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Author (up) Thomas, A.A.; Abrey, L.E.; Terziev, R.; Raizer, J.; Martinez, N.L.; Forsyth, P.; Paleologos, N.; Matasar, M.; Sauter, C.S.; Moskowitz, C.; Nimer, S.D.; DeAngelis, L.M.; Kaley, T.; Grimm, S.; Louis, D.N.; Cairncross, J.G.; Panageas, K.S.; Briggs, S.; Faivre, G.; Mohile, N.A.; Mehta, J.; Jonsson, P.; Chakravarty, D.; Gao, J.; Schultz, N.; Brennan, C.W.; Huse, J.T.; Omuro, A. url  doi
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  Title Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma Type Journal Article
  Year 2017 Publication Neuro-Oncology Abbreviated Journal Neuro Oncol  
  Volume 19 Issue 10 Pages 1380-1390  
  Keywords 1p/19q codeletion; anaplastic oligodendroglioma; autologous stem cell transplant; temozolomide  
  Abstract Background: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy. Methods: Patients with AO/AOA received 6 cycles of TMZ (200 mg/m2 x 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m2/day x 3 days, then busulfan 3.2 mg/kg/day x 3 days), followed by ASCT. Genomic characterization was performed using next-generation sequencing. Results: Forty-one patients were enrolled; 85% had 1p/19q codeleted tumors. After induction, 26 patients were eligible for HDC-ASCT and 21 agreed to proceed. There were no unexpected adverse events or toxic deaths. After median follow-up of 66 months, 2-year progression-free survival (PFS) for transplanted patients was 86%, 5-year PFS 60%, and no patient has died. Among all 1p/19q codeleted patients (N = 33), 5-year PFS was 50% and 5-year overall survival (OS) 93%, with median time to radiotherapy not reached. Next-generation sequencing disclosed typical oligodendroglioma-related mutations, including IDH1, TERT, CIC, and FUBP1 mutations in 1p/19q codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors. Conclusions: TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q codeleted AO. This strategy was associated with promising PFS and OS, suggesting that a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and meta-analyses are publicly available at http://cbioportal.org/study?id=odgmsk2017, accessed 6 January 2017. Clinicaltrials.gov registry: NCT00588523.  
  Address Memorial Sloan Kettering Cancer Center, New York, New York,USA; Northwestern Memorial Hospital, Chicago, Illinois, USA; NorthShore University, Evanston, Illinois,USA; University of Calgary, Calgary, Alberta, Canada; Massachusetts General Hospital, Boston, Massachusetts, USA; MD Anderson Cancer Center, Houston, Texas, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1522-8517 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28472509 Approved no  
  Call Number ref @ user @ Serial 96586  
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