Phase III Trial of Chemotherapy Plus Radiotherapy Compared With Radiotherapy Alone for Pure and Mixed Anaplastic Oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402

Abstract

For patients with AO and AOA, PCV plus RT does not prolong survival. Longer progression-free survival after PCV plus RT is associated with significant toxicity. Tumors lacking 1p and 19q alleles are less aggressive or more responsive or both.

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

“…Combined deletion of chromosomal arms 1p and 19q is a powerful prognostic marker in patients with anaplastic oligodendroglial tumours treated with radiotherapy, alkylating chemotherapy or combined radiochemotherapy (Cairncross et al, 2006;van den Bent, 2006;Wick et al, 2009). To identify genes located on these chromosomal arms that may account for this prognostic effect, we performed microarray-based gene expression profiling comparing oligodendroglial tumours with and without 1p/19q losses (Tews et al, 2006).…”

“…Importantly, we did not only detect frequent 5 0 -CpGisland hypermethylation and reduced expression of PRDX1 in oligodendroglial tumours with 1p and 19q deletions but also provided first evidence that this aberration may be linked to radio-and chemosensitivity of Hs683 glioma cells in vitro. Clinically, it has been well documented in numerous retrospective and prospective studies that 1p/19q deletion in low-grade and anaplastic oligodendroglial tumours predicts response to radiotherapy as well as chemotherapy with TMZ or nitrosourea compounds (Brada et al, 2003;Cairncross et al, 2006;Kouwenhoven et al, 2006;van den Bent, 2006;Wick et al, 2009). The molecular basis for the predictive power of 1p/19q deletion is still unknown.…”

“…Up to 80% of oligodendrogliomas and B50% of oligoastrocytomas show combined deletions of the chromosomal arms 1p and 19q (Reifenberger and Louis, 2003) mediated by an unbalanced t(1;19)(q10;p10) translocation (Griffin et al, 2006;Jenkins et al, 2006). Deletion of 1p/19q was reported as an independent marker for favourable outcome in patients with anaplastic gliomas treated with chemotherapy and/or radiotherapy (van den Bent et al, 2005;Cairncross et al, 2006;Wick et al, 2009).…”

MGMT promoter methylation in malignant gliomas: ready for personalized medicine?

“…14 Similar results were obtained in the EORTC trial 26951, in that MGMT promoter methylation was prognostic for PFS in both armsradiotherapy alone and radiotherapy followed by PCV. 15 The high correlation of MGMT promoter methylation with the 1p19q co-deletion 15,57,58 and isocitrate dehydrogenase (IDH) gene mutations, 59 which are known to be favorable prognostic factors in anaplastic glioma, 14,60,61 might indicate that epigenetic deregulation of MGMT occurs in a specific pathogenetic context in anaplastic gliomas. Since MGMT promoter methylation is prognostic and not predictive for chemotherapy response in anaplastic gliomas, a methylated MGMT promoter should not be used to justify the upfront treatment of these tumors with temozolomide-based radiochemotherapy in the absence of appropriate data from studies such as CATNON (http://clinicaltrials.gov, NCT00626990).…”

Hypermethylation and transcriptional downregulation of the CITED4 gene at 1p34.2 in oligodendroglial tumours with allelic losses on 1p and 19q

“…Recent data indicate that these combined 1p and 19q losses are mediated by an unbalanced t(1;19)(q10;p10) translocation (Griffin et al, 2006;Jenkins et al, 2006). Importantly, 1p/19q deletion is associated with favourable response to radioand chemotherapy as well as prolonged survival (Cairncross et al, 1998(Cairncross et al, , 2006van den Bent et al, 2006). Thus, molecular testing for these losses provides clinically valuable information beyond the conventional histologic classification.…”