Florian Gessler1, Johannes Zappi2, Juergen Konczalla2, Joshua D Bernstock3, Marie-Therese Forster2, Marlies Wagner4, Michel Mittelbronn5, Volker Seifert2, Christian Senft2. 1. Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany. Electronic address: f.gessler@med.uni-frankfurt.de. 2. Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany. 3. Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH), Bethesda, Maryland, USA. 4. Institute of Neuroradiology, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany. 5. Institute of Neurology (Edinger-Institute), University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
Abstract
BACKGROUND AND OBJECTIVE: There is limited information on prognostic factors and outcomes in patients with secondary glioblastoma (sGBM). Herein we report on the outcomes of patients with sGBM and identify clinically relevant prognostic factors. METHODS: We retrospectively analyzed our institutional database for patients with histologic evidence of World Health Organization (WHO) grade II-III gliomas that went on to develop WHO grade IV sGBM. The assessment of the isocitrate dehydrogenase-1 (IDH1) R132H mutation was performed by immunohistochemical staining. RESULTS: Forty-five patients with sGBM were included within our analysis (median age, 41 years). Mutated IDH1 (R132H) protein was present within the gliomas of 24 patients and was absent in 17. Immunohistochemistry assessment could not be performed for 4 patients. The median time between first diagnosis of glioma and sGBM was 158.9 weeks. Median overall survival (OS) after a diagnosis of sGBM was 63.6 weeks. When assessing patient-specific (i.e., therapy-independent) factors, mutated IDH1 (R132H) protein (P = 0.01; hazard ratio (HR), 0.54; confidence interval (CI) 0.33-0.87), WHO grade II tumor as precursor lesion (P = 0.05; HR, 0.49; CI 0.25-0.97), and a frontal tumor location (P = 0.04; HR, 0.48; CI 0.23-0.99) were found to be associated with better OS by multivariate analysis. Our data further indicate that complete tumor removal is associated with better patient survival in sGBM patients within certain risk groups (time period to development of sGBM, >104 weeks; initial WHO grade II tumor, IDH1 mutation, and time period to development of sGBM, >104 weeks; initial WHO grade II or III tumor, IDH1 wild type, frontal lobe localization). CONCLUSIONS: Our retrospective analysis suggested that the presence of an IDH1 (R132H) mutation, frontal tumor location, and WHO grade of the initial tumor are associated with OS after progression to sGBM. In addition, some patients with sGBM may benefit from complete tumor resection depending on these patient-specific parameters. This is a finding that will ultimately need prospective validation.
BACKGROUND AND OBJECTIVE: There is limited information on prognostic factors and outcomes in patients with secondary glioblastoma (sGBM). Herein we report on the outcomes of patients with sGBM and identify clinically relevant prognostic factors. METHODS: We retrospectively analyzed our institutional database for patients with histologic evidence of World Health Organization (WHO) grade II-III gliomas that went on to develop WHO grade IV sGBM. The assessment of the isocitrate dehydrogenase-1 (IDH1) R132H mutation was performed by immunohistochemical staining. RESULTS: Forty-five patients with sGBM were included within our analysis (median age, 41 years). Mutated IDH1 (R132H) protein was present within the gliomas of 24 patients and was absent in 17. Immunohistochemistry assessment could not be performed for 4 patients. The median time between first diagnosis of glioma and sGBM was 158.9 weeks. Median overall survival (OS) after a diagnosis of sGBM was 63.6 weeks. When assessing patient-specific (i.e., therapy-independent) factors, mutated IDH1 (R132H) protein (P = 0.01; hazard ratio (HR), 0.54; confidence interval (CI) 0.33-0.87), WHO grade II tumor as precursor lesion (P = 0.05; HR, 0.49; CI 0.25-0.97), and a frontal tumor location (P = 0.04; HR, 0.48; CI 0.23-0.99) were found to be associated with better OS by multivariate analysis. Our data further indicate that complete tumor removal is associated with better patient survival in sGBM patients within certain risk groups (time period to development of sGBM, >104 weeks; initial WHO grade II tumor, IDH1 mutation, and time period to development of sGBM, >104 weeks; initial WHO grade II or III tumor, IDH1 wild type, frontal lobe localization). CONCLUSIONS: Our retrospective analysis suggested that the presence of an IDH1 (R132H) mutation, frontal tumor location, and WHO grade of the initial tumor are associated with OS after progression to sGBM. In addition, some patients with sGBM may benefit from complete tumor resection depending on these patient-specific parameters. This is a finding that will ultimately need prospective validation.
Authors: Florian Gessler; Joshua D Bernstock; Anne Braczynski; Stephanie Lescher; Peter Baumgarten; Patrick N Harter; Michel Mittelbronn; Tianxia Wu; Volker Seifert; Christian Senft Journal: Neurosurgery Date: 2019-01-01 Impact factor: 4.654
Authors: Ha Son Nguyen; Benjamin Best; Ninh B Doan; Michael Gelsomino; Saman Shabani; Ahmed J Awad; Mayank Kaushal; Martin M Mortazavi Journal: Oncotarget Date: 2018-09-07
Authors: Antje Wick; Annick Desjardins; Cristina Suarez; Peter Forsyth; Ivelina Gueorguieva; Tiana Burkholder; Ann Louise Cleverly; Shawn T Estrem; Shuaicheng Wang; Michael M Lahn; Susan C Guba; David Capper; Jordi Rodon Journal: Invest New Drugs Date: 2020-03-05 Impact factor: 3.850