tbuckley/cabot-search huggingface dataset:
Trastuzumab plus chemotherapy based on the accurate HER2-positivity testing for patients with advanced gastric cancer.
Authors: Tetsuya Kusumoto, Yasue Kimura, Norifumi Tsutsumi, Mitsuhiko Ohta, Masahiko Sugiyama, Eiji Kusumoto, Yoshihisa Sakaguchi, Koji Ikejiri, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2014)

e15075 Background: Accurate HER2 testing in patients with gastric cancer is difficult due to HER2 heterogeneity and incomplete membrane staining in gastric cancer. Our previous study showed that the frequency of the HER2-positivity for 198 gastric cancer samples was identified in 5.1-6.1% (10-12/198) under several IHC conditions, less than the 28.1% observed in the Japanese subgroup analyses of the ToGA study. The aim of the present study was to investigate therapeutic responses based on the results from the HER2-positivity testing in patients with advanced gastric cancer (AGC). Methods: From September 2011 to September 2013, HER2-positivity was evaluated for 32 patients with nonresectable AGC. Objective responses and survival data were evaluated in these patients with AGC who were treated with chemotherapy plus trastuzumab or chemotherapy alone based on the HER2-positivity testing. Results: Of all patients with AGC, eleven patients with HER2-positive tumors were treated with capecitabine or S-1 / cisplatin plus trastuzumab, and partial response was observed in six cases (response rates: 55%) and thereafter R0 gastrectomy was operated in two cases. Twenty-one patients with HER2-negative tumors were treated with S-1 / CDDP and the response rate was 38.1%. Survival data of HER2-positive and -negative tumors showed that the PFSs were 188 days and 199 days, respectively, were not significantly different. Conclusions: Accurate and reliable HER2 testing and scoring allow for appropriate selection of patients eligible for treatment with trastuzumab and might lead to the better objective response.
Oral vinorelbine (NVBo) and anastrozole (A) as neoadjuvant treatment of locally advanced (LA) breast cancer (BC) in hormone receptor positive (HR+) postmenopausal patients: Results of an international phase II trial
Authors: M. Riggi, E. M. Moreno-Lopez, J. Rolski, P. Petruzelka, J. M. Ferrero, E. Tellez-Bernal, N. Vaissiere, C. Lucas
Journal: Journal of Clinical Oncology (2009)

600 Background: Two recent randomized studies with anastrozole, as single agent or with an unspecified cytotoxic, produced an objective response rate (RR) of 24 and 39.5% by ultra-sound (US) [baseline primary tumor diameters (PTD) of 2.6 cm (median) and 3.6 cm (mean), respectively] in LA BC. This trial assessed the effect of the combined NVBo-A therapy. Methods: 55 assessable HR+ patients (pts) with LA breast cancer (tumor size &gt; 3 cm) were expected, including 10 with pharmacokinetics (PK). Pts received 3 (if progression or complete response) to 6 courses of NVBo at day 1(D1) and 8 every 3 weeks (60 mg/m 2 escalated to 80 mg/ m 2 at cycle 2) with 1 mg of A daily. Both US (primary criteria) and calliper assessments were performed at cycle 3 and 6, with surgery within 4 weeks of the last D1 NVBo. Anastrozole interaction on NVBo was studied by comparing NVBo PK between D1 and D8. NVBo interaction on A was assessed by comparing trough concentrations between D8 and D21. Results: Between July 2005 and June 2008, 60 women were enrolled. The first 58 pts were analyzed: at baseline, median age 64.9 years, median and mean PTD 3.7 and 4 cm, respectively; 59% N 1–2 (17% N 2 ), with a feasible breast conservative surgery (BCS) in only 12%; 19% were inoperable. The RR was 59% (95% CI 45–71%) by US and 69% (55–80%) by calliper. Clinical nodal invasion on TNM (N+) regressed by 32%. 10/11 inoperable pts at baseline became operable. Among 51 resections (concurrent events 4 pts, unresectable 3 pts) 20% were BCS. The pCR was 3.9%. Grade (G) 3–4 toxicities: haematological toxicities (neutropenia) in 6 pts; hepatic enzymes G3 1 pt; gastrointestinal toxicities G3 5 pts and 1 G4 musculoskeletal pain. PK interim analysis showed an absence of interaction between the 2 drugs. Conclusions: NBVo plus A led to an increased RR compared with previous experiences with A alone or not (IMPACT, PROACT trials). The operability rate was notably improved from baseline in this population with unfavorable characteristics and BCS was slightly increased. This combination treatment was well tolerated and pts could benefit from an oral therapy allowing preservation of daily living activities. [Table: see text]
Nicotinic acetylcholine receptors affect growth regulation of human mesothelioma cells: New therapeutic strategies
Authors: P. A. Russo, S. Trombino, A. Cesario, C. Falugi, S. Margaritora, G. Motta, P. Granone
Journal: Journal of Clinical Oncology (2004)

3099 Background: Malignant pleural mesothelioma (MPM) is an uncommon locally invasive and rapidly fatal malignancy whose incidence is still increasing in the western world. It is linked to asbestos exposure and genetic susceptibility. Despite the best and most aggressive, often integrated, standard therapeutic approaches, overall survival remains very poor. The actual failure points out clearly the need of novel therapy development for MPM. In this setting one of the promising paths of experimentation is artificial induction of apoptosis. This study presents data suggesting that both human mesothelioma (cell lines and human mesothelioma biopsies) and human normal mesothelial cells express receptors for acetylcholine and that stimulation of these receptors by nicotine prompted cell growth via activation of nicotinic cholinergic receptors. Methods and Results: our data demonstrate that: (1) human mesothelioma cells and human biopsies of mesothelioma as well as of normal pleural mesothelial cells express functionally alpha-7 nicotinic acethlycholine receptors, evaluated by alpha-bungarotoxin-FITC binding, receptor binding assay, western blot and RT-PCR; (2) choline acetyltransferase immunostaining is present in mesothelioma cells; (3) mesothelioma cell growth is modulated by the cholinergic system in which agonists (i.e. nicotine) has a proliferative effect and antagonists (i.e. curare) has an inhibitory effect, evaluated by cell cloning, DNA synthesis and cell cycle; (4) nicotine induces [Ca+2] influx, evaluated by [45Ca2+] uptake, and consequently activation of MAPK pathway (ERK and p90RSK phosphorilation), evaluated by western blot; (5) apoptosis mechanisms in mesothelioma cells are under the control of the cholinergic system (nicotine antiapoptotic via induction of NF-kappaB complexes and phopsphorilation of Bad at Serine112; curare proapoptotic via G0-G1 arrest p21waf-1-dependent, but p53-independent). Conclusions: The involvement of the non-neuronal cholinergic system in mesothelioma appears reasonable and open up new therapeutic strategies. No significant financial relationships to disclose.
Prospective evaluation of a 409-gene next generation sequencing platform to facilitate genotype-matched clinical trial enrollment.
Authors: Scott Kopetz, Beate Litzenburger, Walter Kinyua, Blessy Sajan, Vivek Subbiah, Ralph Zinner, Jennifer J. Wheler, David S. Hong, Apostolia Maria Tsimberidou, Michael J. Overman, Lance C. Pagliaro, Naifa Lamki Busaidy, Shannon Neville Westin, Bonnie S. Glisson, John Heymach, Funda Meric-Bernstam, Kenna Rael Shaw, J. Jack Lee, Russell Broaddus
Journal: Journal of Clinical Oncology (2015)

3608 Background: We initiated a prospective, institution-wide study to determine whether genomic testing with a 409-gene panel in solid tumors can identify new actionable genomic information (beyond that identified by smaller hot-spot panels) and lead to enrollment in genotype matched trials using agents relevant to the alteration(s) identified. Methods: Eligible patients (pts) had no remaining standard of care therapy anticipated to extend life by more than 3 months, ECOG performance status of ≤ 1, and a willingness to consider clinical trial enrollment. The pts’ tumors were initially sequenced using a hotspot panel (predominantly a 50-gene panel, Ion Torrent, Life Technology), and if no actionable alterations were found, then tumor and paired germline were sequenced with a 409-full-length gene panel (Ion Proton). Actionable genes were defined as those for which a matched genotype selected trial exists in the institution. Results: 200 pts across more than 30 tumor types were consented and underwent 409-gene testing. Novel alterations in an actionable gene not found on a previous hot-spot panel were found in 39.5% of pts. Of these 79 pts, the specific somatic gene variant was of known activity based on existing literature in only 23%; for 77% the somatic variant was of unknown significance. Of the 79 pts, 20 pts (25%) were enrolled in a genotype matched trial, with 8 (10%) anticipated to enroll in the next line of therapy. Reasons for non-enrollment were the treating physician’s opinion that there was insufficient evidence for the functional significance of the variant (23, 29%), exclusion criteria or lack of available slots (16, 20%), or other reasons including pt choice (12, 15%). Conclusions: A significant population of pts with variants in potentially actionable cancer genes not evaluated in a traditional hot-spot cancer gene panel can be identified using a 409-gene targeted gene panel. The high number of somatic variants of unknown significance represents a knowledge gap of clinical importance. While many factors contribute to bottlenecks in utilizing the expanded sequencing results, expanded genomic testing combined with robust decision support can facilitate trial enrollment.
What Is the Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in Excluding Prostate Cancer at Biopsy? A Systematic Review and Meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel
Authors: Paul C. Moldovan, Thomas Van den Broeck, Richard Sylvester, Lorenzo Marconi, Joaquim Bellmunt, Roderick C.N. van den Bergh, Michel Bolla, Erik Briers, Marcus G. Cumberbatch, Nicola Fossati, Tobias Gross, Ann M. Henry, Steven Joniau, Theo H. van der Kwast, Vsevolod B. Matveev, Henk G. van der Poel, Maria De Santis, Ivo G. Schoots, Thomas Wiegel, Cathy Yuhong Yuan, Philip Cornford, Nicolas Mottet, Thomas B. Lam, Olivier Rouvière
Journal: European Urology (2017)
Are stereotypes accurate? A perspective from the cognitive science of concepts
Authors: Lin Bian, Andrei Cimpian
Journal: Behavioral and Brain Sciences (2017)

Abstract In his 2012 book, Jussim suggests that people's beliefs about various groups (i.e., their stereotypes) are largely accurate. We unpack this claim using the distinction between generic and statistical beliefs – a distinction supported by extensive evidence in cognitive psychology, linguistics, and philosophy. Regardless of whether one understands stereotypes as generic or statistical beliefs about groups, skepticism remains about the rationality of social judgments.
Impact of school peanut-free policies on epinephrine administration
Authors: Lisa M. Bartnikas, Michelle F. Huffaker, William J. Sheehan, Watcharoot Kanchongkittiphon, Carter R. Petty, Robert Leibowitz, Marissa Hauptman, Michael C. Young, Wanda Phipatanakul
Journal: Journal of Allergy and Clinical Immunology (2017)
ENTEROANASTOMOSIS GUIADA POR ECOENDOSCOPIA CON PRÓTESIS METÁLICAS DE APOSICIÓN LUMINAL: EVALUACIÓN PRELIMINAR DE INDICACIONES, EFICACIA Y SEGURIDAD
Authors: I Peñas Herrero, R Sánchez-Ocaña Hernández, F Santos Santamarta, P Gil Simón, V Busto Bea, A Loza Vargas Luz, R Amo Alonso, J Santos Fernández, M De Benito Sanz, H Núñez Rodríguez, P Díez Redondo, C De La Serna, M Pérez-Miranda
Journal: Endoscopy (2015)

Introducción: La Entero-Anastomosis Endoscópica (EAE) es un procedimiento novel realizado en modelos animales y excepcionalmente en pacientes. Puede utilizarse para lograr acceso a la vía biliar (ABV) en anatomía postquirúrgica o restablecer el tránsito en casos de obstrucción al vaciamiento gástrico (OVG).
Predictive value of BRCA1 expression on the efficacy of chemotherapy based on anti-microtube agents: a pooled analysis across different malignancies and agents.
Authors: Wenhua Liang, Qihua He, Jianrong Zhang, Jianfei Shen, Jiaxi He, Chenglin Yang, Jianxing He
Journal: Journal of Clinical Oncology (2015)

e22246 Background: Breast cancer susceptibility gene 1 (BRCA1) expression has been suggested as a predictor in the cancer treatment with anti-microtube agents. However, existed evidence did not completely agree with each other. We sought to examine the true impact of BRCA1 expression on the efficacy of anti-microtube agents based on literatures. Methods: Electronic database were searched for eligible literatures. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). Results: A total of 13 relevant studies which involved 1,525 cases were enrolled. The involved agents included paclitaxel, docetaxel and vinorelbine. The involved malignancies included non-small cell lung cancer, gastric cancer, esophageal carcinoma, ovarian carcinoma, malignant pleural mesothelioma, breast cancer and small cell lung cancer. Through meta-analyses, we observed a potentially greater ORR in population with high BRCA1 expression vs. low expression (OR 1.63, 95% CI 0.92 to 2.88, P = 0.09) but the heterogeneity is severe (P = 0.01; I² = 61%). Similar results were observed in PFS (high vs. low expression, HR 0.93, 95% CI 0.75 to 1.15, P = 0.49; heterogeneity, P < 0.01, I² = 75%). After stratification by testing methods, a significantly higher ORR in the population of high BRCA expression was shown in the subgroup that used q-PCR to determine the mRNA quantity (OR 2.90, 95% CI 1.92 to 4.39, P < 0.01; I² = 0) whereas the difference in the subgroup using immunohistochemistry (IHC) to determine the protein level was not significant (OR 0.60, 95% CI 0.33 to 1.10, P = 0.10; I² = 0). HR for PFS could also be stratified by testing methods (mRNA vs. IHC, HR 0.847 vs. 1.047). Stratification by regimen (platinum-based vs. non platinum-based) and patient origin (Asian vs. Caucasian) did not reduce the heterogeneity. Conclusions: Based on current results, we still could not draw a valid conclusion that BRCA1 expression is a predictor to the anti-microtube chemotherapy. However, we suggested that detection of BRCA1 level based on q-PCR rather than IHC should be preferentially considered in future investigations or clinical practice.
Updated analysis of <i>KRAS/NRAS </i>and<i> BRAF </i>mutations in study 20050181 of panitumumab (pmab) plus FOLFIRI for second-line treatment (tx) of metastatic colorectal cancer (mCRC).
Authors: Marc Peeters, Kelly Smith Oliner, Timothy Jay Price, Andres Cervantes, Alberto F. Sobrero, Michel Ducreux, Yevhen Hotko, Thierry Andre, Emily Chan, Florian Lordick, Cornelis J. A. Punt, Andrew Strickland, Gregory Wilson, Tudor E. Ciuleanu, Laslo Roman, Eric Van Cutsem, Hua Yu, Andre Scott Jung, Roger Sidhu, Scott D. Patterson
Journal: Journal of Clinical Oncology (2014)

3568 Background: Previously, extended RAS analysis from this study showed a trend toward improvements in HR on OS and PFS with pmab + FOLFIRI vs FOLFIRI in WT RAS group vs WT KRAS exon 2 group. Here we report updated RAS data and new analysis by BRAF status. Methods: The primary objective was to assess the tx effect of pmab + FOLFIRI vs FOLFIRI on OS and PFS based on RAS/BRAF mutation status in the primary analysis population. Bidirectional Sanger sequencing was used to detect mutations in KRAS exons 3, 4 and NRAS exons 2, 3, 4, and BRAF exon 15 in patients (pts) with known WT KRAS exon 2 mCRC. Results: Overall RAS/BRAF ascertainment rate was 85% (n=1014/1186). 18% of WT KRAS exon 2 pts harbored additional RAS mutations (n=107/597). The incidence of BRAF mutations was 8.3% (45/541). Efficacy is shown (table). Tx HR for pts with WT RAS was 0.81 (95% CI: 0.63, 1.03; P=0.08) for OS and 0.70 (95% CI: 0.54, 0.91; P=0.007) for PFS. Conclusions: Improvements continued to be observed in the tx effect of pmab + FOLFIRI vs FOLFIRI on OS and PFS in WT RAS group vs WT KRAS exon 2 group in this update. Pts with MT RAS mCRC are unlikely to benefit by the addition of pmab to FOLFIRI, similar to pts with MT KRAS exon 2 mCRC. BRAF mutations appear to be associated with reduced OS among pts without RAS mutations regardless of tx arm. These findings support RAS testing to determine potentially appropriate pts with mCRC for pmab tx. Clinical trial information: NCT00339183. Pmab + FOLFIRI (N = 303) FOLFIRI (N = 294) HR (95% CI) Descriptive p WT RAS,a n 208 213 Median OS - mos 95% CI 16.2 14.5, 19.7 13.9 11.9, 16.0 0.81 0.63,1.03 0.08 Median PFS - mos 95% CI 6.4 5.5, 7.4 4.6 3.7, 5.6 0.70 0.54,0.91 0.007 MT RAS,b n 299 294 Median OS - mos 95% CI 11.8 10.4, 13.1 11.1 10.2, 12.4 0.91 0.76, 1.10 0.34 Median PFS - mos 95% CI 4.8 3.7, 5.5 4.0 3.6, 5.5 0.86 0.71, 1.05 0.14 WT RAS/WT BRAFc 186 190 Median OS - mos 95% CI 18.7 15.7, 20.3 15.4 13.0, 17.9 0.83 0.64,1.07 0.15 Median PFS - mos 95% CI 6.9 5.8, 8.0 5.5 3.9, 5.9 0.68 0.51,0.90 0.006 WT RAS/MT BRAFd 22 23 Median OS - mos 95% CI 4.7 2.8, 9.0 5.7 3.5, 7.3 0.64 0.32,1.28 0.20 Median PFS - mos 95% CI 2.5 1.7, 3.5 1.8 1.8, 3.1 0.69 0.32,1.49 0.34 a WT in KRAS and NRASexons 2, 3, and 4.b MT in any KRAS or NRAS exon 2, 3, or 4. c WT for all RAS and BRAF exons. d WT for all RAS and MT BRAF exons.
Molecular characterization of clinically defined aggressive variant prostate cancer (AVPCa) in prospectively collected tissues and corresponding patient derived xenografts (PDX).
Authors: Ana Aparicio, Li Shen, Elsa Li Ning Tapia, Jing-Fang Lu, Hsiang-Chun Chen, Jiexin Zhang, Guanglin Wu, Xuemei Wang, Patricia Troncoso, Paul Gettys Corn, Timothy C. Thompson, Bradley McIntosh Broom, Keith A. Baggerly, Christopher Logothetis, Sankar N. Maity
Journal: Journal of Clinical Oncology (2015)

5055 Background: AVPCa shares clinical features with small cell carcinoma (SCC) such as resistance to androgen signaling inhibition and frequent visceral metastases. A prospective clinical trial of platinum doublets (NCT00514540; Aparicio, Clin Can Res 2013;19) gave confidence that clinically defined AVPCa also shares chemotherapy sensitivity with SCC, irrespective of morphology. Here we screen for links between the clinical phenotype and molecular profile of AVPCa and corresponding PDX. Methods: 59 PC samples from 40 men (10 with SCC) registered to NCT00514540, and 8 PDX from 6 of them, were stained for RB, p53, AR, NKX3-1, ASCL1, AURKA, UBE2C and Ki67. We examined relationships between markers. We subjected DNA from 36 of the PC samples and all PDX to OncoScan to determine copy number alterations (CNA). We compared findings to reported TCGA data. We examined associated and downstream molecular events in the PDX. Results: The 40 men with tissues available for study were similar to remaining NCT00514540 patients except for higher ECOG PS and LDH values. 67% stained negative for RB and 32% for AR. Nuclear (N)-AR showed strong positive correlations with RB, NKX3-1, N-AURKA, as did p53 with N-UBE2C and Ki67 with UBE2C. Most common CNA across morphologies were 8q24 amplification, PTEN loss (largely gene-specific) and RB1 loss (often regional). Clustering segregated samples by CNA rate and associated with Tp53 mutational status but not histology. CNA in RB1, PTEN and MYC carried the highest weight in linear discriminant analyses distinguishing AVPCa from TCGA samples. Seven of 8 PDX bore Tp53 mutations. 2 of 3 RB-positive PDX had high levels of hyperphosphorylated RB. Only AR-negative PDX expressed pro-neural transcription factors, albeit heterogeneously. Conclusions: Clinically defined AVPCa of varied morphologies share molecular profile with SCC and are characterized by combined alterations in RB, p53 and/or PTEN. Analysis of corresponding PDX contributed biological insight. The ability of this signature to distinguish AVPCa is being evaluated in an independent prospective clinical trial (Abstract #152334).
Individualized treatment with sunitinib versus standard dosing with sunitinib or pazopanib in patients with metastatic renal cell carcinoma (mRCC): Results from the Canadian Kidney Cancer information system (CKCis).
Authors: Naveen S. Basappa, Aly-Khan A. Lalani, Haocheng Li, Austin Kalirai, Lori Wood, Christian K. Kollmannsberger, Hao-Wen Sim, Anil Kapoor, Sebastien J. Hotte, Piotr Czaykowski, Christina M. Canil, M. Neil Reaume, Georg A. Bjarnason, Marie Vanhuyse, Denis Soulieres, Eric Levesque, Scott A. North, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2017)

468 Background: Recent analysis using CKCis, a prospective database, showed that mRCC patients receiving first-line sunitinib (S) had better survival than patients receiving pazopanib (P) and greater than expected absolute survival in the real world setting. We conducted further analyses to see if an individualized approach (treatment starting at standard dose/schedule with subsequent schedule/dose alterations based on toxicity) using S results in better outcomes in mRCC patients. Methods: Patients within CKCis diagnosed with clear cell mRCC treated with first-line S or P between January 2011 to December 2015 were analyzed by three treatment groups: 1) S as per individualized approach (SI), 2) S as per product monograph (SS), or 3) P as per product monograph (PS). Overall survival (OS) and time-to-treatment failure (TTF) were calculated. Cox regression analysis allowed for adjustment of International Metastatic RCC Database Consortium (IMDC) criteria with age as a continuous variable. Results: A total of 573 patients were identified, 261 patients in SI, 201 patients in SS, and 111 patients in PS. Differences in baseline characteristics were noted (Table). Median OS was improved in SI vs. SS (40.8 vs. 22.6 months (m), p&lt;0.001) and SI vs. PS (40.8 vs. 20.3 m, p&lt;0.001). TTF was better in SI vs. SS (16.6 vs. 5.4 m, p&lt;0.001) and SI vs. PS (16.6 vs. 7.0 m, p&lt;0.001). SS vs. PS showed no difference in median OS (22.6 vs. 20.3 m, p=0.76) or TTF (5.4 vs. 7.0 m, p=0.11). Adjusted hazard ratio showed significance in SS vs. SI (OS 1.81, p=0.004 TTF 2.42, p&lt;0.001) and PS vs. SI (OS 3.16, p&lt;0.001; TTF 2.03, p&lt;0.001). Conclusions: Significant improvement in OS and TTF is seen using an individualized approach to mRCC patients, further supporting the growing body of evidence endorsing this practice. Further prospective validation awaits from the NCT01499121 study. [Table: see text]