Abstract
ObjectiveIsocitrate dehydrogenase (IDH)-wildtype glioblastomas are the most malignant glial tumours. Median survival is only 14–16 months after diagnosis, with patients aged ≥ 65 years reportedly showing worse outcome. This study aimed to further evaluate the prognostic role of age in a homogenously treated patient cohort.MethodsThe study includes 132 IDH-wildtype glioblastoma patients treated between 2013 and 2017 with open resection followed by radiotherapy with concomitant and maintenance temozolomide. Patients were dichotomized into a non-elderly (< 65 years) and an elderly (≥ 65 years) group. Extent of resection and the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were determined for each tumour. Clinical and radiological follow-up data were obtained at 6 weeks after the end of radiation therapy and thereafter in 3-month intervals. Progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate cox regression analyses.ResultsThe elderly group consisted of 58 patients (median age: 70.5 years) and the non-elderly group of 74 patients (median age: 55 years). Median pre- and postoperative operative Karnofsky Performance Scale (KPS), Eastern Cooperative Oncology Group (ECOG) score and National Institutes of Stroke Scale (NIHSS) were not significantly different between the groups, but KPS and ECOG scores became significantly worse in the elderly group at 6 weeks after termination of radiation therapy. Neither PFS nor OS differed significantly between the age groups. Patients with MGMT promoter-methylated tumours survived longer.ConclusionElderly patients in good pre- and postoperative clinical conditions may show similar outcome as younger patients when treated according to standard of care. However, elderly patients may suffer more frequently from clinical deterioration following chemoradiotherapy. In both age groups, MGMT promoter methylation was linked to longer PFS and OS.
Highlights
Isocitrate dehydrogenase (IDH)-wildtype glioblastomas are the most frequent and most malignant intrinsic brain tumours that lead to an average survival of only three months without treatment (Malmstrom A et al 2012; Tamimi and Juweid 2017)
Patients fulfilling the following inclusion criteria were considered for this study and their data were retrospectively analysed: (1) Surgical treatment at the Department of Neurosurgery, Heinrich Heine University Düsseldorf, between 01/2013 and 12/2017, (2) neuropathologically confirmed diagnosis of an IDH-wildtype glioblastoma, World Health Organization (WHO) grade IV (Louis et al 2016), (3) primary surgical resection or surgical resection within four weeks following initial biopsy, (4) preoperative Karnofsky performance scale (KPS) ≥ 70% and (5) postsurgical therapy according to the EORTC-22981/NCIC CE3 protocol
All patients were diagnosed with glioblastoma, IDH-wildtype, WHO grade IV according to the 2016 WHO classification of central nervous system tumours (Louis et al 2016)
Summary
Isocitrate dehydrogenase (IDH)-wildtype glioblastomas are the most frequent and most malignant intrinsic brain tumours that lead to an average survival of only three months without treatment (Malmstrom A et al 2012; Tamimi and Juweid 2017). Standard treatment of glioblastoma patients is, if feasible, a gross total resection of the tumour followed by fractionated tumour irradiation up to 60 Gy with concomitant systemic chemotherapy with temozolomide (TMZ) followed by six cycles of maintenance TMZ therapy (Stummer and Kamp 2009; Weller et al 2017a). This combined chemoradiotherapy prolonged overall survival as compared to radiation therapy alone in glioblastoma patients younger than 70 years in the European Organization for Research and Treatment of Cancer (EORTC)-22,981/26,981/National Cancer Institute of Canada (NCIC) CE3 trial (Stupp et al 2005, 2009).
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