The impact of different volumetric thresholds to determine progressive disease in patients with recurrent glioblastoma treated with bevacizumab

Renske Gahrmann, Marion Smits, René Michel Vernhout, Walter Taal, Giorgios Kapsas, Jan Cees de Groot, Monique Hanse, Maaike Vos, Laurens Victor Beerepoot, Jan Buter, Zwenneke Hendrieke Flach, Bronno van der Holt, Martin van den Bent

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Background: The optimal volumetric threshold for determining progressive disease (PD) in recurrent glioblastoma is yet to be determined. We investigated a range of thresholds in association with overall survival (OS). Methods: First recurrent glioblastoma patients treated with bevacizumab and/or lomustine were included from the phase II BELOB and phase III EORTC26101 trials. Enhancing and nonenhancing tumor volumes were measured at baseline, first (6 weeks), and second (12 weeks) follow-up. Hazard ratios (HRs) for the appearance of new lesions and several thresholds for tumor volume increase were calculated using cox regression analysis. Results were corrected in a multivariate analysis for well-established prognostic factors. Results: At first and second follow-up, 138 and 94 patients respectively, were deemed eligible for analysis of enhancing volumes, while 89 patients were included in the analysis of nonenhancing volumes at first follow-up. New lesions were associated with a significantly worse OS (3.2 versus 11.2 months, HR = 7.03, P <. 001). At first follow-up a threshold of enhancing volume increase of ≥20% provided the highest HR (5.55, p =. 001. At second follow-up, any increase in enhancing volume (≥0%) provided the highest HR (9.00, p <. 001). When measuring nonenhancing volume at first follow-up, only 6 additional patients were scored as PD with the highest HR of ≥25% increase in volume (HR=3.25, p =. 008). Conclusion: Early appearing new lesions were associated with poor OS. Lowering the volumetric threshold for PD at both first and second follow-up improved survival prediction. However, the additional number of patients categorized as PD by lowering the threshold was very low. The per-RANO added change in nonenhancing volumes to the analyses was of limited value.

Original languageEnglish
Article numbervdac032
JournalNeuro-oncology advances
Issue number1
Publication statusPublished - 1 Jan 2022


  • GBM
  • RANO
  • bevacizumab
  • volumetry

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