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Clinical trials for Ewing sarcoma

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https://www.readbyqxmd.com/read/28506520/the-evolving-role-of-proton-beam-therapy-for-sarcomas
#1
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...
May 12, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28321815/immune-therapy-for-sarcomas
#2
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
#3
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
#4
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...
September 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/26795289/response-to-early-treatment-evaluated-with-18f-fdg-pet-and-percist-1-0-predicts-survival-in-patients-with-ewing-sarcoma-family-of-tumors-treated-with-a-monoclonal-antibody-to-the-insulinlike-growth-factor-1-receptor
#12
Joo Hyun O, Brandon S Luber, Jeffrey P Leal, Hao Wang, Vanessa Bolejack, Scott M Schuetze, Lawrence H Schwartz, Lee J Helman, Denise Reinke, Laurence H Baker, Richard L Wahl
UNLABELLED: The aim of this study was to assess the prognostic and predictive value of early quantitative (18)F-FDG PET to monitor therapy with an antibody to the insulinlike growth factor 1 receptor (IGF-1R antibody) in patients with Ewing sarcoma family of tumors (ESFT). METHODS: (18)F-FDG PET images at baseline and approximately 9 d after initiation of IGF-1R antibody therapy in 115 patients with refractory or relapsed ESFT were prospectively obtained as part of the Sarcoma Alliance for Research through Collaboration trial...
May 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/26765686/ewing-sarcoma-the-clinical-relevance-of-the-insulin-like-growth-factor-1-and-the-poly-adp-ribose-polymerase-pathway
#13
REVIEW
Annemiek M van Maldegem, Judith V M G Bovée, Elleke F P Peterse, Pancras C W Hogendoorn, Hans Gelderblom
BACKGROUND: In the last three decades the outcome for patients with localised Ewing sarcoma (ES) has improved significantly since the introduction of multimodality primary treatment. However, for patients with (extra-) pulmonary metastatic and/or non-resectable relapsed disease the outcome remains poor and new treatment options are urgently needed. Currently the insulin-like growth factor 1 receptor (IGF-1R) pathway and the poly-ADP(adenosinediphosphate)-ribose-polymerase (PARP) pathway are being investigated for potential targeted therapies...
January 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/26709919/the-macrophage-inhibitor-cni-1493-blocks-metastasis-in-a-mouse-model-of-ewing-sarcoma-through-inhibition-of-extravasation
#14
Anthony J Hesketh, Caroline Maloney, Christopher A Behr, Morris C Edelman, Richard D Glick, Yousef Al-Abed, Marc Symons, Samuel Z Soffer, Bettie M Steinberg
Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy...
2015: PloS One
https://www.readbyqxmd.com/read/26505995/combinations-of-parp-inhibitors-with-temozolomide-drive-parp1-trapping-and-apoptosis-in-ewing-s-sarcoma
#15
Sonja J Gill, Jon Travers, Irina Pshenichnaya, Fiona A Kogera, Syd Barthorpe, Tatiana Mironenko, Laura Richardson, Cyril H Benes, Michael R Stratton, Ultan McDermott, Stephen P Jackson, Mathew J Garnett
Ewing's sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing's sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy in tumors with BRCA1/2 mutations, which confer deficiency in DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence on PARP1/2 due to their function in DNA single-strand break (SSB) repair...
2015: PloS One
https://www.readbyqxmd.com/read/26364611/rna-helicase-ddx3-a-novel-therapeutic-target-in-ewing-sarcoma
#16
B A Wilky, C Kim, G McCarty, E A Montgomery, K Kammers, L R DeVine, R N Cole, V Raman, D M Loeb
RNA helicase DDX3 has oncogenic activity in breast and lung cancers and is required for translation of complex mRNA transcripts, including those encoding key cell-cycle regulatory proteins. We sought to determine the expression and function of DDX3 in sarcoma cells, and to investigate the antitumor activity of a novel small molecule DDX3 inhibitor, RK-33. Utilizing various sarcoma cell lines, xenografts and human tissue microarrays, we measured DDX3 expression at the mRNA and protein levels, and evaluated cytotoxicity of RK-33 in sarcoma cell lines...
May 19, 2016: Oncogene
https://www.readbyqxmd.com/read/26260582/synergistic-induction-of-apoptosis-by-a-polo-like-kinase-1-inhibitor-and-microtubule-interfering-drugs-in-ewing-sarcoma-cells
#17
Lilly Magdalena Weiß, Manuela Hugle, Sarah Romero, Simone Fulda
Since polo-like kinase 1 (PLK1) is highly expressed in Ewing sarcoma (ES), we evaluated the therapeutic potential of the PLK1 inhibitor BI 6727. Here, we identify a synergistic induction of apoptosis by BI 6727 and several microtubule-interfering drugs in ES cells, including vincristine (VCR), vinblastine (VBL), vinorelbine (VNR) and eribulin. Synergistic drug interaction is confirmed by calculation of combination index (CI). Also, BI 6727 and VCR act in concert to reduce long-term clonogenic survival. Mechanistically, BI 6727/VCR co-treatment cooperates to trigger mitotic arrest, phosphorylation of BCL-2 and BCL-XL and downregulation of MCL-1...
January 15, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/26257296/identification-of-discrete-prognostic-groups-in-ewing-sarcoma
#18
Erin E Karski, Elizabeth McIlvaine, Mark R Segal, Mark Krailo, Holcombe E Grier, Linda Granowetter, Richard B Womer, Paul A Meyers, Judy Felgenhauer, Neyssa Marina, Steven G DuBois
BACKGROUND: Although multiple prognostic variables have been proposed for Ewing sarcoma (EWS), little work has been done to further categorize these variables into prognostic groups for risk classification. PROCEDURE: We derived initial prognostic groups from 2,124 patients with EWS in the SEER database. We constructed a multivariable recursive partitioning model of overall survival using the following covariates: age; stage; race/ethnicity; sex; axial primary; pelvic primary; and bone or soft tissue primary...
January 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/26170970/the-importance-of-src-signaling-in-sarcoma
#19
Quanchi Chen, Zifei Zhou, Liancheng Shan, Hui Zeng, Yingqi Hua, Zhengdong Cai
Src is a tyrosine kinase that is of significance in tumor biology. The present review focuses on Src, its molecular structure, and role in cancer, in addition to its expression and function in sarcoma. In addition, the feasibility of Src as a potential drug target for the treatment of sarcoma is also discussed. Previous studies have suggested that Src has essential functions in cell proliferation, apoptosis, invasion, metastasis and the tumor microenvironment. Thus, it may be a potential target for cancer therapy...
July 2015: Oncology Letters
https://www.readbyqxmd.com/read/26039213/favorable-nk-cell-activity-after-haploidentical-hematopoietic-stem-cell-transplantation-in-stage-iv-relapsed-ewing-s-sarcoma-patients
#20
P Schlegel, T Feuchtinger, C Nitschke-Gérard, U J Eva Seidel, A-M Lang, C Kyzirakos, H-M Teltschik, M Ebinger, M Schumm, E Koscielniak, R Handgretinger, P Lang
Natural killer (NK) cell activity has been shown to have potential activity against Ewing's sarcoma (EWS) especially in tumors with low HLA I expression and high NKG2D expression. Two patients with metastatic relapsed and primary metastatic stage IV EWS who had received two courses of high dose chemotherapy with autologous stem cell rescue were transplanted from a haploidentical parental stem cell donor. Patients are alive in ongoing CR for 10.2 and 3.4 years now. Post transplant local second and first relapses were treated successfully in both patients...
June 2015: Bone Marrow Transplantation
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