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Clinical trials for Ewing sarcoma

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https://www.readbyqxmd.com/read/28888998/tnf-related-apoptosis-inducing-ligand-trail-for-bone-sarcoma-treatment-pre-clinical-and-clinical-data
#1
Kenneth Samora Rankin, Eleftherios Tsiridis, Craig Gerrand, Anja Krippner-Heidenreich, Kenneth Dalgarno, Ricardo Da Conceicao Ribeiro, Emma Haagensen, Dimitra Papanikolaou, Kapriniotis Konstantinos, Zakareya Gamie
Bone sarcomas are rare, highly malignant mesenchymal tumours that affect teenagers and young adults, as well as older patients. Despite intensive, multimodal therapy, patients with bone sarcomas have poor 5-year survival, close to 50%, with lack of improvement over recent decades. TNF-related apoptosis-inducing ligand (TRAIL), a member of the tumour necrosis factor (TNF) ligand superfamily (TNFLSF), has been found to induce apoptosis in cancer cells while sparing nontransformed cells, and may therefore offer a promising new approach to treatment...
September 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28832074/programmed-death-ligand-1-pd-l1-expression-in-malignant-mesenchymal-tumors
#2
Kemal Kösemehmetoğlu, Ece Özoğul, Berrin Babaoğlu, Gaye Güler Tezel, Gökhan Gedikoğlu
OBJECTIVE: Programmed death ligand 1 (PD-L1) found on tumor cells has recently been reported to have a key role in the development and dissemination of many tumors, such as lung and breast carcinomas. In this study, we retrospectively analyzed PD-L1 expression among different types of sarcomas. MATERIAL AND METHOD: Tissue microarrays of 3-4 mm diameter were composed from paraffin blocks of 222 various sarcomas. Slides prepared from microarrays were stained for PD-L1 antibody (Cell Signaling, E1L3N®) using Leica Bond Autostainer...
2017: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/28735378/a-phase-i-ii-trial-and-pharmacokinetic-study-of-mithramycin-in-children-and-adults-with-refractory-ewing-sarcoma-and-ews-fli1-fusion-transcript
#3
Patrick J Grohar, John Glod, Cody J Peer, Tristan M Sissung, Fernanda I Arnaldez, Lauren Long, William D Figg, Patricia Whitcomb, Lee J Helman, Brigitte C Widemann
PURPOSE: In a preclinical drug screen, mithramycin was identified as a potent inhibitor of the Ewing sarcoma EWS-FLI1 transcription factor. We conducted a phase I/II trial to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of mithramycin in children with refractory solid tumors, and the activity in children and adults with refractory Ewing sarcoma. PATIENTS AND METHODS: Mithramycin was administered intravenously over 6 h once daily for 7 days for 28 day cycles...
July 22, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28710342/vincristine-ifosfamide-and-doxorubicin-for-initial-treatment-of-ewing-sarcoma-in-adults
#4
Michael J Wagner, Vancheswaran Gopalakrishnan, Vinod Ravi, J Andrew Livingston, Anthony P Conley, Dejka Araujo, Neeta Somaiah, Maria A Zarzour, Ravin Ratan, Wei-Lien Wang, Shreyaskumar R Patel, Alexander Lazar, Joseph A Ludwig, Robert S Benjamin
BACKGROUND: There are no clinical trials specifically addressing chemotherapy for adults with Ewing sarcoma (ES). Five-year event-free survival (EFS) of adults on pediatric studies of ES (44%-47%) is worse than that of children treated with the same therapy (69%). The object of this study was to review the results of therapy with vincristine, ifosfamide, and doxorubicin (VID) in the multidisciplinary treatment of adults with ES at our institution. MATERIALS AND METHODS: Charts for adults treated for ES from 1995 to 2011 were retrospectively reviewed...
July 14, 2017: Oncologist
https://www.readbyqxmd.com/read/28696044/practice-patterns-of-palliative-radiation-therapy-in-pediatric-oncology-patients-in-an-international-pediatric-research-consortium
#5
Avani Dholakia Rao, Qinyu Chen, Ralph P Ermoian, Sara R Alcorn, Maria Luisa S Figueiredo, Michael J Chen, Karin Dieckmann, Shannon M MacDonald, Matthew M Ladra, Daria Kobyzeva, Alexey V Nechesnyuk, Kristina Nilsson, Eric C Ford, Brian A Winey, Rosangela C Villar, Stephanie A Terezakis
BACKGROUND/OBJECTIVES: The practice of palliative radiation therapy (RT) is based on extrapolation from adult literature. We evaluated patterns of pediatric palliative RT to describe regimens used to identify opportunity for future pediatric-specific clinical trials. DESIGN/METHODS: Six international institutions with pediatric expertise completed a 122-item survey evaluating patterns of palliative RT for patients ≤21 years old from 2010 to 2015. Two institutions use proton RT...
July 11, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28647886/wnt-signaling-in-ewing-sarcoma-osteosarcoma-and-malignant-peripheral-nerve-sheath-tumors
#6
REVIEW
Matthew G Pridgeon, Patrick J Grohar, Matthew R Steensma, Bart O Williams
PURPOSE OF REVIEW: Wnt signaling plays a central role in development and homeostasis, and its dysregulation is a common event in many types of human cancer. Here we explore in detail the contributions of Wnt signaling to the initiation and maintenance of three types of saroma: Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors. This review provides an overview of the Wnt signaling pathway and explores in detail the current knowledge about its role in the initiation or maintenance of three tumor types: Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors...
August 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28626407/systemic-therapy-outcomes-in-adult-patients-with-ewing-sarcoma-family-of-tumors
#7
Mario Valdes, Garth Nicholas, Shailendra Verma, Timothy Asmis
BACKGROUND: The Ewing sarcoma family of tumors (ESFT) is a rare but curable bone neoplastic entity. The current standard of care involves chemotherapy and local disease control with surgery or radiation regardless of the extent of disease at presentation. Data that document the effectiveness of the current approach in the adult patient population are limited. METHODS: We performed a retrospective review including all ESFT patients older than 19 years of age who received systemic therapy between January 2002 and December 2013 at our institution...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28619077/what-is-the-impact-of-local-control-in-ewing-sarcoma-analysis-of-the-first-brazilian-collaborative-study-group-ewing1
#8
Ricardo G Becker, Lauro J Gregianin, Carlos R Galia, Reynaldo Jesus-Garcia Filho, Eduardo A Toller, Gerardo Badell, Suely A Nakagawa, Alexandre David, André M Baptista, Eduardo S Yonamime, Osvaldo A Serafini, Valter Penna, Julie Francine C Santos, Algemir L Brunetto
BACKGROUND: Relapse in localized Ewing sarcoma patients has been a matter of concern regarding poor prognosis. Therefore, we investigated the impact of local control modality (surgery, surgery plus radiotherapy, and radiotherapy) on clinical outcomes such as survival and recurrence in patients with non-metastatic Ewing sarcoma treated on the first Brazilian Collaborative Group Trial of the Ewing Family of Tumors (EWING1). METHODS: Seventy-three patients with localized Ewing sarcoma of bone aged < 30 years were included...
June 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28561686/advances-in-the-treatment-of-pediatric-bone-sarcomas
#9
Patrick J Grohar, Katherine A Janeway, Luke D Mase, Joshua D Schiffman
Bone tumors make up a significant portion of noncentral nervous system solid tumor diagnoses in pediatric oncology patients. Ewing sarcoma and osteosarcoma, both with distinct clinical and pathologic features, are the two most commonly encountered bone cancers in pediatrics. Although mutations in the germline have classically been more associated with osteosarcoma, there is recent evidence germline alterations in patients with Ewing sarcoma also play a significant role in pathogenesis. Treatment advances in this patient population have lagged behind that of other pediatric malignancies, particularly targeted interventions directed at the biologic underpinnings of disease...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28506520/the-evolving-role-of-proton-beam-therapy-for-sarcomas
#10
S Frisch, B Timmermann
As an alternative to conventional photon-based radiotherapy, radiation with protons is recognised to offer considerable advantages. Today, central nervous system tumours, various sarcomatous tumours, childhood cancer and head and neck tumours are commonly treated with proton therapy. This review evaluates current data from clinical and dosimetric trials on the treatment of selected sarcomatous tumours like rhabdomyosarcoma, osteosarcoma, chordoma, chondrosarcoma and Ewing sarcoma. Special considerations for paediatric tumours and future prospects of proton therapy are outlined...
August 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28321815/immune-therapy-for-sarcomas
#11
REVIEW
Peter M Anderson
Absolute lymphocyte count (ALC) recovery rapidly occurring at 14 days after start of chemotherapy for osteosarcoma and Ewing sarcoma is a good prognostic factor. Conversely, lymphopenia is associated with significantly decreased sarcoma survival. Clearly, the immune system can contribute towards better survival from sarcoma. This chapter will describe treatment and host factors that influence immune function and how effective local control and systemic interventions of sarcoma therapy can cause inflammation and/or immune suppression but are currently the standard of care...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28266080/efficacy-comparison-of-six-chemotherapeutic-combinations-for-osteosarcoma-and-ewing-s-sarcoma-treatment-a-network-meta-analysis
#12
Tao Zhang, Song Zhang, Feifei Yang, Lili Wang, Sigang Zhu, Bing Qiu, Shunhua Li, Zhongliang Deng
This study aimed to address the insufficiency of traditional meta-analysis and provide improved guidelines for the clinical practice of osteosarcoma treatment. The heterogeneity of the fixed-effect model was calculated, and when necessary, a random-effect model was adopted. Furthermore, the direct and indirect evidence was pooled together and exhibited in the forest plot and slash table. The surface under the cumulative ranking curve (SUCRA) value was also measured to rank each intervention. Finally heat plot was introduced to demonstrate the contribution of each intervention and the inconsistency between direct and indirect comparisons...
March 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27587590/analysis-of-phase-ii-methodologies-for-single-arm-clinical-trials-with-multiple-endpoints-in-rare-cancers-an-example-in-ewing-s-sarcoma
#13
P Dutton, S B Love, L Billingham, A B Hassan
Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic...
January 1, 2016: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/27573658/assessment-of-imaging-modalities-and-response-metrics-in-ewing-sarcoma-correlation-with-survival
#14
Vadim S Koshkin, Vanessa Bolejack, Lawrence H Schwartz, Richard L Wahl, Rashmi Chugh, Denise K Reinke, Binsheng Zhao, Joo H O, Shreyaskumar R Patel, Scott M Schuetze, Laurence H Baker
PURPOSE: Despite the rapidly increasing use of [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET), the comparison of anatomic and functional imaging in the assessment of clinical outcomes has been lacking. In addition, there has not been a rigorous evaluation of how common radiologic criteria or the location of the radiology reader (local v central) compare in the ability to predict benefit. In this study, we aimed to compare the effectiveness of various radiologic response assessments for the prediction of overall survival (OS) within the same data set of patients with sarcoma...
August 29, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27486883/validation-of-prognostic-scoring-and-assessment-of-clinical-benefit-for-patients-with-bone-sarcomas-enrolled-in-phase-i-clinical-trials
#15
J Andrew Livingston, Kenneth R Hess, Aung Naing, David S Hong, Shreyaskumar Patel, Robert S Benjamin, Joseph A Ludwig, Anthony Conley, Cynthia E Herzog, Pete Anderson, Funda Meric-Bernstam, Razelle Kurzrock, Vivek Subbiah
BACKGROUND: We sought to validate the Royal Marsden Hospital (RMH) and MD Anderson Cancer Center (MDACC) prognostic scoring systems for the selection of bone sarcoma patients for phase I clinical trials and to identify additional risk factors related to survival. PATIENTS AND METHODS: We retrospectively reviewed the baseline characteristics and outcomes of 92 bone sarcoma patients who were referred to MDACC's Phase I Clinical Trials Program. RESULTS: Ninety-two patients with Ewing sarcoma (N = 47), osteosarcoma (N = 22), chondrosarcoma (N = 16), and other tumors (N = 7) were evaluated; 78 were enrolled in at least 1 of 43 different phase I trials...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27443894/ewing-sarcoma-in-patients-over-40-years-of-age-a-prospective-analysis-of-31-patients-treated-at-a-single-institution
#16
Marilena Cesari, Alberto Righi, Luca Cevolani, Emanuela Palmerini, Daniel Vanel, Davide M Donati, Silvia Cammelli, Marco Gambarotti, Cristina Ferrari, Anna Paioli, Alessandra Longhi, Massimo E Abate, Piero Picci, Stefano Ferrari
PURPOSE: Patients with Ewing sarcoma who are 40 years old or older are usually excluded from clinical trials. For this reason, information on this subset of patients is limited. METHODS: Clinical characteristics and treatment-related variables of patients aged 40 years or more, with a diagnosis of Ewing sarcoma, treated at the authors' institution had been prospectively collected since 1999. RESULTS: Thirty-one patients were identified, with ages ranging from 40 to 70 years (median 45 years)...
October 13, 2016: Tumori
https://www.readbyqxmd.com/read/27256563/proteasome-addiction-defined-in-ewing-sarcoma-is-effectively-targeted-by-a-novel-class-of-19s-proteasome-inhibitors
#17
Neerav Shukla, Romel Somwar, Roger S Smith, Sri Ambati, Stanley Munoz, Melinda Merchant, Padraig D'Arcy, Xin Wang, Rachel Kobos, Christophe Antczak, Bhavneet Bhinder, David Shum, Constantin Radu, Guangbin Yang, Barry S Taylor, Charlotte K Y Ng, Britta Weigelt, Inna Khodos, Elisa de Stanchina, Jorge S Reis-Filho, Ouathek Ouerfelli, Stig Linder, Hakim Djaballah, Marc Ladanyi
Ewing sarcoma is a primitive round cell sarcoma with a peak incidence in adolescence that is driven by a chimeric oncogene created from the fusion of the EWSR1 gene with a member of the ETS family of genes. Patients with metastatic and recurrent disease have dismal outcomes and need better therapeutic options. We screened a library of 309,989 chemical compounds for growth inhibition of Ewing sarcoma cells to provide the basis for the development of novel therapies and to discover vulnerable pathways that might broaden our understanding of the pathobiology of this aggressive sarcoma...
August 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/26962160/chemotherapy-for-bone-sarcoma-in-adults
#18
REVIEW
Michael J Wagner, J Andrew Livingston, Shreyaskumar R Patel, Robert S Benjamin
The largest studies of chemotherapy for bone sarcomas are in the pediatric population. Although increasing age is often found to be an adverse prognostic factor in these clinical trials, few studies are aimed at assessing regimens specifically in the adult population. Osteosarcoma and Ewing sarcoma have peak incidences in the pediatric and young adult population but also occur in adults. Chondrosarcoma and giant cell tumor of bone are generally found in adults. In this review, we describe the current status of our knowledge about treating adults with cancers of bone origin...
March 2016: Journal of Oncology Practice
https://www.readbyqxmd.com/read/26919435/new-brain-tumor-entities-emerge-from-molecular-classification-of-cns-pnets
#19
Dominik Sturm, Brent A Orr, Umut H Toprak, Volker Hovestadt, David T W Jones, David Capper, Martin Sill, Ivo Buchhalter, Paul A Northcott, Irina Leis, Marina Ryzhova, Christian Koelsche, Elke Pfaff, Sariah J Allen, Gnanaprakash Balasubramanian, Barbara C Worst, Kristian W Pajtler, Sebastian Brabetz, Pascal D Johann, Felix Sahm, Jüri Reimand, Alan Mackay, Diana M Carvalho, Marc Remke, Joanna J Phillips, Arie Perry, Cynthia Cowdrey, Rachid Drissi, Maryam Fouladi, Felice Giangaspero, Maria Łastowska, Wiesława Grajkowska, Wolfram Scheurlen, Torsten Pietsch, Christian Hagel, Johannes Gojo, Daniela Lötsch, Walter Berger, Irene Slavc, Christine Haberler, Anne Jouvet, Stefan Holm, Silvia Hofer, Marco Prinz, Catherine Keohane, Iris Fried, Christian Mawrin, David Scheie, Bret C Mobley, Matthew J Schniederjan, Mariarita Santi, Anna M Buccoliero, Sonika Dahiya, Christof M Kramm, André O von Bueren, Katja von Hoff, Stefan Rutkowski, Christel Herold-Mende, Michael C Frühwald, Till Milde, Martin Hasselblatt, Pieter Wesseling, Jochen Rößler, Ulrich Schüller, Martin Ebinger, Jens Schittenhelm, Stephan Frank, Rainer Grobholz, Istvan Vajtai, Volkmar Hans, Reinhard Schneppenheim, Karel Zitterbart, V Peter Collins, Eleonora Aronica, Pascale Varlet, Stephanie Puget, Christelle Dufour, Jacques Grill, Dominique Figarella-Branger, Marietta Wolter, Martin U Schuhmann, Tarek Shalaby, Michael Grotzer, Timothy van Meter, Camelia-Maria Monoranu, Jörg Felsberg, Guido Reifenberger, Matija Snuderl, Lynn Ann Forrester, Jan Koster, Rogier Versteeg, Richard Volckmann, Peter van Sluis, Stephan Wolf, Tom Mikkelsen, Amar Gajjar, Kenneth Aldape, Andrew S Moore, Michael D Taylor, Chris Jones, Nada Jabado, Matthias A Karajannis, Roland Eils, Matthias Schlesner, Peter Lichter, Andreas von Deimling, Stefan M Pfister, David W Ellison, Andrey Korshunov, Marcel Kool
Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features...
February 25, 2016: Cell
https://www.readbyqxmd.com/read/26848860/therapeutic-opportunities-in-ewing-sarcoma-ews-fli-inhibition-via-lsd1-targeting
#20
REVIEW
Emily R Theisen, Kathleen I Pishas, Ranajeet S Saund, Stephen L Lessnick
Ewing sarcoma is an aggressive primary pediatric bone tumor, often diagnosed in adolescents and young adults. A pathognomonic reciprocal chromosomal translocation results in a fusion gene coding for a protein which derives its N-terminus from a FUS/EWS/TAF15 (FET) protein family member, commonly EWS, and C-terminus containing the DNA-binding domain of an ETS transcription factor, commonly FLI1. Nearly 85% of cases express the EWS-FLI protein which functions as a transcription factor and drives oncogenesis. As the primary genomic lesion and a protein which is not expressed in normal cells, disrupting EWS-FLI function is an attractive therapeutic strategy for Ewing sarcoma...
April 5, 2016: Oncotarget
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