Radiology 2020 10 28;297(1):164-175. Epub 2020 Jul 28.
From the Department of Neuroradiology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany (P.K., G.B., I.P., M.S., M.F., U.N., S.H., M.B.); Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University Hospital, Aarhus, Denmark (M.B.H., L.Ø.); Neurology Clinic, Heidelberg University Hospital, Heidelberg, Germany (M.N., T.K., A.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Medical Image Computing, German Cancer Research Center (DKFZ), Heidelberg, Germany (F.I., K.H.M.H.); Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany (T.K., W.W.); Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany (F.S., A.v.D.); Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (F.S., A.v.D.); Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (M.W.); Department of Neurology, Medical Faculty Mannheim, MCTN, University of Heidelberg, Mannheim, Germany (M.P.); Pattern Analysis and Learning Group, Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany (K.H.M.H.); Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark (L.Ø.); Brain Tumor Center at Erasmus MC Cancer Institute, Rotterdam, the Netherlands (M.J.v.d.B.); and European Organization for Research and Treatment of Cancer (EORTC), Brussels, Belgium (T.G.).
Background Relevance of antiangiogenic treatment with bevacizumab in patients with glioblastoma is controversial because progression-free survival benefit did not translate into an overall survival (OS) benefit in randomized phase III trials. Purpose To perform longitudinal characterization of intratumoral angiogenesis and oxygenation by using dynamic susceptibility contrast agent-enhanced (DSC) MRI and evaluate its potential for predicting outcome from administration of bevacizumab. Materials and Methods In this secondary analysis of the prospective randomized phase II/III European Organization for Research and Treatment of Cancer 26101 trial conducted between October 2011 and December 2015 in 596 patients with first recurrence of glioblastoma, the subset of patients with availability of anatomic MRI and DSC MRI at baseline and first follow-up was analyzed. Patients were allocated into those administered bevacizumab (hereafter, the BEV group; either bevacizumab monotherapy or bevacizumab with lomustine) and those not administered bevacizumab (hereafter, the non-BEV group with lomustine monotherapy). Contrast-enhanced tumor volume, noncontrast-enhanced T2 fluid-attenuated inversion recovery (FLAIR) signal abnormality volume, Gaussian-normalized relative cerebral blood volume (nrCBV), Gaussian-normalized relative blood flow (nrCBF), and tumor metabolic rate of oxygen (nTMRO) was quantified. The predictive ability of these imaging parameters was assessed with multivariable Cox regression and formal interaction testing. Results A total of 254 of 596 patients were evaluated (mean age, 57 years ± 11; 155 men; 161 in the BEV group and 93 in non-BEV group). Progression-free survival was longer in the BEV group (3.7 months; 95% confidence interval [CI]: 3.0, 4.2) compared with the non-BEV group (2.5 months; 95% CI: 1.5, 2.9; = .01), whereas OS was not different ( = .15). The nrCBV decreased for the BEV group (-16.3%; interquartile range [IQR], -39.5% to 12.0%; = .01), but not for the non-BEV group (1.2%; IQR, -17.9% to 23.3%; = .19) between baseline and first follow-up. An identical pattern was observed for both nrCBF and nTMRO values. Contrast-enhanced tumor and noncontrast-enhanced T2 FLAIR signal abnormality volumes decreased for the BEV group (-66% [IQR, -83% to -35%] and -33% [IQR, -71% to -5%], respectively; < .001 for both), whereas they increased for the non-BEV group (30% [IQR, -17% to 98%], = .001; and 10% [IQR, -13% to 82%], = .02, respectively) between baseline and first follow-up. None of the assessed MRI parameters were predictive for OS in the BEV group. Conclusion Bevacizumab treatment decreased tumor volumes, angiogenesis, and oxygenation, thereby reflecting its effectiveness for extending progression-free survival; however, these parameters were not predictive of overall survival (OS), which highlighted the challenges of identifying patients that derive an OS benefit from bevacizumab. © RSNA, 2020 See also the editorial by Dillon in this issue.