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.
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References
Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507
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.
Scherer H (1940) Cerebral astrocytomas and their derivatives. Am J Cancer 40:159
Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro Oncol 1(1):44–51
Ohgaki H, Dessen P, Jourde B et al (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64(19):6892–6899
Theeler BJ, Yung WK, Fuller GN, De Groot JF (2012) Moving toward molecular classification of diffuse gliomas in adults. Neurology 79(18):1917–1926. doi:10.1212/WNL.0b013e318271f7cb
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):429
Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360(8):765–773. doi:10.1056/NEJMoa0808710
Parsons DW, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science. 321(5897): 1807. doi:10.1126/science.1164382
Labussiere M, Sanson M, Idbaih A et al (2010) IDH1 gene mutations: a new paradigm in glioma prognosis and therapy? Oncologist. 15(2): 196–199. doi:10.1634/theoncologist.2009-0218
Ohgaki H, Kleihues P (2013) The definition of primary and secondary glioblastoma. Clin Cancer Res 19(4):764–772. doi:10.1158/1078-0432.CCR-12-3002
Nobusawa S, Watanabe T, Kleihues P, Ohgaki H (2009) IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 15(19):6002–6007. doi:10.1158/1078-0432.CCR-09-0715
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
Sanson M, Marie Y, Paris S et al (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27(25):4150–4154. doi:10.1200/JCO.2009.21.9832
Wen P, Macdonald D, Reardon D et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28(11):1963–1972. doi:10.1200/JCO.2009.26.3541
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
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):1149–1153
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):626–630
Ichimura K, Pearson DM, Kocialkowski S et al (2009) IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro Oncol 11(4):341–347. doi:10.1215/15228517-2009-025
Sonoda Y, Kumabe T, Nakamura T et al (2009) Analysis of IDH1 and IDH2 mutations in Japanese glioma patients. Cancer Sci 100(10):1996–1998. doi:10.1111/j.1349-7006.2009.01270.x
Labussiere M, Boisselier B, Mokhtari K et al (2014) Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes. Neurology 83:1200–1206
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):2499–2508
Zou Y, Xiao Bai H, Wang Z et al (2015) Comparison of immunohistochemistry and DNA sequencing for the detection of IDH1 mutations in gliomas. Neuro Oncol 17(3):477–478. doi:10.1093/neuonc/nou351
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):345–357
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 2:58
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.
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.
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 34:1281–1282
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Mandel, J.J., Cachia, D., Liu, D. et al. Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma. J Neurooncol 129, 147–154 (2016). https://doi.org/10.1007/s11060-016-2157-2
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DOI: https://doi.org/10.1007/s11060-016-2157-2