MTR-13EVALUATION OF p75 EXPRESSION AND PATTERNS OF RECURRENCE IN PATIENTS WITH MALIGNANT GLIOMAS TREATED WITH BEVACIZUMAB

Abstract

BACKGROUND: There is no standard treatment for patients with recurrent malignant gliomas (MGs) and after antiangiogenic therapy, 15% recur in a distant location suggesting the development of VEGF independent invasive mechanisms. We hypothesized that p75NTR expression could be associated to the pattern of recurrence/progression in patients with MGs treated with bevacizumab. METHODS: Adult patients with MGs (gliomas Grade III and Glioblastoma) treated with bevacizumab who had given written consent were identified. Clinical data were extracted from the charts. Pathology was centrally reviewed by a neuropathologist (JC) who also evaluated p75NTR by immunohistochemistry using a scoring system (intensity index, prevalence index - % of positive cells- and a combination index - the product of the two). Brain MRIs underwent central neuroradiology review (JS). All researchers were blinded to others' results. RESULTS: Thirty patients were included; 83% were male; 87% had glioblastoma and 84% received bevacizumab as second line therapy. Recurrences were 42% local (n = 10), 21% diffuse (n= 5) and 12% distal (n = 3). Six patients (25%) had radiologic stability despite clinical deterioration. There was no association between p75 expression and pattern of progression. In univariate analysis, progression free survival (PFS) was associated with KPS [HR 0.94 (CI 95% 0.89–0.990; p = 0.046], prevalence index for p75 [HR 1.8 (CI 95% 1.17-1.34); p = 0.007], and combined score for p75 expression [HR 1.18 (CI 95% 1.03-1.34); p = 0.012]. Patients with >50% p75 positive cells had shorter PFS [HR 3.3 (CI 95% 1.12-8.89); p = 0.018]. Tumors with any p75 positive cell had worse PFS than p75 negative tumors [HR 3.64 (CI 95% 1.18-11.22); p = 0.024]. CONCLUSION: The expression of p75 was associated with PFS in recurrent MGs. We were not able to find an association between the pattern of recurrence/progression and the expression of p75 in patients with MGs after treatment with Bevacizumab.