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Schaub, Christina; Kebir, Sied; Junold, Nina; Hattingen, Elke; Schäfer, Niklas; Steinbach, Joachim P.; Weyerbrock, Astrid; Hau, Peter; Goldbrunner, Roland; Niessen, Michael; Mack, Frederic; Stuplich, Moritz; Tzaridis, Theophilos; Bähr, Oliver; Kortmann, Rolf-Dieter; Schlegel, Uwe; Schmidt-Graf, Friederike; Rohde, Veit; Braun, Christian; Haenel, Mathias; Sabel, Michael; Gerlach, Rüdiger; Krex, Dietmar; Belka, Claus; Vatter, Hartmut; Pröscholdt, Martin; Herrlinger, Ulrich and Glas, Martin (2018): Tumor growth patterns of MGMT-non-methylated glioblastoma in the randomized GLARIUS trial. In: Journal of Cancer Research and Clinical Oncology, Vol. 144, No. 8: pp. 1581-1589

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We evaluated patterns of tumor growth in patients with newly diagnosed MGMT-non-methylated glioblastoma who were assigned to undergo radiotherapy in conjunction with bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ) within the randomized phase II GLARIUS trial. In 142 patients (94 BEV/IRI, 48 TMZ), we reviewed magnetic resonance imaging scans at baseline and first tumor recurrence. Based on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery images, we assessed tumor growth patterns and tumor invasiveness. Tumor growth patterns were classified as either multifocal or local at baseline and recurrence;at first recurrence, we additionally assessed whether distant lesions appeared. Invasiveness was determined as either diffuse or non-diffuse. Associations with treatment arms were calculated using Fisher's exact test. At baseline, 115 of 142 evaluable patients (81%) had a locally confined tumor. Between treatment arms, there was no significant difference in the fraction of tumors that changed from an initially local tumor growth pattern to a multifocal pattern (12 and 13%, p = 0.55). Distant lesions appeared in 17% (BEV/IRI) and 13% (TMZ) of patients (p = 0.69). 15% of patients in the BEV/IRI arm and 8% in the TMZ arm developed a diffuse growth pattern from an initially non-diffuse pattern (p = 0.42). The tumor growth and invasiveness patterns do not differ between BEV/IRI and TMZ-treated MGMT-non-methylated glioblastoma patients in the GLARIUS trial. BEV/IRI was not associated with an increased rate of multifocal, distant, or highly invasive tumors at the time of recurrence.

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