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DOI: 10.1055/s-0035-1566121
Do Long-Term Survivor Primary Glioblastoma Patients Harbor IDH1 Mutations?
Publikationsverlauf
04. Mai 2015
11. August 2015
Publikationsdatum:
02. März 2016 (online)
![](https://www.thieme-connect.de/media/jnlsa/201603/lookinside/thumbnails/10-1055-s-0035-1566121_151455oa-1.jpg)
Abstract
Background Approximately 3 to 16% of glioblastoma multiforme (GBM) patients are considered long-term survivors (LTS: 3+ years).
Objective Given the improved survival conferred by IDH1 mutations and the fact that these mutations are detected in 12% of newly diagnosed GBM cases, could long-term survivorship be explained by IDH1 mutation status? Our aim was to describe GBM LTS with IDH1 mutations and explore its association with overall survival (OS).
Methods Records of 453 newly diagnosed adult GBM patients treated at a single institution from 2004 to 2010 were reviewed retrospectively for patients who survived at least 36 months postsurgery. Descriptive statistics for clinical characteristics, treatments received, and tumor biomarkers were reported. Estimates for progression-free survival (PFS) and OS were provided.
Results Forty (8.8%) LTS GBM patients were identified, with a median age of 50 years and a median preoperative Karnofsky Performance Score (KPS) of 80. Most patients underwent near-total/gross-total resection (72.5%), postoperative radiation (97.5%), and adjuvant temozolomide (95%). PFS rates at 12, 36, 48, and 72 months were 67.5%, 40%, 32.7%, and 26.2%, respectively. Median OS has not yet been reached; however, the survival rate at 48 months was 62.1%. Among 35 patients with available tumor samples, only 8 (22.9%) had IDH1 mutations. No significant difference in median PFS was found between IDH1 mutation and wild-type patients (46.6 versus 26.3 months; p =0.45).
Conclusions Less than a quarter of our patients' long-term survivorship was associated with favorable IDH1 status. Therefore, IDH1 status does not explain most of the long-term survivorship in the temozolomide era.
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References
- 1 Affronti ML, Heery CR, Herndon II JE , et al. Overall survival of newly diagnosed glioblastoma patients receiving carmustine wafers followed by radiation and concurrent temozolomide plus rotational multiagent chemotherapy. Cancer 2009; 115 (15) 3501-3511
- 2 Krex D, Klink B, Hartmann C , et al; German Glioma Network. Long-term survival with glioblastoma multiforme. Brain 2007; 130 (Pt 10) 2596-2606
- 3 Sonoda Y, Kumabe T, Watanabe M , et al. Long-term survivors of glioblastoma: clinical features and molecular analysis. Acta Neurochir (Wien) 2009; 151 (11) 1349-1358
- 4 Stupp R, Hegi ME, Mason WP , et al; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009; 10 (5) 459-466
- 5 Das P, Puri T, Jha P , et al. A clinicopathological and molecular analysis of glioblastoma multiforme with long-term survival. J Clin Neurosci 2011; 18 (1) 66-70
- 6 Walid MS. Prognostic factors for long-term survival after glioblastoma. Perm J 2008; 12 (4) 45-48
- 7 Shinojima N, Kochi M, Hamada J , et al. The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme. J Neurosurg 2004; 101 (2) 219-226
- 8 Chandler KL, Prados MD, Malec M, Wilson CB. Long-term survival in patients with glioblastoma multiforme. Neurosurgery 1993; 32 (5) 716-720 ; discussion 720
- 9 Vertosick Jr FT, Selker RG. Long-term survival after the diagnosis of malignant glioma: a series of 22 patients surviving more than 4 years after diagnosis. Surg Neurol 1992; 38 (5) 359-363
- 10 Martinez R, Schackert G, Yaya-Tur R, Rojas-Marcos I, Herman JG, Esteller M. Frequent hypermethylation of the DNA repair gene MGMT in long-term survivors of glioblastoma multiforme. J Neurooncol 2007; 83 (1) 91-93
- 11 Hegi ME, Diserens AC, Godard S , et al. Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 2004; 10 (6) 1871-1874
- 12 Rivera AL, Pelloski CE, Gilbert MR , et al. MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro-oncol 2010; 12 (2) 116-121
- 13 Minniti G, Salvati M, Arcella A , et al. Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurooncol 2011; 102 (2) 311-316
- 14 Parsons DW, Jones S, Zhang X , et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321 (5897) 1807-1812
- 15 Yan H, Parsons DW, Jin G , et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360 (8) 765-773
- 16 Combs SE, Rieken S, Wick W , et al. Prognostic significance of IDH-1 and MGMT in patients with glioblastoma: one step forward, and one step back?. Radiat Oncol 2011; 6: 115
- 17 Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 2008; 116 (6) 597-602
- 18 Ichimura K, Pearson DM, Kocialkowski S , et al. IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro Oncol 2009; 11 (4) 341-347
- 19 Sonoda Y, Kumabe T, Nakamura T , et al. Analysis of IDH1 and IDH2 mutations in Japanese glioma patients. Cancer Sci 2009; 100 (10) 1996-1998
- 20 Weller M, Felsberg J, Hartmann C , et al. Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol 2009; 27 (34) 5743-5750
- 21 Hartmann C, Hentschel B, Wick W , et al. 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 2010; 120 (6) 707-718
- 22 Prensner JR, Chinnaiyan AM. Metabolism unhinged: IDH mutations in cancer. Nat Med 2011; 17 (3) 291-293
- 23 Cohen AL, Holmen SL, Colman H. IDH1 and IDH2 mutations in gliomas. Curr Neurol Neurosci Rep 2013; 13 (5) 345
- 24 Fisher JL, Schwartzbaum JA, Wrensch M, Wiemels JL. Epidemiology of brain tumors. Neurol Clin 2007; 25 (4) 867-890 , vii
- 25 Scott JN, Rewcastle NB, Brasher PM , et al. Which glioblastoma multiforme patient will become a long-term survivor? A population-based study. Ann Neurol 1999; 46 (2) 183-188
- 26 Ducray F, El Hallani S, Idbaih A. Diagnostic and prognostic markers in gliomas. Curr Opin Oncol 2009; 21 (6) 537-542
- 27 Horbinski C, Kofler J, Kelly LM, Murdoch GH, Nikiforova MN. Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. J Neuropathol Exp Neurol 2009; 68 (12) 1319-1325
- 28 Marko NF, Toms SA, Barnett GH, Weil R. Genomic expression patterns distinguish long-term from short-term glioblastoma survivors: a preliminary feasibility study. Genomics 2008; 91 (5) 395-406
- 29 Niyazi M, Zehentmayr F, Niemöller OM , et al. MiRNA expression patterns predict survival in glioblastoma. Radiat Oncol 2011; 6: 153
- 30 Srinivasan S, Patric IR, Somasundaram K. A ten-microRNA expression signature predicts survival in glioblastoma. PLoS ONE 2011; 6 (3) e17438
- 31 Liu Y, Shete S, Etzel CJ , et al. Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival. J Clin Oncol 2010; 28 (14) 2467-2474
- 32 Noushmehr H, Weisenberger DJ, Diefes K , et al; Cancer Genome Atlas Research Network. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 2010; 17 (5) 510-522
- 33 Chi AS, Batchelor TT, Dias-Santagata D , et al. Prospective, high-throughput molecular profiling of human gliomas. J Neurooncol 2012; 110 (1) 89-98
- 34 Verhaak RG, Hoadley KA, Purdom E , et al; Cancer Genome Atlas Research Network. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010; 17 (1) 98-110