bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter performance evaluation of the MultiDrugQuant assay kit.
Authors: Krajcsi Peter , Tauber Jakab Katalin , Barath Sandor , Gyimesi Edit , Hevessy Zsuzsanna , Sziraki Kiss Valeria , Szabo Peter , Tokes-Fuzesi Margit , Trucza Eva , Kappelmayer Janos , Marki-Zay Janos 
Published: March 2020

e21140 Background: Multidrug resistance is the most frequent type of resistance to anticancer chemotherapy, which usually results from the overexpression of efflux transporters, such as the MDR1, MRP1 and BCRP. Unfortunatelly, neither the genetic polymorphisms nor the mRNA/protein expression levels correlate closely with the functional activity. On the other hand, although the functional methods separately gave promising results, standardization and reproducibility of these tests failed to conform with values required from routine diagnostic methods. MultiDrugQuant (MDQ) kit was developed as an improved functional assay system, which can measure the multidrug resistance activity of the three, clinically most relevant efflux transporters using flow cytometry in living tumor cells. The present study aimed to carry out the laboratory validation and to evaluate the performance of the MDQ-kit. Methods: Validation of the kit was carried out according to the standards of the Clinical Laboratory Standards Institute in three university centres. Mononuclear cells were separated using Ficoll gradient and tested at 2-5×106/ml within 6 hours after specimen collection. Activities of the multidrug transporters were calculated from the difference between the mean fluorescent intensity of cells w/o the specific inhibitors, respectively. Inaccuracy and comparative measurements were carried out using cell lines with low and high activity of the transporters. Results on different flow cytometers were compared using CD45 CD19 or CD3 monoclonal antibodies for gating the population of interest. Results: The assay proved to be specific and robust at various concentrations of the fluorescent dyes (10-100 % of the original) or inhibitors (50-150 % of the original). Both intraassay and interassay reproducibilities were <5 %. Multidrug resistance activity values determined on different flow cytometers were comparable and eligible. Conclusions: The MDQ assay provides quantitative results on the activity of the MDR1, MRP1 and BCRP in the target cells, which might be used to predict the resistance of these cells to particular cytotoxic agents. Recently, the MDQ-kit has been registered for in vitro diagnostic use in the EU.
The Caris registry: Building a biomarker-focused database to advance patient care.
Authors: Sanders Sheri , Schroeder Wendy , Wright Alan , Field Jeff 
Published: March 2020

e21152 Background: The medical community is continually searching for the best way to treat cancer. The value and utility of biomarkers in guiding treatment decisions is widely accepted but remains a challenge for the bedside clinician and requires ongoing validation and correlation to clinical outcomes. Caris Life Sciences has a dedicated team of scientists who study volumes of scientific literature, synthesize biomarker research and by way of an evidence-based electronic rules engine, translates the application of the literature to biomarker analysis of tumor tissue (The Target Now Report) in support of biomarker-drug association evidence useful in clinical decision-making. Subsequently, Caris initiated the Caris Registry to capture clinical disease, treatment and outcome data from patients who have a Target Now Report. Methods: The Caris Registry is a web-based data entry platform based on an IRB approved protocol. The eligible subject for the Registry will have a qualified Target Now Report. All clinical data elements are defined and supported by the NCI caBIG standardized data dictionary. Disease history/status, treatments and outcomes are captured at enrollment with Day 1 defined as the date of the Target Now Report and every 9 months for 5 years or death whichever is first. Results: As of January 19, 2012, there are 68 participating centers across the country and 43 centers pending IRB submission. There are 852 Target Now cases enrolled with the following cancer lineage distribution: Breast 209, Ovary 169, Lung 117, Colon 79, Endometrium 33, and other 245. There are 323 completed follow up reports and 175 completed end of study reports capturing vital status and cancer related deaths. Conclusions: Caris has successfully launched a scientifically valid and regulatory compliant Registry and database intended to become a robust library of tumor biomarker results linked to clinical outcomes data. As the library grows, data mining could provide vital information access to researchers, pharmaceutical firms, government, academia and insurers for use in drug development, molecular and biomarker research, economic impact assessments, healthcare policy discussion and most importantly directing personalized cancer treatment.
Detection of discordant HER2 status by FISH in circulating tumor cells and disseminated tumor cells in early-stage breast cancer using a microfluidic-based cell enrichment and extraction platform (OncoCEE).
Authors: Krishnamurthy Savitri , Bischoff Farideh Z. , Mayer Julie Ann , Kuerer Henry Mark , Lodhi Ashutosh , Bhattacharyya Anirban , Hall Carolyn S. , Wong Karina , Pham Tam , Pircher Tony J , Lucci Anthony 
Published: March 2020

TPS10631 Background: Evaluation of HER2 in circulating (CTCs) and disseminated (DTC) tumor cells may aid therapy in breast cancer. We report here the discordance in HER2 status in CTCs and DTCs in early stage breast cancer by fluorescence in situ hybridization (FISH) using a microfluidic cell platform (OncoCEE). Methods: Blood (10ml) and BM (1-2ml) from patients with Stage T1 and T2 breast cancer was collected in OncoCEE-Sure collection tubes. Mononuclear cells were recovered using a Percoll density gradient method, incubated with a mixture of 10 primary capture antibodies (Abs), and introduced into streptavidin coated OncoCEE microchannels for tumor cell capture. For blood samples, captured cells were stained with anti cytokeratin (CK) and CD45 Abs for CTC enumeration followed by FISH using probes specific to centromere 17 and HER2. For BM samples, captured cells were subjected to HER2 FISH analysis. The ratio of HER2:CEP17>2.0 in any CK+/ CD45- and CK-/CD45- cell was regarded as positive for HER2. Results: Blood and BM from 68 patients (68 Blood, 54 BM; 54 matched blood and BM) with stage T1N0 (41), T1N1 (6), T2N0 (11), T2N1(2), T2N2 (1), T2N3 (2) with HER2+ (n=7) and HER2- (n=61) breast cancers were studied. The 7 patients with HER2 + primary tumor had HER2+ DTCs in 3/7 (43 %) and HER2 + CTCs in 1/6 (17 %) patients. HER2 + DTCs and HER2 + CTCs occurred in 10/47 (21%) and in 4/57 (7%) patients with HER2- primary breast tumors. The discordance of HER2 status was observed in 14% in CTCs and in 22% in DTCs. Conclusion: 1. The cell enrichment and extraction microfluidic platform (OncoCEE) provides a sensitive approach for evaluation of HER2 in CTCs and DTCs. 2. CTCs and DTCs acquired HER2 gene amplification in 21% and 7% of patients with HER2 negative early stage primary breast cancer. 3. CTCs and DTCs lost HER2 gene amplified status in 57% and 83% of patients with HER2 positive early stage primary breast cancer. 4. The clinical significance of alterations in HER2 status among CTCs and DTCs in early stage breast cancer needs further investigation.
Gemcitabine with nab-paclitaxel in neoadjuvant treatment of pancreatic adenocarcinoma: GAIN-1 study.
Authors: Desai Neelam Vijay , Hughes Steven , Ivey Alison , Hochwald Steven N. , Allegra Carmen Joseph , Trevino Jose Gilberto , Dang Long H. , Behrns Kevin , Lightsey Judith L. , Zlotecki Robert , Liu Chen , Chauhan Shailendra , Zajac-Kaye Maria , Zuluaga Toro Tania , Hou Wei , George Thomas J. 
Published: March 2020

TPS4136 Background: Pancreatic adenocarcinoma remains a deadly disease with a dismal prognosis. Only 15% of patients present with resectable disease with 5-year survival only 20% despite adjuvant therapy. Neoadjuvant treatment may improve R0 resection rates, allows more patients curative surgery, is cost effective, and may improve overall survival by incorporating earlier systemic therapy. Methods: This is a prospective single arm open-label phase II trial using gemcitabine (G) and nab-paclitaxel (A) in the neoadjuvant treatment of resectable and borderline-resectable pancreatic cancer. Patients are stratified by risk group as defined by a predictive model published by Bao et al and the NCCN expert consensus statement (Table): low-risk resectable (Group 1) and high-risk resectable or borderline-resectable (Group 2). Group 1 receives 3 cycles of G+A then surgical resection. 1 cycle = G 1000mg/m2 +A 100mg/m2 IV on Days 1, 8, 15 Q28 days. Group 2 receives 2 cycles of G+A followed by 2 weeks of hypofractionated IMRT (50.4Gy in 10 fx) with G 400mg/m2 IV weekly, then surgical resection. The primary endpoints are R0 resection rate and overall response rates. Secondary endpoints are PFS, OS, 30-day post-op mortality, toxicity, QOL and molecular analysis including DPC4 and SPARC levels in tumor and stroma. Enrollment has just begun with a total accrual goal of 60 patients. This platform will allow targeted systemic therapy and tailored treatment stratification to optimize outcomes in curable pancreatic cancer. This study is registered with Clinicaltrials.gov (NCT01470417). [Table: see text]
What is optimal timing of post prostatectomy radiotherapy? Is adjuvant radiotherapy equivalent to early salvage radiotherapy? The “RAVES” phase III randomized clinical trial.
Authors: Pearse Maria , Kneebone Andrew , Duchesne Gillian M. , Fisher Richard , Fraser-Browne Carol , Frydenberg Mark , Haworth Annette , Jose Chakiath , Joseph David John , Lim Tee , Matthews John , Millar Jeremy , Sidhom Mark , Spry Nigel , Tang Colin , Turner Sandra , Williams Scott G. , Wiltshire Kirsty , Woo Henry , Davis Ian D. 
Published: March 2020

TPS4690 Background: Three randomised trials have demonstrated a significant benefit of adjuvant post prostatectomy radiotherapy in patients with positive margins, extra capsular extension or seminal vesicle involvement, and it should be regarded as current standard of care. However, adopting this approach will expose nearly half of such patients to unnecessary radiotherapy and potential treatment morbidity. Salvage radiotherapy, if given early, is recognised to be effective. The RAVES trial is designed to compare these two approaches, and was developed in collaboration with the Trans Tasman Radiation Oncology Group (TROG), Australian and New Zealand Urogenital and Prostate Trials Group (ANZUP) and the Urological Society of Australia and New Zealand (USANZ). It aims to test the hypothesis that active surveillance with early salvage radiotherapy is non-inferior to adjuvant radiotherapy with respect to risk of biochemical failure (defined as PSA level ≥ 0.40 ng/mL and rising). Methods: Patients must have at least one of the following risk factors: positive margins, extracapsular extension or seminal vesicle involvement. They must start radiotherapy within 4 months of radical prostatectomy (RP) and have an undetectable PSA (≤ 0.10 ng/ml) prior to randomisation. Patients receiving androgen deprivation or who have an artificial hip are excluded. Eligible patients are randomised to either: Arm 1: Adjuvant RT (64Gy in 32#) commenced within 4 months of RP, or Arm 2: Active surveillance with 3 monthly PSA tests and commencement of early salvage RT (64Gy in 32#) if PSA rises ≥ 0.20 ng/ml. Stratification is by seminal vesicle invasion, Gleason Score, pre-operative PSA, margin positivity (no/yes) and radiotherapy institution. A sample size of 470 patients is required to detect a 10% non-inferiority margin in the 5-year biochemical failure-free rate between the adjuvant and active surveillance arms. As of 31 Jan 2012, 186 patients have been recruited across 26 centres in Australia and New Zealand. A meta analysis with the MRC RADICALS and GETUG-17 trials will be prospectively designed to detect a survival difference between the two approaches.
OPTIMA prelim: Optimal personalized treatment of early breast cancer using multiparameter analysis: Preliminary study.
Authors: Stein Rob , Makris Andreas , Hughes-Davies Luke , Dunn Janet A , Bartlett John M. S. , Donovan Jenny , McCabe Christopher , Cameron David A. , Canney Peter , Earl Helena Margaret , Francis Adele , Morgan Adrienne , Pinder Sarah , Rea Daniel , Poole Christopher John , Hall Peter , Hiller Louise , Stallard Nigel , Higgins Helen B 
Published: March 2020

TPS665 Background: “Multi-parameter” prognostic tests such as Oncotype DX are increasingly used to identify women with ER +ve HER2 -ve breast cancer treated with endocrine therapy who are unlikely to benefit meaningfully from adjuvant chemotherapy. The supporting evidence for predictive testing is retrospective and is strongest for women with negative nodes. Randomised trials to validate testing are in progress but more evidence is needed, especially for node positive disease. There is early evidence that other multi-parameter tests which are in development have a predictive utility. Methods: OPTIMA will assess the value of multi-parameter tests in a UK population. OPTIMA prelim, the feasibility phase, will recruit 300 patients from May 2012 (with a 200 patient bridging extension to the main study). Eligible patients will have ER +ve HER2 -ve tumours with involved nodes (pN1-2). Patients will be randomised to the standard arm of both chemotherapy and endocrine therapy, or to the “test-directed treatment” arm in which patients will be assigned either the same chemotherapy and endocrine therapy or endocrine therapy only according to the result of an Oncotype DX test. OPTIMA prelim has 3 objectives. (1) To establish whether randomisation to test-directed treatment is acceptable to patients and clinicians. This will be done through qualitative research with in-depth interviews with OPTIMA researchers and by recording and analysing consultations when the trial is discussed with potential participants. (2) Alternative multi-parameter tests will be evaluated on all patients’ tumours and their performance will be compared to Oncotype DX using statistical and cost-effectiveness analysis to select a candidate test(s) appropriate for NHS use to be evaluated in the main trial. (3) The success of the main trial depends on efficient tumour sample collection and analysis to avoid treatment delays. The obstacles to this will be analysed in detail using a sample tracking database. The main study is an efficacy trial of 2-3 arms with the same design but uses tests selected in OPTIMA prelim. It will compare 5-year relapse free survival of test-directed vs. conventional treatment with a non-inferiority hypothesis.
A multicenter randomized phase III trial of customized chemotherapy versus standard of care for first-line treatment of elderly patients with advanced non-small cell lung cancer (EPIC).
Authors: Simon George R. , Novello Silvia , Vavala Tiziana , Stinchcombe Tom , Gregorc Vanesa , Otterson Gregory Alan , Gitlitz Barbara Jennifer , Langdon Robert M. , Bordoni Rodolfo , Axelrod Rita , Gandara David R. , Scagliotti Giorgio 
Published: March 2020

TPS7619 Background: Personalizing therapy based on an individual patient’s molecular profile is a potentially promising approach to optimize efficacy with the available agents. Optimizing efficacy in the elderly is particularly relevant owing to their increased propensity to suffer therapy-induced toxicity. In this proposal we will attempt to demonstrate optimization of therapy in good performance EGFR mutation negative elderly patients by taking in to consideration the histology of the tumor, the ERCC1 (marker of platinum resistance), RRM1 (for gemcitabine resistance) and TS (for pemetrexed resistance) status. Methods: Untreated advanced stage NSCLC patients age >70 years with measurable disease will be enrolled. Patients will be randomized in a 2:1 randomization to experimental arm (A) or standard arm (B). In arm A, treatment with single or dual-agent chemotherapy will be selected based on histology, ERCC1 (E), RRM1(R) and TS (T) expression at the RNA level. The cut off for high (+, therefore resistant) or low (-, therefore sensitive) expression have been previously defined. Patients with squamousNSCLC who are E-R+ will be treated with single agent carboplatin, E+R- with gemcitabine, E-R- with carboplatin and gemcitabine and E+R+ with docetaxel or vinorelbine. In non-squamous NSCLC patients E-T+ will be treated with carboplatin, E+T- withpemetrexed, E-T- with carboplatin and pemetrexed, E+T+R- with gemcitabine and E+T+R+ with docetaxel or vinorelbine. In arm B treatment with single or dual-agent chemotherapy will be at the discretion of the care provider, i.e., standard of care. The primary endpoint of the trial is overall survival (OS). The secondary endpoint is progression-free survival (PFS). The tertiary endpoint is disease response. Treatment will continue to maximum of 6 cycles if tolerated or until disease progression. A sample size of 453 patients will give us 90% power to detect a three-month improvement in median survival (8 to 11 months; corresponding to a HR of 0.73) with the log rank test at a significance level of 5%(1-sided) allowing for a 10% failure rate in gene analyses.
Topotecan-vincristine-doxorubicin in metastatic neuroblastoma with insufficient response to rapid COJEC: Results of a SIOPEN Group study.
Authors: Amoroso Loredana , Valteau-Couanet Dominique , Castel Victoria , Brock Penelope , Pearson Andrew DJ , Ladenstein Ruth Lydia , Garaventa Alberto 
Published: March 2020

10016 Background: This study evaluated the activity and toxicity of a topotecan-vincristine-doxorubicin (TVD) combination administered to patients with stage 4 neuroblastoma failing to achieve adequate metastatic remission after induction therapy (rapid COJEC) according to the HR-NBL-1 SIOPEN protocol. Methods: Patients above 1 year of age with stage 4 neuroblastoma, who failed to achieve adequate metastatic remission with rapid COJEC were eligible. Topotecan was administered at 1.5 mg/m²/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m² and doxorubicin, 45 mg/m². Tumour response was assessed after 2 TVD courses, according to the INSS criteria. Patients achieving CR or VGPR (metastatic CR) or PR (≤ 3 skeletal MIBG spots and cytomorphological CR on 2 bone marrow aspirates) underwent myeloablative therapy (MAT) followed by PBSC rescue. Patients who failed to achieve PR after 2-4 TVD courses, or developed PD were withdrawn from the study and were treated at physicians’ discretion. Results were recorded in the SIOPEN-R-NET database. Results: Sixty-eight patients who did not achieve CR or VPGR after rapid COJEC were enrolled in the study. Responses of 68 assessable patients after 2 TVD courses included 4 CR, 13 VPGR, 26 PR, 7 MR, 14 NR, 2 PD, 2 missing data (major response rate 65 %). Twenty-five patients who achieved CR or VGPR or PR (metastatic CR) received MAT according to protocol. Thirty-three/68 patients are presently alive, no toxic deaths occurred. Toxicity was mostly hematopoietic. Fifty-three patients experienced grade 4 neutropenia, 47 grade 4 thrombocytopenia and 12 grade 4 anemia after the first course. Forty-nine patients developed grade 4 neutropenia, 41 grade 4 thrombocytopenia and 12 grade 4 anemia after the second course. Twenty-six patients required hospitalisation for systemic antibiotic therapy after the first course, and 19 patients after the second. Grade 3-4 stomatitis requiring a liquid diet or TPN was observed in 17 patients after the first cycle and 9 after the second. Conclusions: This TVD combination was active and tolerable in patients with metastatic neuroblastoma after treatment with rapid COJEC. Clinical trial information: 2006-001489-17.
Outcome of risk-adapted therapy for pediatric acute lymphoblastic leukemia in Egypt.
Authors: Sidhom Iman A. , Mokhles Abir , Soliman Sonya , Shaaban Khaled , Salem Sherine , Yassin Dina , Hassanein Hala , Hamdy Nayera , Rashed Waffa , El-Nashar Amr , Magdi Hadeel , Elhaddad Alaa 
Published: March 2020

10044 Background: With modern risk directed therapy, >80% of children with acute lymphoblastic leukemia (ALL) in western countries are cured. The 5-year event free survival (EFS) and relapse free survival (RFS) of pediatric ALL patients in Egypt were 65% and 75% respectively in a previous study using an intensive treatment protocol for all patients. Aim: To improve cure rates of Egyptian children with ALL using risk adapted therapy. Methods: From July 2007 to December 2010, 706 patients aged 1-18 years with newly diagnosed ALL were treated at Children Cancer Hospital Egypt with a risk directed ALL protocol adopted from St Jude Total Study XV. Results: B-precursor phenotype was encountered in 75.8% and T-cell in 24.2%. Based on initial presentation and response to therapy measured by minimal residual disease (MRD), 42.6%, 45.8% and 11.6% of the patients were classified as low, intermediate and high risk respectively. The 5-year RFS and EFS were 88.2 ± 1.5% and 76.5 ± 1.7% respectively. Adverse events included 4.4% induction deaths, 2.5% failure to achieve induction remission (1.4% remained refractory), 6.8% deaths in remission, 9.2% relapses (3.1% hematological, 1.8% combined hematological and CNS, 4% isolated CNS, 0.3% isolated testicular), 0.9% abandonment of therapy and one patient had secondary myeloid leukemia. The median follow up for patients alive in CR was 43months (range 24–65). The 5-year RFS of the low, intermediate and high risk groups were 92.2 ± 2.4%, 85.3 ± 2.2% and 82.7 ± 4.8% respectively (p=0.001), while the 5-year EFS were 87.6 ± 2.5%, 78.2 ± 2.5% and 57.9 ± 5.7% respectively (p<0.001). Prognostic factors that had statistically significant unfavorable impact on both EFS and RFS by univariate analysis were age ≥10 years, TLC ≥100x109/L, T-cell phenotype, risk groups, MRD d42 ≥1% and MRD W7 ≥0.1%, while MRD d15 ≥1% had statistically significant unfavorable outcome on EFS only. By multivariate analysis, TLC and MRD W7 had prognostic significance on EFS and RFS, MRD d42 on EFS, while MRD d15 had marginal significance on EFS (p=0.055). Conclusions: Risk adapted therapy was effective in improving ALL survival among patients at our institution compared with previous trials, although the outcome remains lower than that in high income countries.