Skip to main content
Top
Published in: Journal of Neuro-Oncology 1/2016

01-08-2016 | Clinical Study

Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma

Authors: Jacob J. Mandel, David Cachia, Diane Liu, Charmaine Wilson, Ken Aldape, Greg Fuller, John F. de Groot

Published in: Journal of Neuro-Oncology | Issue 1/2016

Login to get access

Abstract

IDH1 mutated glioblastoma (GB) has a better prognosis than IDH1 wildtype GB. However, it remains unknown whether patients (pts) with IDH1 mutated GB have a higher 6-month progression free survival (PFS6) or radiographic response (RR) rate on clinical trials for recurrence. Retrospective review of GB pts at MDACC between 2006 and 2012 identified 330 patients in recurrent GB trials. 93 patients (28 %) had either PFS6 or a complete/partial RR per RANO criteria. 49/93 (53 %) patients with PFS6 or a complete/partial RR had tumor tissue for IDH1 testing. A matched cohort of 49 patients on recurrent GB clinical trials that failed to achieve PFS6 or RR (also with tissue for IDH1 testing) was identified for comparison. IDH1 status was obtained in 92/98 (94 %) patients of which 17 (18 %) had an IDH1 mutation. PFS6 was seen in 26/49 (53 %) patients. IDH status was unknown in two of these patients. 5/24 (21 %) were IDH1 mutated compared to 5/24 (21 %) of their matched cohort without PFS6. RR was found in 47/49 (94 %) patients. IDH status was unknown in four of these patients. IDH1 mutation was present in 7/43 (16 %) patients with RR compared to 10/43 (23 %) in the matched cohort without RR (p = 0.48). Median OS for trials at first recurrence was 9.8 months for IDH1 wildtype GB vs. 19.32 months for IDH1 mutated GB (p = 0.14). IDH1 mutation status was not predictive of PFS6 or RR in recurrent GB trials for this data set. However, further examination in larger randomized prospective studies is needed.
Appendix
Available only for authorised users
Literature
2.
go back to reference Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10): 987–96.CrossRefPubMed Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10): 987–96.CrossRefPubMed
3.
go back to reference Scherer H (1940) Cerebral astrocytomas and their derivatives. Am J Cancer 40:159 Scherer H (1940) Cerebral astrocytomas and their derivatives. Am J Cancer 40:159
4.
go back to reference Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro Oncol 1(1):44–51PubMedPubMedCentral Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro Oncol 1(1):44–51PubMedPubMedCentral
5.
go back to reference Ohgaki H, Dessen P, Jourde B et al (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64(19):6892–6899CrossRefPubMed Ohgaki H, Dessen P, Jourde B et al (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64(19):6892–6899CrossRefPubMed
7.
go back to reference Louis DN, Perry A, Burger P (2014) International Society of Neuropathology—Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 24(5):429CrossRefPubMed Louis DN, Perry A, Burger P (2014) International Society of Neuropathology—Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 24(5):429CrossRefPubMed
13.
go back to reference Hartmann C, Hentschel B, Wick W et al (2010) Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol 120(6):707–718. doi:10.1007/s00401-010-0781-z CrossRefPubMed Hartmann C, Hentschel B, Wick W et al (2010) Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol 120(6):707–718. doi:10.​1007/​s00401-010-0781-z CrossRefPubMed
16.
go back to reference Taal W, Oosterkamp HM, Walenkamp AM et al (2014) Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 15(9):943–953. doi:10.1016/S1470-2045(14)70314-6 CrossRefPubMed Taal W, Oosterkamp HM, Walenkamp AM et al (2014) Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 15(9):943–953. doi:10.​1016/​S1470-2045(14)70314-6 CrossRefPubMed
17.
go back to reference Watanabe T, Nobusawa S, Kleihues P et al (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174(4):1149–1153CrossRefPubMedPubMedCentral Watanabe T, Nobusawa S, Kleihues P et al (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174(4):1149–1153CrossRefPubMedPubMedCentral
18.
go back to reference Rohle D, Popovici-Muller J, Palaskas N et al (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 340(6132):626–630CrossRefPubMedPubMedCentral Rohle D, Popovici-Muller J, Palaskas N et al (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 340(6132):626–630CrossRefPubMedPubMedCentral
21.
go back to reference Labussiere M, Boisselier B, Mokhtari K et al (2014) Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes. Neurology 83:1200–1206CrossRefPubMed Labussiere M, Boisselier B, Mokhtari K et al (2014) Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes. Neurology 83:1200–1206CrossRefPubMed
22.
go back to reference Eckel-Passow JE, Lachance DH, Molinaro AM (2015) Glioma Groups Based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372(26):2499–2508CrossRefPubMedPubMedCentral Eckel-Passow JE, Lachance DH, Molinaro AM (2015) Glioma Groups Based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372(26):2499–2508CrossRefPubMedPubMedCentral
24.
go back to reference Mellai M, Piazzi A, Caldera V et al (2011) IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors. J Neurooncol 105(2):345–357CrossRefPubMed Mellai M, Piazzi A, Caldera V et al (2011) IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors. J Neurooncol 105(2):345–357CrossRefPubMed
25.
go back to reference Catteau A, Girardi H, Monville F et al (2014) A new sensitive PCR assay for one-step detection of 12 IDH1/2 mutations in glioma. Acta Neuropathol Commun 2:58CrossRefPubMedPubMedCentral Catteau A, Girardi H, Monville F et al (2014) A new sensitive PCR assay for one-step detection of 12 IDH1/2 mutations in glioma. Acta Neuropathol Commun 2:58CrossRefPubMedPubMedCentral
26.
go back to reference Loussouarn D, Le Loupp AG, Frenel JS et al (2012) Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas. Int J Oncol 40(6):2058–2062.PubMed Loussouarn D, Le Loupp AG, Frenel JS et al (2012) Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas. Int J Oncol 40(6):2058–2062.PubMed
27.
go back to reference Preusser M, Capper D, Hartmann C. (2011) Euro CNS research committe. IDH testing in diagnostic neuropathology: review and practical guideline article invited by the Euro-CNS research committee. Clin Neuropathol 30(5):217–230.CrossRefPubMed Preusser M, Capper D, Hartmann C. (2011) Euro CNS research committe. IDH testing in diagnostic neuropathology: review and practical guideline article invited by the Euro-CNS research committee. Clin Neuropathol 30(5):217230.CrossRefPubMed
28.
go back to reference Kruser TJ, Mehta MP, Kozak KR (2016) Identification of patients who benefit from bevacizumab in high-grade glioma—an easy question turned difficult: treat the scan or the patient? J Clin Oncol 34:1281–1282CrossRefPubMed Kruser TJ, Mehta MP, Kozak KR (2016) Identification of patients who benefit from bevacizumab in high-grade glioma—an easy question turned difficult: treat the scan or the patient? J Clin Oncol 34:1281–1282CrossRefPubMed
Metadata
Title
Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma
Authors
Jacob J. Mandel
David Cachia
Diane Liu
Charmaine Wilson
Ken Aldape
Greg Fuller
John F. de Groot
Publication date
01-08-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-016-2157-2

Other articles of this Issue 1/2016

Journal of Neuro-Oncology 1/2016 Go to the issue