Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma
Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytomas (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.
Patients with AO/AOA received 6 cycles of TMZ (200mg/m2 X5/28-day). Responding patients were eligible for HDC (thiotepa 250mg/m2/day X3 days then busulfan 3.2mg/kg/day X3 days), followed by ASCT. Genomic characterization was performed using next generation sequencing (NGS).
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. NGS disclosed typical oligodendroglioma-related mutations including IDH-1, TERT, CIC and FUBP1 mutations in 1p/19q-codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH-1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors.
TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q-codeleted AOs. This strategy was associated with promising PFS and OS, suggesting a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and metaanalyses are publicly available at https://cbioportal.mskcc.org/study?id=odg_msk_2017#summary.
Pharmacology, Toxicology and Pharmaceutical Science
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Mathematics
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Nursing and Health Professions
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Other
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 June 2018.
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#15,152,619
of 23,305,591 outputs
Outputs from Neuro-Oncology
#1,944
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Outputs of similar age
#185,681
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Outputs of similar age from Neuro-Oncology
#56
of 82 outputs
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