Radiotherapy in relation to temozolomide: Subgroup analysis of molecular markers of the randomized phase III study by the EORTC/NCIC-CTG/TROG/MRC-CTU (EORTC 22033-26033) in patients with a high risk low-grade glioma.

Central Nervous System Tumors
Session Type and Session Title: 
Oral Abstract Session, Central Nervous System Tumors
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 2006)
Brigitta G. Baumert, Monika E. Hegi, Warren P. Mason, Gail Ryan, Khê Hoang-Xuan, Jacoline E Bromberg, Martin J. Van Den Bent, Mohamed Ben Hassel, Christine Marosi, Alba Ariela Brandes, Jeremy Rees, Andreas von Deimling, Christian Hartmann, Johan M Kros, Denis A. Lacombe, Thierry Gorlia, David Capper, Sebastian Kurscheid, Roger Stupp; University of Bonn Medical Centre, Bonn, Germany; University of Lausanne Hospitals, Lausanne, Switzerland; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; APHP-CHU Pitié-Salpêtrière, Paris, France; Erasmus MC, Rotterdam, Netherlands; Daniel den Hoed Cancer Center, Rotterdam, Netherlands; Departments of Medical Oncology and Radiotherapy, Centre Eugène Marquis, Rennes, France; University of Vienna, Wien, Austria; Department of Medical Oncology, Azienda USL, Bologna, Italy; National Hospital for Neurology and Neurosurgery, London, United Kingdom; Institute of Pathology, Dept Neuropathology, University of Heidelberg, INF 224, and CCU Neuropathology German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neuropathology, Institute of Pathology, Medizinische Hochschule, Hannover, Germany; Department of Neuropathology, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam, Netherlands; EORTC, Bruxelles, Belgium; European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Neuropathology, University of Heidelberg Medical Center, Heidelberg, Germany; Laboratory of Brain Tumor Biology and Genetics, Dept. Neurosurgery, University Hospital Lausanne, Lausanne, Switzerland; University Hospital Zurich & University of Zurich, Zurich, Switzerland

Abstract Disclosures


Background: A subgroup analysis based on molecular markers of patients randomized between standard radiotherapy (RT) and temozolomide (TMZ) alone in the randomized EORTC22033 trial. Methods: A posthoc analysis of molecular markers was done for 407 patients (of 477 randomized). The IDH status was determined by immunohistochemistry for the most common IDH mutant, complemented by sequencing of IDH1 and 2 for all negative cases. The status of 1p/19q codeletion was evaluated by LOH or FISH, the MGMTpromoter methylation status on the HM450k beadchip (Illumina) and classified by MGMTSTP27. Results: IDH1 and IDH2 mutations were detected in 83% (327/392) and 2.8% (n = 9). Co-deletions of 1p/19q were identified in 33% (n = 117/357). MGMT was methylated in 90% (135/150), of which 86% were IDH mutant (128/140). For 318 patients the status for both IDH1/2 and 1p/19q codel was available: 269 (85%) were IDHmt, 104 (39%) IDHmt/codel and 49 (15%) IDHwt. Mutation of the IDH 1 or 2 (IDHmt) regardless of 1p/19q co-deletion was a positive prognostic factor. Exploratory analysis of these 318 patients showed that patients with IDHmt/non-codel tumors had a shorter PFS after treatment with TMZ than after RT (HR 1.86; 95% CI, 1.21-2.87; logrank p = 0.0043), while no difference was observed between these treatments for patients with IDHwt, and IDHmt/codel tumors. Conclusions: Subgroup analysis suggests that PFS is longer in patients with IDHmut/non-codel tumors when treated in first-line with RT compared to treatment with TMZ. With still only a few events no such difference is visible in 1p/19q co-deleted tumors. However, maturation of survival data is needed to derive more firm conclusions. Clinical trial information: NCT00182819

TreatmentProgression-free survival
(95% CI)
P-ValueMedian (95% CI)
RT-IDHmt/codel45171.000.000061.6 (42.3, N)
RT-IDHwt29255.4 (2.9, 10.1)0.000019.1 (11.3, 25.7)
RT- IDHmt/non-codel89371.1 (0.6, 2.0)0.665555.4 (47.9, 65.9)
TMZ-IDHmt/codel59241.1 (0.6, 1.9)0.850955.0 (37.9, N)
TMZ-IDHwt20153.1 (1.6, 6.3)0.001323.7 (5.6, 42.3)
TMZ-IDHmt/non-codel76472.1 (1.2, 3.6)0.010336.0 (28.4, 46.9)