tbuckley/cabot-search huggingface dataset:
Human chimeric anti-CD44 antibody ARH460–16–2 binds leukemic cells and malignant plasma cells
Authors: T. Guillaume, N. Robillard, H. Avet-Loiseau, J. Delaunay, J. L. Harousseau, S. E. Hahn, L. A. da Cruz, D. S. Pereira, D. B. Rubinstein, D. S. Young
Journal: Journal of Clinical Oncology (2008)

14010 Background: CD44, a cell surface transmembrane glycoprotein, is involved in both cell-to-cell interactions via its ligand hyaluronic acid, and in signal transduction via protein kinase cascades. The molecule is highly expressed not only on a variety of tumor types, but has recently been found to be expressed on tumorogenic stem cells from several solid and hematologic malignancies, most pointedly AML. ARH460–16–2, a chimeric monoclonal antibody against a conformation-dependent glycosylated epitope of CD44, was identified by its ability to induce apoptosis in vitro and confirmed to be an effective in vivo tumor suppressive agent in breast cancer xenografts. The humanized form of this antibody is currently developed for clinical use in solid tumors; the present study extends therapeutic relevance to hematologic malignancies. Methods: In an effort to identify the hematologic malignancies where anti-CD44 therapy might be most effective, binding of ARH460–16–2 to chronic and acute leukemias and to the plasma cells of both overt multiple myeloma and in MGUS was analyzed by FACS. Results: ARH460–16–2 bound 15/15 AML, 8/10 ALL, and 14/14 CLL samples. Fresh malignant plasma cells from patients with multiple myeloma bound ARH460–16–2 in a majority (17/23). Plasma cell expression was heterogeneous: while some malignant plasma cells of the same individual bound at high levels, other had little or no expression. In MGUS, tumoral plasma cells (CD19-, CD45-) bound ARH460–16–2 (7/9) as well. However, binding of ARH460–16–2 in MGUS was found to be more homogeneous than in myeloma. Conclusions: The marked level of binding of ARH460–16–2 to hematologic malignancies suggests that CD44 may be a therapeutically useful target in hematologic malignancies. Because of this, and because of the association of CD44 with tumorogenic stem cells, ARH460–16–2 might also prove to be effective in target-specific therapy in hematologic malignancies either alone or in association with cytotoxic drugs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Arius Research
Adoptive Immunotherapy Following Umbilical Cord Blood Transplantation Using The Sleeping Beauty System and Artificial Antigen Presenting Cells To Generate Donor-Derived T Cells Expressing a CD19-Specific Chimeric Antigen Receptor
Authors: Partow Kebriaei, Helen Huls, Harjeet Singh, Simon Olivares, Matthew Figliola, Pappanaicken R Kumar, Bipulendu Jena, Rineka N Jackson, Tingting Liu, Ian K. McNiece, Gabriela Rondon, Perry Hackett, Richard E Champlin, Elizabeth J Shpall, Laurence J N Cooper
Journal: Blood (2013)
Effect of insurance status and distance from treatment center on the overall survival of patients with non-small cell lung caner treated in an academic center
Authors: T. Armaghany, G. Mills, R. Shi, S. Runhua, H. Ataei
Journal: Journal of Clinical Oncology (2009)

e17557 Background: A large proportion of patients withcancer treated in academic centers do not have insurance and they travel from far distances to get medical care. We have retrospectively analyzed the outcome of 230 patients with non small cell lung caner in our cancer center and evaluated the effect of insurance status and their distances from our center on overall survival. These patients have traveled from many different regional cities to our center since mid-1996 to November 2008. Methods: We have performed a multivariate analysis on 230 patients with all stages of non small cell lung cancer correcting for sex, race, age, comorbidity, stage of cancer, body mass index, histology, chemotherapy, performance status, smoking history, distance from our center and insurance status. The distance ranged from 0.4 to 343 miles with mean of 69 (standard deviation of 71) . Age ranged from 30 to 89 with a mean number of 57 (standard deviation of 10).Insurance status was divided into 3 categories of no insurance, medicaid and with insurance. Chi square test was used to compare the distribution of the stages of lung cancer patients with other categorial variables. The log rank test was used to compare the survival of different categorical variables and Cox proportional regression was used for multivariate analysis of overall survival. Results: There were no statistical significant differences on overall survival considering distance of travel or insurance status.(P value for distance was 0.505 and for insurance it was 0.648). Smokers and patients with a poor performance status (ECOG 3 and 4) had a statiatically significant worse overall survival. (P value for smoking was 0.0036 and p value for ECOG equal or above 4 was &lt;0.0001). Conclusions: The results from our study indicate that travel distance and payer status do not effect overall survival in lung cancer patients at our center. No significant financial relationships to disclose.
Use of physical activity as a health tool for cancer patients and oncologists
Authors: K. Karvinen, K. D. DuBose, R. R. Allison
Journal: Journal of Clinical Oncology (2009)

9634 Background: Regular physical activity can be beneficial to health for both patients and their providers. Research suggests that health care providers can potentially provide an important role in changing patients’ health behaviors. The purpose of this study is to (a) explore factors that influence whether or not oncologists recommend physical activity to their patients and (b) to examine physical activity levels of oncologists. Methods: 199 practicing medical and radiation oncologists throughout the United States responded to a mailed survey (response rate = 30%). Oncologists self-reported their physical activity promotion practices, their own physical activity behaviors, and provided demographic and practice related information. Results: Approximately 64% of oncologists reported inquiring about their patients’ physical activity on most or all visits. Further, 57% of oncologists reported regularly meeting American College of Sports Medicine guidelines for physical activity (i.e., 150 minutes of moderate or 60 minutes of vigorous physical activity per week). Potential predictors of physical activity promotion (i.e., age, ethnicity, number of years practicing, tumor types treated and own physical activity participation) were tested using univariate statistics. A logistic regression analysis indicated that number of years practicing (OR = 2.84, 95% CI = 1.465–5.521) and their own physical activity participation (OR = 1.87, 95% CI = 1.025–3.426) were both significant and independent predictors of physical activity promotion. No other factors were identified as predictors of physical activity promotion. Conclusions: Approximately half of oncologists do not meet public health physical activity guidelines and fewer than two thirds regularly inquire about the physical activity levels of their patients. Data from this study suggest that these findings are linked: inactive oncologists tend to promote physical activity less to their patients. More physical activity adoption by oncologists may ultimately lead to increased activity levels in their patients, leading to greater health benefits for both patients and providers. No significant financial relationships to disclose.
Does lobular carcinoma in situ (LCIS) affect biology of future breast cancer? Surveillance Epidemiology and End Results (SEER) database review.
Authors: Anteneh A. Tesfaye, Mohammad Mozayen, Ioana Morariu, David S. Eilender
Journal: Journal of Clinical Oncology (2012)

37 Background: Lobular carcinoma in situ (LCIS) is a recognized risk factor of breast cancer. Data evaluating the behavior of breast cancer arising after LCIS is lacking. Our study compared the characteristics of breast cancer arising after LCIS with the breast cancer arising de novo. Methods: From the 1973-2009 SEER database, women with breast cancer who were diagnosed and treated between 1990 and 2009 were abstracted. Patients were divided to group A: breast cancer after LCIS, group B: de novo breast cancer. Age, ethnicity, staging, tumor size, grade and hormone receptor status were reviewed. Data were analyzed using chi square, Kaplan-Meier, Life table, and Cox proportional hazard model. Results: Patients with LCIS were 7,258 with 547 (7.5%) developing breast cancer subsequently. The mean (SD) time to develop breast cancer after LCIS was 68 (2.14) months. Of the total 557,309 patients with breast cancer, group A had 547 patients and group B had 556,762 patients. The median tumor size was 1.3 and 1.8 cm in groups A and B respectively (p&lt;0.0001). Grade 1 and 2 tumors were 78.5% and 60.8% in groups A and B respectively (p&lt;0.0001). Local disease alone was seen in 70% and 61% of groups A and B respectively (p&lt;0.0001). ER-PR negative tumor was seen in 14.9% and 24.5 % in groups A and B (p&lt;0.0001). On univariate analysis, 5 year cancer specific survival was 91% and 85% in groups A and B respectively (p&lt; 0.0001). Unlike grade, hormone receptor status and stage, prior history of LCIS was not an independent predictor of survival on multivariate analysis (see Table). Conclusions: Breast cancer diagnosed after prior LCIS has favorable features like smaller tumor, lower grade, earlier stage and less ER-PR negativity. Some of these might be a result of more diligent subsequent screening. A history of LCIS per se is not an independent prognostic factor in breast cancer. [Table: see text]
Detection of circulating tumor cells (CTCs) in patients with hepatocellular carcinoma (HCC)
Authors: B. C. Zee, C. Wong, T. Kuhn, R. Howard, W. Yeo, J. Koh, E. Hui, A. T. Chan
Journal: Journal of Clinical Oncology (2007)

15037 Background: Allard et al. (2004) has established the accuracy, sensitivity, reliability and linearity of circulating tumor cells (CTCs) detection using the CellSearch System. 57% prostate cancers, 37% breast cancers, 37% ovarian cancers, 30% colorectal cancers, and 20% lung cancers specimens had &gt;= 2 CTCs per 7.5 mL of blood. Only 0.3% healthy non-malignant disease subjects had &gt;= 2 CTCs per 7.5 mL of blood. Cristofanilli et al.(2004,2005) have shown that CTCs at baseline and first follow-up were a significant prognostic factor for survival in metastatic breast cancer patients. However, HCC data on CTCs are not available. Methods: 20 locally advance or metastatic HCC patients who had not received prior treatment had been recruited after informed consent and 7.5 mL of blood were collected using the CellSave Preservative tubes (Veridex LLC, Raritan, NJ) that prevents CTCs degradation. The CellSearch system (Veridex LLC) similar to the previous studies was used to analyze the specimen. The CellSearch system consists the CellPrep system, the CellSearch Epithelial Cell Kit, and the CellSpotter Analyzer. All the procedures and interpretation of results followed closely with the quality control procedure of Veridex LLC including accreditation of trained laboratory personnel. Results: 13/20 (65%) had locally advanced disease and the rest had metastatic HCC. All patients had multiple lesions. 9/20 (45%) patients had detectable CTCs, 7/20 (35%) had &gt;= 2 CTCs, and about 5/20 (20%) had 5 or more CTCs. For locally advanced HCC 4/13 (31%) patients had &gt;= 2 CTCs per 7.5 mL of blood. For HCC patients with metastatic diseases 3/7 (43%) patients had &gt;= 2 CTCs per 7.5 mL of blood. Conclusions: HCC patients with locally advance or metastatic disease had detectable CTCs in 7.5 mL of blood. We expected that the performance of CTCs in HCC is similar to that of breast cancer. Future study of using CTCs as prognostic factor at baseline and during treatment for HCC is being planned. No significant financial relationships to disclose.
Overexpression of aquaporin-1 in non-small cell lung cancer.
Authors: S. Kola, A. Yeldandi
Journal: Journal of Clinical Oncology (2010)

e21078 Background: In 2003, Peter Agre and Roderick MacKinnon were awarded the Nobel Prize in chemistry for their pioneering discoveries concerning the aquaporins. The aquaporins are channel proteins that regulate water transport across cell membranes. Since most tumors exhibit high vascular permeability and interstitial fluid pressure, a possible role of the aquaporins in tumor development, growth, and spread has been suggested. Studies on the function of aquaporin-1 (AQP-1), which is located in the alveolar epithelial cells of the lung, may provide insights leading to the design of novel therapeutic approaches for lung cancer. The purpose of this study was to investigate the expression of AQP-1 in various types of lung cancers (52 adenocarcinomas, 12 bronchoalveolar carcinomas, 25 squamous cell carcinomas) by immunohistochemical staining. Methods: Tissue microarrays (TMAs) of lung cancers were stained with AQP-1 antibodies to identify expression of AQP-1 in non-small cell lung cancer. The immunohistochemical results found for each tissue sample were then correlated with the respective patient's clinical features, including their age, gender, stage, histology, and grade. Results: Results of this study demonstrate a significant correlation between AQP-1 expression and histological subtypes of lung cancer. AQP-1 was overexpressed in 69% (36 of 52) and 67% (8 of 12) of adenocarcinomas and bronchoalveolar carcinomas, respectively, compared to only 36% (9 of 25) of squamous cell carcinomas (p = 0.0049). Only 33% of normal lung tissue overexpressed AQP-1, compared to 60% of all lung cancer tissue studied (p = 0.1941). There was no correlation between AQP-1 stain intensity and lung cancer grade or stage. Conclusions: Based on tumor-specific overexpression, it is proposed that increased levels of AQP-1 may play a role in tumorigenesis. While more regarding the molecular composition of AQP-1 related to tumorigenesis remains to be elucidated, the protein has the potential to become a targeted therapy and the discovery of AQP-1 inhibitors could have biologic and clinical implications in lung cancer. No significant financial relationships to disclose.
Sentinel node biopsy in breast cancer after neoadjuvant therapy
Authors: M. Hauschild, A. Thomas, S. Maza, S. Kuemmel, T. Fischer, P. Mallmann, D. L. Munz, J. U. Blohmer
Journal: Journal of Clinical Oncology (2004)

691 Background: Sentinel lymph node biopsy (SNL) for breast cancer is becoming clinical standard. However there is a discussion on the accuracy of SNL after neoadjuvant chemotherapy. The question is whether SNL biopsy is reliable or the false negative rate is too high? Methods: Twenty-nine patients were treated with neoadjuvant chemotherapy in a period of six months. We included patients with histological confirmed breast cancer stage II or III. Following they underwent SLN biopsy and the complete axillary lymph node dissection. At the same operation each patient received a breast conserving surgery or a mastectomy. Lymph node mapping was performed with Technetium99 Nanocolloid. Results: The mean age was 52 years (41–63yrs.). The clinical examination showed in 90% none palpable lymph nodes. The axillary ultrasonography indicated positive lymph node in 45% (13/29). The SNL identification rate was 100% (29/29). In 27/29 patients (93%) SLNs accurately predicted the axillary status. Eight patients of the 29 had positive SNLs (28%), and in 6 of those 8 patients, the SNL was the only positive node (75%). Two patients had false-negative SLN biopsy (7). SNL biopsy had a sensitivity of 80% and a specificity of 87,5%. Compared with the 45% positive nodes by ultrasound before chemotherapy, only 31% (4/13) showed furthermore positive SNLs after neoadjuvant chemotherapy. Conclusions: According to the prior studies SNL biopsy was possible after neoadjuvant chemotherapy. But there was a false negative rate of 7%. It is questionable if SLN biopsy is an option for patients who received neodadjuvant chemotherapy. No significant financial relationships to disclose.
Randomized trial of high- versus low-intensity breathing training for dyspnea due to intrathoracic cancer: Cost-effectiveness.
Authors: Miriam Johnson, Mona Kanaan, Gerry Richardson, Sam Nabb, Rachael Barton, David Torgerson, Sara Booth
Journal: Journal of Clinical Oncology (2014)

54 Background: About 90% of patients with lung cancer experience dyspnea. Breathing training is helpful, but multiple sessions may be onerous. Methods: UK multisite phase 3 RCT, comparing three weekly sessions of breathing training to a single session for refractory dyspnea due to intrathoracic cancer. Primary outcome: self-report “worst” dyspnea/24 hours, (0–10 numerical rating scale [NRS], 0=none; 10=worst imaginable). Secondary outcomes: “average”, distress due to dyspnea (NRS); quality of life (QoL) (CRQ-SAS; EQ-5D); health service utilisation. Primary analysis point: 4 weeks for dyspnea/QoL. An economic analysis addressed cost-effectiveness from the perspective of UK National Health Service (NHS) and personal social services in a budget constrained system; costs at NHS 2012/13 prices. Primary outcome: Quality Adjusted Life Year (QALY) over 8 weeks. Results: 156 were randomized: age 69 (SD 9.4); 40% women; Karnofsky performance status 71% (SD 9.5); 133 primary lung. “Worst” score improved, 6.8 (SD1.9) at baseline to 5.8 (SD 2.4) at week 4. There was no detected difference in area under curve (AUC): three 22.9(SD 7.1) versus single 22.7(SD 7.1); P = 0.83; 95% difference CI (-2.3, 2.9), or for AUC “average”, or CRQ-SAS. AUC “distress” was less in the single group (16.2 versus 12.3; P = 0.01). Using complete cases, three sessions were associated with a QALY reduction of 0.006 (95% CI -0.18 to +0.006) over 8 weeks and 0.008 (95% CI -0.022 to 0.006) with multiple imputation, and showed increase in costs when adjusted for baseline health related QoL (Mean increased cost £37; 95% CI -506 to +581). Conclusions: Three sessions conferred no benefits over one and had a worse QALY profile. Though statistically insignificant, a single session seems to be a cost-effective way to provide breathing training, minimising the burden of healthcare visits. Clinical trial information: ISRCTN49387307.
Population pharmacokinetic (PK) analysis of ABT-869 in solid tumors and acute myelogenous leukemia (AML) patients
Authors: N. Gupta, P. M. Diderichsen, J. Steinberg, J. L. Ricker, R. Humerickhouse, W. Awni, R. Pradhan
Journal: Journal of Clinical Oncology (2009)

3567 Background: ABT-869 is an orally bioavailable, potent and specific inhibitor of all vascular endothelial growth factor and platelet derived growth factor family receptor tyrosine kinases. The objectives of this analysis were to understand the population pharmacokinetics of ABT-869 and explore the effect of several demographic/disease state covariates influencing ABT-869 disposition. Methods: A population PK analysis of 181 patients (pts) enrolled in two phase 1 (multiple types of solid tumors and AML) and three phase 2 monotherapy studies (non-small cell lung cancer, hepatocellular carcinoma [HCC] and renal cell carcinoma) was conducted. Approximately 90% of pts received ABT-869 based on body-weight dosing while the remaining pts had flat dosing. Available plasma concentrations obtained after intensive and sparse pre-dose PK sampling were analyzed by population PK using the non linear mixed effects modeling (NONMEM) approach. Potential covariates including body weight, body surface area (BSA), age, sex, creatinine clearance (CrCL) and disease state (HCC vs. non-HCC pts) were tested. Results: The mean body weight of enrolled pts was 71 kg and 57% were Asian, 36% Caucasian and 7% other races. The ABT-869 plasma concentration time profile was well described by a one-compartment model with first order absorption and elimination process. Oral clearance (CL/F) was not affected by body weight (range 35–177 kg); however, apparent volume of distribution (V/F) increased by 6L per 0.1 mg/m 2 increase in BSA. CrCL (39.9–290.3 ml/min) was not a significant covariate on V/F and CL/F suggesting renally impaired pts do not require a different dose/dosing regimen. HCC pts had ∼40% lower CL/F values than pts with other malignancies suggesting a lower dose would be appropriate for HCC (Child Pugh A and B) pts. Conclusions: Population PK analysis showed that ABT-869 PK can be well described by a one-compartment model with first order absorption and elimination. Race and impaired renal function does not appear to alter PK. HCC pts had lower CL/F value therefore a lower dose may be recommended in these patients. Implications of increased V/F with increasing body size and appropriate dosing strategy are undergoing further analysis. [Table: see text]
Positron Emission Tomography: Another Useful Test for Staging Esophageal Cancer
Authors: Charles J. Lightdale
Journal: Journal of Clinical Oncology (2000)

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.2000.18.18.3199 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10986051 Positron Emission Tomography: Another Useful Test for Staging Esophageal Cancer Charles J. Lightdale, MDxCharles J. LightdaleSearch for articles by this author Show More Columbia University College of Physicians and Surgeons New York, NY https://doi.org/10.1200/JCO.2000.18.18.3199 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Trastuzumab plus capecitabine and docetaxel as first-line therapy for metastatic breast cancer: Phase II results
Authors: C. G. Gennatas, V. Michalaki, S. Gennatas
Journal: Journal of Clinical Oncology (2009)

1111 Background: In human epidermal growth factor 2 (HER-2)-positive advanced breast cancer, taxanes plus trastuzumab are among the most widely applied options in the first-line setting. The addition of capecitabine to docetaxel significantly improves overall survival in anthracycline-pretreated metastatic breast cancer. We evaluated the efficacy and tolerability of trastuzumab plus capecitabine and docetaxel regimen as first-line therapy. Methods: Patients who had received adjuvant anthracyclines received docetaxel 75 mg/m 2 day 1 and capecitabine 950 mg/m 2 twice daily, days 1–14, every 3 weeks until disease progression or unacceptable toxicity. Trastuzumab was administered at a dose of 6 mg/kg every 3 weeks. Time to progression (TTP) was defined as primary end point. Results: Twenty eight patients were evaluable (median age 52 years, range 34–70). The regimen achieved objective responses in 11 patients (39%), including complete response in three patients (11%) and partial response in eight patients (28.5%). The median overall survival time was 25.5 months, and the median progression-free survival time was 7.8 months. The safety profile of the combination was favorable and predictable, with a low incidence of grade 3/4 adverse events. The most common adverse events were hand-foot syndrome, and GI toxicities. Severe myelosuppression was rare and cardiac toxicity did not occur. Conclusions: These data confirm that the combination of trastuzumab plus capecitabine and docetaxel is highly active in patients with HER-2-overexpressing anthracycline-pretreated breast cancer, and is well tolerated. No significant financial relationships to disclose.
Abstract 15346: Blood Pressure Control Does Not Improve with Long-Term Continuous Positive Airway Pressure Above Conventional Antihypertensive Treatment: a 3-Year Follow-Up
Authors: Alexandros Kasiakogias, Costas Tsioufis, Costas Thomopoulos, Ioannis Andrikou, Eirini Andrikou, Ioannis Bafakis, Louiza Lioni, Konstantinos Kintis, Christodoulos Stefanadis
Journal: Circulation (2012)

Introduction: Even though obstructive sleep apnea (OSA) is strongly associated with hypertension, studies have generally shown only a mild blood pressure (BP)-lowering effect of continuous positive...