MSK Anaplastic Oligodendroglioma Cohort (MSK, JCO 2017)

Overview

The odg_msk_2017 dataset comprises clinical and genomic data from a multicenter, investigator-initiated phase II trial (NCT00588523) sponsored by Memorial Sloan Kettering Cancer Center (MSK), enrolling 41 patients with newly diagnosed anaplastic oligodendroglioma (AO) or anaplastic oligoastrocytoma (AOA) between August 2005 and November 2012. The study tested whether induction temozolomide followed by myeloablative high-dose thiotepa/busulfan chemotherapy with autologous stem-cell transplant (HDC-ASCT) could defer radiotherapy. Of the 41 enrolled patients, 19 had adequate tissue for NGS using the MSK-IMPACT 410-gene panel (IMPACT410), providing the genomic characterization deposited to cBioPortal. Eighty-five percent of patients had 1p/19q-codeleted tumors. Full clinical and genomic data are publicly available at cbioportal.org/study?id=odg_msk_2017.

Composition

  • 41 patients enrolled; 38 received TMZ induction; 21 completed HDC-ASCT.
  • Histologies: 36 anaplastic oligodendroglioma (AO; 88%), 5 anaplastic oligoastrocytoma (AOA; 12%).
  • 1p/19q status (FISH): 33/39 (85%) codeleted, 6 non-codeleted, 2 unknown.
  • Patient characteristics: 27 men / 14 women; median age 44 years (range 30–66); median KPS 90.
  • NGS subset: 19 tumors with adequate DNA sequenced on IMPACT410 (hybridization-capture, Illumina HiSeq 2500, full exon coverage of 410 cancer-related genes); 14 codeleted, 5 1p/19q-intact.
  • Actionability annotation: OncoKB database (accessed 6 January 2017).
  • Median follow-up: 65.7 months.
  • Cancer type: ODG3 — Oligodendroglioma, IDH-mutant, 1p/19q-codeleted, Grade 3.

Assays / panels (linked)

Papers using this cohort

  • PMID:28472509 — Thomas et al., JCO 2017: Phase II trial reporting 5-year PFS of 60% and 5-year OS of 100% in transplanted patients; NGS confirmed canonical oligodendroglioma genomic signatures (TERT 95%, IDH1 68%, CIC 53%) and exposed a false-positive 1p/19q FISH call with a glioblastoma-like NGS profile; no transplanted patient had died at time of analysis. PMID:28472509

Notable findings derived from this cohort

  • Induction TMZ + HDC-ASCT achieves 2-year PFS 86% and 5-year OS 100% in 21 transplanted patients, enabling radiotherapy deferral in 52% of 1p/19q-codeleted patients at 5 years. PMID:28472509
  • NGS on 19 tumors confirmed canonical oligodendroglioma signatures: TERT promoter mutation 95% (18/19), IDH1 R132H 68% (13/19), CIC 53% (10/19), FUBP1 26% (5/19), NOTCH1 32% (6/19). PMID:28472509
  • 1p/19q-intact tumors displayed glioblastoma-like NGS signatures (EGFR amplification/mutation, NF1, MDM2 amplification, wild-type IDH1/IDH2). PMID:28472509
  • NGS exposed a false-positive 1p/19q FISH call: one patient classified as codeleted by FISH carried a glioblastoma-like NGS signature (PTEN loss, CDKN2A/CDKN2B deletion, IDH1/2 wild-type) and died at 13 months after early progression. PMID:28472509
  • OncoKB-actionable alterations were individually rare: CDK4 amplification (2/19), TSC1 (1/19) at Level 2B; IDH1/IDH2, KRAS Q61H, PIK3CA at Level 3B. PMID:28472509

Sources

  • cBioPortal study odg_msk_2017 (http://cbioportal.org/study?id=odg_msk_2017).
  • Thomas AA, et al. Temozolomide Induction Therapy Followed by High-Dose Chemotherapy With Autologous Stem-Cell Transplantation in Newly Diagnosed Anaplastic Oligodendroglioma: A Phase 2 Study. JCO. 2017. PMID:28472509

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