bluuebunny/crossref_metadata_2025_split huggingface dataset:
62cuatsm and 62cuptsm PET is a useful imaging tool for hypoxia and perfusion in lung cancer.
Authors: Zhang Tian , Das Shiva K. , Crawford Jeffrey , Wong Terence , Dewhirst Mark W. , Vlahovic Gordana 
Published: March 2020

e22166 Background: Hypoxia is a characteristic of many tumors and portends a worse prognosis in lung, cervical, prostate, and rectal cancers. Unlike the others, lung cancers present a unique challenge in measuring hypoxia, with invasive biopsies and higher rates of complications. Noninvasive imaging studies detecting hypoxia using isotopes of copper-diacetyl-bis (N4-methylthiosemicarbazone), CuATSM, have predicted prognosis and treatment outcomes in some small feasibility trials. These images, however, may not identify all areas of hypoxia. Hence, we hypothesize that the addition of another positron emission tomography (PET) imaging agent, copper-pyruvaldehyde-bis (N4-methylthiosemicarbazone), 62CuPTSM, which can detect areas of perfusion, can augment the information obtained in 62CuATSM PET scans. Methods: In order to characterize tumors based on both perfusion and hypoxia, ten patients were studied using both 62CuATSM and 62CuPTSM PET scans. All patients signed informed consent; the protocol was approved by the Duke University Medical Center institutional review board. 62CuATSM and 62CuPTSM SUV values at steady state were tabulated and the ratios of 62CuATSM to 62CuPTSM calculated. In addition, proteomic arrays looking at specific proangiogenic, survival, and proinflammatory targets were assessed. Results: Six out of ten patients had fully evaluable PET scans. Our initial experience of characterizing lung tumor hypoxia using 62CuATSM/62CuPTSM PET scans showed that visualization of areas with hypoxia normalized for perfusion is feasible. All studied tumors exhibited some hypoxia. Despite the small sample size, a positive relationship was noted between serum epidermal growth factor (EGF) levels and 62CuATSM detected hypoxia. Conclusions: This initial series of 62CuATSM/62CuPTSM PET scans demonstrate that evaluating pulmonary lesions by visualizing hypoxia and perfusion is a feasible and novel technique to provide more information. Further investigation is warranted to assess the potential role of 62CuATSM and 62CuPTSM PET imaging techniques combined with proteomics as alternatives to invasive biopsy techniques in clinical care.
Time for early predictive biosignatures to personalize the clinical approach of advanced tumor patients?
Authors: Yamaguchi Nise Hitomi , Spada Manoela Tavares Arruda , Ribeiro Rachel , Silverio Flavio , Tamura Paula , Moura Fernando , Oliveira Aline Crisitna Conceicao , Cordeiro Eivete , Anciaes Fabiana Sequim , Kobayashi Kleber , Donatangelo Silvio , Oliveira Nivia Fernanda 
Published: March 2020

e22176 Background: The Institute of Advances in Medicine is a private referral center in Brazil that treats patients with advanced disease, often after failure to previous lines of treatments. Predictive response assays allow physicians to make better informed choices when establishing the therapeutic strategy for each patient. Methods: 48 patients (21 male; 27 female), 54.5 y old (33-80y) with advanced disease were submitted to molecular diagnostic investigation using paraffin-embedded tumor samples from Brazil, shipped to Caris Target Now-US in accordance with the Brazilian Federal Sanitary Agency regulations. We have considered the samples diversity, different tumor sites, tissue availability and technical conservation. Results: More than 1920 IHC, FISH or CISH, RT-PCR, RFLP, sequencing and mutational analysis by PCR were performed, with a list of drugs with Potential Clinical Benefit (PCB) or Potential Lack of Benefit (PLB) for the 48 primary tumors: 11 colorectal, 9 breast, 6 NSCLC, 22 other sites. Drugs were listed in the PCB column that were usual drugs in first and second line treatments for their cancer types. However, many patients were classified with PLB with drugs that they had used before and were not active. These data were analyzed for Performance Status, Previous Treatments actually given and current commercially available anticancer agents, such as chemotherapeutic and new molecular targeted agents to help the decision for future treatments. Conclusions: When the test was performed, patients had already been treated (and had had disease progression) with drugs that were listed as potentially lacking benefit. Time is ripen for testing tumors prior to beginning clinical treatment, since it may provide a better understanding of the tumor biology and the probable clinical response, making it possible to distinguish which therapeutic schedule is preferable. The present availability of reliable predictive assays for assessing tumor sensitiveness (or lack of it) to anticancer drugs makes it imperative to change guidelines. The ever growing health costs in the public health systems around the world may also benefit from such strategy since only drugs with a potential for response will be chosen.
A novel approach to improve detection of somatic DNA variants in solid tumors by next-generation sequencing from FFPE samples.
Authors: Udar Nitin , Haigis Robert , Gros Thomas , Lucio-Eterovic Agda Karina , Zhang Qingxiu , Zenali Maryam , Ross Mark , Jaeger Erich 
Published: March 2020

e22177 Background: Low frequency variant detection by sequencing is a highly desired goal for therapy selection in cancer especially the detection of actionable targets. The lower limit of detection using Sanger sequening is ~20% minor allele frequency (MAF). Deep sequencing of target genes using next generation sequencing (NGS) is gaining popularity. Formalin Fixed Paraffin Embedded (FFPE) tissue is the most common sample type in solid tumor histopathology. However, because the fixation process fragments DNA and damages it at varying frequencies, downstream processes can potentially misclassify modified bases and generate artifacts. We have developed a protocol that addresses both of these issues in a multiplex assay that involves deep sequencing using NGS of targets implicated in lung, gastric, colon, melanoma and ovarian cancers. Methods: The sample set includes 168 FFPE samples and 82 non FFPE samples. TruSeq Custom Amplicon technology was used to generate libraries for targets across 26 genes. Deep sequencing was done on a NGS platform (Illumina-MiSeq). Results: The DNA quality test, which surveys multiple genomic targets by qPCR, was an accurate determinant of DNA amplifiability and yielded a 99% sample success rate. A sensitivity of <5% MAF was achieved by sequencing at a depth of 1,000X for all targets. In order to differentiate true low frequency variants from fixation and other artifacts, our novel approach investigates each of the two DNA strands independently. The information is bioinformatically combined to distinguish true variants from artifacts. Testing of the FFPE samples with a 5% MAF cut off using the two strand approach reduced the potential false positive rate by ~ 40% when compared to information from only one strand of DNA. A comparative analysis of matched FF and FFPE sample showed that a high percentage of false positive calls were present even in the fresh frozen samples at this high level of sensitivity, if only using information from one strand. Conclusions: This protocol, efficiently and accurately detect low frequency variants by NGS in DNA extracted from FFPE tissues.
Development of an automated RNA-based nuclease protection assay for the detection of expressed EML-ALK fusions, EGFR, and KRAS mutations in NSCLC.
Authors: Rounseville Matthew , Maddula Krishna , Seligmann Bruce , Botros Ihab , Modur Vijay 
Published: March 2020

e22185 Background: The management of patients for NSCLC requires appropriate molecular pathology assessment to determine treatment. However current methods require the use of more than one technology including sequencing for EGFR and KRAS mutation and in situ hybridization for EML-ALK fusion, resulting in slow turnaround, and technical as well as logistical complexities. Here, we report the development of an automated microarray based quantitative nuclease protection assay that determines gene fusions, deletions and point mutations in target genes such as EML4/ALK, EGFR and KRAS from expressed mRNA directly from FFPE tissue without prior RNA extraction. Methods: We designed mutation and fusion specific probes for nuclease protection and measured the sensitivity, specificity, and reproducibility of gene mutations and fusions using in vitro transcribed RNA and cell lysates known to contain the target mutations. In addition to synthetic samples, we also screened 88 lung cancer specimen for EML-ALK fusions. Results: Mutations in KRAS (G12D, G12C, G12V); EGFR (D761Y, T790M, L858R); EML-ALK fusions (v1 v2, v3a, v3b-3, v4, v5a, v5b-3 and v6) were detected at concentrations of 3 copies/cell in 15,000 cells even when present as low as 5% of wild type IVT RNA. The sensitivity corresponds to an amount of FFPE sample ranging from 0.3 to 0.6 square cm of a 5mm FFPE section per replicate assay making it suitable for needle biopsy specimen. Six samples with probable EML4-ALK fusions were identified in the 88 adenomatous NSCLC samples and will be subjected to further confirmation. Additional clinical validation of all the assays will be presented in our poster. Conclusions: An automated, multiplexed, EGFR and KRAS mutation and EML-ALK gene fusion from expressed mRNA is feasible. The assay can be run directly on FFPE sections, does not require RNA extraction or amplification, and is completed within 24 hours.
Aneuploidy and neoplasia: Case of recurrent polysomy occurring at different times.
Authors: Adiga Giridhar U. , Ramesh K H , Tong Tommy R , Jodlowski Tomasz 
Published: March 2020

e22196 Background: Recurring polysomies in diverse tumors at different times may suggest common neoplastic mechanisms. Following case demonstrates similar polysomies in breast, endometrial and cholangiocarcinoma arising at different times. Methods: A 79-year-old African American female was diagnosed poorly differentiated cholangiocarcinoma. Tumor markers (CEA, AFP, CA19-9) were normal. FISH analysis with D3Z1 (centromere 3), D7Z1 (centromere 7), CDKN2A (9p21) and D17Z1 (centromere 17) DNA probes (Abbott Molecular, IL. USA) revealed polysomy of chromosomes 3, 7, 9 and 17. Oncology history includes tumors noted in the table. Medical history includes aortic aneurysm, hypertension, IPF, obesity, CKD, DJD, cholecystectomy and adjuvant tamoxifen. She was never pregnant, non smoker non alcoholic and no prior chemical exposures. Her maternal aunt had unclear pelvic cancer at 70. Her niece had duodenal cancer in 40s. Possible common initiating neoplastic mechanism or predisposition was speculated in view of multiple tumors. Archived specimens of previous tumors were tested using the same FISH probe set. Results: Similar pattern of aneuploidy was noted in cholandiocarcinoma, DCIS and endometrial polyp specimen and no such abnormalities in parathyroid adenoma and in normal tissue. Conclusions: Occurrences of similar polysomy in tumors originating from diverse tissues at different times but not in normal tissue suggest common predisposition and/or similar, nonrandom, neoplastic molecular events. Uncommon and previously not described polysomy pattern was noted in DCIS and in endometrial polyp. [Table: see text]
Clinical significance of cytokines levels in exhaled breath condensate (EBC) and serum of lung cancer patients.
Authors: Lamprodimou Georgia , Athanasiadis Athanasios , Kerenidi Theodora , Doufexis Dimitrios , Lada Martha , Tsilioni Irini , Roussos George , Vavougios George , Gourgoulianis Konstantinos 
Published: March 2020

e22202 Background: Cytokines are known to play an important role in carcinogenesis.The aim of this study is to measure pre-treatment concentrations of cytokines IL6, IL10, IL1β and IL8, in EBC and serum of lung cancer patients and to assess any possible association with clinicopathological variables and survival. Methods: From February 2010 to May 2011 we enrolled 73 patients with previously untreated lung cancer, 67 males and 6 females, age 67.7±9.5 years, 46 smokers and 27 ex-smokers, and 30 healthy individuals as controls. Sixty-one patients had NSCLC and 12 SCLC (5 stage I, 3 stage II, 19 stage III and 46 stage IV). EBC was collected using the Ecoscreen device (Viasys, Germany). Serum and EBC levels of cytokines were analyzed by commercially available enzyme-immunosorbent assay kits (ELISA). Results: All cytokines but IL8 were detectable in both materials. IL8 was not detected in EBC. All cytokines were significantly increased in patients with lung cancer in comparison to controls (IL6: serum P<0.0001, EBC P=0.001; IL10: serum P= 0.006, EBC P=0.037; IL1β: serum P= 0.032, EBC P=0.005; IL8 serum P=0.001). Moreover, a statistically significant correlation was found between IL10 levels in EBC and serum (P=0.001, Rho=0.334). In EBC, higher levels of IL6 were found in patients with T3-T4 disease than in those with T1-T2 [4.27 pg/ml (2.46-5.99) vs 3.12 pg/ml (1.35-5.03), P=0.036]. Furthermore, smokers had higher serum levels of IL6 compared to ex-smokers [10.19 pg/ml (4.92-17.38) vs 4.46 pg/ml (1.88-11.53), P=0.009]. Finally, lower serum levels of IL6 < median value (9.55pg/ml) were associated with improved survival (median overall survival 338 days vs 237 days Log Rank test, P= 0.046). Conclusions: Elevated levels of measured cytokines were found in both EBC and serum of lung cancer patients. Particularly, IL6 levels were related to T-stage and smoking status, while lower serum levels of IL6 with survival. These findings suggest that cytokines should be further studied in order to evaluate their diagnostic and prognostic significance. EBC could provide a simple, noninvasive and economic method for the monitoring of biomarkers in patients with lung cancer.
Lapatinib in combination with capecitabine plus oxaliplatin (CapeOx) in HER2 positive advanced or metastatic gastric (A/MGC), esophageal (EAC), or gastroesophageal (GEJ) adenocarcinoma: The LOGiC trial.
Authors: Hecht J. Randolph , Bang Yung-Jue , Qin Shukui , Chung Hyun-Chul , Xu Jian-Ming , Park Joon Oh , Jeziorski Krzysztof , Shparyk Yaroslav , Hoff Paulo M. , Sobrero Alberto F. , Salman Pamela , Li Jin , Protsenko Svetlana , Buyse Marc E. , Afenjar Karen , Kaneko Tomomi , Kemner Allison , Santillana Sergio , Press Michael F. , Slamon Dennis J. 
Published: March 2020

LBA4001 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Correlation of molecular alterations with efficacy of everolimus in hormone-receptor–positive (HR+), HER2-negative advanced breast cancer: Preliminary results from BOLERO-2.
Authors: Hortobagyi Gabriel N. , Piccart-Gebhart Martine J. , Rugo Hope S. , Burris Howard A. , Campone Mario , Noguchi Shinzaburo , Perez Alejandra T. , Deleu Ines , Shtivelband Mikhail , Provencher Louise , Masuda Norikazu , Dakhil Shaker R. , Anderson Ian , Chen David , Damask Amy , Huang Alan , McDonald Robert , Taran Tanya , Sahmoud Tarek , Baselga José 
Published: March 2020

LBA509 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Trial of zoledronic acid and interleukin-2 to expand tumoricidal γδ T cells in vivo in patients with refractory neuroblastoma.
Authors: Pressey Joseph Gerald , Adams Julia M , Kelly David R , Lamb Lawrence S 
Published: March 2020

TPS10073 Background: CD3+ γδ+ T cells comprise 2 to 5% of the circulating T cells. Vγ9Vδ2+ cells are the dominant circulating γδ T cell and recognize non-peptide phosphoantigens and stress-associated NKG2D ligands expressed on malignant cells. Strategies that incorporate the tumoricidal properties of γδ T cells represent a promising means of harnessing the innate immune system to treat malignancies including neuroblastoma (NB). Indeed, γδ T cells from both healthy volunteers and NB patients exert a potent cytotoxic effect on NB cell lines and autologous NB in vitro following expansion and activation in culture. Vγ9Vδ2+ cells can also be induced to proliferate in vivo. By blocking farnesyl pyrophosphate synthase in the mevalonate pathway of isoprenoid synthesis in monocytes, the aminobisphosphonate zoledronic acid (ZOL) promotes the accumulation of isopentenyl pyrophosphate which is sensed by γδ T cells. IL-2 is also required for robust expansion γδ T cells. Methods: The trial is a prospective, non-randomized trial that assesses two dose levels of recombinant IL-2 (aldesleukin) in combination with ZOL. To be eligible for the study patients must be 2 to 21 years of age with refractory neuroblastoma with no known curative therapeutic options. Patients must also have adequate organ function and performance status. ZOL is given intravenously on day 1, and aldesleukin is given subcutaneously on days 1 to 5 and 15 to 19 of every 28 day cycle. The single-institution study is being conducted at the University of Alabama at Birmingham. Correlative studies include evaluating the absolute count, phenotype, activation, and effector/memory progression of γδ T cells by flow cytometry and the biological function of autologous expanded/activated γδ T cells by in vitro cytotoxicity assays employing established human NB cell lines. In order to determine the ability of in vivo expanded/activated γδ T cells to infiltrate NB tissue, bone marrow core biopsies obtained before and after the first course of therapy from patients with bone marrow metastasis are assayed for T cell infiltration by immunohistochemistry. The study has currently enrolled 1 of the planned 6 patients. Clinical trial information: NCT01404702.
A randomized, double-blinded, placebo-controlled, multi-institutional, cross-over, phase II.5 study of saracatinib (AZD0530), a selective Src kinase inhibitor, in patients with recurrent osteosarcoma localized to the lung.
Authors: Baird Kristin , Reinke Denise K. , Pressey Joseph Gerald , Mascarenhas Leo , Federman Noah , Marina Neyssa , Chawla Sant P. , Lagmay Joanne Pigues , Goldberg John M. , Milhem Mohammed M. , Loeb David Mark , Butrynski James E. , Janeway Katherine A. , Turpin Brian , Staddon Arthur P. , Spunt Sheri L. , Rodler Eve T. , Schuetze Scott , Okuno Scott H. , Helman Lee J. 
Published: March 2020

TPS10591 Background: Osteosarcoma is a rare cancer and 33% of patients who have completed primary treatment will recur. The Src pathway has been implicated in the metastatic behavior of several tumors including osteosarcoma where 95% of samples express Src or have evidence of downstream activation of this pathway. Saracatinib (AZD0530) is a potent and selective Src kinase inhibitor. The recommended phase II dose in adults was found to be 175mg daily. The primary goal of this study is to determine if treatment with Saracatinib can increase progression free survival (PFS) for patients who have undergone complete resection of metastatic osteosarcoma nodules in the lung. Secondary goals are evaluation of overall survival, time to treatment failure, and evaluation of several biological correlatives. Methods: This is a multi-institutional, phase II.5, placebo-controlled study with an accrual goals of 88 randomized patients. Patients between 15 and 75 years, with histological confirmation of recurrent osteosarcoma, localized to the lung, who have potential for complete surgical resection, are eligible for enrollment. After complete resection, patients are randomized to treatment with saracatinib or placebo, of a daily oral dose of 175 mg, continuously for up to 1 year or until progression. Patients who recur in the lung while on-study and who are amenable to complete surgical resection will be un-blinded. Those patients who received placebo may have the option to undergo surgical resection. If fully resected, they will be offered therapy with saracatinib under the same treatment guidelines as above. As of January 2013, 38 patients have enrolled and 32 patients met the criteria to be randomized and began oral therapy with either saracatinib or placebo. An interim analysis is planned after 40 patients have been randomized. Clinical trial information: NCT00752206.
The prospective MammaPrint MINT (Multi-Institutional Neo-adjuvant Therapy) study.
Authors: Cox Charles E. , Blumencranz Peter William , Saez Ruben A. , Wesolowski Robert , Stork Lisette , De Snoo Femke , Gibson Jessica , Howard Nicole , Avisar Eli 
Published: March 2020

TPS11122 Background: Patients with locally advanced breast cancer (LABC) are often treated with neo-adjuvant chemotherapy to reduce the size of the tumor before definitive surgery. Complete pathologic Response (pCR) predicts better long term outcome. Genomics assays that measure specific gene expression patterns in a patient's primary tumor have become important prognostic and predictive tools for early breast cancer. This study is designed to test the ability of molecular profiling, as well as traditional pathologic and clinical prognostic factors to predict responsiveness to neo-adjuvant chemotherapy in patients with LABC. Methods: Women ≥ 18 yrs with histologically-proven invasive breast cancer T2(≥3.5cm)-T4,N0M0 or T2-T4N1M0, with measurable disease, adequate bone marrow reserves and normal renal and hepatic function who signed informed consent are enrolled. Axillary lymph nodes will be staged according to protocol. MammaPrint risk profile, BluePrint molecular subtyping profile, TargetPrint ER, PR and HER2 single gene readout, and the 56-gene TheraPrint Research Gene Panel will be analysed using the whole genome expression array. Patients will receive neo-adjuvant chemotherapy treatment according to protocol. Response will be measured by centrally assessed Residual Cancer Burden (RCB). Objectives are: (1) To determine the predictive power of MammaPrint and BluePrint for sensitivity to neo-adjuvant chemotherapy as measured by pCR. (2) To identify and/or validate predictive gene expression profiles of clinical response or resistance to neo-adjuvant chemotherapy. (3) To compare TargetPrint ER, PR and HER2 with local and centralized IHC and/or CISH/FISH assessment. (4) To identify correlations between TheraPrint and response to neo-adjuvant chemotherapy. (5) To compare BluePrint molecular subtype with IHC-based subtype classification. To achieve a difference of 20% in chemotherapy sensitivity for patients stratified by MammaPrint, a total of 226 samples is needed (significance level 0.05 and power of 0.90). So far 45 patients have been enrolled from multiple institutions. Clinical trial information: NCT01501487.