Early vessel normalization improves glioblastoma outcomes

Abstract

A subset of patients with glioblastoma who respond by showing increased tumour perfusion after early antiangiogenic therapy are more likely to benefit from anti-VEGF treatment combined with radiation and chemotherapy than patients who don’t respond. Furthermore, vascular normalization is associated with longer overall survival in patients with hyperpermeable (but uncompressed) tumours, according to two new studies. Rakesh Jain, senior author on both studies, first hypothesized in 2001 that anti-VEGF therapy works by ‘normalizing’ leaky vessels that surround tumours, improving the delivery of drugs and oxygen, which are also necessary for effective radiotherapy. Drugs that inhibit the VEGF pathway only benefit a subset of patients with solid tumours, and determining biomarkers that can distinguish which patients are more likely to respond to treatment had yet to be identified. In the first study, the researchers used MRI techniques to measure changes in blood tumour vasculature, including vessel architectural imaging, to monitor changes after anti-VEGF therapy. “Early increased tumour perfusion, often seen after one treatment with a pan-VEGFR kinase inhibitor, was associated with a twothirds increase in survival time in patients harbouring glioblastoma, compared with those patients who had no increase in blood perfusion,” explain four authors of the study—Batchelor, Emblem, Duda and Jain—in a joint statement. This effect, seen in half of the patients who underwent anti-VEGF therapy and chemoradiation, was not observed in patients who received chemotherapy alone. Moreover, these changes are associated with improved oxygenation and various plasma biomarkers.