tbuckley/cabot-search huggingface dataset:
The usefulness of interphase fluorescence in situ hybridization at diagnosis of myeloma in addition to metaphase cytogenetics
Authors: S. Park, C. Kim, H. Kim, D. Hong, S. Lee, J. Won, H. Park, S. Bae, Y. Lee, E. Kim, Y. Jung
Journal: Journal of Clinical Oncology (2009)

e19558 Background: Multiple myeloma is characterized by the accumulation of malignant plasma cells within the bone marrow and regarded as incurable, but remissions may be induced with steroids, chemotherapy, thalidomide and stem cell transplants. The clinical heterogeneity of myeloma is dictated by the cytogenetic aberrations present in the clonal plasma cells. Fluorescence in situ hybridization (FISH) overcomes the limitations of standard cytogenetics and allows for the detection of numerical and structural chromosomal abnormalities in both metaphase spreads and interphase nuclei. Methods: We evaluated the chromosome abnormalities in 34 MM patients using conventional cytogenetics and interphase FISH with 6 probes such as IGH/CCND1, IGH/FGFR3, IGH/MAF, DS13S319/LAMP1, IGH/BAP, and p53/CEP17. Results: Cytogenetic abnormalities were found in 24 (70.6%) of the 28 MM patients. 10 (35.7%) patients had abnormal metaphases by conventional cytogenetics. Interphase FISH results were abnormal in 21 (61.8%) patients and 11 (52.3%) patients had abnormal interphase FISH but normal metaphases. The evidence of the loss of D13S319 with or without loss of LAMP1 was found in 6 (21.4%) patients, and loss of p53±CEP17 for 2 patients, IGH-BAP for 9 (26.5%) patients, IGH/FGFR3 for 2 patients, and IGH/CCND1 for 7 (20.6%) patients, respectively. However, there were none positive for IGH/MAF. Chromosome 13 abnormalities and IGH rearrangement is correlated with poor clinical outcome. Conclusions: Interphase FISH can provide useful information to evaluate the presence of prognostic chromosome abnormalities in addition to metaphase cytogenetics. And it should be used in the routine evaluation of multiple myeloma. No significant financial relationships to disclose.
Expression and prognostic significance of tissue hypoxia markers in head and neck squamous cell carcinomas (HNSCC)
Authors: A. Koong, C. Kong, S. Zhao, D. Richardson, K. O’Byrne, H. Pinto, N. C. Denko, A. J. Giaccia, Q.-T. Le
Journal: Journal of Clinical Oncology (2005)

5559 Background: Previous investigators have reported that tumor hypoxia is related to prognosis in HNSCC. We and others have recently identified several hypoxia-induced proteins using gene array and proteomic analyses in a HNSCC cell line. Here, we investigate the in-vivo expression of these proteins on a HNSCC tissue array and their relationship to pO2 and prognosis. Methods: We constructed a tumor tissue array from HNSCC patients who had pretreatment pO2 measurements using the Eppendorf microelectrode. We performed immunohistochemical staining of the tissue arrays for known hypoxia-upregulated proteins (CA IX, cortactin, XBP-1, EphrinA-1, HIG-2, DHFR, Galectin-1 and IKK-β). Mann-Whitney tests and logistic regression method were used to determine the relationship between the expression of these markers and tumor pO2. Cox proportional hazard model and log rank tests were used to determine the relationship between the markers and prognosis. Results: 101 patients formed the cohort of this study, of which 95 had evaluable pO2. Markers that correlated with median tumor pO2 were XPB-1 (p = 0.04), Galectin-1 (p = 0.05) and IKK-β (p = 0.04). EphrinA-1 was of borderline significance (p = 0.07). CA IX did not correlate with tumor pO2. On logistic regression analysis, the only factor that had borderline correlation with tumor pO2 was ephrinA-1 (p = 0.06). CA-IX and EphrinA-1 were prognostic factors for freedom from relapse (FFR), cause-specific survival (CSS) and overall survival (OS); galectin-1 for FFR and CSS; and IKK-β and DHFR for FFR. However, none of these factors maintained prognostic significance on multivariate analysis when adjusted for tumor site, stage and treatment. Conclusions: Although we found that the expression of several proteins correlated with tumor hypoxia and treatment outcomes, we did not find that the expression of a single protein predicted for all of these parameters. More accurate prediction of clinical outcomes will likely be achieved by evaluating the expression of a panel of markers rather than individual makers on tissue arrays. No significant financial relationships to disclose.
An open, pharmacokinetic (PK) and mass balance study of <sup>14</sup>C-AZD2171, incorporating DCE-CT evaluations
Authors: A. H. Reid, A. Tang, J. Spicer, E. Gallerani, D. Mears, S. Settatree, T. A. Yap, T. Puchalski, M. Harrison, J. S. De-Bono
Journal: Journal of Clinical Oncology (2007)

14140 Background: AZD2171 is an oral, highly potent and selective VEGF signaling inhibitor in clinical development. Methods: Patients with solid metastatic tumors received a single radiolabeled oral dose of 14 C- AZD2171 45 mg; blood samples and all excretions were collected for evaluating the PK and metabolic profiles. After sufficient radioactivity recovery, patients started once-daily oral dosing with AZD2171 30 mg. The primary objective of the study was to determine the rates and routes of excretion of AZD2171 using 14 C-AZD2171. Efficacy (RECIST), safety and tolerability were secondary objectives. The potential effects of AZD2171 on DCE-CT vascular parameters were also explored. Results: Six patients received treatment and remained on study for 64–171 days. In 5/6 patients, the amount of radioactivity recovered in the urine and feces samples within 168-hours post- dosing ranged from 84.8–93.0%; the analogous amount in the remaining patient was only 34.1%. In all patients, mean radioactivity recovered was 58.8% in feces and 20.8% in urine. Radioactivity appeared to be confined to plasma. Three patients (2 renal cell carcinoma; 1 mesothelioma) had a best RECIST response of stable disease (SD); 1 patient had a confirmed reduction in max tumor diameter of 10% to &lt;30%. Two patients had progressive disease and 1 patient was non-evaluable. The most common adverse events (AEs) were diarrhea (n=5) and hypertension (n=3); no grade 3 or 4 AEs occurred more than once. There was evidence of reductions in DCE-CT parameters post treatment, particularly perfusion, permeability surface product (PSP) and positive enhancement integral. For each of these parameters, a decrease from baseline outside the baseline reference range was recorded for 3 patients (including 2 with SD) at 1 month after the start of daily dosing of AZD2171. Overall, within-patient variability (W-PV) was generally low for all DCE-CT parameters measured and was consistently lower than between-patient variability. The W-PV was largest for PSP (18%) and lowest for mean transit time (7%). Conclusions: The primary route of AZD2171 elimination appears to be hepatic. AZD2171 was well tolerated and clinically meaningful disease stabilization was seen. Changes in tumor vascular parameters were detected by DCE-CT. [Table: see text]
Clonal involvement of granulocytes and monocytes, but not of T and B lymphocytes and natural killer cells in patients with myelodysplasia: analysis by X-linked restriction fragment length polymorphisms and polymerase chain reaction of the phosphoglycerate kinase gene
Authors: H van Kamp, WE Fibbe, RP Jansen, M van der Keur, E de Graaff, R Willemze, JE Landegent
Journal: Blood (1992)
Risk of symptomatic central nervous system (CNS) progression and secondary hemorrhage in patients with non-squamous non-small cell lung cancer (NSCLC) receiving bevacizumab (BV)-based first-line therapy
Authors: V. Archer, M. Reck, A. B. Sandler, D. H. Johnson, G. Kong, D. K. Strickland, J. Bennouna
Journal: Journal of Clinical Oncology (2008)

8114 Background: Preliminary data on the safety of Bv in subjects with advanced or metastatic NSCLC with previously treated brain metastases due to NSCLC revealed no CNS hemorrhagic events (Akerley, IASLC 2007). This preliminary safety report investigates the occurrence of NSCLC progression and CNS hemorrhage among patients receiving Bv. Methods: E4599 and AVAiL are randomized, phase III studies combining Bv with carboplatin/paclitaxel (CP) and cisplatin/gemcitabine (CG), respectively, in the first-line treatment of non- squamous NSCLC. As the presence of CNS metastases rendered a subject ineligible, both studies required baseline imaging of the CNS and as clinically indicated thereafter. In both studies, Bv was continued until disease progression or unacceptable toxicity (including Grade ≥3 hemorrhage and Grade ≥2 non-pulmonary hemorrhage in E4599 and AVAiL, respectively). Results: See Table. Conclusions: Among treated subjects with documented CNS progression, Bv does not appear to increase the risk of CNS hemorrhage compared to controls. In AVAiL, CNS progression is less frequent in subjects treated with Bv in this series. E4599 AVAiL CP CP + Bv 15 mg/kg CG CG + Bv 7.5 mg/kg CG + Bv 15 mg/kg N 441 427 327 330 329 Progression Event in CNS n (%) 14 (3.2) 13 (3.0) 12 (3.7) 7 (2.1) 4 (1.2) CNS hemorrhages in treated patients with documented CNS progression event 0 1 0 0 0 CNS hemorrhages, in all treated patients (with and without CNS progression) 1 3 2 2 1 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, Roche Boehringer Ingelheim, Eli Lilly, Genentech™ BioOncology, Idera, Merck, Roche, Taiho Genentech™ BioOncology Bayer, Boehringer Ingelheim, Eli Lilly, Genentech™ BioOncology, Roche Genentech™ BioOncology
An anti-C3b/iC3b monoclonal antibody (Mab) as an adjuvant to rituximab killing of non-Hodgkin's lymphoma (NHL) and chronical lymphocytic leukemia (CLL) cells
Authors: W. Peng, X. Zhang, G. Inghirami, K. Takeshita, A. Pecora, L. Nardone, L. Casey, G. Spitalny
Journal: Journal of Clinical Oncology (2004)

2621 Background: Complement-dependent cytotoxicity (CDC) is a key mechanism of Rituximab action in killing NHL cells both in vitro and in vivo. Here we present the studies of a mouse/human chimeric Mab (ETI-210) specific for human complement C3 cleavage products, C3b and iC3b, in enhancing Rituximab ability to kill NHL cells in vitro and ex vivo.Methods: In the CDC assay, Raji cells, DB cells, primary NHL and CLL cells were treated with Rituximab and the anti-C3b/iC3b in the presence of normal human serum at 37 degrees for 1 hour or longer. Cell death, determined by propidium iodide staining, was measured by a flow cytometric method. Results: The anti-C3b/iC3b Mab increased the cell killing of NHL cell lines tested in the one-hour treatment of Rituximab plus anti-C3b/iC3b Mab in the presence of human complement. The difference in cell killing between Rituximab plus anti-C3b/iC3b and Rituximab alone was 40%–70%. The enhancing effect of the anti-C3b/iC3b was also seen in long-term treatment (1 - 2 days). In the absence of human serum, the cell killing by Rituximab plus the anti-C3b/iC3b Mab was much lower than in the presence of serum. The addition of excess purified iC3b to the CDC assay under the experimental conditions only caused a minimal inhibition of cell killing. The anti-C3b/iC3b Mab was also tested ex vivo against primary cells from 11 NHL and 10 CLL patients. In 3 NHL samples, the anti-C3b/iC3b Mab enhanced Rituximab-mediated killing; in the remaining samples enhancement was observed but was not significant since Rituximab alone already caused above 90% killing. The antibody also increased Rituximab-mediated killing in 6 out of 10 CLL samples. Conclusions: The anti-C3b/iC3b Mab is able to substantially enhance Rituximab-mediated killing of lymphoma cells via complement-mediated lysis. This Mab has therapeutic applications in NHL and CLL treatment. No significant financial relationships to disclose.
Safety and efficacy of first-line epirubicin–docetaxel (ED) versus epirubicin–cyclophosphamide (EC): A multicenter randomized phase III trial in metastatic breast cancer (MBC)
Authors: J.-U. Blohmer, M. Hauschild, J. Hilfrich, A. Kleine-Tebbe, S. Kuemmel, W. Lichtenegger
Journal: Journal of Clinical Oncology (2004)

627 Background: Following good phase III results for docetaxel–doxorubicin combinations, ED has been evaluated in phase I/II trials and is compared with EC in this phase III study. Methods: Patients (pts) were randomized to EC (E 90 mg/m2 + C 600 mg/m2 q 3 weeks x 6 cycles) or ED (E 75 mg/m2 + D 75 mg/m2 q 3 weeks x 6 cycles). Primary endpoints were overall response rate (ORR: complete response [CR] + partial response [PR]), and stable and progressive disease (SD+PD). Secondary endpoints were time to progression (TTP), toxicity (Tox), and overall survival (OS). Heavy pretreatment (surgery + hormonal therapy [HT] + radiotherapy [RT] + chemotherapy [CT]) and high baseline tumor load (>2 metastatic sites) were noted. Key eligibility criteria were MBC, measurable disease, failure of prior HT or estrogen-/progesterone-negative, Karnofsky performance status (KPS) >70%, and life expectancy of ≥12 weeks. Adjuvant treatment and pretreatment for MBC were allowed. Prior adjuvant therapy included E ≤360 mg/m2 and C (no dose restrictions). Pts previously treated with D were excluded. Results: There were no differences between groups (EC=107/ED=120) in median age (55/57y) or median KPS (90/90%). More pts in the ED arm were heavily pretreated or had high baseline tumor load. In 182 evaluable pts (EC=84/ED=98), ORR=44(33–55)%/53(42–63)%, pls=0.11. WHO grade III–IV Tox (% of all treatment cycles; EC=604/ED=647) were: leukopenia 40.6/52.7; platelets 2.3/1.1; febrile neutropenia 0.8/0.9; nausea and vomiting 2.2/4.0; alopecia 20.0/20.8. In EC/ED arms, Tox-related dose reductions occurred in 2.8/6.7% and therapy delays in 14.7/10.2% of cycles. One death (ED arm) was treatment-related. Conclusions: Despite more frequent heavy pretreatment and high tumor burden in the ED arm, ED and EC have similar safety profiles and there was a trend towards higher efficacy in the ED arm. Final results will be available in Dec 2004. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; Pharmacia; Amgen
In vitro drug resistance profiles correlate with DNA ploidy and p53 expression in 3,106 endometrioid and papillary serous adenocarcinomas of the uterus
Authors: I. Yu, W. Huang, E. Mechetner
Journal: Journal of Clinical Oncology (2006)

5037 Background: Although chemotherapy is widely used to treat advanced and recurrent endometrial cancer, no patient-tailored protocols were developed, resulting in intermittent and incomplete clinical response. The utility of the Extreme Drug Resistance (EDR) assay to predict clinical resistance to chemotherapy was proven in several cancer types, including ovarian cancer. This study is the first attempt to evaluate the efficacy of the EDR assay in endometrioid (E) and papillary serous (PS) tumors and correlate it with the expression of two major biomarkers, DNA ploidy and p53. Methods: 2520 E and 586_PS adenocarcinomas were tested in the EDR assay using in vitro incubation in suprapharmacologic exposures of 4-HC (the active species of cyclophosphamide), cisplatin, carboplatin, and doxorubicin. The results were defined as EDR (one standard deviation more resistant than the database median), intermediate drug resistance (IDR - between the median and EDR), and low drug resistance (LDR - lower than the median). DNA ploidy was assessed in flow cytometry; p53 expression was quantitated on paraffin sections by immunohistochemistry. Results: Compared to E, the more clinically aggressive PS tumors were significantly associated with high (IDR + EDR) in vitro resistance to all EDR-tested drugs: 4-HC (p = 0.0010; χ 2 statistics), cisplatin (p = 0.0064), carboplatin (p = 0480), doxorubicin (p = 0.0001). PS tumors showed significantly higher non-diploid status (p &lt; 0.0001) and p53-positivity (p &lt; 0.0001). For all EDR-tested drugs, increased in vitro resistance closely correlated with the non-diploid and high p53 status. Conclusions: These data document close correlation between the EDR assay results and biological behavior of endometrial tumors in terms of their clinical aggressiveness and biomarker expression and justify further studies on combined EDR and biomarker testing in assay-guided chemotherapy. [Table: see text] No significant financial relationships to disclose.
Molecular predictors of chemotherapy response in high-grade gliomas.
Authors: C. Battelli, H. Blaszyk, K. Carrier, L. Lucas, J. E. Florman, I. F. Emery
Journal: Journal of Clinical Oncology (2010)

e12505 Background: High-grade gliomas are the most common primary brain tumors in adults and are virtually incurable. Currently, optimal management includes resection, postoperative radiation and chemotherapy with temozolomide. However, even when this most aggressive treatment is delivered, the median survival is just over a year. We hypothesized that insensitivity to chemotherapy can be attributed to 3 possible mechanisms: (a) alterations in DNA repair pathways; (b) alterations in cell cycle checkpoints; and (c) selection of cells with “stem-like” phenotypes. Methods: In a retrospective study, we analyzed tumor tissue from 58 patients that had surgical resection of their GBM or AA between Dec 02 and Dec 08. We also analyzed tumor tissue from 13 patients with resected recurrent disease. DNA repair proteins (MGMT, MSH2), death avoidance proteins (p53, pAKT, XIAP), and stem cell markers (Nestin, CD133, ABCG2) were detected by immunohistochemistry. Correlative analyses between each marker and Overall Survival (OS) were performed by the Kaplan-Meier method. Results: The median OS of our population was 20 months. As expected, performance status and histology were associated with outcome. In addition, we found that 2 of the 8 markers analyzed, pAKT and ABCG2, had a statistically significant association with OS. pAKT is a key member of an activated EGFR pathway, which promotes cell survival. ABCG2 is a toxin pump used as a marker for stem cells. Our results indicate that higher expression of pAKT and ABCG2 reduces the effectiveness of therapy and leads to decreased survival. Comparative analyses between primary and recurrent tumors indicate that the expression of the 8 proteins remains relatively unchanged with the notable exception of MGMT. MGMT confers resistance to temozolomide by reversing alkylation damage. The prevalence of this protein was higher in recurrences than in primaries. Conclusions: This study supports the relevance of the EGFR pathway in gliomas and suggests a role for anti-EGFR therapy in patients with increased pAKT expression. The apparent selection of higher MGMT expressing cells in recurrent disease discourages the use of alkylating agents in second line therapy and highlights the potential of agents that reduce MGMT levels. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough
Phase I study of docetaxel, cisplatin and 5-fluorouracil (TPF) as first-line chemotherapy in patients with advanced esophageal cancer. Hokkaido Gastrointestinal Cancer Study Group (HGCSG) study
Authors: S. Yuki, Y. Komatsu, N. Machida, M. Ozasa, K. Miyashita, T. Kato, S. Furukawa, M. Kudo, H. Akita, M. Asaka, Y. Sakata
Journal: Journal of Clinical Oncology (2005)

4181 Background: This study was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and efficacy of a combination chemotherapy using docetaxel, cisplatin and 5-fluarouracil (TPF) in patients with advanced esophageal cancer. Methods: Patients with previously untreated measurable advanced esophageal cancer were included in this trial. Patients received this combination chemotherapy repeated every 28 days until progression disease. Starting dose (dose level 1) were docetaxel 50 mg/m2 on day 1, fixed dose intravenously cisplatin (15 mg/m2/day) and continuous infusion 5-FU (800 mg/m2/day) on day 1–4. Nine patients received this combination chemotherapy (TPF) at the two different dose level. DLT was defined as follows (according to NCI-CTC version 2.0); Grade 4 neutropenia lasting for more than 4days, Grade 4 anemia and thrombocytopenia, Grade 3 neutropenia accompanied fever (≥38°C), and Grade 3 non-hematological toxicity (except for nausea, appetite loss, general fatigue). Maximal Tolerated Dose (MTD) is determined when the incidence of critical toxicity exceeds 50% at a certain dose level. Results: MTD was dose level 1: docetaxel 50 mg/m2, cisplatin 15 mg/m2, and 5-fluorouracil 800 mg/m2/day. DLTs were diarrhea on level 1, and febrile neutropenia, diarrhea, and stomatitis on level 2. The major toxicity were Neutropenia (Grade 3 and 4, 56%), Leukocytopenia (Grade 3, 44%), Anemia (Grade 3, 11%), Diarrhea (Grade 3, 33%) and stomatitis (Grade 3, 11%). The overall response rate was 44.4% and recommend dose’s response rate was 66.7%. Conclusions: The recommended dose of docetaxel in this study was determined to be 50 mg/m2. This combination chemotherapy of recommended dose appeared to be highly active with a response rate of 66.7% and to have acceptable toxicities. Phase II multicenter study has already started. No significant financial relationships to disclose.
Does Palliative Care Palliate?
Authors: Alice B. Kornblith
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.8.2111 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11304762 Does Palliative Care Palliate? Alice B. Kornblith, PhDxAlice B. KornblithSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.2001.19.8.2111 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology