Adjuvant Procarbazine, Lomustine, and Vincristine  Chemotherapy in Newly Diagnosed Anaplastic Oligodendroglioma: Long-Term Follow-Up of EORTC Brain Tumor Group Study 26951

Bent, Martin J. van den; Brandes, Alba A.; Taphoorn, Martin J.B.; Kros, Johan M.; Kouwenhoven, Mathilde C.M.; Delattre, Jean‐Yves; Bernsen, H.J.J.A.; Frénay, Marc; Tijssen, Cees; Grisold, Wolfgang; Sípos, László; Enting, Roelien H.; French, Pim J.; Dinjens, Winand N.M.; Vecht, Charles J.; Allgeier, Anouk; Lacombe, Denis; Gorlia, Thierry; Hoang-Xuân, Khê

doi:10.1200/jco.2012.43.2229

Cited by 1,019 publications

(657 citation statements)

References 37 publications

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“…[4][5][6]  Anaplastic oligodendroglial tumors with 1p/19q co-deletions should no longer be treated with radiotherapy alone, but with alkylating agent chemotherapy, with or without radiotherapy. [4][5][6]  The introduction of molecular markers into the next WHO Classification of Tumors of the Nervous System is inevitable.…”

Section: Key Advancesmentioning

confidence: 99%

Improving outcome in newly diagnosed malignant glioma

Weller

Wick

2014

Nat Rev Neurol

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In 2013, two discoveries-that alkylating agent chemotherapy prolongs survival when added to radiotherapy for patients with anaplastic oligodendroglial tumours with 1p19q codeletion, and that bevacizumab prolongs progression-free survival in patients with newly diagnosed glioblastoma-have dominated debate in neuro-oncology. These findings could help to define new standards of care in malignant glioma. promoter methylation, and isocitrate dehydrogenase (IDH) 1 or 2 mutation, and the introduction of temozolomide (TMZ) chemoradiotherapy for newly diagnosed

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Section: Key Advancesmentioning

confidence: 99%

Improving outcome in newly diagnosed malignant glioma

Weller

Wick

2014

Nat Rev Neurol

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“…Chromosome 1p and 19q codeletion, the genetic hallmark of oligodendrogliomas associated with long survival and chemo-radio sensitivity, represents the prototype molecular marker with unequivocal diagnostic, prognostic, and therapeutic utilities in diffuse gliomas. [3][4][5][6][7] Isocitrate dehydrogenase (IDH) mutation is probably the most important molecular marker discovered in diffuse gliomas with breakthrough clinical values in the recent years. 8 Apart from its use in difficult diagnostic situations, [8][9][10] mutation of this enzyme also stratifies diffuse gliomas prognostically.…”

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confidence: 99%

TERT promoter mutations contribute to subset prognostication of lower-grade gliomas

Chan

Zhang

et al. 2015

Modern Pathology

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Recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) have been found in various cancers including diffuse gliomas. Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas. However, the clinical significance of TERT promoter mutations in lower-grade gliomas remains undetermined. The aim of this study is to evaluate the status of TERT promoter and the respective prognostic significance in a cohort of 237 lower-grade gliomas comprising grades II and III astrocytomas, oligodendrogliomas, and oligoastrocytomas. Mutually exclusive mutations in TERT promoter, C228T and C250T, were identified in 16/105 (15%) diffuse astrocytomas, 16/63 (25%) anaplastic astrocytomas, 13/18 (72%) oligodendrogliomas, 3/3 (100%) anaplastic oligodendrogliomas, 17/45 (38%) oligoastrocytomas, and 2/3 (67%) anaplastic oligoastrocytomas. Mutations co-occurred with 1p/19q codeletion (Po0.001) and are associated with oligodendroglial histology (Po0.001). Kaplan-Meier's survival analysis showed that TERT promoter mutation (P ¼ 0.037), Isocitrate dehydrogenase (IDH) mutation (Po0.001), and 1p/19q codeletion (Po0.001) were associated with favorable overall survival (OS). In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P ¼ 0.027) and OS (P ¼ 0.004). Consistent with this observation, in the subset of 97 IDH-mutated astrocytomas, 14 TERT promoter-mutated tumors showed longer PFS (P ¼ 0.001) and OS (P ¼ 0.001). In contrast, among the subset of 74 IDH wild-type lower-grade gliomas with intact 1p/19q, TERT promoter mutation was associated with shorter PFS (P ¼ 0.001) and OS (P ¼ 0.001). Similarly, in the subset of 65 IDH wild-type astrocytomas, 16 TERT promoter-mutated tumors exhibited unfavorable PFS (P ¼ 0.007) and OS (P ¼ 0.008). Our results indicate that when combined with IDH status, TERT promoter mutation contributes to prognostic subgroups of lower-grade astrocytic tumors or 1p/19q intact lower-grade gliomas and this may further refine future molecular classification of lower-grade gliomas.

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“…Updated results of the primary analysis confirmed that disease control overall was mainly the same after RT or CT. 2 However, the secondary (and exploratory) analyses were perhaps the most intriguing and surprising. For example, despite the observation from other trials that (IDH mutation and) codeletion predicts the greatest chemosensitivity of anaplastic gliomas, 6,7 CT was, disappointingly to us, at best equi-efficacious as RT in the CIMP codel molecular subgroup of NOA-04. 2 An analogous observation was reported recently for (IDH mutant and) codeleted low-grade (WHO grade II) gliomas.…”

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confidence: 56%

“…In IDH mutant codeleted (ie, CIMP codel ) anaplastic gliomas, combined PCV and RT is clearly superior to RT alone 6,7 ; CT alone appears to be, at best, equi-efficacious with RT alone in both anaplastic 2 and low-grade gliomas. 8 Therefore, we agree with Wick et al, who are probably correct when they conclude by extrapolation that CT alone likely leads to shorter survival than combined CT and RT.…”

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confidence: 98%