Boron neutron capture therapy with bevacizumab may prolong the survival of recurrent malignant glioma patients: four cases

Abstract

Background and importance: Recurrent malignant gliomas (RMGs) are very difficult to control, and no standard treatments have been established for them. We performed boron neutron capture therapy (BNCT) for patients with RMG. BNCT enables high-dose particle radiation to be applied selectively to tumor cells. However, RMG cases generally receive nearly 60 Gy X-ray irradiation prior to re-irradiation by BNCT. Therefore, even with tumor-selective particle radiation BNCT, radiation necrosis in the brain and symptomatic pseudoprogression may develop. In four of our recent patients with RMG after BNCT, we applied the anti-VEGF antibody bevacizumab to treat two pathological entities. This approach appeared to prolong survival. Here we present the case reports of these four consecutive patients with RMG and discuss the novel use of bevacizumab in this context.

Clinical presentation: Four patients with RMGs were treated with BNCT at our institutes. Upon the referral for BNCT, they were assessed as belonging to the recursive partitioning analysis (RPA) class 3 (n = 3 patients) or RPA class 4 (n = 1 patient) (the RPA classification for RMG was advocated by Carson et al. in 2007). The estimated median survival times for RPA classes 3 and 4 were 3.8 and 10.8 months, respectively, after some treatment at the recurrence. We applied BNCT for these four patients and administered bevacizumab when the lesions were considered radiation necrosis or symptomatic pseudoprogression. The class 3 patients survived after the BNCT for 14, 16.5 and > 23 months, and the class 4 patient survived > 26 months, with favorable improvements in clinical symptoms.

Conclusion: BNCT with the addition of bevacizumab for radiation necrosis or symptomatic pseudoprogression improved the clinical symptoms and prolonged the survival in RMG patients.

Figure 1

Sequential change of T2-weighted MRI (upper column), Gd-enhanced T1-weighted MRI (middle column) and F-BPA-PET (lower column) of Case 1, a 44-year-old male. The timing of the MRIs is depicted above the MRIs. F-BPA-PET images were taken just before the BNCT and at 1 month and 10 months after the BNCT. These PET images show the gradual decrease of the tracer uptake as a promising effect of the BNCT. BV was started 10 months after the BNCT, and the MRI showed marked improvement of both perifocal edema and contrast enhancements by BV treatment.

Figure 2

Sequential change of T2-weighted MRI (upper column), Gd-enhanced T1-weighted MRI (middle column) and F-BPA-PET (lower column) of Case 2, a 41-year-old man. The timing of the MRI is depicted above the MRI. F-BPA-PET images were taken just before the BNCT, 1 month after and 12 months after the BNCT. These PET images show the gradual decrease of the tracer uptake as a promising effect of BNCT. BV was started 13 months after the BNCT, and an MRI showed a marked positive effect of the BV treatment on the perifocal edema and contrast enhancements.