A novel tool to analyse MRI recurrence patterns in glioblastoma

¹ Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen; Department of Neurooncology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg; Germany
² University of Lausanne Hospitals, Multidisciplinary Oncology Center, 46 Rue du Bugnon, Lausanne 1011, Switzerland
³ Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen, Germany
⁴ Neuro-Oncology Unit, Daniel den Hoed Oncology Center, PO Box 5201, 3008AE Rotterdam, The Netherlands
⁵ Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen, Germany
⁶ Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany
⁷ Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen; Department of Neurooncology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg; Germany
⁸ Department of Internal Medicine I, Clinical Division of Oncology, Medical University Vienna, 6i, Wahringer Gürtel 18-20, A-1097 Vienna, Austria
⁹ Princess Margaret Hospital, 610 University Avenue, Suite 18-717, Toronto, ON M5G 2M9, Canada
¹⁰ Neuro-Oncology Unit, Daniel den Hoed Oncology Center, PO Box 5201, 3008AE Rotterdam, The Netherlands
¹¹ Department of Communication Sciences & Disorders, University of South Carolina, Columbia, SC 29208, United States
¹² Section Neuropsychology, Department of Cognitive Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany

^* To whom correspondence should be addressed. E-mail: wolfgang.wick{at}med.uni-heidelberg.de.

	Abstract

At least 10% of glioblastoma relapses occur at distant and even contralateral locations. This disseminated growth limits surgical intervention and contributes to neurological morbidity. Preclinical data pointed towards a role for temozolomide in reducing radiotherapy-induced gliomas cell invasiveness. Our objective was to develop and validate a new analysis tool of magnetic resonance imaging (MRI) data to examine the clinical recurrence pattern of glioblastomas. MRIcro software was used to map location and extent of initial preoperative and recurrent tumours on MRI of 63 patients of the EORTC 26981/22981/NCIC CE.3 study into the same stereotaxic space. This allowed us to examine changes of site and distance between the initial and the recurrent tumour on the group level. Thirty of the 63 patients were treated using radiotherapy while the other patients completed a radiotherapy-plus-temozolomide treatment. Baseline characteristics (median age, Karnofsky performance score) and outcome data (progression-free survival, overall survival) of the patients included in this analysis resemble those of the general study cohort. The patient groups did not differ in the promotor methylation status of methyl-guanyl-methly-transferase (MGMT). Overall frequency of distant recurrences was 20%. Analysis of recurrence pattern revealed no difference in the size of the recurrent tumour nor a differential effect on the distance of the recurrences from the preoperative tumour location between the groups. The data show the feasibility of group-wise recurrence pattern analysis. An effect of temozolomide treatment on the recurrence pattern in the EORTC 26981/22981/NCIC CE.3 study could not be demonstrated.

Key Words: brain tumor, invasiveness, MRIcro, relapse pattern, temozolomide

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