RADIATION ONCOLOGY—ORIGINAL ARTICLE Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management Michael Back, 1,2,3,4,5 Dasantha T Jayamanne, 1,4 David Brazier, 1,4 Alison Newey, 1,4 Dale Bailey, 6,7 Geoffrey P Schembri, 6 Edward Hsiao, 6 Mustafa Khasraw, 1,4,5 Matthew Wong, 2 Marina Kastelan, 1,5 Linxin Guo, 1 Stephen Clarke 1,4 and Helen Wheeler 1,4,5 1 Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales, Australia 2 Central Coast Cancer Centre, Gosford Hospital, Gosford, New South Wales, Australia 3 Genesis Cancer Care, Sydney, New South Wales, Australia 4 Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia 5 The Brain Cancer Group, Sydney, New South Wales, Australia 6 Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia 7 Faculty of Health Sciences, University of Sydney, Sydney, New South Wales, Australia M Back FRANZCR, MBA; DT Jayamanne FRANZCR; D Brazier FRANZCR; A Newey FRANZCR; D Bailey MAppSc (Physics), PhD; GP Schembri FRACP; E Hsiao FRANZCR; M Khasraw FRACP, PhD; M Wong FRACP, PhD; M Kastelan MN, NP; L Guo MHSc, BSc (Hons); S Clarke PhD; H Wheeler FRACP. Correspondence Associate Professor Michael F. Back, Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards Sydney NSW 2065, Australia. Email: michael.back@health.nsw.gov.au Conflict of interest: The authors declare no conflict of interest. Submitted 1 September 2018; accepted 7 December 2018. doi:10.1111/1754-9485.12850 Abstract Introduction: Assess survival of patients with anaplastic glioma (AG) and the relationship to molecular subtype. Methods: Patients with AG managed with IMRT between 2008 and 2014 were entered into a prospective database assessing relapse-free survival (RFS) and overall survival (OS). Isocitrate dehydrogenase (IDH) mutations were assessed prospectively from 2011, and subsequent testing of historical patients allowing categorisation under WHO 2016 classification as anaplastic astrocytoma IDH wild type (AAwt), anaplastic astrocytoma IDH mutated (AAmut), anaplastic oligodendroglioma (AOD) or other glial tumour (OTH). Kaplan-Meier estimates of survival distribution were calculated for the primary endpoint of overall survival and Log-rank test used to determine associated factors. Results: One hundred and fifty-six patients were included with median follow- up for survivors of 4.7 years. Fifty-six per cent were managed after initial diagnosis, whilst 18% received IMRT at second or later relapse. Seventy-three per cent had temozolomide as part of initial therapy. A total of 118 or 75% of patients had IDH mutated glioma, of which 61 were AOD and 57 AAmut. There were 68 relapses and 52 deaths for a 6yrRFS of 51.2% and 6yrOS of 62.5%. AAwt was associated with worse survival (P < 0.001); and delay of RT until second or later relapse (P = 0.03). Within the 118 patients with IDH mutated tumours, 6yrOS for AOD and AAmut were 90.0% and 62.5%, respec- tively (P = 0.003). Also two or more craniotomies (P < 0.001), delayed RT (P = 0.006) and age <40 years (P = 0.022) were associated with worse sur- vival on univariate analysis but only AAmut subtype and number of cran- iotomies on multivariate analysis. Conclusion: Within AG, molecular classification predicts for survival, and should influence current decision-making. Key words: anaplastic glioma; IDH mutation; radiation therapy. Introduction Anaplastic or WHO Grade III Glioma has been known to be a heterogeneous group of tumours with varying natu- ral history. 1–3 Patients may present with a range of clinical and radiological features; however, these may have only minimal impact on the prediction of eventual progression-free or overall survival. 4,5 Aggressive surgi- cal approaches with aim of maximal debulking of tumour, as appropriately utilised in glioblastoma, may potentially © 2019 The Royal Australian and New Zealand College of Radiologists Journal of Medical Imaging and Radiation Oncology  (2019) – 1 Journal of Medical Imaging and Radiation Oncology