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. 2022 Mar 9;4(1):vdac032.
doi: 10.1093/noajnl/vdac032. eCollection 2022 Jan-Dec.

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

Renske Gahrmann  1 , Marion Smits  1 , René Michel Vernhout  2 , Walter Taal  3 , Giorgios Kapsas  1 , Jan Cees de Groot  4 , Monique Hanse  5 , Maaike Vos  6 , Laurens Victor Beerepoot  7 , Jan Buter  8 , Zwenneke Hendrieke Flach  9 , Bronno van der Holt  2 , Martin van den Bent  3
Affiliations

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

Renske Gahrmann et al. Neurooncol Adv. .

Abstract

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.

Keywords: GBM; RANO; bevacizumab; volumetry.

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Figures

Figure 1.
Figure 1.
Flow diagram of all patients included from the BELOB and EORTC 26101 trials (n = 183), reasons for excluding patients (in order) per analysis and number of patients included in the final analyses.
Figure 2.
Figure 2.
Kaplan-Meier curves of patients with and without a new lesion at first follow-up. The median overall survival (measured from first follow-up) was 2 versus 8.5 months, respectively.
See this image and copyright information in PMC

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