Imaging studies may predict tumor response to antiangiogenic drugs

Advanced imaging techniques may be able to distinguish which patients' tumors will respond to treatment with antiangiogenic drugs and which will not. In patients with newly diagnosed glioblastoma treated with the antiangiogenic drug cediranib, those who developed rapidly 'normalized' abnormal blood vessels around their tumors and increased blood flow within tumors survived significantly longer than did patients in whom cediranib did not increase blood flow.

"Two recent phase III trials of another antiangiogenic 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," explained co-lead and corresponding author Tracy Batchelor, MD, director of the Pappas Center for Neuro-Oncology at the Massachusetts General Hospital Cancer Center in Boston. "Our results also verify that normalization of tumor vasculature appears to be the way that antiangiogenic drugs enhance the activity of chemotherapy and radiation treatment."

Antiangiogenic 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' tumors of their blood supply. Since that time, however, new evidence has suggested that the drugs' benefits come through their ability to 'normalize' the abnormal, leaky vessels that usually surround and penetrate tumors, improving delivery of both chemotherapy drugs and the oxygen that is required for effective radiation therapy.

Patients in the current study were participants in a clinical trial of cediranib plus radiation and chemotherapy for postsurgical treatment of newly diagnosed glioblastoma. Among participants in that trial, 40 also had advanced brain imaging with vessel architectural imaging (VAI) and other magnetic resonance imaging techniques. The report appeared in PNAS (2013; doi:10.1073/pnas.1318022110).

All but one of the participants in the overall trial showed some evidence of vascular normalization and reduced edema, which can be dangerous within the brain. Of the 40 who had imaging studies, only 20 were found to have persistent improvement in vessel perfusion. VAI also revealed improved oxygen delivery only in the patients with improved perfusion. Those patients survived about 9 months longer—26 months, compared with 17 months—than did those whose perfusion levels remained stable or worsened. A comparison group of glioblastoma patients treated with radiation and chemotherapy only survived an average of 14 months.

"It's quite likely that the results we've found with cediranib will apply to other antiangiogenics," Batchelor says. "In fact a presentation at a recent meeting showed that patients with improved perfusion from bevacizumab were also the ones in that study who lived longer. More research is needed, but these findings suggest that magnetic resonance imaging techniques should play an essential role in future studies of antiangiogenic drugs in glioblastoma and possibly other types of solid tumors."

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