complications on overall survival (OS) and relapse-free survival (RFS) following curative gastrectomy. Methods: Three hundred and sixty-seven patients pts who underwent curative gastrectomy for gastric cancer between June 2003 and December 2004 at Shizuoka Cancer Center were included. Clinicopathological features and effects of postoperative intra-abdominal infectious complications on OS and RFS were investigated. In this study, postoperative intra-abdominal infectious complications were defined as Clavien-Dindo grade II or more severe pancreas fistula, anastomotic leak, or intra-abdominal abscess. Results: Median age was 63 years, male-female ratio was 2:1. Pathological stage was Stage I; 225 patients, stage II; 72 patients, stage III; 64 patients, and stage IV; 6 patients. Median observation periods of survivors were 71 months. Of 367 patients, 32 patients (8.7%) had intra-abdominal infectious complications. Overall 5-year survival rate was significantly better in patients without complications than in those with complications (86.1 vs 67.9%, P&lt;0.001). The same trend was observed even after stratification by pathological stage (Stage II; 76.9 vs 66.7%, P=0.254, Stage III; 62.1 vs 40.9%, P=0.218) although each difference was not statistically significant. Relapse free 5-year survival rate was significantly better in patient without complications (85.0 vs 64.9%, P=0.002), and the same trend was also observed after stratification by pathological stage. Conclusions: Postoperative intra-abdominal infectious complications adversely affect overall and relapse free survival of patients following curative gastrectomy. Reduced incidence of infectious complications may be beneficial to improve long-term outcome of patients with gastric cancer.
Lipid profiles and the risk of kidney cancer in the Swedish AMORIS study.
Authors: M. Van Hemelrijck, H. Garmo, N. Hammar, G. Walldius, M. Lambe, I. Jungner, L. Holmberg
Journal: Journal of Clinical Oncology (2011)

342 Background: Since multiple epidemiologic studies showed a link between obesity and kidney cancer (KCa), the lipid metabolism is thought to play a role in development of KCa. With the exception of cholesterol and total fat intake, the association between changes in lipid biomarkers and KCa has not often been researched. We assessed the link between lipid profiles and KCa risk in a large prospective cohort study. Methods: A cohort based on 85,261 persons (&gt; 20 years old) with baseline measurements of glucose, triglycerides (TG), total cholesterol, HDL, LDL, apolipoprotein A-I and apoB was selected from the Swedish Apolipoprotein Mortality Risk (AMORIS) study. Multivariate Cox proportional hazards models were used to analyze associations between quartiles and dichotomized values of these lipid components and KCa risk. All models were adjusted for age, gender, socioeconomic status, fasting status, history of kidney disease prior to baseline (ICD9: 580-93), and glucose, cholesterol, and TG levels (depending on the covariate of interest). Results: During a mean follow-up of 12 years, 161 persons developed KCa (58% men). The mean age at baseline was 46 years. TG were the only lipid component for which a statistically significant association was found with risk of KCa (Hazard Ratio (HR): 1.05 (95%CI: 0.59-1.87), 1.77 (1.05-2.98), and 1.77 (1.04-3.02) for the second, third, and fourth quartile, compared to the first, with p-value for trend: 0.008). The lipid ratio of TG and HDL also showed a statistically significant positive association with risk of KCa (HR: 1.21 (0.71-2.08), 1.56 (0.94-2.58), and 1.92 (1.17-3.17) for the second, third, and fourth quartile, compared to the first, with p-value for trend: 0.004). No other associations were found between lipid components and KCa risk. Conclusions: This detailed analysis of lipid components and risk of KCa found a relation between levels of TG and KCa risk. In contrast to previous studies, we did not find an association between cholesterol levels and KCa risk. Lipid profiles based on the markers used in this study do not seem to reflect the etiological pathway that has previously been shown between obesity and KCa. Further mechanistic studies are required to assess the link between lipid deregulation and KCa. No significant financial relationships to disclose.
Specifically Targeting the Interface Between HER1-HER3 Heterodimer on Breast Cancer to Limit Off-Target Effects Using Chimeric Antigen Receptor Designs with Improved T-Cell Energy Balance
Authors: Bipulendu Jena, Natalya Belousova, George T McNamara, David Rushworth, Tiejuan Mi, Helen Huls, Richard E. Champlin, Laurence JN Cooper
Journal: Blood (2014)
Protein BIII-tubulin expression as a prognostic and/or predictive factor of response to docetaxel in patients with hormone-refractory prostate cancer.
Authors: Quionia Perez, Carlos Alvarez, Lucrecia Ruiz, Eduardo Gutierrez, David Rodriguez, Noemi Villanueva, Jose Pablo Berros, Paula J. Fonseca, Jose Maria Vieitez, Emilio Esteban
Journal: Journal of Clinical Oncology (2012)

84 Background: Docetaxel is a standard treatment for hormone-refractory prostate cancer. Preclinical-clinical studies suggest that the determination of the BIII-tubulin is associated with response to taxanes. This study analyzes the role of that subunit of microtubules in prostate biopsies of patients with HRPC treated with docetaxel. Methods: Thirty two patients with prostate biopsy who received docetaxel in first-line chemotherapy between 2006 and 2011 were included in this retrospective cohort analysis. The clinic-pathological characteristics, PSA response, progression-free survival (PFS) and overall survival (OS) were collected. The findings were correlated with the overexpression of BIII-tubulin protein measured by immunohistochemistry techniques (IHC) with a purified and monoclonal Ac mouse. Results: The median age and Karnofstky index (KI) were 68 years (range 49-77) and 80% (60-90) respectively. Five patients (15.6%) had received only one anti-hormone treatment, fifteen (46.8), two and twelve (37.5) more than two lines. Twenty patients (62.5) had only one metastatic localization. The median of PSA value before the docetaxel treatment was 302 (4-3745). With a median of eight cycles (3-10) of docetaxel (75mg/m2/ /3s) 41% of patients achieved biochemical response with a median PFS and OS of 4.9 and 19.6 months respectively. Moderate-intense overexpression of BIII-tubulin was identified in five patients (15.6) and minimal or absent in 27 (84.4). In univariate analysis, over-expression was correlated with KI, but not with Gleason score. PSA responses to docetaxel was observed in four patients (80%) with over-expression compared with 20% of those with minimal or absent BIII-tubulin staining. The median PFS and OS for patients with over-expression was 8.6 and 20 months respectively compared to 4.3 and 17 months for those with minimal or absent BIII-tubulin. Conclusions: Over-expression of BIII-tubulin in tumor prostate tissue, applying the present technique is unusual. Its presence appears to be related with higher biochemical response to docetaxel and improvement in PFS and OS. These findings are discordant with those previously published.
Scientists welcome government climbdown on “anti-lobbying” clause
Authors: Anne Gulland
Journal: BMJ (2016)

Ministers have backtracked on a plan to impose a ban on research bodies and charities that are in receipt of taxpayers’ money from speaking out against government policy.

The government unveiled what critics described as an “anti-lobbying” clause when it introduced new standards for bodies in receipt of government grants in February. However, academics and charities warned that it would prevent them from speaking freely on government policy.1 In April the government exempted some scientists from the clause and put the …