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Molecular markers in low-grade gliomas: predictive or prognostic?


Hartmann, C; Hentschel, B; Tatagiba, M; Schramm, J; Schnell, O; Seidel, C; Stein, R; Reifenberger, G; Pietsch, T; von Deimling, A; Loeffler, M; Weller, M (2011). Molecular markers in low-grade gliomas: predictive or prognostic? Clinical Cancer Research, 17(13):4588-4599.

Abstract

PURPOSE: To investigate whether TP53 mutation, 1p/19q codeletions, MGMT promoter methylation, and IDH1 mutation predict natural course of disease or response to radiotherapy or chemotherapy, or both, in low-grade glioma patients.EXPERIMENTAL DESIGN: Cohort A consisted of 89 patients with diffuse astrocytoma WHO grade II (n=40), oligoastrocytoma (n=23) or oligodendroglioma (n=26), who did not receive radiotherapy or chemotherapy after first operation and were monitored until progression (PD) (n=59) and beyond or until the end of follow-up (n=30). Cohort B consisted of 50 patients with WHO grade II gliomas who received radiotherapy or chemotherapy at diagnosis. Tumors were analysed for TP53 mutations, 1p/19q codeletions, MGMT promoter methylation, and IDH1 mutations.RESULTS: Median progression-free survival (PFS) in cohort A was 4.1 years (95% CI 3.1-5.1). No molecular marker was prognostic for PFS after surgery alone using multivariate adjustment for histology, age and extent of resection. IDH1 mutations were associated with prolonged survival from the diagnosis of PD in OA II/O II and with overall survival (OS) in all tumors. 1p/19q codeletion and IDH1 mutation were prognostic for PFS and OS in cohort B.CONCLUSIONS: Neither parameter is a sensitive prognostic biomarker in WHO grade II glioma patients who do not receive radiotherapy or chemotherapy after surgery. Limitations of this study include the selection of patients with favourable outcome, the non-randomized allocation of treatment, and the insufficient sample size to distinguish between effects of radiotherapy versus chemotherapy. Regardless of histology, IDH1 mutation status is the strongest prognostic marker for OS.

PURPOSE: To investigate whether TP53 mutation, 1p/19q codeletions, MGMT promoter methylation, and IDH1 mutation predict natural course of disease or response to radiotherapy or chemotherapy, or both, in low-grade glioma patients.EXPERIMENTAL DESIGN: Cohort A consisted of 89 patients with diffuse astrocytoma WHO grade II (n=40), oligoastrocytoma (n=23) or oligodendroglioma (n=26), who did not receive radiotherapy or chemotherapy after first operation and were monitored until progression (PD) (n=59) and beyond or until the end of follow-up (n=30). Cohort B consisted of 50 patients with WHO grade II gliomas who received radiotherapy or chemotherapy at diagnosis. Tumors were analysed for TP53 mutations, 1p/19q codeletions, MGMT promoter methylation, and IDH1 mutations.RESULTS: Median progression-free survival (PFS) in cohort A was 4.1 years (95% CI 3.1-5.1). No molecular marker was prognostic for PFS after surgery alone using multivariate adjustment for histology, age and extent of resection. IDH1 mutations were associated with prolonged survival from the diagnosis of PD in OA II/O II and with overall survival (OS) in all tumors. 1p/19q codeletion and IDH1 mutation were prognostic for PFS and OS in cohort B.CONCLUSIONS: Neither parameter is a sensitive prognostic biomarker in WHO grade II glioma patients who do not receive radiotherapy or chemotherapy after surgery. Limitations of this study include the selection of patients with favourable outcome, the non-randomized allocation of treatment, and the insufficient sample size to distinguish between effects of radiotherapy versus chemotherapy. Regardless of histology, IDH1 mutation status is the strongest prognostic marker for OS.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:26 May 2011 10:50
Last Modified:05 Apr 2016 14:55
Publisher:American Association for Cancer Research
ISSN:1078-0432
Publisher DOI:10.1158/1078-0432.CCR-10-3194
PubMed ID:21558404
Permanent URL: http://doi.org/10.5167/uzh-48154

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