tbuckley/cabot-search huggingface dataset:
Translation of gene expression profiles into a nine antibody IHC multivariate index assay for colorectal carcinoma
Authors: M. T. Schreeder, R. S. Seitz, R. Beck, B. Z. Ring, D. T. Ross
Journal: Journal of Clinical Oncology (2007)

21042 Introduction: Pathologic stage is the most powerful predictor of outcome in colorectal cancer. However, in early stage disease there continues to be a need for better identification of patients at high risk of disease progression after surgical resection. We have undertaken a large scale effort translating gene expression profiles into immunohistochemical biomarkers that classify carcinoma in novel ways. Herein we report the identification of a colorectal tailored antibody “panel of diversity” that distinguishes tumor heterogeneity and propose a multivariate index assay (MIA) for predicting outcome. Methods: 744 stage I-III consecutive colon cancer patients treated by the CCIH between 1992 and 2000 were identified. Clinical followup through 2005 was obtained from the tumor registry and verified by chart review . Tissue micorarrays (TMA) were constructed from these patients resected primary tumors. Over 700 antibodies targeted by carcinoma gene expression experiments or literature review were first screened on a 30 case TMA. Of these, 34 were selected as showing subjectively high quality stains and the ability to classify patient populations. These antibodies were used to stain the clinical TMA and scored using a semi-quantitative scale. We used a number of approaches including Cox, RPART, and Bayesian to derive candidate MIA's to predict recurrence. Results: 13 antibodies showed a significant or near significant association with either overall recurrence or recurrence at 5 years. We have previously shown these antibodies to have similar prognostic abilities in other solid tumor carcinomas. We propose a model combining nine markers (p53, CCNA2, TFF3, RERG, AKR1C1, TLE3, IRX3, SYP, TTC7) as an MIA for predicting outcome in Stage II patients. The model is independent of pathologic stage. Conclusions: This colon tailored antibody ‘panel of diversity’ is a tool for characterizing the biologic diversity in colon cancer cohorts. The identification of nine prognostic markers that can be effectively combined using an MIA suggests that combination of multiple markers will be useful for developing sensitive and specific prognostic assays. The model proposed herein should be validated using additional cohorts to evaluate its overall clinical utility. No significant financial relationships to disclose.
Nation-Wide Survey of Infant Leukemia in Japan: A Report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).
Authors: Takako Miyamura, Katsuyoshi Koh, Daisuke Tomizawa, Kanji Sugita, Koji Kato, Takashi Sato, Yoshihiro Takahashi, Atsushi Ogawa, Masahiro Hirayama, Akira Kikuchi, Megumi Oda, Daiichiro Hasegawa, Kazutoshi Koike, Yutaka Saikawa, Michiki Hatanaka, Keizo Horibe, Eiichi Ishii
Journal: Blood (2008)
Circulating tumor cells in patients with castration-resistant metastatic prostate cancer
Authors: D. C. Danila, M. A. Leversha, R. Gonzalez-Espinoza, A. Anand, B. Gu, G. A. Gignac, S. Larson, G. Heller, M. Fleisher, H. I. Scher
Journal: Journal of Clinical Oncology (2007)

5076 Background: Blood-based assays are urgently needed to provide molecular information on the specific targets expressed in tumor cells to optimize treatment selection. Antibody-capture technologies have been applied to isolate circulating tumor cells (CTC) from small volumes of peripheral blood from patients with progressive castrate metastatic prostate cancer. It has been demonstrated previously that CTC isolated from these patients represent authentic prostate cancer cells. Methods: CTC, positive for EpCAM (epithelial cellular adhesion molecule) and nuclear DAPI, and CD45 negative, were isolated from 120 patients with clinical castrate metastatic disease. All patients had rising PSA levels and were on stable treatment regimens at the time of CTC sampling. We tested the association between CTC counts and PSA levels, and the extent of disease to bone, and soft tissue metastasis by Wilcoxon rank sum. Fluorescence in situ hybridization was performed for AR and ERBB2 genes by an adapted method in CTC. Results: The average age in this patient cohort was 69 years, and median PSA at the time when CTC were drawn was 111 ng/mL (range 0.86–12147 ng/mL). The patterns of metastatic spread included disease in soft tissue only in 12 patients (10%), in bone and soft tissue in 67 (56%), and in bone only in 41 patients (34%). CTC counts ranged from 0 to 1958 cells per 7.5 mL of blood. A large number of patients (54, 45%) had 10 or more circulating tumor cells, while only 33 patients (27.5%) had 1 or less CTC per sample of blood. Significantly higher numbers of CTC were detected in patients with bone metastasis compared to those without bone metastasis (11 vs. 2.5, p&lt;0.01). In patients with marked amplification of AR locus (five patients), tetraploidy was noted in the majority of cases (four cases). Two patients without AR amplification showed apparent tetraploidy, while no analyzed samples (nine) had amplification of ERBB2. Conclusions: The analysis of cancer-related gene alterations in CTC is feasible in a hospital-based laboratory. Further gene expression studies focused on the patients with higher numbers of CTC in correlation with clinical outcomes, as well as the investigation of CTC gene expression during specific treatments are under way. No significant financial relationships to disclose.
Evaluation of Germline Genetic Testing Criteria in a Hospital-Based Series of Women With Breast Cancer
Authors: Siddhartha Yadav, Chunling Hu, Steven N. Hart, Nicholas Boddicker, Eric C. Polley, Jie Na, Rohan Gnanaolivu, Kun Y. Lee, Tricia Lindstrom, Sebastian Armasu, Patrick Fitz-Gibbon, Karthik Ghosh, Daniela L. Stan, Sandhya Pruthi, Lonzetta Neal, Nicole Sandhu, Deborah J. Rhodes, Christine Klassen, Prema P. Peethambaram, Tufia C. Haddad, Janet E. Olson, Tanya L. Hoskin, Matthew P. Goetz, Susan M. Domchek, Judy C. Boughey, Kathryn J. Ruddy, Fergus J. Couch
Journal: Journal of Clinical Oncology (2020)

To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer.
Multicenter phase II study of combined neoadjuvant docetaxel and androgen ablation (ADT) prior to radical prostatectomy (RP) for patients (pts) with high risk localized prostate cancer (LCaP): Pathologic outcomes and 3-year follow-up analyses
Authors: E. Winquist, K. N. Chi, J. Chin, L. Goldenberg, L. Klotz, S. Berry, F. Saad, P. Perrotte, D. Ruether, J. Trachtenberg, M. E. Gleave
Journal: Journal of Clinical Oncology (2007)

5002 Background: Pts with high risk LCaP (cT3, Gleason score &gt; 7 &amp;/or PSA &gt; 20) have an increased risk of relapse with a biochemical failure rate of &gt;50% at 3 years after RP. Docetaxel is active in hormone refractory prostate cancer &amp; potentially beneficial if combined with ADT for treatment naïve disease. The objectives of this trial were to assess the pathologic outcomes &amp; feasibility of docetaxel + ADT in men with LCaP prior to RP. Methods: A phase II multi-center study of newly diagnosed previously untreated pts with clinically LCaP with high-risk features. All pts received ADT (buserelin acetate 6.3 mg q8 weeks x 3 and anti-androgen for 4 weeks) plus docetaxel (35 mg/m 2 weekly for 6 out of 8 weeks for 3 cycles) prior to RP. Results: 72 men with a median age of 59 years (range 46–78) were enrolled at 6 sites. Baseline characteristics included: clinical stage T1C, T2 &amp; T3 in 14%, 47% &amp; 39%; and Gleason score &lt;7, 7 &amp; &gt;7 in 10%, 30% &amp; 60% of pts; respectively. Median baseline PSA was 10.8 μg/L (range 1.6–65.6) with PSA &lt; 10 in 47%, 10–20 in 24% &amp; &gt;20 in 29% of pts. Eight pts did not complete protocol therapy because of toxicity (n=4), withdrawal of consent (n=1), or other reasons (n=3). 1 pt had myocardial infarction day 1 post-operatively &amp; 1 pt had DVT 1.5 months after RP. No other major post-operative complications were reported. Of the 64 pts completing protocol therapy, 2 had a complete pathologic response and pathologic stage was T2 in 34 (53%) and T3 in 28 (44%) pts. Four pts had N1 disease &amp; positive surgical margins were identified in 17 (27%). On multivariate Cox regression analysis only baseline Gleason score (=7 vs. &gt;7) was associated with PSA recurrence-free survival (hazard ratio 4.58, 95% CI 1.32–15.93). At a median follow-up of 42.7 months (range 25.6–65.6), 19 (30%) pts have relapsed. Three pts have died at 32.0, 40.0 &amp; 40.3 months, with all deaths attributed to prostate cancer. Conclusions: Combined ADT and docetaxel prior to RP was feasible and resulted in encouraging pathologic outcomes and PSA- recurrence free survival. These data further support the rationale for randomized trials determining the efficacy of chemo-hormonal therapy in pts with clinically LCaP. [Table: see text]
A decision analytic model of prostate cancer screening using prostate-specific antigen and digital rectal exam
Authors: J. H. Hayes, M. J. Barry, P. W. Kantoff, J. E. Stahl
Journal: Journal of Clinical Oncology (2007)

5155 Background: PSA-based screening has been widely adopted in the US although a mortality benefit has yet to be demonstrated. The disutility of screening and quality of life of men diagnosed and treated after screening are critical issues in assessing its benefit and harm. The purpose of this model is to estimate the effect of one-time screening for prostate cancer using Prostate Specific Antigen (PSA) and DRE (digital rectal exam) on life expectancy (LE) and Quality Adjusted Life Expectancy (QALE) in the context of current diagnostic and treatment practice. Methods: A semi-Markov state transition simulation describes the relevant health states. Two strategies were compared: 1) Screening - single screening PSA and DRE; 2) No Screening - patients diagnosed after developing symptoms. Markov cycle length was 1 year. Transition probabilities and utility weights were developed from review of the literature and expert opinion. Sensitivity analyses were performed on all parameters. A PSA threshold of 4 ng/mL and age 65 were used for the base case. The model was created using TreeAge software. Results: For our base case, a single screening conferred a LE benefit of 0.37 y (15.86 vs 15.49 y) and a QALE benefit of 0.20 QALYs (15.62 vs 15.42 QALYs). Predicted 10 y cancer specific survival for screen-diagnosed men was 95.7% vs SEER 97.7%. The model predicted 9.5% of screened patients would have metastatic disease at diagnosis vs 5% in SEER (4% unknown stage); in unscreened men, this rate was 18/100,000 vs 15/100,000 in SEER. Sensitivity Analyses of Utilities (SA): The single screen model was relatively insensitive to SA of utilities: a 20% single cycle toll on one-time PSA screening disutility was required to eliminate the benefit of screening. The disutility of positive PSA with negative biopsy slightly affected QALE: a toll of 0.25 QALYs decreased QALE from 15.62 to 15.61 QALYs. Conclusions: Our model reveals a modest benefit to one-time screening for prostate cancer. This one-time screening model is relatively insensitive to utility SA; however, the importance of incorporating psychological effects of PSA screening in recurrent screening is to be determined. The impact of serial screening, lead time, PSA threshold, and cost effectiveness on LE and QALE is being analyzed. No significant financial relationships to disclose.
Gemcitabin (G) plus cisplatin (P) versus etoposid (E) plus cisplatin in advanced/metastatic non-small cell lung cancer (NSCLC): Preliminary results of a randomized monocentric study
Authors: A. Bousahba, F. Bereksi-Reguig
Journal: Journal of Clinical Oncology (2007)

18155 Background: we performed a randomized monocentric study to compare the treatment response of two chemotherapy doublets EP versus GP. Survival rates and toxicity are the secondary endpoints. Methods: from December 2003 to October 2006, patients with non-operable stage IIIB /IV histological or cytological proven NSCLC, ECOG PS = 2, were randomized to: (A) gemcitabin 1250 mg/m 2 on d 1, 8 plus cisplatin 80 mg/m 2 on d1 q3w for 6 cycles or (B) cisplatin at same dose followed by etoposid 100 mg / m 2 on d1, 2, 3 q3w. The sample size was estimated at 64 patients per treatment arm to provide a power of 0.80 to detect a 20% difference in response rate between the two groups at the 5% level. Results: one hundred thirteen chemonaïve patients were enrolled (A: 57, B: 56), median age 61 years (arm A) and 57.5 years (arm B), stage IIIB (42.1% A vs 41.1% B), two or more metastatic sites (34% A, 39% B), PS 1 (68.4% A, 69.6% B). 360 cycles were administered 187 (A) and 173 (B) with a median of 3 cycles per patient in each group. Two patients were excluded from analysis. One hundred one patients were evaluable for toxicity, 90 for response. 47 pts were evaluable in A and 43 pts in B with treatment response in intent to treat principle respectively: complete response (1.8% - 0%), partial responses (29.1% and 20.7%). The objective response rate was 30.9% (95% CI 18.8%-43.2%) in A, 20.7% (95% CI 9.8%-31.6%) in B, no change (36.4% and 37.7%) and progressive disease (18.2% and 22.6%). Median duration of objective response 8.2 months (A) and 8.3 months (B), median time to progression : 8.0 months (A) and 7.5 months (B). Incidences of grade 3–4 toxicities were respectively in arms A and B: nausea-vomiting (37%-12.5%), leucopenia (5.6%-14.6%), neutropenia (13%-37.5%), thrombopenia (0–2.1%), anemia (13%-6.3%). Febril neutropenia occurred in 1.9% (A) and 8.3% (B). One toxic death occurred in arm B. Conclusions: preliminary analysis indicates that GP had a more favourable toxicity profile and a higher activity is suggested for the GP regimen. The enrolment is continued. No significant financial relationships to disclose.
Abstract 17143: Repopulated Pediatric-sized Decellularized Heart: A Tool For Ex Vivo Tests
Authors: Camila Hochman-Mendez, Fernanda Mesquita, Joern Huelsmann, Karis R Tang-Quan, Ernesto C da Costa, Po-Feng Lee, Luiz Sampaio, Doris A Taylor
Journal: Circulation (2019)

Background: Most drugs that fail in development or in post-market analysis do so because of cardiotoxicity. Yet in vitro assays do not always predict clinical events even with advanced uses of hiPS...
Abstract P106: Stable versus Changing BMI Trajectories in Relation to Cardiometabolic Risk Factor Trajectories in Adolescent Girls: The NHLBI Growth and Health Study
Authors: Jessica G Woo, Stephen R Daniels, Elaine M Urbina
Journal: Circulation (2020)

Introduction: Adolescence is a period of increased independence in lifestyle choices, as well as shifts in cardiometabolic risk factors. Understanding how stability or change in BMI status may be superimposed on risk factor changes will enable focused attention on girls whose risk factors are likely to deteriorate during adolescence. Methods: Girls were enrolled at age 10 into the NHLBI Growth and Health Study (NGHS) at 3 centers (n=2379) and assessed annually to age 19. Ideal cardiovascular risk factors (smoking, dietary sodium, dietary saturated fat, BMI, blood pressure (BP), total cholesterol (TC) and glucose), and related risk factors (HDL and LDL cholesterol, and triglycerides (TG)) were assessed. Trajectories of adherence to ideal risk factor definitions were evaluated using group-based modeling, with risk factor trajectories layered over BMI trajectories in change-over-change analysis. Results: Four trajectories of BMI across adolescence were: ideal (51%), deteriorating (14%), improving (11%) and poor (25%). Two to 4 trajectories were identified for other risk factors, with similar trajectory shapes (e.g., ideal, improving, deteriorating and poor). Ideal smoking prevalence only deteriorated, with trajectories differing by timing of smoking uptake (early, middle or late adolescence). Most adolescent girls had poor adherence to diet metrics throughout adolescence, with diet intake trajectories improving somewhat at different ages (early or later adolescence) in a small percent of participants. Stable poor or ideal BMI trajectories were associated primarily with stable risk factor trajectories (poor or ideal, respectively), for LDL, HDL, TG, BP (all p=0.0001). The poor BMI trajectory was also associated with late adolescent deteriorating glucose (p=0.0001) and TC trajectories (p=0.02). Changing BMI trajectories, either improving or deteriorating, can unmask the sensitivity of risk factors to change in BMI status. The improving BMI trajectory was more likely to be in the later-improving saturated fat (p=0.003), improving HDL (p=0.0002) and moderate-improving TG trajectories (p=0.01) and less likely to be in the low-deteriorating BP trajectory (p=0.04) compared to the deteriorating BMI trajectory. Smoking trajectories did not differ by BMI trajectory. Conclusions: Stable poor BMI is associated with poor, but not with deteriorating cardiometabolic risk profiles during adolescence, suggesting these changes must have occurred before age 10. Decreasing ideal TC and glucose appear to be late adolescent responses to persistently poor BMI. However, improving BMI status during adolescence is associated with improving dietary saturated fat intake and blood lipid profiles, while deteriorating BMI is associated with deteriorating BP and lipids. Thus, specific ideal health factors may be differentially sensitive to BMI changes in adolescent girls.
Covert COVID-19 and false-positive dengue serology in Singapore
Authors: Gabriel Yan, Chun Kiat Lee, Lawrence T M Lam, Benedict Yan, Ying Xian Chua, Anita Y N Lim, Kee Fong Phang, Guan Sen Kew, Hazel Teng, Chin Hong Ngai, Li Lin, Rui Min Foo, Surinder Pada, Lee Ching Ng, Paul Anantharajah Tambyah
Journal: The Lancet Infectious Diseases (2020)
Abstract 17568: Subclinical Myocardial Dysfunction as Detected by Elevated Natriuretic Peptide Levels Confer Increased Long-Term Risk in Patients Without Clinical Diagnosis of Heart Failure and Renal Dysfunction
Authors: W. H. Wilson Tang, Yuping Wu, Stanley L Hazen
Journal: Circulation (2017)

Background: The recent heart failure clinical guidelines have put forward a new recommendation for patients at risk of developing heart failure that natriuretic peptide biomarker-based screening fo...
Safety of VEGF-targeted tyrosine kinase inhibitors in patients (Pts) with metastatic renal cell carcinoma (mRCC) and central nervous system (CNS) metastases
Authors: J. S. Unnithan, T. Choueiri, J. Garcia, R. Dreicer, W. Laura, R. Bukowski, B. Rini
Journal: Journal of Clinical Oncology (2007)

5047 Background: Hemorrhagic complications have been reported in pts treated with various angiogenesis inhibitors, however, reports of intracranial bleeding are rare. Intracranial hemorrhage has been reported during therapy with multitargeted tyrosine kinase inhibitors (TKIs) at higher dose levels during phase I evaluation. Given the occurrence of CNS metastases in RCC and the common use of TKIs, a review of the safety of TKIs in RCC pts with CNS metastases was undertaken. Methods: All pts with mRCC and CNS metastases who were treated with TKIs at the Cleveland Clinic Taussig Cancer Center were investigated. Results: Between 8/2005 and 10/2006, 23 pts with mRCC and CNS metastases were treated utilizing either sunitinib or sorafenib. 7/23 pts received sequential therapy with both TKIs. The median time to development of CNS metastases was 16.0 months (range: 0 - 288 months). Thirteen pts received sunitinib (50 mg daily, 4 out of 6 weeks) and 10 pts received sorafenib (400 mg BID continuously). All 23 pts had known CNS lesions at initiation of TKI treatment and had received prior therapy to the CNS. This consisted of either surgery and whole brain radiation therapy (WBRT; 4pts), WBRT alone (3 pts), conformal radiotherapy in the form or gamma knife or Intensity Modulated Radiation Therapy (13 pts), WBRT and gamma knife (2 pts) or surgical resection alone (1 pt). The median TKI treatment duration (including sequential TKI therapy), was 5.6 months (range: 0.3–20.3 months). No evidence of CNS intratumoral bleeding or other hemorrhagic complications have been observed. Three pts developed new metastatic foci in the brain while on sunitinib. Overall, the median time to progression was 6.5 months (0.9 - 20.3 months). Conclusions: These data suggest sunitinib or sorafenib can be safely administered to RCC pts with previously treated CNS metastases The safety of these agents in patients with untreated CNS lesions is unclear, and therefore pretreatment CNS imaging should be considered. [Table: see text]
Safety and Pharmacodynamics of Oral TLR-7 agonist GS-9620 in patients with Chronic Hepatitis B
Authors: Edward J Gane, Eric Sicard, Stuart C Gordon, Daniel Gruener, Stuart K Roberts, Suzanne Kim, Wendy Cheng, Carla S Coffin, Richard Fedorak, Paul Y Kwo, Barbara A Leggett, Daryl Lau, Young-Suk Lim, Stefan Pflanz, Benedetta Massetto, Mani Subramanian, John G McHutchison, Bradley Freilich, Kumar Visvanathan
Journal: Hepatology (2013)
Association Between Renin-Angiotensin System Blockade Discontinuation and All-Cause Mortality Among Persons With Low Estimated Glomerular Filtration Rate
Authors: Yao Qiao, Jung-Im Shin, Teresa K. Chen, Lesley A. Inker, Josef Coresh, G. Caleb Alexander, John W. Jackson, Alex R. Chang, Morgan E. Grams
Journal: JAMA Internal Medicine (2020)

<h3>Importance</h3> It is uncertain whether and when angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) treatment should be discontinued in individuals with low estimated glomerular filtration rate (eGFR). <h3>Objective</h3> To investigate the association of ACE-I or ARB therapy discontinuation after eGFR decreases to below 30 mL/min/1.73 m<sup>2</sup>with the risk of mortality, major adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD). <h3>Design, Setting, and Participants</h3> This retrospective, propensity score–matched cohort study included 3909 patients from an integrated health care system that served rural areas of central and northeastern Pennsylvania. Patients who initiated ACE-I or ARB therapy from January 1, 2004, to December 31, 2018, and had an eGFR decrease to below 30 mL/min/1.73 m<sup>2</sup>during therapy were enrolled, with follow-up until January 25, 2019. <h3>Exposures</h3> Individuals were classified based on whether they discontinued ACE-I or ARB therapy within 6 months after an eGFR decrease to below 30 mL/min/1.73 m<sup>2</sup>. <h3>Main Outcomes and Measures</h3> The association between ACE-I or ARB therapy discontinuation and mortality during the subsequent 5 years was assessed using multivariable Cox proportional hazards regression models, adjusting for patient characteristics at the time of the eGFR decrease in a propensity score–matched sample. Secondary outcomes included MACE and ESKD. <h3>Results</h3> Of the 3909 individuals receiving ACE-I or ARB treatment who experienced an eGFR decrease to below 30 mL/min/1.73 m<sup>2</sup>(2406 [61.6%] female; mean [SD] age, 73.7 [12.6] years), 1235 discontinued ACE-I or ARB therapy within 6 months after the eGFR decrease and 2674 did not discontinue therapy. A total of 434 patients (35.1%) who discontinued ACE-I or ARB therapy and 786 (29.4%) who did not discontinue therapy died during a median follow-up of 2.9 years (interquartile range, 1.3-5.0 years). In the propensity score–matched sample of 2410 individuals, ACE-I or ARB therapy discontinuation was associated with a higher risk of mortality (hazard ratio [HR], 1.39; 95% CI, 1.20-1.60]) and MACE (HR, 1.37; 95% CI, 1.20-1.56), but no statistically significant difference in the risk of ESKD was found (HR, 1.19; 95% CI, 0.86-1.65). <h3>Conclusions and Relevance</h3> The findings suggest that continuing ACE-I or ARB therapy in patients with declining kidney function may be associated with cardiovascular benefit without excessive harm of ESKD.