Imaging studies may predict tumour response to anti-angiogenic drugs

Advanced imaging techniques may be able to distinguish which patients’ tumours will respond to treatment with anti-angiogenic drugs and which will not. Massachusetts General Hospital (MGH) researchers studied patients newly diagnosed with the dangerous brain tumour glioblastoma and treated with the anti-angiogenic agent cediranib. They report that those patients for whom cediranib rapidly ‘normalised’ abnormal blood vessels around their tumours and increased blood flow within tumours survived significantly longer than did patients in whom cediranib did not increase blood flow.
‘Two recent phase III trials of another anti-angiogenic drug, bevacizumab, showed no improvement in overall survival for glioblastoma patients, but our study suggests that only a subset of such patients will really benefit from these drugs,’ explains Tracy Batchelor, MD, director of the Pappas Center for Neuro-Oncology at the MGH Cancer Center and co-lead and corresponding author of the current study. ‘Our results also verify that normalisation of tumour vasculature appears to be the way that anti-angiogenic drugs enhance the activity of chemotherapy and radiation treatment.’
Anti-angiogenic drugs, which block the action of factors that stimulate the growth of blood vessels, were first introduced for cancer treatment under the theory that they would act by ‘starving’ tumours of their blood supply. Since that time, however, new evidence has suggested that the drugs’ benefits come through their ability to ‘normalise’ the abnormal, leaky vessels that usually surround and penetrate tumours, improving delivery of both chemotherapy drugs and the oxygen that is required for effective radiation therapy. This hypothesis was first proposed and has subsequently been developed by Rakesh K. Jain, PhD, senior author of the current study and director of the Steele Laboratory for Tumor Biology in the MGH Department of Radiation Oncology.
A 2007 clinical study led by Batchelor found evidence suggesting that cediranib, which has not yet received FDA approval, could temporarily normalise tumour vasculature in recurrent glioblastoma, but it was not clear what role normalisation might have in patients’ survival. In the past few years, several research teams with leadership from Batchelor, Jain and other co-authors of the current paper reported evidence that cediranib alone improved blood perfusion within recurrent glioblastoma tumors in a subset of patients and improved their survival. A Nature Medicine study published earlier this year used a technique called vessel architectural imaging (VAI), developed at the Martinos Center for Biomedical Imaging at MGH, to reveal that cediranib on its own improved the delivery of oxygen within tumours of some patients with recurrent glioblastoma.
Patients in the current study were participants in a clinical trial of cediranib plus radiation and chemotherapy for post-surgical treatment of newly diagnosed glioblastoma. Among participants in that trial, 40 also had advanced brain imaging with VAI and other MR imaging techniques. While all but one of the participants in the overall trial showed some evidence of vascular normalisation and reduced oedema