tbuckley/cabot-search huggingface dataset:
Randomized Phase III Trial of Trastuzumab Plus Capecitabine With or Without Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Who Experienced Disease Progression During or After Trastuzumab-Based Therapy
Authors: Ander Urruticoechea, Mohammed Rizwanullah, Seock-Ah Im, Antonio Carlos Sánchez Ruiz, István Láng, Gianluca Tomasello, Hannah Douthwaite, Tanja Badovinac Crnjevic, Sarah Heeson, Jennifer Eng-Wong, Montserrat Muñoz
Journal: Journal of Clinical Oncology (2017)

Purpose To assess the efficacy and safety of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy and received a prior taxane. Patients and Methods Patients were randomly assigned to arm A: trastuzumab 8 mg/kg → 6 mg/kg once every 3 weeks plus capecitabine 1,250 mg/m2 twice a day (2 weeks on, 1 week off, every 3 weeks); or arm B: pertuzumab 840 mg → 420 mg once every 3 weeks plus trastuzumab at the same dose and schedule as arm A plus capecitabine 1,000 mg/m2 on the same schedule as arm A. The primary end point was independent review facility-assessed progression-free survival (IRF PFS). Secondary end points included overall survival (OS) and safety. Hierarchical testing procedures were used to control type I error for statistical testing of IRF PFS, OS, and objective response rate. Results Randomly assigned (intent-to-treat) populations were 224 and 228 patients in arms A and B, respectively. Median IRF PFS at 28.6 and 25.3 months' median follow-up was 9.0 v 11.1 months (hazard ratio, 0.82; 95% CI, 0.65 to 1.02; P = .0731) and interim OS was 28.1 v 36.1 months (hazard ratio, 0.68; 95% CI, 0.51 to 0.90). The most common adverse events (all grades; incidence of ≥ 10% in either arm and ≥ 5% difference between arms) were hand-foot syndrome, nausea, and neutropenia in arm A, and diarrhea, rash, and nasopharyngitis in arm B. Conclusion The addition of pertuzumab to trastuzumab and capecitabine did not significantly improve IRF PFS. An 8-month increase in median OS to 36.1 months with pertuzumab was observed. Statistical significance for OS cannot be claimed because of the hierarchical testing of OS after the primary PFS end point; however, the magnitude of OS difference is in keeping with prior experience of pertuzumab in metastatic breast cancer. No new safety signals were identified.
FRI0011 The effect of steroid injection after arthroscopic synovectomy in rheumatoid knee synovitis
Authors: SI Kuzmanova, PC Solakov, AN Atanasov, SA Andreev, K Klinkanov
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The study assesses the therapeutic result from a single application of local corticosteroid (betamethasone 7 mg) seven days after the performance of an arthroscopic synovectomy of the knee joint in patients with rheumatoid arthritis (RA). <h3>Objectives</h3> An arthroscopic shaver-synovectomy with a consecutive tidal lavage with 4 – 5L saline was performed in 73 RA patients (51F/22M) with mean disease duration 4,5 (± 1.8) years and active synovitis of the knee joints. In 23 patient (15F/8M) after the arthroscopic synovectomy (AS) an application of a local corticosteroid was not performed (control group). <h3>Methods</h3> The assessment of the results was done on 1st, 3rd and on 6th month after AS according to the Knee Society Rating System, using a scale for assessment of the knee joint in respect of the changes of the pain, range of motion (ROM), joint stability and some functional parameters. <h3>Results</h3> A higher degree of reducing of the pain, improvement in the joint stability of the gait and of the ability of climbing and descending scales in all patients with local application of corticosteroid after AS was found compared to controls (p &lt; 0.001) <h3>Conclusion</h3> The results confirm the better effect from the administration of a local corticosteroid one week after an arthroscopic synovectomy in rheumatoid knee synovitis. <h3>References</h3> Sharma A, Baethge BA, Acebes JC, <i>et al</i>. Arthroscopic lavage treatment in rheumatoid arthritis of the knee. J Rheumatol. 1996;23(11):1872–4 Srinivasan A, Amos M, Webley M. The effect of joint washout of steroid injection compared with either joint washout of steroid injection alone in rheumatoid knee effusion. Br J Rheumatol. 1995;1:219–27
Better Care Fund no more than a “ruse” to cover up funding pressures, say MPs
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Funding arrangements for integrating health and social care in England were a “complicated ruse” designed to “paper over the funding pressures on adult social care,” MPs have said in a report.1

Meg Hillier, chair of the House of Commons Public Accounts Committee, which produced the report, described the Better Care Fund as a “money merry go round.” She told The BMJ that “one off short term initiatives [such as the Better Care Fund] were not a way to solve long standing problems” such as improving health and social care in the …
P09.20 Effect of age on outcome in the GLARIUS trial
Authors: S. Kebir, N. Schaefer, E. Hattingen, J. Steinbach, A. Weyerbrock, P. Hau, R. Goldbrunner, M. Proescholdt, U. Herrlinger, M. Glas
Journal: Neuro-Oncology (2017)

Background: The phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase (MGMT) non-methylated glioblastoma in a 2:1 ratio to experimental bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ). BEV/IRI prolonged progression-free survival but overall survival (OS) was similar in both treatment arms. Whether elderly patients derive benefit from BEV/IRI treatment is a controversial issue. In an explorative subgroup analysis, the association of age and BEV/IRI treatment was addressed. Methods: Patients included in the modified intention-to-treat population were stratified according to their age at tumor diagnosis into a <65 years (y) or ≥65 y group. Characteristics (gender, Karnofsky Performance Score (KPS), extent of resection, and mini-mental status examination score) were then compared between groups. In a Kaplan-Meier analysis, we compared OS between age groups in each treatment arm. A Cox regression analysis was used to detect whether age was an independent prognostic factor. Results: In the BEV/IRI arm, 95 patients (82%) were younger than 65 y and 21 (18%) were at least 65 y old. In the TMZ arm, the number of patients was very small with 41 patients (76%) being <65 y and 13 patients (24%) ≥65 y old. In each treatment arm, canonical prognostic factors (KPS, extent of resection) were balanced between age groups. Among patients treated with BEV/IRI, those <65 y survived significantly longer than those ≥65 y (median OS, 17.5 vs. 13.4 months, p<0.001). Among TMZ-treated patients, no significant difference was found between age groups (median OS, 20.0 vs. 17.3 months, p=0.567). In addition, there is a tendency among elderly patients to benefit more from TMZ than from BEV/IRI treatment (median OS, TMZ, 20.0 months versus BEV/IRI, 13.4 months; p=0.08). In a multivariable Cox regression model, higher age emerged as an independent negative prognostic factor in BEV/IRI treated patients only (Hazard Ratio, 2.72, p<0.001). Conclusions: In the GLARIUS trial, elderly patients tended to benefit from TMZ more than from BEV/IRI treatment. Among BEV/IRI treated patients, those <65 y had a longer OS as compared to elderly patients. The conclusiveness of this analysis is limited by a small sample size.
Short course treatment for MDR TB: jumping the gun?
Authors: Anna Turkova, Beate Kampmann
Journal: Thorax (2017)

Multidrug-resistant (MDR)-TB is threatening TB control worldwide. The conventional treatment lasts 20–24 months, is often toxic and half of the treated patients have poor outcomes. WHO has recently recommended a shorter regimen with treatment duration of 9–12 months, aiming for higher effectiveness, tolerability, adherence and completion rates.1 This shorter regimen is recommended for patients with pulmonary TB who have not been previously exposed to second-line drugs for more than 1 month and have no confirmed or suspected resistance to drugs in the regimen, except high-dose isoniazid. Recommendations were based on the promising results of large observational cohorts in Asia and Africa.

In Thorax, Yanina Balabanova and colleagues assessed the proportion of adult smear-positive pulmonary MDR-TB cases who might have …
P06.09 In vitro assessment of human IL-12Fc function on porcine and canine peripheral blood mononuclear cells
Authors: L. Schellhammer, M. Beffinger, A. Parshenkov, B. Becher, A. Bienemann, N. Granger, T. Buch, J. vom Berg
Journal: Neuro-Oncology (2017)

Introduction: Despite state-of-the-art surgical methods combined with radio- and chemotherapy the clinical prognosis of brain cancer patients remains poor. The brain is an immune privileged site and brain cancers are known to form a highly immunosuppressive microenvironment, suggesting that patients could benefit from immunomodulatory drugs. Multiple therapies targeting the immune system are currently under development, including application of a potent activator of immune responses, interleukin (IL)-12. This cytokine stimulates the cytotoxic function of lymphocytes and can trigger rejection of gliomas in preclinical studies. Even though IL-12 has a relatively short half-life, systemic IL-12 can quickly lead to severe adverse reactions. Local application or targeting is therefore mandatory. Local IL-12 therapy is currently tested in early stage clinical trials of intratumoral genetherapy using viral vectors (ClinicalTrials.gov identifiers NCT02026271 and NCT02062827). An alternative approach is the use of convection-enhanced delivery (CED). This way IL-12 could be dosed precisely to the tumour focus with minimal systemic leakage. Furthermore, to increase the local half-life of IL-12, we have fused it with the Fc part of human IgG4 (IL-12Fc). Using CED, we are aiming to validate efficacy and safety of local IL-12Fc monotherapy in a preclinical setting with canine brain tumours. Materials and Methods: Canine peripheral blood mononuclear cells (PBMCs) were stimulated with increasing concentrations of human IL-12Fc or with recombinant human or canine IL-12 in presence or absence of concanavalin A. Interferon-γ (IFN-γ) production was measured by ELISA. Phosphorylation of STAT4 was measured by western blot. Porcine PBMCs were stimulated in the presence of recombinant porcine IL-2 and IL-18. IFN-γ production was measured by ELISA. Results: Human IL-12Fc is able to stimulate canine and porcine PBMCs to secrete IFN-γ in a dose-dependent manner. Furthermore, stimulation with hIL-12Fc leads to phosphorylation of STAT4. Conclusions: Human IL-12 immunotherapeutics are able to stimulate canine PBMCs and thus therapy of spontaneous brain tumours in dogs can be used for preclinical testing. To estimate leakage and brain perfusion in the dog and ultimately in humans, we will next test CED of hIL-12Fc in large white landrace pigs. We are aiming to initiate a trial to assess the efficacy of local delivery of human IL-12Fc as therapy for canine brain tumours.
P01.18 Recurrent glioblastomas reveal molecular subtypes associated with mechanistic implications of drug-resistance
Authors: S. Kwon, S. Kang, C. Park, S. Jung, E. Park, J. Lee, S. Kim, H. Woo
Journal: Neuro-Oncology (2017)

Introduction: Previously, transcriptomic profiling studies have shown distinct molecular subtypes of glioblastomas. It has also been suggested that the recurrence of glioblastomas could be achieved by transcriptomic reprograming of tumors, however, their characteristics are not yet fully understood. Here, to gain the mechanistic insights on the molecular phenotypes of recurrent glioblastomas, gene expression profiling was performed on the 43 cases of glioblastomas including 15 paired primary and recurrent cases. Materials and Methods: Total RNA was extracted from frozen tumor section. For microarray experiments, cRNA was used for hybridization to a human HT12-v4 Illumina Beadchip gene expression array and fluorescence signals were obtained using Illumina bead Array Reader confocal scanner. For validation analysis, two independent gene expression data of REMBRANDT and TCGA were obtained from their websites, respectively. For subtype prediction, three independent methods of unsupervised hierarchical clustering, consensus clustering, and nearest template prediction were applied. The functional profiling of biological function and signaling pathways were performed using DAVID software. Results: Unsupervised clustering analyses revealed two subtypes of G1 and G2, which were characterized by proliferation and neuron-like gene expression traits, respectively. While the primary tumors were classified as G1 subtype, the recurrent glioblastomas showed two distinct expression types. Compared to paired primary tumors, the recurrent tumors in G1 subtype did not show expression alteration. By contrast, the recurrent tumors in G2 subtype showed expression changes from proliferation type to neuron-like one. We also observed the expression of stemness-related genes in G1 recurrent tumors and the altered expression of DNA-repair genes (i.e., AURK, HOX, MGMT, and MSH6) in the G2 recurrent tumors, which might be responsible for the acquisition of drug resistance mechanism during tumor recurrence in a subtype-specific manner. Conclusions: We suggest that recurrent glioblastomas may choose two different strategies for transcriptomic reprogramming to escape the chemotherapeutic treatment during tumor recurrence. Our results might be helpful to determine personalized therapeutic strategy against heterogeneous glioma recurrence.
Abstract O.73: Long-term Results Of Percutaneous Transluminal Coronary Rotational Atherectomy For Localized Stenosis Caused By Kawasaki Disease
Authors: Etsuko Tsuda, Shinsuke Hoshino, Yasuhide Asaumi, Yosuke Hayama, Osamu Yamada
Journal: Circulation (2015)

We report the results of percutaneous transluminal coronary rotational atherectomy (PTCRA) for localized stenosis caused by Kawasaki disease (KD). Thirteen male and a female, aged 5 to 29 years (median 13 years), underwent PTCRA and the interval from the PTARA to the latest angiogram ranged from 3 months to 16 years (median 6 years). The target vessels were the left anterior descending artery (3 patients), the left circumflex (2), left main trunk (2) and the right coronary artery (7). The immediate results of PTCRA were successful in all patients, and the mean stenosis degree improved from 86 ± 11% to 36 ± 13%. Five cardiac events occurred within one year (acute myocardial infarction 2, transient complete atrioventricular block 1 and re-PTCRA 2). The survival rate and cardiac event free rate at 15 years after PTCRA were 93% and 71%, respectively. For the graft patency, 4 pts who underwent PTCRA within 10 yeas old, had asymptomatic occlusion within 1 year. The patency rate at 15 years after PTCRA was 69%, in 10 pts who underwent it more than 10 years old. Cardiac events and restenosis occurred within a year after PTCRA. The results in patients less than 10 years old was poor. If a graft is patent in one year after procedure, long-term patency may be expected in patients more than 10 years old.
Osteoblasts support megakaryopoiesis through production of interleukin-9
Authors: Min Xiao, Yongkui Wang, Chen Tao, Zhenyu Wang, Jun Yang, Zhenguo Chen, Zhipeng Zou, Mangmang Li, Anling Liu, Chunhong Jia, Bin Huang, Bo Yan, Pinglin Lai, Changhai Ding, Daozhang Cai, Guozhi Xiao, Yu Jiang, Xiaochun Bai
Journal: Blood (2017)
P18.02 Prospective evaluation of quality of life in patients with recurrent high grade glioma treated with re-irradiation by tomotherapy based IMRT
Authors: P. Gupta, T. Gupta
Journal: Neuro-Oncology (2017)

OBJECTIVE: To evaluate the impact of re-irradiation on performance status and survival in patients with recurrent glioma.METHOD: A retrospective analysis was performed on 14 patients who received re-irradiation for recurrent glioma from Dec 2013 to Feb 2015.The GTV was defined as the contrast-enhancing lesion on T1-weighted MRI.No CTV was defined.Median GTV-PTV margin was 1.25cm (range 0.7 -2.1).All patients received VMAT, 2 non co-planar arcs.The dose delivered was 30Gy in 5 fractions.Performance status and corticosteroid dosages had been recorded prospectively for all patients.A cohort of 22 recurrent glioma patients were identified in the 5 months prior to Dec 2013.This group did not receive reirradiation.Overall survival from initial diagnosis was calculated using the Kaplan-Meier method using SPSS.RESULTS: REIRRRADIATION COHORT: Median age was 49 (range 22-59).At initial diagnosis, 5 patients had glioblastoma (GBM), 2 WHO grade II astrocytoma and 7 WHO Grade II oligodendroglioma.All low grade (LGG) patients had radiological evidence of transformation to higher grade.All patients initially had surgical debulking followed by radiation to a median dose of 60Gy (range 54Gy-60Gy).At time of reirradiation, patients had a mean KPS of 70% (range 60-90) and had progressed through at least one line of chemotherapy.Re-irradiation volumes overlapped previously irradiated fields in 14 patients.1 week post XRT median KPS was 70% (range 60-90). 1 month post XRT median KPS was 90% (range 70-90).Median dexamethasone dose prescribed was 2mg pre-XRT (range 0-12), 4mg 1 week post XRT (range 0-8) and 4 mg 1 month post XRT (range 0-10).All patients completed treatment and no severe acute or late complications were observed.Progression free survival from the time of irradiation was 4.2 months (range 1-7) for GBM, 6.1 months (range 1 -8) for LGG.Median survival from date of reirradiation was 8 months for GBM (range 5-11) and 11 months for LGG (range 5-18).Median overall survival from date of diagnosis for GBM was 34 months (range 26 -46), and 126 months (range 49-192) for LGG.As a comparison, a similar cohort of patients aged <65, KPS >70% who had progressed through at least one line of chemotherapy after primary radiotherapy were identified from July 2013-Dec 2013.12 were GBM patients: median survival from date of 2 nd line treatment was 11 months (4-29) and median overall survival was 31 months (14-46).10 LGG patients were identified with a median survival from date of 2 nd line treatment of 12 months and median overall survival was 61.5 months (19-101).CONCLUSION: Re-irradiation is a safe and feasible treatment for recurrent glioma and the majority of patients experienced an improvement in performance status after treatment.However in this small, retrospective study there was no signal that reirradiation was associated with improved survival when compared with similar cohorts managed without reirradiation. P17.
P09.32 High therapy compliance in patients treated with Optune® therapy does not depend on demographic data, stage of disease or treatment duration
Authors: M. Misch, J. Onken
Journal: Neuro-Oncology (2017)

Introduction: Optune is a novel treatment that is approved for the treatment of patients with newly diagnosed glioblastoma (GBM) and also for patients with recurrent high grade glioma (HGG). Alternating electric fields of low intensity (1-3 V / cm) and intermediate frequency (200 kHz) are delivered to the tumor in the brain. Here we report our experience with TTFields in 30 patients at Charité over the last year and the factors that could affect therapy compliance. Materials and Methods: Since June 2015 twenty-six patients with a diagnosed HGG have been treated with Optune in our hospital. Patients were carefully introduced to the therapy. Compliance is a crucial indicator for the acceptance but also for the efficacy of the therapy. According to the EF-11 trial and PRiDe registry optune therapy should be applied at least 18 h per day (Compliance >75 %) to be efficient. Compliance reports were generated at the monthly routine check of the device. Results: Patients had newly diagnosed GBM (n=17) or first recurrence of HGG (n=9). Mean age at therapy start was 47.9 years (range 25-70). Gender distribution female to male was 1:1.7. Mean treatment compliance was 87% in the total population (range 67-96%) independent of age, sex (female 85.3 ± 5.8 % vs. male 87.6 ± 7.3 % [Mean±SD], p=0.41) and stage of disease (newly diagnosed 88.5 ± 5.4 % vs. recurrent 84.2 ± 8.0 % [Mean±SD], p=0.12). Regression analysis reveals no negative correlation between age and compliance or inter-sex differences. Our data showed that the compliance is not negatively correlated with time on treatment and compliance in time course was stable once therapy was established. Conclusions: Therapy compliance is not negatively influenced by age. In contrast, older patients even at the age of around 70 years showed a remarkable average compliance far above 80%. Furthermore, compliance was equal in female and male population. In the light of a female to male ratio of 1:1.7 reflecting a typical GBM patient population (1:1.64), we assume that Optune is accepted by both male and female patients without difference. In addition, there was no significant difference of compliance between patients with newly diagnosed and recurrent GBM suggesting that the stage of the disease does not play a big role in the acceptance and feasibility of the treatment. Since the therapy takes time to be fully effective, compliance should be maintained on a high level. Compliance did not correlate negatively with time on treatment nor drop substantially below 75% in time course. Once patients are on therapy they are compliant over the course of treatment, making Optune suitable for long-term therapy.
Multilayer Nanofilms via Inkjet Printing for Stabilizing Growth Factor and Designing Desired Cell Developments
Authors: Moonhyun Choi, Hee Ho Park, Daheui Choi, Uiyoung Han, Tai Hyun Park, Hwankyu Lee, Juhyun Park, Jinkee Hong
Journal: Advanced Healthcare Materials (2017)

Biologically versatile basic fibroblast growth factor (bFGF), well known for roles of signaling molecules between cells and regulating various cellular processes, has been proven to utilize specific functionalities. However, the remarkable functions are inclinable to dwindle with decrease of bFGFs' activity. In nanoscale, developing thin films with intrinsic characteristics of building molecules can facilitate handling various materials for desired purposes. Fabricating nanofilm and handling sensitive materials without detriment to activity via highly productive manufacturing are significant for practical uses in the field of biomedical applications. Herein, a multilayered nanofilm fabricating system is developed by inkjet printing to incorporate bFGF successfully. It is demonstrated that water mixed with glycerol as biological ink maintains stability of bFGFs through simulation and experimental study. With highly stable bFGFs, the proliferation of human dermal fibroblast is enhanced and the undifferentiated state of induced pluripotent stem cell is maintained by the controlled release of bFGF.