Intratumoral and peritumoral post-irradiation changes, but not viable tumor tissue, may respond to bevacizumab in previously irradiated meningiomas

Abstract

The efficacy of bevacizumab has not been determined for treatment-refractory meningiomas. We treated meningiomas with low-dose bevacizumab and compared the radiological responses of non-irradiated meningiomas with previously irradiated meningiomas. In addition, we assessed intraparenchymal radiation necrosis following bevacizumab treatment.Six patients with meningiomas (three anaplastic, one atypical, and two grade I) who were previously treated with multiple sessions of radiotherapy and subsequently developed perilesional edema were treated with bevacizumab. Of six patients, two patients with anaplastic meningiomas developed three tumors following radiotherapy, which were defined as non-irradiated tumors. There were 12 pre-existing extra-axial tumors that were previously irradiated. Some of these tumors demonstrated adjacent intraparenchymal contrast enhancement. These tumors were defined as post-irradiated tumors. Four patients had intraparenchymal radiation necrosis. Low-dose bevacizumab was administered biweekly over 3-6 cycles to all patients.Four tumors decreased in contrast-enhanced volume, nine tumors were unchanged, and two tumors progressed. Of the three non-irradiated tumors, two tumors increased in volume (126 % and 198 %) and one tumor was stable (-5 %). The median reduction rates determined by contrast volume were -31 % and -71 % in post-irradiated tumors and radiation necrosis, respectively. Non-irradiated tumors had a significantly poorer response to bevacizumab than post-irradiated tumors and radiation necrosis (p = 0.0013 and p = 0.0005, respectively, Tukey-Kramer test).Low-dose bevacizumab did not demonstrate efficacy in the treatment of non-irradiated meningiomas. Responses to low-dose bevacizumab could be related to its effect on post-irradiation changes, rather than its effect on biologically active tumor tissue in post-irradiated meningiomas. Radiological responses to low-dose bevacizumab may distinguish biologically active tumors from post-irradiation changes in progressive meningiomas following radiotherapy.

Fig. 1

MR images before and after bevacizumab in Case 1 (before, a, b; after, d, e) and Case 2 (before, c; after, f). There were three non-irradiated tumors (a, white arrow: tumor 1; b, white arrow: tumor 2; c, white arrow: tumor 7). After bevacizumab, both Tumors 1 and 2 showed progression (d, e: arrows). Tumor 7 did not changed after bevacizumab treatment (f: arrow). On the other hand, a post-irradiated tumor decreased after bevacizumab. Tumor 6 decreased to −79 % (c, f: arrowheads). Intraparenchymal radiation necrosis was disappeared (c, f: black arrow)

Fig. 2

MR images before and after bevacizumab in Case 3 (before, a; after, d) and Case 6 (before, b, c; after, e, f). Intraparenchymal radiation necrosis decreased to −65 % and −51 % after bevacizumab in Cases 3 and 6, respectively (black arrows). Regarding post-irradiated tumors, Tumor 9 (Case 3) (a, d, arrowhead) did not change (0 %) and Tumor 13 (Case 6) (b, e, arrowhead) showed 65 % decrease after bevacizumab

Fig. 3

Graph demonstrating the reduction rate of non-irradiated meningiomas, post-irradiated meningiomas, and intraparenchymal radiation necrosis. Non-irradiated tumors responded significantly poorer than post-irradiated tumors and radiation necrosis (p = 0.0013, p = 0.0005, respectively, Tukey-Kramer test)