Low-Dose Bevacizumab for the Treatment of Focal Radiation Necrosis of the Brain (fRNB): A Single-Center Case Series

Abstract

Focal radiation necrosis of the brain (fRNB) is a late adverse event that can occur following the treatment of benign or malignant brain lesions with stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS). Recent studies have shown that the incidence of fRNB is higher in cancer patients who received immune checkpoint inhibitors. The use of bevacizumab (BEV), a monoclonal antibody that targets the vascular endothelial growth factor (VEGF), is an effective treatment for fRNB when given at a dose of 5-7.5 mg/kg every two weeks. In this single-center retrospective case series, we investigated the effectiveness of a low-dose regimen of BEV (400 mg loading dose followed by 100 mg every 4 weeks) in patients diagnosed with fRNB. A total of 13 patients were included in the study; twelve of them experienced improvement in their existing clinical symptoms, and all patients had a decrease in the volume of edema on MRI scans. No clinically significant treatment-related adverse effects were observed. Our preliminary findings suggest that this fixed low-dose regimen of BEV can be a well-tolerated and cost-effective alternative treatment option for patients diagnosed with fRNB, and it is deserving of further investigation.

Keywords: VEGF inhibitor; bevacizumab; case series; low-dose regimen; radiation necrosis of the brain; radiotherapy; stereotactic radiation therapy.

Figure 1

Swimmer plot of the bevacizumab disposition. Loading dose = 400 mg I.V.; maintenance dose = 100 mg I.V. Survival indicates the time between first loading dose and data base lock or death.

Figure 2

Change in T2-weighted FLAIR-hyperintensity and T1-weighted gadolinium enhancing volumes between baseline MRI and the most recent MRI at the end of BEV treatment (first row). Evolution in time of T2-weighted FLAIR-hyperintensity and T1-weighted gadolinium enhancing volumes during treatment (second row). * Indicates a re-challenge with a low-dose bevacizumab regimen after an elective discontinuation of bevacizumab treatment.

Figure 3

Schematic overview of events and MRI images with regard to the Case Illustration 1. First row: T1-weighted gadolinium MRI. Second row: T2-weighted FLAIR MRI (axial). Third row: T2-weighted FLAIR MRI (coronal) illustrating fRNB crossing over the tentorium.

Figure 4

Schematic overview of events and MRI images with regard to Case Illustration 2. First row: T1-weighted gadolinium MRI (abnormality marked by arrow). Second row: T2-weighted FLAIR MRI. Third row: ¹⁸F-FDG PET-CT.