Antiangiogenic therapies for malignant gliomas: new markers for targeted treatment

Bevacizumab has shown activity in different tumor types, including high grade gliomas (HGG). However, the use of bevacizumab and other antiangiogenic drugs in the clinical setting limited by the lack of markers to predict responses. We report that the combined treatment with bevacizumab and irinotecan is effective in recurrent HGG patients, particularly in those with local disease, with mild toxicity. Median OS and PFS were 33 and 18 weeks, respectively. PFS at 6 and 12 months were 32% and 12%. OS at 6 months was 60%. Patients with distant intracerebral disease or leptomeningeal dissemination at baseline magnetic resonance had shorter PFS and OS. We analyzed circulating endothelial cells (CECs) and their progenitors (CEPs), as previous studies supported their involvement in responses to bevacizumab. Higher levels of CD109+ CECs, CEPs and CD45dimCD34+CD133+ hematopoietic committed progenitors before treatment were associated with longer PFS. Moreover, long-term responders showed higher baseline CD109+ CECs and CD45dimCD34+VEGFR2+ hematopoietic progenitors. These findings pave the way for larger studies further addressing the potential of CECs and CEPs as biomarkers to target patient populations that may benefit from bevacizumab and possibly other antiangiogenic drugs.