Magnetic resonance imaging and o-(2-[18F]fluoroethyl)-l-tyrosine positron emission tomography for early response assessment of nivolumab and bevacizumab in patients with recurrent high-grade astrocytic glioma

Otto Mølby Henriksen; Simone Maarup; Benedikte Hasselbalch; Hans Skovgaard Poulsen; Ib Jarle Christensen; Karine Madsen; Vibeke Andrée Larsen; Ulrik Lassen; Ian Law

doi:10.1093/noajnl/vdae178

Magnetic resonance imaging and o-(2-[¹⁸F]fluoroethyl)-l-tyrosine positron emission tomography for early response assessment of nivolumab and bevacizumab in patients with recurrent high-grade astrocytic glioma

Neurooncol Adv. 2024 Oct 24;6(1):vdae178. doi: 10.1093/noajnl/vdae178. eCollection 2024 Jan-Dec.

Authors

Affiliations

¹ Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
² Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
³ The DCCC Brain Tumor Center, Danish Comprehensive Cancer Center, Copenhagen, Denmark.
⁴ Department of Radiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
⁵ Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.

Abstract

Background: In the present study, early response assessment by o-(2-[¹⁸F]fluoroethyl)-l-tyrosine (FET) positron emission tomography (PET) and contrast-enhanced magnetic resonance imaging (MRI) were investigated in a phase II open-label single-center study of nivolumab plus bevacizumab for recurrent high-grade astrocytic glioma.

Methods: Twenty patients with nonresectable first recurrence of high-grade astrocytic glioma after EORTC/NCIC protocol underwent [¹⁸F]FET PET/MRI at baseline and after 2 cycles of treatment. Whole brain values of contrast-enhancing volume on MRI (CEV), of the mean (TBR_mean) and maximal tumor-to-background ratio (TBR_max), and of metabolically active volume (MTV) on [¹⁸F]FET PET were obtained. Regional changes in [¹⁸F]FET uptake were assessed by parametric response mapping (PRM). Prediction of overall survival (OS) and response (OS > 11 months) were assessed by Cox and receiver operating characteristic (ROC) analysis, respectively. Also, MRI (response assessment in neuro-oncology [RANO] 2.0) and PET-based (PET RANO 1.0) response assessment criteria were compared.

Results: In ROC analysis responders were separated (P < .05) from nonresponders by lower MTV at follow-up (AUC 0.771, cutoff 18.3 mL), larger decrease in MTV (AUC 0.757, cutoff -5.3 mL), larger decrease in both TBR_max (AUC 0.814, cutoff -0.53) and relative TBR_max (AUC 0.829, cutoff -11%) and smaller PRM progressive volume (AUC 0.843, cutoff 4.0 mL). Change in CEV did not predict response. RANO 2.0 and PET RANO response assessment criteria had similar and only borderline prognostic values.

Conclusions: The study indicates that [¹⁸F]FET PET is superior to contrast-enhanced MRI for early response assessment in patients with recurrent high-grade astrocytic glioma treated with nivolumab and bevacizumab.

Keywords: antiangiogenic treatment; high-grade astrocytic glioma; immunotherapy; positron emission tomography; response assessment.