tbuckley/cabot-search huggingface dataset:
NRG BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical ablation for newly oligometastatic breast cancer.
Authors: Steven J. Chmura, Kathryn A. Winter, Joseph Kamel Salama, Wendy A. Woodward, Virginia F. Borges, Hania A Al-Hallaq, Martha Matuszak, Nora T. Jaskowiak, Michael T. Milano, Hanna Bandos, Julia R. White
Journal: Journal of Clinical Oncology (2016)

TPS1098 Background: This randomized Phase II trial evaluates if stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) of all metastatic sites in newly oligo-metastatic breast cancer who have received, or planned to receive, up to 12 months of first line systemic therapy without progression will significantly improve median progression free survival (PFS). If this aim is met, a phase III component evaluates if SBRT/SR improves 5 year OS. Secondary aims include local control in the metastases, new metastases, and technical quality. Translational primary endpoint is to determine whether < 5 CTCs is an independent prognostic marker for improved PFS and OS. Methods: A 2016 amendment expanded eligibility criteria to pathologically confirmed metastatic breast cancer to ≤ 2 sites and < 12 months of standard first line systemic therapy. Registration must occur <365 days of initial metastatic diagnosis. Primary disease must be controlled prior to registration. CNS metastases are ineligible. ER/PR and HER-2 neu is required on either the primary or metastatic site. Randomization is to standard systemic therapy with local radiotherapy/ surgery for palliation when necessary versus ablative therapy of all metastases with SBRT and/or SR. Statistics: For the phase IIR portion to detect a signal for improved median PFS from 10.5 months to 19 months with 95% power, 146 patients are required. The Phase III requires an additional 246 patients to definitively determine if ablative therapy improves 5-year overall survival from 28% to 42.5% (HR = 0.67), with 85% power and one-sided type I error of 0.025. For the translational research assuming a two-sided probability of type I error of 0.05, patients accrued in the Phase II-R/III portions will provide sufficient power of at least 91% to detect whether < 5 CTC's is prognostic. Contact Information: Protocol: CTSU member web site https://www.ctsu.org. Pt enrollment: OPEN at https://open.ctsu.org or the OPEN tab on CTSU member web site. Support: Supported by NRG Oncology grants U10CA180868 and U10CA180822 from the National Cancer Institute (NCI). Clinical trial information: NCI-2014-01810.
Pertuzumab and trastuzumab: Exploratory biomarker correlations with clinical benefit in patients with metastatic HER2-positive breast cancer.
Authors: J. Cortes, J. Baselga, P. Fumoleau, K. A. Gelmon, G. Ross, V. McNally, G. V. Bianchi, M. Venturi, H. Paul, L. Gianni
Journal: Journal of Clinical Oncology (2010)

1066 Background: Pertuzumab (P), a fully humanized monoclonal antibody, targets the dimerization epitope of human epidermal growth factor receptor (HER) 2, preventing dimerization of HER2 with other HER family members like HER3 and inducing antibody-dependent cell- mediated cytotoxicity. As a single agent it has activity against HER2-positive breast cancer, but in combination with trastuzumab (H) the level of activity is greatly enhanced, with an overall clinical benefit rate of 50% in 66 patients (pts) who had been treated in 2 cohorts in a phase II study (Gelmon et al ASCO 2008, abs 1026). Pts had a tumor sample and serum sample for assessing biomarkers which might be prognostic or predictive of good outcomes. Methods: Pts with metastatic HER2-positive breast cancer who had progressed on H-based therapy as their last treatment for metastatic disease and who had measurable disease at baseline were enrolled. Tumor samples were collected at the time of primary surgery. Treatment with H was restarted and P was introduced concurrently. Response rate and stabilization of disease lasting ≥6 months (SD) as well as progression-free survival were evaluated. Proteins and mRNA of potential prognostic or predictive significance (HER2, shed HER2, HER3, epidermal growth factor receptor, amphiregulin, betacellulin, c-Myc, p-Akt, PIK3CA, PTEN, transforming growth factor-α) were measured using immunohistochemistry and/or real-time reverse transcriptase quantitative polymerase chain reaction, immunoassay or fluorescence in situ hybridization. Results: 66 pts were recruited, among whom there were 4 complete responses, 12 partial responses, and a further 17 pts experiencing SD ≥6 months, giving an overall clinical benefit rate of 50%. Assessment of the above biomarkers suggests that low mRNA for both HER2 and HER3 correlates with favorable clinical outcomes. Conclusions: The data appear to support the view that HER2 and HER3 mRNA expression may have predictive or prognostic value for P and H combination treatment outcomes in pts with HER2-positive disease and further investigation is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, Roche Diagnostics GmbH Genentech, GlaxoSmithKline, Johnson & Johnson, Novartis, Pfizer, Roche, sanofi-aventis, Wyeth Roche GlaxoSmithKline, Roche, sanofi-aventis Roche Roche
Efficacy and Safety of Crisaborole Topical Ointment, 2%, a Novel, Nonsteroidal, Topical, Anti-Inflammatory, Phosphodiesterase Inhibitor in 2 Phase 3 Studies in Children and Adults with Mild-to-Moderate Atopic Dermatitis
Authors: Mark Boguniewicz, Amy S. Paller, Wynnis L. Tom, Mark G. Lebwohl, Robin L. Blumenthal, Robert S. Call, Lawrence F. Eichenfield, Douglass W. Forsha, William C. Rees, Eric L. Simpson, Linda F. Stein Gold, Andrea L. Zaenglein, Matty H. Hughes, Lee T. Zane, Adelaide A. Hebert
Journal: Journal of Allergy and Clinical Immunology (2016)
Secondary malignancies after stem cell transplantation
Authors: A. Campos, N. M. Costa, C. P. Vaz, A. Carvalhais, S. Roncon, F. Campilho, P. Pimentel
Journal: Journal of Clinical Oncology (2004)

6651 Background: Several reports have suggested that patients who undergo stem cell transplantation (SCT) are at increased risk of developing therapy-related secondary malignancies because of several risk factors, including malignant primary disease, conditioning with radiation and/or chemotherapy, and graft-versus-host disease (GVHD). Methods: Between June of 1989 and December 2003, 582 patients underwent SCT in a total of 698 transplants (343 autologous and 355 allogeneic). Twelve post-transplant malignancies were identified in 10 patients (11 after autologous and 1 after allogeneic SCT), 7 male and 4 female, with a median age of 32 years (range: 1–55). Total body irradiation or other radiation modalities were never used in conditioning regimen. Results: At 10 years the actuarial probability of a second neoplasm after SCT was 6.0% (± 2.5%), being 3.2% (± 3.2%) for allogeneic, and 8.0% (± 3.5%) for autologous SCT. The mean follow-up time was 29 months (± 1.3). The median time from SCT to diagnosis of second neoplasm was 10.5 months (range: 2.96–71.5), and overall survival at 10 years was 40% (± 17%). The patient characteristics with secondary malignancies after autologous SCT are listed in table 1. The remaining patient, a man with primary diagnosis of acute myeloid leukaemia M5, underwent allogeneic SCT conditioned with busulfan and cyclophosphamide. He developed a late severe chronic GVHD with mouth involvement, being treated mainly with cyclosporine and prednisone. Five years later a squamous cell carcinoma of the tongue was diagnosed, and led to patient death. Conclusions: We found a low incidence of secondary malignancies after allogeneic SCT. The follow-up time is necessarily insufficient for allogeneic SCT. There is a trend between autologous SCT for Hodgkin disease and secondary myelodysplastic syndrome. More studies are necessary to define risks factors, mainly for patients with a long expectancy of life after SCT. Table 1 No significant financial relationships to disclose.
Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials
Authors: Mayank Goyal, Bijoy K Menon, Wim H van Zwam, Diederik W J Dippel, Peter J Mitchell, Andrew M Demchuk, Antoni Dávalos, Charles B L M Majoie, Aad van der Lugt, Maria A de Miquel, Geoffrey A Donnan, Yvo B W E M Roos, Alain Bonafe, Reza Jahan, Hans-Christoph Diener, Lucie A van den Berg, Elad I Levy, Olvert A Berkhemer, Vitor M Pereira, Jeremy Rempel, Mònica Millán, Stephen M Davis, Daniel Roy, John Thornton, Luis San Román, Marc Ribó, Debbie Beumer, Bruce Stouch, Scott Brown, Bruce C V Campbell, Robert J van Oostenbrugge, Jeffrey L Saver, Michael D Hill, Tudor G Jovin
Journal: The Lancet (2016)
Analysis of recurrence pattern and survival in locally advanced rectal cancer treated with neoadjuvant chemoradiation and surgery: 25 years of experience.
Authors: Javier A. Cienfuegos, Jorge Baixauli, Fernando Rotellar, Iosu Sola, Jorge Arredondo, Patricia Martfnez-Ortega, Carmen Beorlegui, Jose Luis Hernandez-Lizoain
Journal: Journal of Clinical Oncology (2015)

744 Background: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (CRT) followed by total mesorectal excision (TME). Despite the significant reduction (~ 40%) in local recurrence, the overall survival (OS) and disease free survival (DFS) remain stable during last decade. We aimed to study the pattern of recurrence and it’s relationship with clinico-pathological data in 356 patients with LARC treated with CRT and TME in last 25 years. Methods: From a total of 621 patients, 356 with LARC were analyzed. In 55 (15.4%) the tumor was localized in upper third, in 120 (33.7%) in middle third and in 181 (50.8%) in distal third. The median dose of radiotherapy for the 3 groups was between 47.5 - 48.52 Gy. Chemotherapy was based on 5-FU or capecitabine combined with oxaliplatin. Type of surgery, pathological response grade, circumferential resection margin, lymphovascular invasion, colloid response, local recurrence incidence, distal relapse, OS and DFS were analyzed. Results: The median interval between the end of CRT and surgery was 40 days. 52 low anterior resection were carried-out in upper third (94.5%), 112 (93.3%) in middle third and 92 (50.8%) in distal third. Four patients from the middle third (3.3%) underwent abdominoperineal resection and 72 (39.8%) in the distal location. No differences were observed in number of lymphoid nodes, vascular perineural invasion, and pathological response grade. A pathological complete response was assessed in 5 patients (9.1%) in upper third, in 12 (10%) in middle third, as well in 32 (17.7%) in distal third. Median follow-up of 187 months. The 5-10 year DFS for the 3 groups was 75%, 76%, and 69%, and 75%, 71%, and 66% respectively. The local recurrence rate was 3.6%, 4.2%, and 6.1%. The distal recurrence was more frequent in the lung, 10.9%, 16.7%, 23.8%, with tendency to be significant (p&lt;0.007) in distal third. Conclusions: In spite of the good local control with the association of preoperative CRT and TME in treatment of LARC, the development of distant metastases, especially in distal third, gives rise to new therapeutics schemes. Further research is warranted as to the benefits of adjuvant chemotherapy.
Radioimmunolocalization of colorectal carcinoma. A correlation among RIL results, surgical findings, serum tumor marker levels and the presence of CEA and CA 19.9 in tumor tissue: The experience of the Hospital de la Santa Creu i Sant Pau
Authors: J.R. Germá-Lluch, I. Alvarez, I. Carrió, F.M. Nogueras, E. Marcuello, M. Estorch, Li. Berná
Journal: Annals of Oncology (1991)
The efficacy of sentinel lymph node and lymphatic tracts detection using fluorescence navigation with indocyanine green in breast cancer: An analysis of 410 patients
Authors: K. Yamagami, T. Hashimoto, M. Yamamoto
Journal: Journal of Clinical Oncology (2008)

633 Background: Sentinel node biopsy (SNB) in breast cancer is a promising surgical technique to avoid unnecessary axillary lymph node dissection. For the higher detection rate of sentinel lymph node (SLN), recommended method is the two mapping procedures: the blue dye- and gamma probe-guided method. In case of blue dye method alone with blind procedure, intensive training is necessary to obtain a satisfactory detection rate and to avoid false-negative results. Whereas gamma probe method using radio isotope is complicated and also contains blind process. To visualize lymphatic drainage pathway and SLN in breast cancer, we proposed the fluorescence imaging with indocyanine green (ICG), which is no need to handle with radioactive agents. The aim of this study was to investigate into the efficacy of fluorescence navigation using ICG leading to SNB. Methods: We examined the SLN detection in 410 patients who underwent their surgery for breast cancer between April 2004 and December 2007. Fluorescence images were obtained using a charge coupled device camera with a cut filter as a detector, and light emitting diodes at 760 nm as the light source. Followed by an injection into the areolar of mixture of ICG and blue dye (indigocarmin), using such a device, the subcutaneous fluorescent lymphatic channels were marked and carefully dissection was performed to identify the fluorescent lymph nodes. Results: Subcutaneous lymphatic channels were detectable by fluorescence in 401 patients (97.8%). Fluorescent channels showed the appropriate axillary incision. However, they were not clearly observable by blue color. SLN identified in 399 of 410 cases (detection rate 97.3%). Detail is as follows: (blue stain, fluorescence); (+,+) 381 (92.9%), (+,- ) 0 (0 %), (-,+) 18 (4.4%), (-,-) 11 (2.7%). Eighteen cases of SLN, which were detectable by fluorescence, could not be recognized by the blue stain. Conclusions: Using fluorescence navigation with ICG made it easy to detect SLN, even in the condition that blue color of node is difficult to be defined by inspection, or the node is embedded in the fat, resulting in higher detection ratio and minimum invasive SNB. This novel method might reform the way of SLN identification fundamentally. No significant financial relationships to disclose.
Detection of an Immunogenic HERV-E Envelope with Selective Expression in Clear Cell Kidney Cancer
Authors: Elena Cherkasova, Claire Scrivani, Susan Doh, Quinn Weisman, Yoshiyuki Takahashi, Nanae Harashima, Hisayuki Yokoyama, Ramaprasad Srinivasan, W. Marston Linehan, Michael I. Lerman, Richard W. Childs
Journal: Cancer Research (2016)

Abstract VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of kidney cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E). In this study, we define a transcript encoding the entire envelope gene of HERV-E as expressed selectively in ccRCC tumors, as distinct from normal kidney tissues or other tumor types. Sequence analysis of this envelope transcript revealed long open reading frames encoding putative surface and transmembrane envelope proteins. Retroviral envelopes are known to be capable of eliciting immunity in humans. Accordingly, we found that HLA-A*0201–restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript–stimulated CD8+ T cells, which could recognize HLA-A*0201–positive HERV-E–expressing kidney tumor cells. Overall, our results offer evidence of unique HERV-E envelope peptides presented on the surface of ccRCC cells, offering potentially useful tumor-restricted targets for T-cell–based immunotherapy of kidney cancer. Cancer Res; 76(8); 2177–85. ©2016 AACR.
Scheduled asthma management in general practice – Generally increases asthma control in those who attend
Authors: Vibeke Backer, Dorthe Knudsen, Henrik Ommen
Journal: European Respiratory Journal (2011)

Background:  Successful asthma management involves guideline-based treatment and regular follow-up. We aimed to study the level of disease control and change over time in asthmatic individuals managed by their general practitioner (GP) and a dedicated asthma nurse when using a systematic asthma consultation guide based on Global Initiative of Asthma guidelines (GINA guidelines).   Methods:  Patients aged 18 years or older with doctor-diagnosed asthma were included. All visits included evaluation of respiratory symptoms, exacerbations, treatment, compliance, lung function, and follow-up appointments. In total, 130 primary care clinics across Denmark participated.   Results:  At the initial visit (baseline), 722 patients (37.3%) were classified as well-controlled, 759 (39.2%) as partly controlled and 456 (23.5%) as uncontrolled. At the time of data analysis (Jan 2011), 641 patients had been offered a both a baseline and a follow-up visit. A higher level of asthma control was found at the follow-up visit compared to the baseline visit (uncontrolled asthma 29.7% and 16.5%, respectively, p   Conclusion:  Although most asthmatic individuals received asthma treatment, a substantial number still were partly or poorly controlled. The overall asthma control improved significantly when a systematic asthma management approach was introduced by educated health care staff.
A randomized phase II trial of sorafenib versus sorafenib plus low-dose interferon-alfa: Clinical results and biomarker analysis
Authors: N. M. Tannir, A. J. Zurita, J. V. Heymach, H. T. Tran, L. C. Pagliaro, P. Corn, A. M. Aparicio, R. Ashe, J. J. Wright, E. Jonasch
Journal: Journal of Clinical Oncology (2008)

5093 Background: Sorafenib was shown to significantly prolong progression-free survival (PFS) in pts with mRCC after cytokine failure. We have previously shown that low-dose interferon alfa (IFN-α) was comparable in efficacy and was better tolerated than intermediate-dose IFN-α in pts with mRCC. Therefore, we sought to evaluate the benefit and toxicity of sorafenib plus low-dose (LD) IFN- α in mRCC. In addition, we assessed the ability of plasma and serum biomarkers to correlate with outcome. Methods: Pts enrolled in this randomized phase II trial had conventional mRCC, no prior systemic therapy, PS 0/1 and no brain metastases. Only 1 patient had not undergone prior nephrectomy. Pts received sorafenib 400mg PO BID or same dose sorafenib plus LD IFN-α 0.5 million units SC BID. Primary endpoint was PFS. Plasma levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF- bb) were measured at baseline before treatment using multiplex bead suspension arrays. Results: From 6/24/05 through 6/18/07, 80 pts (61 males) were enrolled (40/arm). 72 pts were evaluable for response. By Motzer et al’s criteria, 52%, 46%, and 3% of pts had favorable-risk, intermediate-risk, or poor-risk prognosis, respectively. Median follow-up was 14 mos (range, 3.5- 28.7). Median PFS time for all pts was 7.4 months (95% CI, 5.5- 9.2 months). Median PFS time for the sorafenib arm was 5.7 mos (95% CI, 5.5- 9.2), compared to 7.6 mos (95% CI, 5.2–11.1) for the combination arm (P=NS). Median OS times were not reached for either arm. 6 pts on the sorafenib arm died compared to 10 pts on the combination arm. A higher percentage of pts required dose reductions or therapy discontinuation on the combination arm. PFS times for all pts were significantly longer for those pts with baseline VEGF and PDGF levels above the median (P=0.04 for both markers). The plasma levels of these two markers were positively correlated (Spearman’s correlation coefficient = 0.60, P < 0.0001). Conclusions: In this randomized phase II trial, there were no significant differences in efficacy between sorafenib and sorafenib plus LD IFN-α. Higher baseline VEGF and PDGF-bb levels correlated with longer PFS. Sponsored by NCI-CTEP. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration NCI-CTEP Bayer/Onyx Bayer/Onyx
Abstract 15540: Effects of Broad Spectrum Tyrosine Kinase Inhibitor on Pulmonary Circulation Homeostasis
Authors: Seferian Andrei, Tu Ly, Phan Carole, Huertas Alice, Montani David, Humbert Marc, Guignabert Christophe
Journal: Circulation (2013)

Rationale: The platelet derived growth factor (PDGF) pathway is altered in pulmonary hypertension (PH) and imatinib a tyrosine kinase inhibitor (TKI) of PDGF has shown encouraging results in animal...
Activation by Chemical Carcinogens of γ-Glutamyl Transpeptidase in Rat and Mouse Liver 2
Authors: Silvio Fiala, Emerich S. Fiala
Journal: JNCI Journal of the National Cancer Institute (1973)

Feeding a diet containing carcinogenic 3′-methyl-4-dimethylaminoazobenzene (3′-MeDAB), 2-acetylaminofluorene (2-AAF), thioacetamide, DL-ethionine or administering dimethylnitrosamine in drinking water gradually increased γ-glutamyl transpeptidase (glutathionase) in rat liver. A single large dose of strong hepatocarcinogens such as dimethylnitrosamine, 2-AAF, or 3′-Me-DAB led to higher levels of glutathionase within 24–48 hours. Diet containing carcinogenic o-aminoazotoluene (o-AAT) also activated glutathionase gradually in mouse liver. Continuous feeding of diet containing the noncarcinogenic 2-methyl-4-dimethylaminoazobenzene caused only a temporary increase of glutathionase. Hypophysectomy inhibited the activation of glutathionase in liver of rats fed 3′-Me-DAB or 2-AAF. For 70 and 110 days, respectively, the increased activity of glutathionase depended on the continued administration of 3′-MeDAB or dimethylnitrosamine. After these periods, high glutathionase activity in rat liver became a permanent feature independent of further carcinogen. The results suggest that the activation of glutathionase in rat liver is related, almost from the beginning, to the carcinogenic process induced by chemical compounds.
Plasticity of the human visual system after retinal gene therapy in patients with Leber’s congenital amaurosis
Authors: Manzar Ashtari, Hui Zhang, Philip A. Cook, Laura L. Cyckowski, Kenneth S. Shindler, Kathleen A. Marshall, Puya Aravand, Arastoo Vossough, James C. Gee, Albert M. Maguire, Chris I. Baker, Jean Bennett
Journal: Science Translational Medicine (2015)

Imaging reveals increased structural and functional plasticity in human visual pathways after retinal gene therapy.
Two Nights of Recovery Sleep Reverses the Effects of Short-term Sleep Restriction on Diabetes Risk
Authors: Josiane L. Broussard, Kristen Wroblewski, Jennifer M. Kilkus, Esra Tasali
Journal: Diabetes Care (2016)

Sleep restriction is associated with insulin resistance and an increased risk for type 2 diabetes (1–3). Here, we investigated whether only 2 nights of recovery sleep, as may occur on weekends, reverses the negative effects of short-term sleep restriction on glucose homeostasis.

Nineteen healthy young lean men were studied under controlled laboratory conditions during normal sleep and sleep restriction in a randomized order, as previously reported (1,2,4). The institutional review board of The University of Chicago approved the protocol, and all participants gave written informed consent. During normal sleep, participants were allowed 8.5 h in bed (2300–0700) for 4 consecutive nights. During sleep restriction, participants were allowed 4.5 h in bed (0100–0530) for 4 consecutive nights, immediately followed by recovery sleep for 2 consecutive nights with 12 h in bed on the first night (2200–1000) and 10 h in bed on the second night (2200–0800). A frequently sampled intravenous glucose tolerance test (ivGTT) was performed at 1000 after 4 nights of normal sleep, 4 nights of sleep restriction, and 2 nights …