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Clinical trials for Ewing sarcoma

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https://www.readbyqxmd.com/read/29610659/survival-is-influenced-by-approaches-to-local-treatment-of-ewing-sarcoma-within-an-international-randomised-controlled-trial-analysis-of-eicess-92
#1
Jeremy Whelan, Allan Hackshaw, Anne McTiernan, Robert Grimer, David Spooner, Jessica Bate, Andreas Ranft, Michael Paulussen, Herbert Juergens, Alan Craft, Ian Lewis
Background: Two national clinical trial groups, United Kingdom Children's Cancer and Leukaemia Group (CCLG) and the German Paediatric Oncology and Haematology Group (GPOH) together undertook a randomised trial, EICESS-92, which addressed chemotherapy options for Ewing's sarcoma. We sought the causes of unexpected survival differences between the study groups. Methods: 647 patients were randomised. Cox regression analyses were used to compare event-free survival (EFS) and overall survival (OS) between the two study groups...
2018: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/29582320/soft-tissue-sarcomas-new-opportunity-of-treatment-with-parp-inhibitors
#2
Monica Mangoni, Mariangela Sottili, Giulia Salvatore, Domenico Campanacci, Guido Scoccianti, Giovanni Beltrami, Camilla Delli Paoli, Luca Dominici, Virginia Maragna, Emanuela Olmetto, Icro Meattini, Isacco Desideri, Pierluigi Bonomo, Daniela Greto, Lorenzo Livi
BACKGROUND: Poly(ADP-ribose) polymerases (PARP) are a large family of enzymes involved in several cellular processes, including DNA single-strand break repair via the base-excision repair pathway. PARP inhibitors exert antitumor activity by both catalytic PARP inhibition and PARP-DNA trapping, moreover PARP inhibition represents a potential synthetic lethal approach against cancers with specific DNA-repair defects. Soft tissue sarcoma (STSs) are a heterogeneous group of mesenchymal tumors with locally destructive growth, high risk of recurrence and distant metastasis...
March 26, 2018: La Radiologia Medica
https://www.readbyqxmd.com/read/29500442/radiomics-features-differentiate-between-normal-and-tumoral-high-fdg-uptake
#3
Chih-Yang Hsu, Mike Doubrovin, Chia-Ho Hua, Omar Mohammed, Barry L Shulkin, Sue Kaste, Sara Federico, Monica Metzger, Matthew Krasin, Christopher Tinkle, Thomas E Merchant, John T Lucas
Identification of FDGavid- neoplasms may be obscured by high-uptake normal tissues, thus limiting inferences about the natural history of disease. We introduce a FDG-PET radiomics tissue classifier for differentiating FDGavid- normal tissues from tumor. Thirty-three scans from 15 patients with Hodgkin lymphoma and 68 scans from 23 patients with Ewing sarcoma treated on two prospective clinical trials were retrospectively analyzed. Disease volumes were manually segmented on FDG-PET and CT scans. Brain, heart, kidneys and bladder and tumor volumes were automatically segmented on PET images...
March 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29371919/sensitizing-ewing-sarcoma-to-chemo-and-radiotherapy-by-inhibition-of-the-dna-repair-enzymes-dna-protein-kinase-dna-pk-and-poly-adp-ribose-polymerase-parp-1-2
#4
Britta Vormoor, Yvonne T Schlosser, Helen Blair, Abhishek Sharma, Sarah Wilkinson, David R Newell, Nicola Curtin
Background: DNA-PK and PARP inhibitors sensitize cancer cells to chemo- and radiotherapy. ETS transcription factors (EWS-FLI1) have been described as biomarkers for PARP-inhibitor sensitivity. Sensitivity to single agent PARP inhibitors has so far been limited to homologous recombination repair (HRR) deficient tumors, exploiting synthetic lethality. Results: In clonogenic assays, single agent rucaparib LD50 values for continuously exposed cells were similar to those observed in HRR-defective cells (CAPAN-1 cell line, BRCA2 defective); however, both ES cell lines (TC-71, CADO-ES1) had functional HRR...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29273680/igf-system-in-sarcomas-a-crucial-pathway-with-many-unknowns-to-exploit-for-therapy
#5
Caterina Mancarella, Katia Scotlandi
The insulin-like growth factor (IGF) system has gained substantial interest due to its involvement in regulating cell proliferation, differentiation and survival during anoikis and after conventional and targeted therapies. However, results from clinical trials have been largely disappointing, with only a few but notable exceptions, such as trials targeting sarcomas, especially Ewing sarcoma. This review highlights key studies focusing on IGF signaling in sarcomas, specifically studies underscoring the properties that make this system an attractive therapeutic target, and identifies new relationships that may be exploited...
December 22, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28988646/pembrolizumab-in-advanced-soft-tissue-sarcoma-and-bone-sarcoma-sarc028-a-multicentre-two-cohort-single-arm-open-label-phase-2-trial
#6
RANDOMIZED CONTROLLED TRIAL
Hussein A Tawbi, Melissa Burgess, Vanessa Bolejack, Brian A Van Tine, Scott M Schuetze, James Hu, Sandra D'Angelo, Steven Attia, Richard F Riedel, Dennis A Priebat, Sujana Movva, Lara E Davis, Scott H Okuno, Damon R Reed, John Crowley, Lisa H Butterfield, Ruth Salazar, Jaime Rodriguez-Canales, Alexander J Lazar, Ignacio I Wistuba, Laurence H Baker, Robert G Maki, Denise Reinke, Shreyaskumar Patel
BACKGROUND: Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma. METHODS: In this two-cohort, single-arm, open-label, phase 2 study, we enrolled patients with soft-tissue sarcoma or bone sarcoma from 12 academic centres in the USA that were members of the Sarcoma Alliance for Research through Collaboration (SARC)...
November 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28888998/tnf-related-apoptosis-inducing-ligand-trail-for-bone-sarcoma-treatment-pre-clinical-and-clinical-data
#7
REVIEW
Zakareya Gamie, Konstantinos Kapriniotis, Dimitra Papanikolaou, Emma Haagensen, Ricardo Da Conceicao Ribeiro, Kenneth Dalgarno, Anja Krippner-Heidenreich, Craig Gerrand, Eleftherios Tsiridis, Kenneth Samora Rankin
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...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28832074/programmed-death-ligand-1-pd-l1-expression-in-malignant-mesenchymal-tumors
#8
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
#9
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...
September 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28710342/vincristine-ifosfamide-and-doxorubicin-for-initial-treatment-of-ewing-sarcoma-in-adults
#10
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...
October 2017: Oncologist
https://www.readbyqxmd.com/read/28696044/practice-patterns-of-palliative-radiation-therapy-in-pediatric-oncology-patients-in-an-international-pediatric-research-consortium
#11
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...
November 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28647886/wnt-signaling-in-ewing-sarcoma-osteosarcoma-and-malignant-peripheral-nerve-sheath-tumors
#12
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
#13
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
#14
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
#15
REVIEW
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
#16
REVIEW
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
#17
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
#18
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...
January 2018: 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
#19
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
#20
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
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