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

doi:10.1093/noajnl/vdac032

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^*

^*Corresponding author for this work

Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	vdac032
Journal	Neuro-oncology advances
Volume	4
Issue number	1
DOIs	https://doi.org/10.1093/noajnl/vdac032
Publication status	Published - 15-Apr-2022

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Gahrmann, R., Smits, M., Vernhout, R. M., Taal, W., Kapsas, G., de Groot, J. C., Hanse, M., Vos, M., Beerepoot, L. V., Buter, J., Flach, Z. H., van der Holt, B., & van den Bent, M. (2022). The impact of different volumetric thresholds to determine progressive disease in patients with recurrent glioblastoma treated with bevacizumab. Neuro-oncology advances, 4(1), Article vdac032. https://doi.org/10.1093/noajnl/vdac032

@article{63cd70ded38047228da1e4e52c2198f2,

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

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.",

author = "Renske Gahrmann and Marion Smits and Vernhout, {Ren{\'e} Michel} and Walter Taal and Giorgios Kapsas and {de Groot}, {Jan Cees} and Monique Hanse and Maaike Vos and Beerepoot, {Laurens Victor} and Jan Buter and Flach, {Zwenneke Hendrieke} and {van der Holt}, Bronno and {van den Bent}, Martin",

note = "{\textcopyright} The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.",

year = "2022",

month = apr,

day = "15",

doi = "10.1093/noajnl/vdac032",

language = "English",

volume = "4",

journal = "Neuro-oncology advances",

issn = "2632-2498",

publisher = "Oxford University Press",

number = "1",

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Gahrmann, R, Smits, M, Vernhout, RM, Taal, W, Kapsas, G, de Groot, JC, Hanse, M, Vos, M, Beerepoot, LV, Buter, J, Flach, ZH, van der Holt, B & van den Bent, M 2022, 'The impact of different volumetric thresholds to determine progressive disease in patients with recurrent glioblastoma treated with bevacizumab', Neuro-oncology advances, vol. 4, no. 1, vdac032. https://doi.org/10.1093/noajnl/vdac032

TY - JOUR

T1 - The impact of different volumetric thresholds to determine progressive disease in patients with recurrent glioblastoma treated with bevacizumab

AU - Gahrmann, Renske

AU - Smits, Marion

AU - Vernhout, René Michel

AU - Taal, Walter

AU - Kapsas, Giorgios

AU - de Groot, Jan Cees

AU - Hanse, Monique

AU - Vos, Maaike

AU - Beerepoot, Laurens Victor

AU - Buter, Jan

AU - Flach, Zwenneke Hendrieke

AU - van der Holt, Bronno

AU - van den Bent, Martin

N1 - © The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

PY - 2022/4/15

Y1 - 2022/4/15

N2 - 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.

AB - 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.

U2 - 10.1093/noajnl/vdac032

DO - 10.1093/noajnl/vdac032

M3 - Article

C2 - 35419519

SN - 2632-2498

VL - 4

JO - Neuro-oncology advances

JF - Neuro-oncology advances

IS - 1

M1 - vdac032

ER -

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

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