tbuckley/cabot-search huggingface dataset:
Risk and Benefit Information and Use of Aspirin—Reply
Authors: Samia Mora, JoAnn E. Manson
Journal: JAMA Internal Medicine (2017)

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Features of adult clinical trial participants with glioblastoma (GB) at The University of Texas MD Anderson Cancer Center (MDACC).
Authors: Mark Daniel Anderson, Diane Liu, Jimin Wu, Marta Penas-Prado, John Frederick De Groot
Journal: Journal of Clinical Oncology (2014)

2038 Background: GB is the most common primary brain tumor in adults and has a poor prognosis. Less than 10% of pts are treated on clinical trials. Methods: In this IRB-approved retrospective study, our database was screened for GB pts from 2007-2012. 510 adult patients (pts) with primary GB were identified who participated on a clinical trial. 112 adult pts with primary GB were identified who were clinical trial eligible, but elected not to enroll in a clinical trial. Results: Median age was 54 years (18-83). 307 pts with a primary GB were consented for a newly diagnosed protocol (NDP) and their median OS was 25 months and their median PFS was 12.6 months. Median OS for pts who only enrolled on a recurrent GB protocol (RP) was 19 months from time of diagnosis. These 2 groups had differences in employment, education, symptoms, tumor location, performance status, extent of resection and location of therapy. Pts that were eligible for a clinical trial, but did not enroll, tended to be older, have a lower KPS, live farther away, but had no differences in outcome. Active smokers were less likely to participate in clinical trials. Many pts who enrolled on a clinical trial enrolled in more than one, but receiving dose dense TMZ reduced clinical trial enrollment at recurrence. Age, KPS at presentation, and extent of resection were confirmed as prognostic factors associated with OS. Also, location of radiation therapy (MDACC versus community facility; p=0.02) was associated with OS. 383 pts were identified who either did not follow up for enrollment (n=161, due to distance, evaluation as a second opinion, unknown) or were ineligible for clinical protocols (n=221, prior therapy, early progression or death, treatment toxicity/medical comorbidities, tumor location, insurance denial). Conclusions: Clinical trial eligible GB pts at MDACC have overall better prognoses than historical controls, consistent with other studies. Caution should be taken when interpreting efficacy from single institution, single arm clinical trials. Location of radiation therapy may represent an important variable associated with survival and requires additional investigation. Travel is a significant barrier to clinical trial enrollment.
A phase 2 study of orally administered PLX3397 in patients with recurrent glioblastoma.
Authors: Nicholas A. Butowski, Howard Colman, John Frederick De Groot, Antonio Marcilio Padula Omuro, Lakshmi Nayak, Timothy F. Cloughesy, Adhirai Marimuthu, Arie Perry, Joanna J Phillips, Brian West, Michael Prados, Keith B. Nolop, Henry H Hsu, Keith L. Ligon
Journal: Journal of Clinical Oncology (2014)

2023 Background: PLX3397 is an oral, small molecule that potently and selectively inhibits CSF1R, Kit, and Flt3-ITD kinases. CSF1R is expressed on microglia/macrophages and tumor cells within glioblastoma (GB). Many glioma cell lines express the CSF1R ligands, CSF-1 and IL-34 and the KIT ligand, SCF, and depletion of microglia in preclinical GB models reduces tumor burden and spread. Methods: This study of recurrent GB measured the 6-month PFS rate (PFS6), median duration of response, overall response rate (ORR), overall survival (OS), safety, and plasma and tumor pharmacokinetics (PK) and pharmacodynamics (PD) during PLX3397 treatment. Results: 38 recurrent GB patients were treated with PLX3397 at 1000 mg daily, with Cohort 1 (14 patients) treated 7 days in advance of recurrent surgery and Cohort 2 (24 patients) without surgery. PLX3397 was well tolerated; common (>10%) treatment-related adverse events included fatigue, constipation, nausea, hair color change, elevation in AST/ALT, anorexia, and headache. The primary endpoint of PFS6 was 11.4% with no complete or partial responses. 7/38 (18%) of patients experienced stable disease.Plasma PK Cmax was median 8090 ng/mL (range 3100-13400) with Tmax of 2 hr. Cohort 1 tumor tissue PK was median 5500 ng/g (range 1320-69400). PD effects observed in blood in both Cohorts included elevated plasma CSF-1 and reduced CD14dim/CD16+ monocytes. In pre-surgical patients (Cohort 1), tissue PD effects observed included possible changes in tumor macrophage/microglia morphology, IBA1 IHC, FACS, and pERK IHC compared to control patient tissues. PDGFRA amplification was seen in 13/36 archival samples. Conclusions: PLX3397 is a potent inhibitor of tumor-associated macrophages and microglia, readily entered GB tissue, and demonstrated expected PD effects. As a single agent, PLX3397 showed no significant improvement in PFS, although further research toward identifying a responsive subset of GB patients is ongoing. PLX3397 is well-tolerated and its safety profile is conducive to testing its combination with other treatments; A Phase 2 trial combining PLX3397 with RT and Temodar in newly diagnosed GB has been initiated. Clinical trial information: NCT01349036.
The prognostic value of detection methylation level panel of gene in DNA circulating after and before treatment in patients with breast cancer.
Authors: Joaquina Martínez-Galán, Blanca Torres-Torres, Jesús Soberino, Sandra Ríos, Cynthia S. González Rivas, Julia Ruiz Vozmediano, Lucia Castillo, Juan Ramón Delgado
Journal: Journal of Clinical Oncology (2012)

67 Background: Objective of this study was to determine the concordance of promoter methylation of 14-3-3σ and ESR1 in circulating DNA of breast cancer patients with response and their association with clinicopathological parameters and disease prognosis. Methods: Plasmawas sampled prospectively from 110 patients diagnosed of breast cancer. A PCR quantitative technique was used to analyze the utility of circulating DNA with CpG island hypermethylation of ESR1, 14-3-3σ, Rar-B and APC genes promoter regions as breast cancer biomarkers. Results: The cutoff points for the genes methylated promoters were established from the ROC curves, selecting values that gave the maximal likelihood ratio. Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p=0.0179); and presence of methylated 14-3-3σ was associated with T3-4 stage (p&lt;0.05) and nodal positive status (p&lt;0.05). Mean serum values of methylated genes before treatment was for ESR1:0.009µg/ml, 14-3-3σ:0.047µg/ml, Rar B:0.0001µg/ml and APC:0.012µg/ml. Mean serum values of methylated genes after treatment was for ESR1:0.003 µg/ml, 14-3-3σ:0.038µg/ml, Rar-B:0 µg/ml and APC:0.001µg/ml. In the light of the discriminatory power of ESR1 and 14-3-3σ and the finding that serum levels of methylated gene promoters changed after breast cancer treatment, post-treatment modifications in these two promoters were analyzed. We observed lower methylated ERS1,14-3-3-σ and APC values after surgery, respect pretreatment levels, but without an overall statistically significant difference.With a median follow-up of 8 years, we found that patients with a significant decrease of sera methylated levels of these genes after surgery had better time to progression an overall survival respect patients without this observation. Conclusions: These findings cast some doubts on the utility for early cancer diagnosis of highly sensitive techniques to identify hypermethylation of specific gene promoters in DNA extracted from serum. Although numerous issues remain to be resolved, the quantitative measurement of circulating methylated DNA is a promising tool for cancer prognostic assessment.
A T2* MRI Prospective Survey on Heart and Liver Iron In Thalassemia Major Patients Treated with Deferasirox Versus Deferiprone and Desferrioxamine In Monotherapy
Authors: Alessia Pepe, Giuseppe Rossi, Antonella Meloni, Maria Chiara Dell'Amico, Anna Spasiano, Marcello Capra, Paolo Cianciulli, Vincenzo Caruso, Brunella Favilli, Eliana Cracolici, Massimo Lombardi, Aurelio Maggio
Journal: Blood (2010)
Determining Effects of Superfine Sheep wool in INfantile Eczema (DESSINE): a randomized paediatric crossover study
Authors: J.C. Su, R. Dailey, M. Zallmann, E. Leins, L. Taresch, S. Donath, S.S. Heah, A.J. Lowe
Journal: British Journal of Dermatology (2017)

Despite limited evidence, woollen clothing has traditionally been considered to be an irritant that should be avoided by individuals with atopic dermatitis (AD). Wool fibres come in a range of diameters, and have beneficial thermodynamic and moisture transport properties. This study examines the effects of superfine merino wool on symptoms in participants with mild‐to‐moderate AD. The trial was a 12‐week, randomized, assessor‐blinded, crossover, prospective, cohort study of 39 patients with mild‐to‐moderate AD, aged between 4 weeks and 3 years, comparing superfine merino wool ensembles with standard cotton clothing chosen by parents. Participants were assigned to wool or cotton clothing and assessed every 3 weeks for 6 weeks, before crossing over to wear the other clothing material for a further 6‐week period, with similar 3‐weekly reviews. The primary end point was the SCORing Atopic Dermatitis (SCORAD) index after each 6‐week period, with Atopic Dermatitis Severity Index (ADSI), Infants' Dermatitis Quality Of Life Index (IDQOL) and topical steroid use as secondary end points to measure AD severity and quality of life. Overall, compared with baseline, superfine wool ensembles were associated with a reduction in mean SCORAD of 2·5 [95% confidence interval (CI) −4·7 to −0·4] at 3 weeks and 7·6 (95% CI −10·4 to −4·8) at 6 weeks when compared with the cotton ensembles. A similar change was observed in ADSI and IDQOL scores for the same period. Body steroid use was also reduced. Conversely, changing ensembles from wool to cotton resulted in an increase in scores. Superfine merino wool may assist in the management of childhood AD.
Patients’, general population’s, and students’ knowledge of oncological terminology.
Authors: Anna Kieszkowska-Grudny, Monika Rucinska, Robert Ciesak, Malgorzata Gustek, Mateusz Szmit, Monika Wieladek, Sergiusz Nawrocki
Journal: Journal of Clinical Oncology (2014)

e20568 Background: Breast cancer (BRC) is the most common malignancy in women and lung cancer (LC) in men. All cancer pts should receive and understand information about diagnosis, treatment, side effects and prognosis. The aim of this study was to compare the knowledge about illness and oncology treatment among BRC and LC pts with general population(Gp) and students(sts) of technical, humanities and medical universities. Methods: 666 responders (20-75y.old) were included (50BRC, 50LC, 142Gp, 55sts of humanities, 113 of natural history, 123 of technical and 133 of medicine before course of oncology) between Dec 2009 and Jan 2014. All pts were under radiotherapy, 72% BRC and 78% LC pts have been treated previously by chemotherapy. All pts before treatment have been informed by doctors (also in written form) about their cancer, treatment and side effects. All responders filled out a questionnaire with closed questions and 5 responses including one correct.The questions concerned the meaning of medical terminology, such as: neoplasm, cancer, radiotherapy, chemotherapy, side effects, itching, peeling skin, and disturbances of sleep, swallowing and heart rhythm. Statistics were Chi2 test, correlation and descriptive statistics. The significance level: p<0,05. Results: Significant differences were noted in right answers in each question between all groups. Only 2% pts (only BRC) answered correctly all 10 questions. In general, BCR pts were better educated than LC pts. The widest knowledge was in medical sts group- 62% answered correctly for all questions, however 28% don’t understand cancer definition. Correct answers were correlated with source of group (sts more correct), age, sex (women more correct), education and place of living. Only 26% of responders understood meaning of cancer, 49%-neoplasm, 63%–radiotherapy, and 76%-chemotherapy. Conclusions: Knowledge about cancer and treatment is not deep enough. Gp was more correct than pts groups. Most varies depending on age, education and place of living. CHT is better understood than RTH. Pts knowledge, even they are informed in written, is the lowest. Probably, the stress associated with the disease and selective attention during visits are limiting cognitive possibilities of pts.
Prolonged Response to HER2-Directed Therapy in a Patient With HER2-Amplified, Rapidly Progressive Metastatic Colorectal Cancer
Authors: Aparna Parikh, Chloe Atreya, W. Michael Korn, Alan P. Venook
Journal: Journal of the National Comprehensive Cancer Network (2016)

HER2 gene amplifications and activating mutations in the HER2 receptor tyrosine kinase are present in 4% of metastatic colorectal cancers (mCRCs). HER2-targeted therapy is not standard of care, although preclinical and clinical data suggest that patients with HER2 amplifications and/or HER2-activating mutations may benefit from HER2-directed therapy. HER2 amplifications and activating mutations have also been implicated in resistance to anti-epidermal growth factor receptor-based therapy. This report describes a patient with KRAS, NRAS, and BRAF wild-type mCRC who experienced disease progression on first-line treatment with FOLFIRI and cetuximab after only 5 months, and subsequently experienced progression on second-line treatment with capecitabine and oxaliplatin plus bevacizumab after 2 months with significant functional decline. Next-generation sequencing of the primary tumor identified HER2 amplification, and we were able to obtain trastuzumab-DM1 for off-label use. The patient had symptomatic clinical benefit from trastuzumab-DM1 and had radiographic disease control for 7 months. On progression, therapy was changed to trastuzumab and pertuzumab, but the patient's disease progressed 3 months later. Treatment with the trastuzumab-DM1 resulted in a sustained response that was longer than his prior responses in the first and second lines of treatment, with a dramatic improvement in the patient's functional status. This case represents the first report, to our knowledge, of successful single-agent treatment of HER2-amplifed CRC with trastuzumab-DM1. Clinical trials targeting patients with HER2-mutated and -amplified metastatic colon cancer are currently underway. Molecular insights from investigating HER2 activation and the impact of HER2-directed therapies in a wide variety of solid tumors will create the needed evidence base to more broadly inform patient care.
NIMG-63. OPTIMAL PATIENT AND FAMILY EDUCATION IS KEY TO IMPROVING THE EFFICACY OF TUMOR TREATING FIELDS PLUS CHEMOTHERAPY IN TREATMENT OF GBM
Authors: Marlon Saria, Minhdan Nguyen, Judy Truong, Annie Heng, Najee Boucher, Amy Eisenberg, Santosh Kesari
Journal: Neuro-Oncology (2016)

Current treatment for glioblastoma (GBM) include tumor treating fields (TTFields) in combination with adjuvant temozolomide (TMZ). TTFields are FDA-approval for recurrent and newly diagnosed GBM. TTFields are delivered though a portable, noninvasive device (Optune®, Novocure, Inc, USA) that provides localized treatment. The Optune device captures compliance data through reports that show usage over 28 days of treatment delivered throughout the day. Single-use transducer arrays connected to an electric field generator are applied to the scalp to deliver TTFields. Patient compliance is critical to optimize the overall (OS) survival advantage demonstrated by treated patients. In EF-11, which compared TTFields and provider’s choice chemotherapy in recurrent GBM, patients who received daily treatment for >18 hours daily showed higher OS than <18 hours/daily. Cognitive and emotional functioning measured by the EORTC QLQ-C30 improved from baseline in the TTFields arm. In EF-14, comparing TTFields plus TMZ versus TMZ alone in newly-diagnosed GBM, cognitive functioning, emotional functioning, physical functioning, role functioning, and social functioning did not significantly decline with TTFields plus TMZ. It is imperative that patients and their family be educated on complying with 18 hour/daily treatment duration. Discussions on short, daily treatment breaks, daily exercise regimen if feasible, and other resources (‘loosely woven’ cranial prosthesis, wigs, sun-protecting hats) can help educate and facilitate compliance with 18 hour/daily treatment duration. The noninvasive aspect of TTFields precludes typical systemic side effects associated with chemotherapy. Adverse events associated with TTFields are mild to moderate (grade 1-2) skin irritation, which are easily managed, reversible, and didn’t result in treatment discontinuation. The correlation of patient compliance with improved survival and reduced toxicities underscores importance of providing comprehensive patient/family education on use of TTFields in GBM by the treatment team. Data analyses on patient and family education provided by an interdisciplinary treatment team is ongoing and will be presented.
Intranasal Fluticasone Propionate Delivered by Exhalation Delivery System (FLU-EDS) Versus Flonase® Nasal Spray and Flovent® HFA: a Randomized Comparison of Bioavailability
Authors: John Messina, Jennifer Carothers, Mohammad Obaidi, Elliot Offman, Ramy Mahmoud
Journal: Journal of Allergy and Clinical Immunology (2017)
Evaluation of the safety and efficacy of pathotropic nanoparticles bearing a dominant negative cyclin G1 construct for chemoresistant osteosarcoma and other sarcomas: Phase I, II, and III studies
Authors: S. P. Chawla, V. S. Chua, L. Fernandez, D. Quon, A. Saralou, W. C. Blackwelder, F. L. Hall, E. M. Gordon
Journal: Journal of Clinical Oncology (2009)

10513 Background: (1) To evaluate the safety/anti-tumor potential of intravenous (i.v.) Rexin-G in chemotherapy-resistant sarcoma (Phase I/II), and (2) to confirm the efficacy/safety of i.v. Rexin-G in chemotherapy-resistant osteosarcoma (Phase II). Methods: Twenty patients in the Phase I/II study and 22 patients in the Phase II study received 1–2 × 10e11 cfu Rexin-G i.v., 2–3 times a week for 4 weeks. Treatment was continued if the patient had &lt; Grade 1 toxicity. Results: Treatment-related adverse events included chills (n=1), presyncope (n=1), photophobia (n=1) of Grade 1 severity, and fatigue (n=4) of Grade 1–2 severity. In the Phase I/II sarcoma study, 3/6 patients had stable disease at Dose Level 0, median progression free survival (PFS) was 5 weeks, and overall survival (OS) was 14 weeks, while 10/14 patients had stable disease at Dose Level I-II, median PFS was 16 weeks and median OS was 34 weeks. Cox regression analysis showed a dose-response relationship between PFS/OS and Rexin-G dosage (p = 0.02 and 0.005, respectively). The Table below shows the results for evaluable patients (n=17) in the Phase II study for osteosarcoma. Kaplan-Meier analysis shows a dose-response relationship between overall survival and Rexin-G dosage in the combined Phase I/II sarcoma and Phase II osteosarcoma studies (p = 0.02; n=42). Two patients achieved surgical remissions which are sustained for &gt;26 weeks. Conclusions: These studies suggest that (i) intravenous Rexin-G is safe and well-tolerated, and (ii) Rexin-G controls tumor growth and prolongs progression-free survival and overall survival in a dose-dependent manner in chemotherapy-resistant osteosarcoma and sarcoma. [Table: see text] [Table: see text]
Outgrowing eosinophilic esophagitis: it is possible
Authors: Melanie A. Ruffner, Terri F. Brown-Whitehorn, Antonella Cianferoni, Laura M. Gober, Michelle Shuker, Amanda Muir, Chris A. Liacouras, Jonathan M. Spergel
Journal: Journal of Allergy and Clinical Immunology (2017)
Killing of Drug-Sensitive and Resistant Myeloma Cells and Disruption of Their Bone Marrow Stromal Interaction by HuLuc63, a Novel Humanized Anti-CS1 Monoclonal Antibody.
Authors: Yu-Tzu Tai, Weihua Song, Xian-Feng Li, Peter Burger, Robert Schlossman, Audie Rice, Anne van Abbema, Paul Richardson, Nikhil C. Munshi, Daniel Afar, Kenneth C. Anderson
Journal: Blood (2006)
ACTR-16. PHASE 2 STUDY EVALUATING SAFETY, PHARMACOKINETICS (PK), PHARMACODYNAMICS (PD) AND EFFICACY OF THE ORAL TRANSFORMING GROWTH FACTOR-BETA (TGF-β) RECEPTOR I KINASE INHIBITOR GALUNISERTIB WHEN COMBINED WITH CHEMORADIOTHERAPY IN NEWLY DIAGNOSED MALIGNANT GLIOMA
Authors: Annick Desjardins, Cristina Suarez, Peter Forsyth, Ivelina Gueorguieva, Ann Cleverly, Tiana Burkholder, Durisala Desaiah, Michael M Lahn, Susan C Guba, Wolfgang Wick, Jordi Rodon
Journal: Neuro-Oncology (2016)

Preclinical data suggested an additive antitumor effect of TGF-β inhibitors when combined with temozolomide-based chemoradiation (TMZ/RT). Our Phase 1 data showed manageable safety; thus, a Phase 2 randomized study was conducted to evaluate the safety, PK, PD and efficacy of galunisertib (300 mg/day) combined with TMZ/RT, compared to TMZ/RT alone in patients with newly diagnosed glioma. TMZ/RT was administered as approved and galunisertib given as intermittent dosing (14 days on/14 days off=1 cycle). Safety was assessed using CTCAE, version 4. PK, PD and time-to-event variables were determined. 56 patients with glioma (100% of patients with WHO Grade IV) were treated with galunisertib plus TMZ/RT (N=40) and TMZ/RT alone (N=16). Most patients at baseline were white (96.4%), male (59%), less than 60 years of age (50%), and with ECOG 0–1 (100%). Only two study treatment-related grade 3 or 4 treatment-emergent adverse event rates observed in the two arms were > 10%: (Galunisertib/TMZ/RT:TMZ/RT): lymphocytopenia (20%:6.3%); thrombocytopenia (15%:6.3%). Time-to-events (months) including median overall survival (18.2 vs 17.9) and time-to-treatment failure (7.1 vs 8.8) showed no significant differences between the two treatment arms. No change in the PK profile of galunisertib was shown when combined with TMZ/RT. In the combination therapy, area under the curve (0-∞) at steady state was calculated to be 5.0 (47%) mg*h/L following 300 mg/day (n=48). The analysis correlating changes in T-regulatory cells with overall survival is ongoing and will be presented at the meeting. There was no evidence to suggest an improved survival probability between the two treatment arms. Additionally, the safety profile was manageable and not significantly different between the two treatment arms.