title: Comparison of 2D (RANO) and volumetric methods for assessment of recurrent glioblastoma treated with bevacizumab-a report from the BELOB trial.
abstract: The current method for assessing progressive disease (PD) in glioblastoma is according to the Response Assessment in Neuro-Oncology (RANO) criteria. Bevacizumab-treated patients may show pseudo-response on postcontrast T1-weighted (T1w) MRI, and a more infiltrative non-enhancing growth pattern on T2w/fluid attenuated inversion recovery (FLAIR) images. We investigated whether the RANO criteria remain the method of choice for assessing bevacizumab-treated recurrent glioblastoma when compared with various volumetric methods.
  
  
  
  Patients with assessable MRI data from the BELOB trial (n = 148) were included. Patients were treated with bevacizumab, lomustine, or both. At first and second radiological follow-up (6 and 12 wk), PD was determined using the 2D RANO criteria and various volumetric methods based on enhancing tumor only and enhancing plus non-enhancing tumor. Differences in overall survival (OS) between PD and non-PD patients were assessed with the log-rank test and a Cox model. Hazard ratios (HRs) and their 95% CIs were determined.
  
  
  
  For all patients together, all methods (except subtraction of non-enhancing from enhancing volume at first follow-up) showed significant differences in OS between PD and non-PD patients (P < .001). The largest risk increase for death in case of PD at both first and second follow-up was found with the RANO criteria: HR = 2.81 (95% CI, 1.92-4.10) and HR = 2.80 (95% CI, 1.75-4.49), respectively. In the bevacizumab-treated patients, all methods assessed showed significant differences in OS between PD and non-PD patients. There were no significant differences between methods.
  
  
  
  In the first 12 weeks, volumetric methods did not provide significant improvement over the RANO criteria as a posttreatment prognostic marker.
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Renske
authors.initials: R
authors.lastname: Gahrmann
authors.affiliation: Brain Tumor Center at Erasmus MC Cancer Institute Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: van den Bent
authors.affiliation: Clinical Trial Center, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.affiliation: Clinical Trial Center, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
authors.forename: René Michel
authors.initials: RM
authors.lastname: Vernhout
authors.affiliation: Brain Tumor Center at Erasmus MC Cancer Institute Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Walter
authors.initials: W
authors.lastname: Taal
authors.affiliation: Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Vos
authors.affiliation: Department of Radiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan Cees
authors.initials: JC
authors.lastname: de Groot
authors.affiliation: Department of Internal Medicine, Elisabeth Tweesteden Ziekenhuis, Tilburg, The Netherlands.
authors.forename: Laurens Victor
authors.initials: LV
authors.lastname: Beerepoot
authors.affiliation: Department of Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Buter
authors.affiliation: Department of Radiology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Zwenneke Hendrieke
authors.initials: ZH
authors.lastname: Flach
authors.affiliation: Department of Neurology, Catharina Hospital, Eindhoven, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Hanse
authors.affiliation: Department of Radiology, Antoni van Leeuwenhoek ziekenhuis, Amsterdam, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Jasperse
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Marion
authors.initials: M
authors.lastname: Smits
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*; D003287:Contrast Media; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D000068258:Bevacizumab; D008130:Lomustine
keywords: RANO; bevacizumab; recurrent glioblastoma; volumetry