Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas

Abstract

Pseudoprogression has been recognized and widely accepted in the treatment of malignant gliomas, as transient increases in the volume of the enhanced area just after chemoradiotherapy, especially using temozolomide. We experienced a similar phenomenon in the treatment of malignant gliomas and meningiomas using boron neutron capture therapy (BNCT), a cell-selective form of particle radiation. Here, we introduce representative cases and analyze the pathogenesis. Fifty-two cases of malignant glioma and 13 cases of malignant meningioma who were treated by BNCT were reviewed retrospectively mainly via MR images. Eleven of 52 malignant gliomas and 3 of 13 malignant meningiomas showed transient increases of enhanced volume in MR images within 3 months after BNCT. Among these cases, five patients with glioma underwent surgery because of suspicion of relapse. In histology, most of the specimens showed necrosis with small amounts of residual tumor cells. Ki-67 labeling showed decreased positivity compared with previous samples from the individuals. Fluoride-labeled boronophenylalanine PET was applied in four and two cases of malignant gliomas and meningiomas, respectively, at the time of transient increase of lesions. These PET scans showed decreased lesion:normal brain ratios in all cases compared with scans obtained prior to BNCT. With or without surgery, all lesions were decreased or stable in size during observation. Transient increases in enhanced volume in malignant gliomas and meningiomas immediately after BNCT seemed to be pseudoprogression. This pathogenesis was considered as treatment-related intratumoral necrosis in the subacute phase after BNCT.

Fig. 1.

Two representative cases of pseudoprogression of newly diagnosed glioblastoma multiforme treated by boron neutron capture therapy (BNCT). (A-1–A-4) Gadolinium (Gd)-enhanced MR images of case 5: prior to BNCT (A-1), 5 weeks after BNCT (A-2), 2 months after BNCT (A-3), and 6 months after BNCT and 3 months after second craniotomy (A-4). Case 5 was operated on 3 months after BNCT for the suspicion of tumor progression (judged from A-3). The operated lesion was stable for more than 3 months without chemotherapy. (B-1–B-4) Gd-enhanced MR images of case 35: prior to BNCT (B-1), 1 month after BNCT (B-2), 2 months after BNCT (B-3), and 7 months after BNCT (B-4).

Fig. 2.

Hematoxylin and eosin (H&E) and Ki-67 staining of specimens obtained from the first and second craniotomy of case 5. (A and B) H&E staining of the specimen of first craniotomy (A) and second craniotomy (3 months after boron neutron capture therapy [BNCT]; B). (C and D) Ki-67 staining of the specimen of the first craniotomy (C) and second craniotomy (3 months after BNCT; D). Original magnification, ×200 for A–D.

Fig. 3.

Two representative cases of pseudoprogression of recurrent malignant meningiomas treated by boron neutron capture therapy (BNCT). (A-1–A-4) Gadolinium (Gd)-enhanced MR images of case 50: prior to BNCT (A-1), 48 h after BNCT (A-2) 1 month after BNCT (A-3), and 2 months after BNCT (A-4). (B-1–B-4) Gd-enhanced MR images of case 56: prior to BNCT (B-1), 1.5 months after BNCT (B-2), 2.5 months after BNCT (B-3), and 6 months after BNCT (B-4).