Abstract
To evaluate the value of the contrast enhancing pattern on pre-treatment MRI for predicting the response to anti-angiogenic treatment in patients with IDH-wild type recurrent glioblastoma. This retrospective study enrolled 65 patients with IDH wild-type recurrent glioblastoma who received standard therapy and then received either bevacizumab (46 patients) or temozolomide (19 patients) as a secondary treatment. The contrast enhancing pattern on pre-treatment MRI was visually analyzed and dichotomized into contrast enhancing lesion (CEL) dominant and non-enhancing lesion (NEL) dominant types. Quantitative volumetric analysis was used to support the dichotomization. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to stratify progression free survival (PFS) according to the treatment in the entire patients, CEL dominant group, and NEL dominant group. In all patients, the PFS of those treated with bevacizumab was not significantly different from those treated with temozolomide (log-rank test, P = 0.96). When the contrast enhancing pattern was considered, bevacizumab was associated with longer PFS in the CEL dominant group (P = 0.031), whereas temozolomide showed longer PFS in the NEL dominant group (P = 0.022). Quantitative analysis revealed mean values for the proportion of solid-enhancing tumor of 13.7% for the CEL dominant group and 4.3% for the NEL dominant group. Patients with the CEL dominant type showed a better treatment response to bevacizumab, whereas NEL dominant types showed a better response to temozolomide. The contrast enhancing pattern on pre-treatment MRI can be used to stratify patients with IDH wild-type recurrent glioblastoma according to the effect of anti-angiogenic treatment.
Highlights
Anti-angiogenic treatment targeting vascular endothelial growth factor (VEGF) signaling represents a mainstay in the treatment of recurrent glioblastoma [1]
Patients with the contrast enhancing lesion (CEL) dominant type showed a better treatment response to bevacizumab, whereas non-enhancing lesion (NEL) dominant types showed a better response to temozolomide
There were no significant differences in age at diagnosis, Karnofsky performance status at recurrence, or O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status between the CEL dominant and NEL dominant groups
Summary
Anti-angiogenic treatment targeting vascular endothelial growth factor (VEGF) signaling represents a mainstay in the treatment of recurrent glioblastoma [1]. A predictive imaging biomarker for bevacizumab is defined by that there is a clear benefit of the bevacizumab in biomarker subgroup (positive) but a clear lack of benefit in the other biomarker subgroup (negative) [3, 4] This biomarker would be useful for selecting those patients with recurrent glioblastoma who are likely to benefit from treatment with bevacizumab. Because of the single-arm nature of the studies, which did not include a control treatment group, these imaging biomarkers were prognostic rather than predictive [3, 4]. They are based on advanced MRI techniques, and the diversity of imaging acquisition protocols and post-processing techniques used between institutions may impede the replication of single-center study results [10]
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