tbuckley/cabot-search huggingface dataset:
Exploiting an Anti-CD3/CD33 Bispecific Antibody to Redirect Donor T Cells Against HLA Loss Leukemia Relapses
Authors: Pier Edoardo Rovatti, Laura Zito, Eleonora Draghi, Monika Herrmann, Anetta Marcinek, Bettina Brauchle, Cesare Covino, Mattia Di Bono, Matteo Giovanni Carrabba, Massimo Bernardi, Karl-Peter Hopfner, Cristina Toffalori, Fabio Ciceri, Marion Subklewe, Luca Vago
Journal: Blood (2019)
Talazoparib (TALA) vs physician’s choice of chemotherapy (PCT) in Asian patients (Pts) with HER2- advanced breast cancer (ABC) and a germline BRCA1/2 mutation (gBRCA1/2mut): Data from phase III EMBRACA
Authors: K.-H. Lee, S.-B. Kim, J. Sohn, A. Goodwin, T. Usari, S. Lanzalone, Y.-H. Im
Journal: Annals of Oncology (2019)
The Bayesian brain: What is it and do humans have it?
Authors: Dobromir Rahnev
Journal: Behavioral and Brain Sciences (2019)

Abstract It has been widely asserted that humans have a “Bayesian brain.” Surprisingly, however, this term has never been defined and appears to be used differently by different authors. I argue that Bayesian brain should be used to denote the realist view that brains are actual Bayesian machines and point out that there is currently no evidence for such a claim.
Characterization of 25 monoclonal antibodies to factor VIII-von Willebrand factor: relationship between ristocetin-induced platelet aggregation and platelet adherence to subendothelium
Authors: HV Stel, KS Sakariassen, BJ Scholte, EC Veerman, TH van der Kwast, PG de Groot, JJ Sixma, JA van Mourik
Journal: Blood (1984)
Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer
Authors: Colby S. Shemesh, Pascal Chanu, Kris Jamsen, Russ Wada, Gianluca Rossato, Francis Donaldson, Amit Garg, Helen Winter, Jane Ruppel, Xin Wang, Rene Bruno, Jin Jin, Sandhya Girish
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> The iMATRIX-atezolizumab study was a phase I/II, multicenter, open-label study designed to assess the safety and pharmacokinetics of atezolizumab in pediatric and young adult patients. We describe the pharmacokinetics (PK), exposure-safety, and immunogenicity of atezolizumab in pediatric and young adults with metastatic solid tumors or hematologic malignancies enrolled in this study. <h3>Methods</h3> Patients aged &lt; 18 years (<i>n</i>&nbsp;= 69) received a weight-adjusted dose of atezolizumab (15 mg/kg every 3 weeks [q3w]; maximum 1200 mg); those aged ≥ 18 years (<i>n</i>&nbsp;= 18) received a flat dose (1200 mg q3w). A prior two-compartment intravenous infusion input adult population-PK (popPK) model of atezolizumab was used as a basis to model pediatric data. <h3>Results</h3> A total of 431 atezolizumab serum concentrations from 87 relapse-refractory pediatric and young adult patients enrolled in the iMATRIX-atezolizumab study were used for the popPK analysis. The dataset comprised predominantly patients aged &lt; 18 years, including two infants aged &lt; 2 years, with a wide body weight and age range. The clearance and volume of distribution estimates of atezolizumab were 0.217 L/day and 3.01 L, respectively. Atezolizumab geometric mean trough exposures were ~ 20% lower in pediatric patients versus young adults; this was not clinically meaningful as both groups achieved the target concentration (6 μg/mL). Safety was similar between pediatric and young adult patients with no exposure-safety relationship observed. Limited responses (4/87) precluded an exposure-response assessment on outcomes. A comparable rate (13% vs 11%) of atezolizumab anti-drug antibodies was seen in pediatric and young adult patients. <h3>Conclusions</h3> These findings demonstrate a similar exposure-safety profile of atezolizumab in pediatric and young adult patients, supportive of weight-based dosing in pediatric patients. <h3>Trial registration</h3> NCT02541604.
Doctors call for action on poverty to reverse stalled life expectancy in Scotland
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Public health doctors have called for urgent action from government to tackle stalled life expectancy in Scotland.

Experts have identified low incomes faced by many people in Scotland as the leading cause of the trend, with those in the poorest areas living shorter lives than seven years ago.

At its annual conference in Dunblane, the Faculty of Public Health called for “sustained action” on poverty across all public policy making.

President of the faculty, Maggie Rae, said: “Many people are trying to survive on low …
Linsitinib (OSI-906) for the Treatment of Adult and Pediatric Wild-Type Gastrointestinal Stromal Tumors, a SARC Phase II Study
Authors: Margaret von Mehren, Suzanne George, Michael C. Heinrich, Scott M. Schuetze, Jeffrey T. Yap, Jain Q. Yu, Amanda Abbott, Samuel Litwin, John Crowley, Martin Belinsky, Katherine A. Janeway, Jason L. Hornick, Douglas B. Flieder, Rashmi Chugh, Lori Rink, Annick D. Van den Abbeele
Journal: Clinical Cancer Research (2019)

Most gastrointestinal stromal tumors (GIST) have activating mutations of
Inducing labour at 41 weeks may be safer than “wait and see” approach, study finds
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Inducing labour at 41 weeks rather than waiting until 42 weeks may be safer in low risk pregnancies, a study has found.1

The researchers recommended that their results should be “interpreted cautiously” but that pregnant women should be told the risks of expectant management and be offered induction at 41 weeks. Current practice in the UK and Scandinavia is to induce delivery in all women who have not gone into labour by 42 weeks.

The SWEdish Post-term Induction Study (SWEPIS) study, published in The BMJ ,1 included 2760 women with a low risk uncomplicated pregnancy treated at 14 hospitals in Sweden in 2016-18 …
Prognostic Impact of Chromosomal Abnormalities and Copy Number Alterations Among Adults with B-Cell Precursor Acute Lymphoblastic Leukaemia Treated on UKALL14
Authors: Anthony V. Moorman, Ellie Butler, Emilio Barretta, Amy A. Kirkwood, Claire Schwab, Thomas Creasey, Daniel A. Leongamornlert, Elli Papaemmanuil, Pip Patrick, Laura Clifton-Hadley, Bela Wrench, Tobias F Menne, Andrew K McMillan, Christine J. Harrison, Clare J Rowntree, David I Marks, Adele K. Fielding
Journal: Blood (2019)
Post-Remission Treatment with Chemotherapy or Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) in Adult Patients with High-Risk (HR) Philadelphia Chromosome-Negative (Ph-neg) Acute Lymphoblastic Leukemia (ALL) According to Their Minimal Residual Disease (MRD). Final Results of the Pethema ALL-HR-11 Trial
Authors: Josep-Maria Ribera, Mireia Morgades, Juana Ciudad, Pau Montesinos, Pere Barba, Irene García-Cadenas, María José Moreno, Susana Vives, Jordi Esteve, Cristina Gil, Silvia Monsalvo, María Teresa Artola, Jordi Ribera, Eulàlia Genescà, Mar Tormo, Marta Cervera, Daniel Martínez-Carballeira, Andrés Novo, José González-Campos, Beatriz Soria, Arancha Bermúdez, Aurelio López Martínez, Santiago Mercadal, Rosa Fernández-Martín, Rosa Coll, Josefina Serrano, Maria Luz Amigo, Pilar Martínez-Sánchez, Juan-Miguel Bergua, Alfons Serrano-Maestro, Alberto Giménez Conca, Susana Barrena, Isabel Granada, Evarist Feliu, Alberto Orfao
Journal: Blood (2019)
Clinical Impact of Ibrutinib with R-CHOP in Untreated Non-GCB DLBCL Co-Expressing BCL2 and MYC Genes in the Phase 3 Phoenix Trial
Authors: Peter Johnson, Sriram Balasubramanian, Brendan Hodkinson, Michael Schaffer, Lori Parisi, S. Martin Shreeve, Steven Sun, Jessica Vermeulen, Laurie H Sehn, Louis Staudt, Anas Younes, Wyndham Wilson
Journal: Blood (2019)
Are both necessity and opportunity the mothers of innovations?
Authors: Gili Greenbaum, Laurel Fogarty, Heidi Colleran, Oded Berger-Tal, Oren Kolodny, Nicole Creanza
Journal: Behavioral and Brain Sciences (2019)

Abstract Baumard's perspective asserts that “opportunity is the mother of innovation,” in contrast to the adage ascribing this role to necessity. Drawing on behavioral ecology and cognition, we propose that both extremes – affluence and scarcity – can drive innovation. We suggest that the types of innovations at these two extremes differ and that both rely on mechanisms operating on different time scales.
Updated results of activity of durvalumab in advanced endometrial cancer (AEC) according to mismatch repair (MMR) status: The phase II PHAEDRA trial (ANZGOG1601)
Authors: Y. Antill, P.S. Kok, M.R. Stockler, K. Robledo, S. Yip, M. Parry, D. Smith, A. Spurdle, E. Barnes, M.L. Friedlander, S. Baron-Hay, C. Shannon, J. Coward, P.J. Beale, G. Goss, T. Meniawy, J. Andrews, M. Kelly, L. Mileshkin
Journal: Annals of Oncology (2019)
Updates in Treatment Strategies for Hodgkin Lymphoma
Authors: Ranjana H. Advani
Journal: Journal of the National Comprehensive Cancer Network (2019)

Several options are available for frontline treatment of advanced-stage Hodgkin lymphoma (HL) and treatment of relapsed HL, each with inherent advantages and disadvantages. Clinicians must balance risk with benefit for the individual patient. At the NCCN 2019 Annual Congress: Hematologic Malignancies, Dr. Ranjana H. Advani summarized the current frontline treatment options for advanced-stage HL and outlined novel and emerging agents that may be incorporated as therapy options for relapsed disease.
Patterns of palliative care among patients receiving palliative radiotherapy.
Authors: Jie Jane Chen, Bhupendra Rawal, Monica Shalini Krishnan, Lauren Michelle Hertan, Diana D. Shi, Claudia Sofia Roldan, Mai Anh Huynh, Alexander Spektor, Tracy A. Balboni
Journal: Journal of Clinical Oncology (2019)

55 Background: Few studies have examined how palliative care (PC) delivered by a dedicated PC team is integrated at the time of radiotherapy (RT) consultation. We aimed to characterize patterns of PC in relation to RT, predictors of PC, and outcomes based on PC integration. Methods: We retrospectively reviewed 162 patients with metastatic cancer who received palliative RT at a single institution (7/2017-2/2018). PC integration was defined as: no PC, concurrent PC (PC initiated +/- 4 weeks within RT consult), established PC (any PC visit in the 6 months prior to RT consult), and subsequent PC (PC initiated &gt; 4 weeks after RT consult). Logistic regression analyses determined predictors of receiving any PC. Cox proportional hazards regression identified predictors of OS. Results: Median follow-up was 7.8 months (range: 0.3-20.6). Patients (56% female; 84% white; median age: 64 years (range: 22-94)) had a median of 2 metastatic sites (range: 1-6) and 2 prior courses of palliative chemotherapy (range: 0-7). Of the 74 patients (46%) with any PC, 24 (32%) had concurrent PC, 21 (28%) had established PC, and 29 (39%) had subsequent PC. The most common reasons for PC initiation were pain (58%) and goals of care/end-of-life care management (20%). Nearly half (49%) of PC consults occurred in an inpatient setting; a minority (22%) of RT consults were inpatient. On multivariate analysis, receiving any PC significantly differed by race (non-white vs white, OR = 6.40 [95% CI 1.98-20.69], p = 0.002), cancer type (lung vs non-breast other histology, OR = 0.15 [95% CI 0.06-0.35], p &lt; 0.001), and RT consult setting (inpatient vs outpatient, OR = 3.32 [95% CI 1.36-8.13], p = 0.009). On multivariate analysis, male sex (HR = 1.51 [95% CI 1.01-2.27], p = 0.046) and ECOG 2-4 (HR = 2.22 [95% CI 1.47-3.36], p &lt; 0.001) predicted worse OS. Age, marital status, language, insurance type, metastatic burden, prior palliative chemotherapy, and PC integration were not independent predictors of OS. Conclusions: At our institution, dedicated PC occurred in &lt; 50% of patients receiving palliative RT for metastatic cancer. We need initiatives to increase PC for all palliative RT patients, especially in the outpatient setting and for those with lung cancer who were less likely to receive dedicated PC.
Association of the Work Schedules of Hospitalists With Patient Outcomes of Hospitalization
Authors: James S. Goodwin, Shuang Li, Yong-Fang Kuo
Journal: JAMA Internal Medicine (2019)

<h3>Importance</h3> The working schedules of hospitalists vary widely. Discontinuous schedules, such as 24 hours on and 48 hours off, result in several hospitalists providing care during a patient’s hospital stay. Poor continuity of care during hospitalization may be associated with poor patient outcomes. <h3>Objective</h3> To determine whether admitted patients receiving care from hospitalists with more discontinuous schedules experience worse outcomes. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used conditional models to assess Medicare claims data for 114 777 medical admissions of patients with a 3-day to 6-day length of stay from January 1, 2014, through November 30, 2016, who received all general medical care from hospitalists in 229 hospitals in Texas. Data were analyzed from November 2018 to June 2019. <h3>Exposures</h3> For each admission, the weighted mean of schedule continuity for the treating hospitalists, assessed as the percentage of all their working days in that year that were part of a block of 7 or more consecutive working days, was calculated. <h3>Main Outcomes and Measures</h3> The primary outcome was patient mortality in the 30 days after discharge. Secondary outcomes were readmission rates and Medicare costs in the 30 days after discharge, and discharge destination. <h3>Results</h3> Of the 114 777 patient admissions, the mean (SD) age was 79.9 (8.3) years, and 70 047 (61.0%) were women. For admissions in the lowest quartile for continuity of hospitalist schedules, the hospitalists providing care worked 0% to 30% of their total working days as part of a block of 7 or more consecutive days vs 67% to 100% for hospitalists providing care for patients in the highest quartile for continuity. Patient characteristics were not associated with the continuity of working schedules for the hospitalist(s) providing care. In conditional logistic regression models, admitted patients cared for by hospitalists in the highest quartile of schedule continuity (vs the lowest quartile) had lower 30-day mortality after discharge (adjusted odds ratio [aOR], 0.88; 95% CI, 0.81-0.95), lower readmission rates (aOR, 0.94; 95% CI, 0.90-0.99), higher rates of discharge to the home (aOR, 1.08; 95% CI, 1.03-1.13), and lower 30-day postdischarge costs (−$223; 95% CI, −$441 to −$7). The results were similar across a range of different methods for defining continuity of hospitalist schedules and selecting the cohort. <h3>Conclusions and Relevance</h3> Hospitalist schedules vary widely. Admitted patients receiving care from hospitalists with schedules that promote inpatient continuity of care may experience better outcomes of hospitalization.
Less Chronic Graft-Versus-Host Disease, Immunosuppressive Therapy and Better Survival after Anti-Thymocyte Globulin in Unrelated Donor Stem Cell Transplant Recipients: Longer Follow-up of a Multicentre Cell Therapy Transplant Canada Randomized Trial
Authors: Jean Roy, Tony Panzarella, Stephen Couban, Félix Couture, Gerald M. Devins, Mohamed Elemary, Stephen Ronan Foley, Genevieve Gallagher, John Kuruvilla, Stephanie J. Lee, John Moore, Thomas J Nevill, Gizelle Popradi, Kirk R. Schultz, David Szwajcer, Cynthia L Toze, Irwin Walker
Journal: Blood (2019)
The zinc fingers and homeoboxes 2 protein ZHX2 and its interacting proteins regulate upstream pathways in podocyte diseases
Authors: Camille Macé, Maria Del Nogal Avila, Caroline B. Marshall, Joubert Kharlyngdoh, Ranjan Das, Eduardo Molina-Jijon, Hector Donoro Blazquez, Suresh Shastry, Elisabeth Soria, Jack Wetzels, Henry Dijkman, Carmen Avila-Casado, Lionel C. Clement, Sumant S. Chugh
Journal: Kidney International (2019)
Gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent in breast implant-associated ALCL.
Authors: Camille Laurent, Alina Nicolae, Cécile Laurent, Fabien Le Bras, Corinne Haioun, Virginie Fataccioli, Nadia Amara, José Adélaïde, Arnaud Guille, Jean-Marc Schiano, Bruno Tesson, Alexandra Traverse-Glehen, Marie-Pierre Chenard, Lénaïg Mescam, Anne Moreau, Catherine Chassagne-Clement, Joan Somja, Fréderic Escudié, Marc André, Nadine Martin, Laetitia Lacroix, François Lemonnier, Anne-Sophie Hamy, Fabien Reyal, Marie Bannier, Lucie Oberic, Nais Prade, François-Xavier Frénois, Asma Beldi-Ferchiou, Marie-Helene Delfau-Larue, Reda Bouabdallah, Daniel Birnbaum, Pierre Brousset, Luc Xerri, Philippe Gaulard
Journal: Blood (2019)
Longitudinal immune characterization of syngeneic tumor models to enable model selection for immune oncology drug discovery
Authors: Molly A. Taylor, Adina M. Hughes, Josephine Walton, Anna M. L. Coenen-Stass, Lukasz Magiera, Lorraine Mooney, Sigourney Bell, Anna D. Staniszewska, Linda C. Sandin, Simon T. Barry, Amanda Watkins, Larissa S. Carnevalli, Elizabeth L. Hardaker
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> The ability to modulate immune-inhibitory pathways using checkpoint blockade antibodies such as αPD-1, αPD-L1, and αCTLA-4 represents a significant breakthrough in cancer therapy in recent years. This has driven interest in identifying small-molecule-immunotherapy combinations to increase the proportion of responses. Murine syngeneic models, which have a functional immune system, represent an essential tool for pre-clinical evaluation of new immunotherapies. However, immune response varies widely between models and the translational relevance of each model is not fully understood, making selection of an appropriate pre-clinical model for drug target validation challenging. <h3>Methods</h3> Using flow cytometry, O-link protein analysis, RT-PCR, and RNAseq we have characterized kinetic changes in immune-cell populations over the course of tumor development in commonly used syngeneic models. <h3>Results</h3> This longitudinal profiling of syngeneic models enables pharmacodynamic time point selection within each model, dependent on the immune population of interest. Additionally, we have characterized the changes in immune populations in each of these models after treatment with the combination of α-PD-L1 and α-CTLA-4 antibodies, enabling benchmarking to known immune modulating treatments within each model. <h3>Conclusions</h3> Taken together, this dataset will provide a framework for characterization and enable the selection of the optimal models for immunotherapy combinations and generate potential biomarkers for clinical evaluation in identifying responders and non-responders to immunotherapy combinations.
Interrelationships of factors of social development are more complex than Life History Theory predicts
Authors: Boris Kotchoubey
Journal: Behavioral and Brain Sciences (2019)

Abstract Life History Theory (LHT) predicts a monotonous relationship between affluence and the rate of innovations and strong correlations within a cluster of behavioral features. Although both predictions can be true in specific cases, they are incorrect in general. Therefore, the author's explanations may be right, but they do not prove LHT and cannot be generalized to other apparently similar processes.
Afatinib versus gefitinib or erlotinib in first-line setting for Malaysia patients with EGFR mutant advanced lung adenocarcinoma
Authors: C.S. Chai, C.K. Liam, O. Po Lin, Y.K. Pang, G.F. Ho, A. Alip, C.K. Wong, M.E. Poh, J.L. Tan
Journal: Annals of Oncology (2019)
Borderline Estrogen Receptor–Positive Breast Cancers in Black and White Women
Authors: Halei C Benefield, Emma H Allott, Katherine E Reeder-Hayes, Charles M Perou, Lisa A Carey, Joseph Geradts, Xuezheng Sun, Benjamin C Calhoun, Melissa A Troester
Journal: JNCI Journal of the National Cancer Institute (2019)

Some breast tumors expressing greater than 1% and less than 10% estrogen receptor (ER) positivity (ER-borderline) are clinically aggressive; others exhibit luminal biology. Prior ER-borderline studies included few black participants.
Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease
Authors: Annelise M. Poss, J. Alan Maschek, James E. Cox, Benedikt J. Hauner, Paul N. Hopkins, Steven C. Hunt, William L. Holland, Scott A. Summers, Mary C. Playdon
Journal: Journal of Clinical Investigation (2019)

BACKGROUND. Ceramides are sphingolipids that play causative roles in diabetes and heart disease, with their serum levels measured clinically as biomarkers of cardiovascular disease (CVD).
Bone marrow mesenchymal stem cells-derived exosomes for penetrating and targeted chemotherapy of pancreatic cancer
Authors: Yu Zhou, Wenxi Zhou, Xinli Chen, Qingbing Wang, Chao Li, Qinjun Chen, Yu Zhang, Yifei Lu, Xiaoyi Ding, Chen Jiang
Journal: Acta Pharmaceutica Sinica B (2019)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable malignancy, with an only 6% 5-year relative survival rate. The dismal therapeutic effect is attributed to the chemotherapy resistance and unique pathophysiology with abundant inflammatory cytokines and abnormal hyperplasia of extracellular matrix (ECM). Based on the theory that bone marrow mesenchymal stem cells (BM-MSCs) can influence the tumorous microenvironment and malignant growth of PDAC, we employed exosomes (Exos) derived from BM-MSCs as PDAC-homing vehicles to surpass the restrictions of pathological ECM and increase the accumulation of therapeutics in tumor site. To overcome chemoresistance of PDAC, paclitaxel (PTX) and gemcitabine monophosphate (GEMP)-an intermediate product of gemcitabine metabolism-were loaded in/on the purified Exos. In this work, the Exo delivery platform showed superiorities in homing and penetrating abilities, which were performed on tumor spheroids and PDAC orthotopic models. Meanwhile, the favorable anti-tumor efficacy in vivo and in vitro, plus relatively mild systemic toxicity, was found. Loading GEMP and PTX, benefitting from the naturally PDAC selectivity, the Exo platform we constructed performs combined functions on excellent penetrating, anti-matrix and overcoming chemoresistance (Scheme 1). Worth expectantly, the Exo platform may provide a prospective approach for targeted therapies of PDAC.
Biological activity of weekly ONC201 in adult recurrent glioblastoma patients
Authors: Isabel Arrillaga-Romany, Yazmin Odia, Varun V Prabhu, Rohinton S Tarapore, Krystal Merdinger, Martin Stogniew, Wolfgang Oster, Joshua E Allen, Minesh Mehta, Tracy T Batchelor, Patrick Y Wen
Journal: Neuro-Oncology (2019)

ONC201 is a dopamine receptor D2 (DRD2) antagonist that penetrates the blood-brain barrier. ONC201 efficacy has been shown in glioblastoma animal models and is inversely correlated with dopamine receptor DRD5 expression. ONC201 is well tolerated in adult recurrent glioblastoma patients with dosing every 3 weeks and has achieved an objective radiographic response in a patient harboring the H3 K27M mutation.In a window-of-opportunity arm, 6 adult subjects initiated ONC201 prior to re-resection of recurrent glioblastoma with intratumoral concentrations as the primary endpoint. An additional 20 adults with recurrent glioblastoma received single agent weekly oral ONC201 at 625 mg, with progression-free survival at 6 months (PFS6) by Response Assessment in Neuro-Oncology (RANO) criteria as the primary endpoint.The window-of-opportunity arm achieved its primary endpoint with intratumoral ONC201 concentrations at ~24 hours following the second weekly dose ranging from 600 nM to 9.3 µM. Intratumoral pharmacodynamics assessed by activating transcriptional factor 4, death receptor 5, and apoptosis induction relative to archival samples were observed with the strongest intensity and uniformity among patients with low DRD5 tumor expression. The primary endpoint of PFS6 by RANO was not achieved at 5% in this molecularly unselected cohort; however, 1 of 3 patients enrolled with the H3 K27M mutation had a complete regression of enhancing multifocal lesions that remained durable for >1.5 years. No treatment modifications or discontinuations due to toxicity were observed, including in those who underwent re-resection.Weekly ONC201 is well tolerated, and meaningful intratumoral concentrations were achieved. ONC201 may be biologically active in a subset of adult patients with recurrent glioblastoma.