bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoteomic insights in oncology: What have we learned from measuring millions of proteins?
Authors: Brody Ed , Foreman Trudi , Gill Rosalynn D , Mehan Mike , Nikrad Malti , Ostroff Rachel , Stewart Alex , Williams Steve , Zichi Dom 
Published: March 2020

e21142 Background: We have assayed over 8400 blood samples from 10 different malignancies, generating over 8 million quantitative protein measurements using SOMAscan, a new proteomic assay based on modified aptamers. It is capable of simultaneously measuring more than a thousand proteins from small volumes of biological samples such as plasma, tissues or cells. Methods: Bioinformatic analysis has revealed biomarker panels for early detection, differential diagnosis or prognosis in 6 of these cancers: lung, mesothelioma, ovarian, pancreatic, bladder, and renal cell carcinoma. Individual classifiers have been built with 7-13 biomarkers and AUC ranges of 0.84-0.99. These analyses have revealed unique biomarkers for each cancer, as well as common markers. Results: Several themes emerge from our extensive survey of oncology proteomic profiles. Many of the proteins correlate with disease burden or histopathological grade, and thus have utility for diagnosis, prognosis and recurrence monitoring. Parallels between serum and lung tumor tissue protein measurements demonstrate that many of the blood biomarkers arise from the tumor environment. Inflammatory response proteins are identified in many cancers and reveal important connections between tumor development and host response. Patterns can be found for biological processes in tumor biology, including angiogenesis, apoptosis, inflammation, metabolism and tumor invasion. Conclusions: With this new proteomics technology – which is fast, economical, highly scalable and flexible – we now have a powerful tool that enables proteome-wide proteomics, biomarker discovery and advancing the next generation of evidence-based, “personalized” diagnostics and therapeutics for oncology.
The detection of circulating tumor cells in patients with renal cell carcinoma using the AccuCyte platform and customized markers.
Authors: Ramirez Arturo , Tykodi Scott S. , Huang Sherry , Drovetto Nicholas Alan , Stilwell Jackie L. 
Published: March 2020

e21148 Background: Enumeration of circulating tumor cells (CTCs) in peripheral blood represents a prognostic marker for select solid tumors. Commercially available technologies for CTC detection rely on enrichment of EpCAM-expressing cells. However, not all tumor histologies demonstrate high constitutive EpCAM expression, including renal cell carcinoma (RCC). New techniques for more complex immunophenotypic characterization of CTCs are therefore of great interest. Methods: The AccuCyte system for characterization of rare blood cell populations retains all nucleated cells for analysis. Fluorochrome-conjugated monoclonal antibodies (mAbs) are added to 3 ml peripheral blood samples processed by density separation with a specialized tube and float. Centrifugation deposits all nucleated cells (Buffy coat) onto a surface designed for imaging with an automated fluorescence microscope. Sensitivity for CTC identification was measured by spiking blood from healthy donors with defined numbers of MDA-MD-453 breast tumor cells analyzed with mAbs to EpCAM and CD45. Peripheral blood samples from 4 patients (pts) with metastatic RCC and whose primary tumor had been resected were analyzed with a mAb specific for the RCC-associated antigen carbonic anhydrase IX (CAIX), as well as mAbs for CD10, EGFR and EpCAM. Results: In 13 blood samples from healthy donors, an average of 89% of spiked-in MDA-MD-453 tumor cells defined as EpCAM+/CD45- were detected by AccuCyte analysis with linearity from 0 to 139 cells (slope=0.8899; r2=0.9351) and a sensitivity of approximately 1 CTC per 106 nucleated blood cells. 3 of 4 peripheral blood samples from pts with clear cell RCC contained putative CTCs (range 1-6 cells/ml) defined as CD45-/CAIX+ nucleated cells. 3 CTCs from one patient were also CD10+ or EGFR+. All putative CTCs were EpCAM-. Conclusions: The detection of EpCAM-/CAIX+ cells in RCC pts demonstrates the adaptability of the AccuCyte platform for CTC (or other rare blood cell) identification defined by customized markers. Further development of marker panels for CTC analyses in pts with RCC and other tumor histologies as well as automation of image analysis is ongoing.
Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane.
Authors: Blackwell Kimberly L. , Miles David , Gianni Luca , Krop Ian E , Welslau Manfred , Baselga José , Pegram Mark D. , Oh Do-Youn , Dieras Veronique , Olsen Steven R. , Fang Liang , Lu Michael W , Guardino Ellie , Verma Sunil 
Published: March 2020

LBA1 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
A randomized, multicenter trial of epirubicin, oxaliplatin, and capecitabine (EOC) plus panitumumab in advanced esophagogastric cancer (REAL3).
Authors: Waddell Tom Samuel , Chau Ian , Barbachano Yolanda , Gonzalez de Castro David , Wotherspoon Andrew , Saffery Claire , Middleton Gary William , Wadsley Jonathan , Ferry David Raymond , Mansoor Wasat , Crosby Tom David Lewis , Coxon Fareeda Y , Smith David , Waters Justin S. , Iveson Timothy , Falk Stephen , Slater Sarah , Okines Alicia Frances Clare , Cunningham David 
Published: March 2020

LBA4000 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Updated analysis of the phase III, double-blind, randomized, multinational study of radium-223 chloride in castration-resistant prostate cancer (CRPC) patients with bone metastases (ALSYMPCA).
Authors: Parker Chris , Nilsson Sten , Heinrich Daniel , O'Sullivan Joe M. , Fossa Sophie D. , Chodacki Ales , Wiechno Pawel J. , Logue John P. , Seke Mihalj , Widmark Anders , Johannessen Dag Clement , Hoskin Peter , Bottomley David , Coleman Robert Edward , Vogelzang Nicholas J. , O'Bryan-Tear C. Gillies , Garcia-Vargas Jose E. , Shan Minghua , Sartor A. Oliver 
Published: March 2020

LBA4512 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Open-label phase III randomized controlled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919.
Authors: Gelmon Karen A. , Boyle Frances , Kaufman Bella , Huntsman David , Manikhas Alexey , Di Leo Angelo , Martin Miguel , Schwartzberg Lee Steven , Dent Susan Faye , Ellard Susan , Tonkin Katia Sonia , Nagarwala Yasir M. , Pritchard Kathleen I. , Whelan Timothy Joseph , Nomikos Dora , Chapman Judy-Anne W. , Parulekar Wendy 
Published: March 2020

LBA671 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
TAILOR: Phase III trial comparing erlotinib with docetaxel in the second-line treatment of NSCLC patients with wild-type (wt) EGFR.
Authors: Garassino Marina Chiara , Martelli Olga , Bettini Anna , Floriani Irene , Copreni Elena , Lauricella Calogero , Ganzinelli Monica , Marabese Mirko , Broggini Massimo , Veronese Silvio , Gherardi Giorgio , Longo Flavia , Fabbri Maria Agnese , Tomirotti Maurizio , Alabiso Oscar , Sarobba Maria Giuseppa , Labianca Roberto , Marsoni Silvia , Farina Gabriella , Scanni Alberto 
Published: March 2020

LBA7501 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Phase III, randomized, open-label, multicenter trial (BREAK-3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAFV600E-mutated melanoma.
Authors: Hauschild Axel , Grob Jean Jacques , Demidov Lev V. , Jouary Thomas , Gutzmer Ralf , Millward Michael , Rutkowski Piotr , Blank Christian U. , Mirakhur Beloo , Guckert Mary E. , Swann R. Suzanne , Haney Patricia , Martin Anne-Marie , Ouellet Danielle , Grotzinger Kelly , Goodman Vicki L. , Chapman Paul B. 
Published: March 2020

LBA8500^ The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
METRIC phase III study: Efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS) compared with chemotherapy (C) in patients (pts) with BRAFV600/k mutant advanced or metastatic melanoma (MM).
Authors: Robert Caroline , Flaherty Keith T. , Hersey Peter , Nathan Paul D. , Garbe Claus , Milhem Mohammed M. , Demidov Lev V. , Hassel Jessica C. , Rutkowski Piotr , Mohr Peter , Dummer Reinhard , Trefzer Uwe , Larkin James M. G. , Utikal Jochen , Casey Michelle , Sherman Laurie Jill , Crist Wendy A. , Wu Frank S. , Patel Kiran , Schadendorf Dirk 
Published: March 2020

LBA8509 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Emerging findings in the Cancer Research UK stratified medicine program.
Authors: Shaw Emily , Tuff Alice , Sharpe Rowena , Jones Louise K. , Turtiaien Tarita , Griffiths Michael , Butler Rachel , Gonzalez de Castro David , Mason Malcolm David , Collins V. Peter , Rae Frances , Evans T.R. Jeffry , Johnston Stephen R. D. , Rogan Jane , Hanby Andrew , Peach James , Johnson Peter W. M. 
Published: March 2020

TPS10633^ Background: Molecular analysis of tumours may be used to identify those predicted to benefit from novel targeted therapies. The Cancer Research UK programme is piloting plans to apply such testing broadly across the UK healthcare system, linking molecular phenotype to clinical outcomes. Methods: The Stratified Medicine Programme (SMP) aims to develop a model for high quality, large-scale molecular characterization of cancer specimens through an initiative developed in partnership with AstraZeneca, Pfizer, the UK Department of Health and academic researchers. Phase One of the SMP is a two year feasibility study. It aims to demonstrate the submission of consented blood samples and sections of surplus diagnostic formalin-fixed paraffin-embedded tumour tissue from 9,000 patients at centres across the UK to one of three ‘technology hubs’ for mutation testing of genes of potential clinical interest (KRAS, BRAF, NRAS, PIK3CA, TP53, PTEN, TMPRSS2-ERG, EGFR, EML4-ALK and KIT) in six selected tumour types. The tests are technically validated and will be completed in clinically relevant timescales. Data including pathological and treatment information and clinical outcome is also collected for the recruited patients, linked to the genetic data and stored in a central data repository hosted within the National Cancer Registration Service. The study opened in September 2011 at 7 sites across the UK and by the end of 2011, 760 patientswith breast, lung, prostate, colorectal, ovarian cancer or metastatic malignant melanoma had consented to participate. 142 sets of molecular results had been returned to clinical teams. Updated figures will be presented at the meeting, by which time the programme is projected to have accrued 4000 subjects. By 2013, we hope to have developed a scalable model for routine, high quality, prospective molecular characterisation of tumours for NHS cancer patients, with consent for the collection, storage and research use of population-scale genetic and clinical outcome data. We will report the emerging results from the Stratified Medicines Programme and early insights into implications for wider implementation across the UK healthcare system.
Clinical pharmacokinetics (PK) of BMS-936558, a fully human anti-PD-1 monoclonal antibody.
Authors: Agrawal Shruti , Feng Yan , Kollia Georgia , Saeger Sally , Ullmann Martin , McDonald Dan , Gupta Ashok Kumar , Roy Amit , Masson Eric 
Published: March 2020

TPS2622 Background: BMS-936558 is a fully human IgG4 monoclonal antibody targeted against human Programed Death-1 (PD1) receptor on activated T and B lymphocytes. Blocking of PD-1 prevents these activated cells from becoming anergic, thereby maintaining anti-tumor immunologic activity. Methods: The PK of BMS-936558 was characterized with data from a single ascending dose (SAD) and a multiple ascending dose (MAD) study in subjects with advanced solid malignancies. Subjects received a single IV infusion of 0.3 to 10 mg/kg BMS-936558 in the SAD study (MDX-1106-01 Study) and 0.1 to 10 mg/kg BMS-936558 every two weeks in the MAD study (MDX-1106-03/CA209003 Study). The PK of BMS-936558 was characterized by non-compartmental analysis of intensively sampled PK data from a SAD study, as well as by population PK analysis of available intensive and sparse PK data from the SAD and MAD studies, respectively. Results: The PK of BMS-936558 is linear in the studied dose range with dose-proportional increase in Cmax and AUC with low to moderate (20-44%) inter-subject variability. Geometric mean clearance ranged from 0.13 - 0.19 mL/h/kg, whereas mean volume of distribution ranged from 83 -113 mL/kg. The range of mean terminal elimination half-life of BMS-936558 is 17 to 25 days which is consistent with half-life of endogenous IgG4. BMS-936558 PK was adequately described by a linear two-compartment model, and there was no evidence of a contribution of target mediated drug disposition to drug elimination within tested dose range. Body weight and gender are potentially clinically significant covariate for both clearance and volume of distribution (> 20% effect); and baseline CRP, LDH, and albumin are potentially clinically significant covariates for CL. The body weight normalized dosing employed produces trough concentrations that are approximately constant over a wide range of body weights. Conclusions: The pharmacokinetics of BMS-936558 is dose-proportional and body weight normalized dosing is appropriate to ensure consistent exposure over a wide range of body weights.
A phase I study determining the safety and tolerability of combination therapy with pazopanib, a VEGFR/PDGFR/raf inhibitor, and GSK1120212, a MEK inhibitor, in advanced solid tumors enriched with patients with advanced differentiated thyroid cancer.
Authors: Ahmed Shabina Roohi , Azad Nilofer Saba , Ball Douglas Wilmot , Rudek Michelle A. , Nelkin Barry , Cosgrove David , Gong Jing , Finkelstein Daniel , Zahurak Marianna , Janku Filip , Downs Melinda , O'Connor Ashley , Markus Susan , Carducci Michael Anthony , Sherman Steven I. , Kurzrock Razelle 
Published: March 2020

TPS3117 Background: Mutations of the RAS/RAF/MEK/ERK signaling pathway, especially RAS, BRAF and IGF-I/II receptor genes play a critical role in the development of many different types of cancers, including breast, colorectal, melanoma, NSCLC, and thyroid. Differentiated thyroid cancer (DTC) is the most common endocrine malignancy, but there is currently no approved therapy for advanced radioiodine-resistant disease. In DTC xenograft models, vertical inhibition of this pathway, achieved by targeting the vascular endothelial growth factor receptor (VEGFR) and MEK, has shown greater clinical efficacy than with either agent alone. Pazopanib (P) is a small molecule tyrosine kinase inhibitor that selectively inhibits VEGFR1-3, PDGFR-α, PDGFR-b, c-kit, and FGFR 1-3. Phase II data in advanced DTC from Bible, et al, indicate a 49% response rate with a PFS of 11.7 months in a patients with PD within 6 months. GSK1120212 (G) is a potent, highly selective, allosteric inhibitor of MEK1/2. In a phase I/II study, Infante et al. reported an ORR of 81% in BRAF mutant melanoma patients when G was combined with a RAF inhibitor. Methods: A phase I, open label, dose escalation trial with P+G is currently accruing pts with advanced malignancies. The study is a standard 3+3 design with an expansion cohort of 25 pts with advanced DTC for correlative endpoints and PK studies. Pts will be treated with P at 400 mg QD, 600 mg QD and 800 mg QD, with G held constant at 1 mg QD; G will then be escalated to 1.5 mg QD and 2 mg QD. Eligibility includes advanced solid tumor, good end organ function and performance status, and PD within 6 months in the expansion cohort. The primary objective is to determine the safety and tolerability of the combination and determine the MTD. Secondary objectives include assessing preliminary efficacy as defined by RECIST criteria and PFS, and exploration of PK/PD endpoints. Serial tumor biopsies will be evaluated for changes in signaling through p-ERK. RAS and RAF mutation sites will be sequenced in order to correlate with PD endpoints and disease response. Currently, DL1 has accrued with no DLTs.
MAVERICC: A randomized phase II study of mFOLFOX6-bevacizumab (BV) versus FOLFIRI-BV with prospective biomarker stratification in previously untreated metastatic colorectal cancer (mCRC).
Authors: Thomas Sachdev P. , Badarinath Suprith , Greenberg Richard H. , Huh Sang Y. , Sivarajan Kulumani M , Feng Shibao , Scherer Stefan , Litz Curry Christine , Langer Christiane , Lenz Heinz-Josef 
Published: March 2020

TPS3635^ Background: The identification of prognostic and predictive biomarkers could significantly improve the risk-benefit ratio and cost-effectiveness of 1st-line mCRC regimens. This is the first prospective study of tumoral ERCC1 (chemo-resistance marker to platinum compounds) and plasma VEGF-A as potential biomarkers for oxaliplatin- and BV-containing regimens, respectively, in an effort to further define the optimal chemotherapy backbone with biologic therapies, including BV, for mCRC. Methods: In this randomized, open-label, global, phase II study, patients (N=360) with histologically or cytologically confirmed CRC and ≥1 measurable metastatic lesion are stratified at screening by tumoral ERCC1 mRNA expression (high vs low, cutoff of 1.7 [ERCC1/β-actin mRNA]). Eligibility criteria include completion of adjuvant therapy >12 months before screening and an ECOG performance status ≤1. Blood samples are collected to quantify plasma VEGF-A levels. Patients within each ERCC1 stratification group are randomized 1:1 to mFOLFOX6-BV or FOLFIRI-BV administered in 2-week cycles. BV will be given at a dose of 5 mg/kg IV q2w. Patients will remain on study treatment until disease progression (PD) or unacceptable toxicity. If oxaliplatin or irinotecan need to be discontinued, BV and 5-fluorouracil or capecitabine are to be continued until PD. The primary objectives are: 1) to assess ERCC1 and VEGF-A as biomarkers of progression-free survival (PFS) for oxaliplatin- and BV-containing regimens in 1st-line mCRC, and 2) within ERCC1 high patients, to test whether FOLFIRI-BV is associated with a prolonged 1st-line PFS compared to mFOLFOX6-BV. Secondary objectives include assessing the impact of these markers on overall survival, objective response, hepatic metastases resection, and safety. Exploratory endpoints include correlative analyses with additional tumor tissue, blood, and SNP markers. The first patient was enrolled in August 2011. An interim biomarker distribution assessment of the first 100 patients is planned, and the evaluation of the primary endpoints is estimated for early 2015. Clinicaltrials.gov: NCT01374425.
PAN1: A randomized phase II study evaluating potential predictive biomarkers in the treatment of metastatic pancreatic cancer.
Authors: Chua Yu Jo , Karapetis Christos Stelios , Underhill Craig , Nott Louise M. , Goldstein David , Cronk Michelle F. , Gebski Val , Wong Nicole , Sjoquist Katrin Marie , Biankin Andrew Victor ,   Australasian Gastrointestinal Trials Group (AGITG)
Published: March 2020

TPS4137 Background: Biomarker-based selection of cancer treatments has already entered routine clinical practice in some cancer types. Recent retrospective data suggests the human equilibrative nucleoside transporter 1 (hENT1) to be promising predictive marker for benefit from gemcitabine in pancreatic cancer, at least in resected disease. Methods: 80 patients will be randomised to receive either gemcitabine or FOLFOX chemotherapy (folinic acid (FOL) fluorouracil (F) and oxalipatin (OX)) with stratification based on hENT1 status. All patients will be required to have tumour samples tested for hENT1 prior to randomisation, with both hENT1 positive and negative patients eligible for inclusion. Patients will continue their assigned treatment until progression, or unacceptable toxicity. Primary endpoint: Progression free survival in each chemotherapy arm (FOLFOX/gemcitabine). Secondary endpoints: efficacy/activity of gemcitabine and FOLFOX as assessed by OS (overall survival), TTP (time to progression), RR (response rate according to RECIST v1.1), CA19.9 response; Percentage of eligible patients able to be randomised within 14 days of screening; PFS in each biomarker-selected cohort (hENT1 positive/negative); Treatment related toxicity in each chemotherapy group (CTCAE v4.0) and in biomarker cohorts (hENT1 positive/negative); establishment of a tissue bank from patients treated with and without gemcitabine for further biomarker studies. Eligibility: Adult patients with radiologically and histologically confirmed metastatic pancreatic adenocarcinoma who have not previously received treatment for metastatic disease, and who have tumour tissue available for hENT1 testing are eligible for the study. Patients who do not have tumour tissue available will be required to undergo core biopsy to obtain tissue for hENT1 testing. Status: Opened to accrual July 2011.