Radiographic patterns of recurrence and pathologic correlation in malignant gliomas treated with bevacizumab

Abstract

Interpretation of MRI abnormalities in patients with malignant gliomas (MG) treated with bevacizumab is challenging. Recent reports describe quantitative analyses of diffusion-weighted imaging abnormalities not available in standard clinical settings, to differentiate tumor recurrence from treatment necrosis. We retrospectively reviewed bevacizumab treated MG patients who underwent surgery or autopsy to correlate radiographic recurrence patterns with pathologic findings. 32 patients with MG (26 glioblastoma, three anaplastic astrocytoma and three anaplastic oligodendroglioma) were identified. Recurrence patterns: local enhancing (n = 23), distant enhancing (n = 1), nonenhancing (n = 7) and leptomeningeal (n = 1). Histology: tumor (n = 25), mixed tumor/necrosis (n = 5) and all necrosis (n = 2). On diffusion-weighted imaging, 5/32 had restricted diffusion (three mixed and two necrosis). Irrespective of radiographic recurrence pattern, tumor was found in 94% of cases. Restricted diffusion correlated with necrosis.

Radiological Recurrence Patterns after Bevacizumab Treatment of Recurrent High-Grade Glioma: A Systematic Review and Meta-Analysis

“…Against this background, several studies have tried to classify the radiological recurrence patterns after the failure of bevacizumab treatment for recurrent glioblastoma as these patterns may reflect different biological subgroups requiring specific treatment patterns (4,(11)(12)(13)(14)(15)(16)(17). According to these studies, the radiological recurrence patterns after bevacizumab treatment failure differed from those of other conditions in which the treatment did not contain bevacizumab (4,(11)(12)(13)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). However, there is no established radiological recurrence pattern to define bevacizumab treatment failure in patients with recurrent glioblastoma; thus, there is no conclusive evidence that the specific patterns of progression after bevacizumab treatment can be associated with patient outcome including survival.…”

“…However, 12 of the 17 studies showed an unclear risk of bias in the blinding of participants and personnel domain, as they did not make clear statements in this regard (4, 16-20, 22-25, 27, 28). In the measurement of exposure domain, five studies showed a low risk of bias as multiple readers performed the radiologic assessment (11,12,17,21,26), five of 17 studies showed a high risk of bias because only a single reader assessed the radiologic response (13,16,20,22,24), and the other seven studies showed an unclear risk of bias (4,18,19,23,25,27,28). Finally, in the selection of patients domain, only one study showed a low risk of bias because of its prospective design (24) while the others showed high risks of bias due to their retrospective designs (4, 11-13, 16-23, 25-28).…”

“…Only one article reported a prospective study (24); the other studies were retrospective (4, 11-13, 16-23, 25-28). Seven studies included recurrent highgrade glioma (4,16,18,23,25,26,28) while the other 10 studies specifically included recurrent glioblastoma (11-13, 17, 19-22, 24, 27). The tumor response assessment criteria used after treatment varied according to the center from which the studies originated, as described in Table 1.…”

“…In terms of prior treatment history before bevacizumab, eight studies included patients having undergone surgery, chemotherapy, and radiation therapy (4, 11, 13, 18-21, 23, 24, 28); four studies included chemotherapy and radiation therapy (17,22,26,27); two studies included chemotherapy (12,16); and one study included radiation therapy (25). Four studies also included patients with a prior treatment history with an antiangiogenic agent (16,21,26,28). Regarding combination options during bevacizumab treatment, eight studies included both patients treated with bevacizumab only and with bevacizumab in combination with chemotherapy (4,11,13,18,19,(26)(27)(28); four studies included only patients treated with bevacizumab in combination with chemotherapy (16,21,22,24); two studies included only patients treated with bevacizumab only (12,20); and one study included patients treated with bevacizumab only, with bevacizumab in combination with radiation therapy, and bevacizumab in combination with chemotherapy (17).…”

“…Four studies also included patients with a prior treatment history with an antiangiogenic agent (16,21,26,28). Regarding combination options during bevacizumab treatment, eight studies included both patients treated with bevacizumab only and with bevacizumab in combination with chemotherapy (4,11,13,18,19,(26)(27)(28); four studies included only patients treated with bevacizumab in combination with chemotherapy (16,21,22,24); two studies included only patients treated with bevacizumab only (12,20); and one study included patients treated with bevacizumab only, with bevacizumab in combination with radiation therapy, and bevacizumab in combination with chemotherapy (17). One study did not provide detailed information on the treatment combination (23).…”