Kate Johnson

June 01, 2011

June 1, 2011 (Montreal, Quebec) — Antiangiogenic agents that target vascular endothelial growth factor (VEGF) might have an advantage over those targeting antiprotein-kinase C beta (PKC) when combined with chemoradiation in the treatment of newly diagnosed glioblastoma multiforme, researchers suggested here at the International Society for Magnetic Resonance in Medicine 19th Annual Meeting and Exhibition.

The study used diffusion-weighted imaging to compare treatment response in 3 groups of patients with glioblastoma multiforme undergoing radiotherapy: those receiving temozolomide only (n = 31); those receiving temozolomide plus an anti-VEGF agent (n = 27); and those receiving temozolomide plus an anti-PKC agent (n = 44).

All patients were participants in phase 2 clinical trials and had undergone surgical resection before starting chemoradiation, explained lead investigator Laleh Jalilian, MD, a radiologist from the University of California at San Francisco.

Imaging was done after surgery but before chemoradiation, again midway through treatment (by 1 month), and finally after treatment (by 2 months).

The scans focused on percent change in tumor volume and normalized apparent diffusion coefficient values — a clinical marker for the diffusion of water in the brain, explained Dr. Jalilian.

The study showed marked differences in tumor response between the 2 antiangiogenic agents.

In both contrast-enhancing lesions and noncontrast-enhancing lesions, median normalized anatomic volumes decreased significantly in patients treated with anti-VEGF, but not in those treated with anti-PKC or temozolomide alone. This difference was most pronounced in noncontrast-enhancing lesions between the mid- and posttreatment scans, where the anti-PKC group demonstrated a 36% median increase in volume, and the anti-VEGF group demonstrated a 42% median decrease.

"From these data, we concluded that anti-VEGF therapy may decrease tumor edema more effectively than anti-PKC therapy," said Dr. Jalilian.

In the analysis of apparent diffusion coefficient values, imaging showed that they remained unchanged overall with anti-VEGF therapy, but increased with temozolomide alone and with temozolomide plus anti-PKC.

"When [apparent diffusion coefficient] values increase, we believe that this means that water is able to diffuse more easily in brain tissue," explained Dr. Jalilian in correspondence with Medscape Medical News. "This occurs in chemotherapy and radiation therapy because these therapies affect normal tissue architecture; . . . they kind of break down the normal tissue architecture."

The fact that apparent diffusion coefficient values remained unchanged in patients treated with anti-VEGF therapy "means that possibly the tissue architecture is not breaking down as much during the radiation therapy . . . and that possibly the anti-VEGF treatment is helping out in a sense," she said.

"Clinically, if this is the case, maybe — maybe — you could theoretically administer even higher doses of radiation to a brain tumor patient and not see tissue damage. This is one theoretical advantage of using an anti-VEGF drug, although no one has really looked into this yet."

With the growing paradigm shift toward administering concurrent antiangiogenic therapy with chemoradiation, these findings underscore the importance of tailoring diffusion-weighted imaging monitoring of treatment response according to specific antiangiogenic agents, said Dr. Jalilian. "The specific antiangiogenic agent that is used should be considered when interpreting imaging responses."

Although serial scanning is not currently available to monitor response to treatment for individual patients, the findings offer important insight into the differences that might be expected from different treatments, said Meng Law, MD, professor of radiology and neurosurgery, and director of neuroradiology at the Keck School of Medicine, University of Southern California in Los Angeles, who was comoderator of the session.

In addition, information about how different treatments affect tumor growth will become increasingly important on an individual level, he said.

"I think that's kind of where we're headed in so-called 'personalized medicine,' where each person responds individually to different drug regimens. Having these very early results should influence what happens next to further therapy," Dr. Law stated.

Dr. Jalilian and Dr. Law declared have disclosed no relevant financial relationships.

International Society for Magnetic Resonance in Medicine (ISMRM) 19th Annual Meeting and Exhibition: Abstract 249. Presented May 10, 2011.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.