Imaging studies may predict tumor response to anti-angiogenic drugs

November 4, 2013, Massachusetts General Hospital

Advanced imaging techniques may be able to distinguish which patients' tumors will respond to treatment with anti-angiogenic drugs and which will not. In patients newly diagnosed with the dangerous brain tumor glioblastoma, Massachusetts General Hospital (MGH) researchers report, those for whom treatment with the anti-angiogenic drug cediranib 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. The report appears in PNAS Early Edition.

"Two recent phase III trials of another anti-angiogenic drug, bevacizumab, showed no improvement in overall survival for 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 normalization of vasculature appears to be the way that anti-angiogenic drugs enhance the activity of chemotherapy and 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' 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 and the oxygen that is required for effective radiation therapy. This hypothesis was first proposed and has subsequently been developed by Rakesh 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 normalize tumor vasculature in recurrent glioblastoma, but it was not clear what role normalization 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 tumors of some patients with .

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 VAI and other MR imaging techniques. While all but one of the participants in the overall trial showed some evidence of vascular normalization and reduced edema – tissue swelling that 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 ended up surviving 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 anti-angiogenics," 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 MR imaging techniques should play an essential role in future studies of anti-angiogenic drugs in glioblastoma and possibly other types of solid tumors. We've received National Cancer Institute funding to study this approach with bevacizumab treatment, and we will also be investigating tumor delivery of chemotherapy and oxygen status using combined MR/PET techniques at the Martinos Center's MR/PET facility."

Jain adds, "We originally introduced the normalization hypothesis for anti-angiogenic in 2001, but it's taken more than a decade to confirm that vascular normalization actually increases tumor perfusion and that increased perfusion, rather than tumor starvation, is what improves survival. This study provides compelling evidence that normalization-induced increased vessel is the mechanism of benefit in glioblastoma ." Jain is the Cook Professor of Radiation Oncology (Tumor Biology), and Batchelor is the Armenise-Harvard Professor of Neurology at Harvard Medical School.

Explore further: New MR analysis technique reveals brain tumor response to anti-angiogenesis therapy

More information: Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation, www.pnas.org/cgi/doi/10.1073/pnas.1318022110

Related Stories

New MR analysis technique reveals brain tumor response to anti-angiogenesis therapy

August 18, 2013
A new way of analyzing data acquired in MR imaging appears to be able to identify whether or not tumors are responding to anti-angiogenesis therapy, information that can help physicians determine the most appropriate treatments ...

Angiogenesis inhibitor improves brain tumor survival by reducing edema

March 30, 2009
The beneficial effects of anti-angiogenesis drugs in the treatment of the deadly brain tumors called glioblastomas appear to result primarily from reduction of edema - the swelling of brain tissue - and not from any direct ...

Blood-pressure drug may help improve cancer treatment

October 1, 2013
Use of existing, well-established hypertension drugs could improve the outcome of cancer chemotherapy by opening up collapsed blood vessels in solid tumors. In their report in the online journal Nature Communications, Massachusetts ...

Biological therapy with cediranib improves survival in women with recurrent ovarian cancer

September 30, 2013
Women with ovarian cancer that has recurred after chemotherapy have survived for longer after treatment with a biological therapy called cediranib, according to new results to be presented today (Monday) at the 2013 European ...

Brain cancer survival improved following FDA approval of bevacizumab, study finds

August 19, 2013
A new population-based study has found that patients with glioblastoma who died in 2010, after the Food and Drug Administration (FDA) approval of bevacizumab, had lived significantly longer than patients who died of the disease ...

Combination treatment may improve survival of breast cancer patients with brain metastases

November 1, 2012
Adding an angiogenesis inhibitor to treatment with a HER2-inhibiting drug could improve outcomes for patients with HER2-positive breast cancer who develop brain metastases. In their report published online in PNAS Plus, Massachusetts ...

Recommended for you

Researchers artificially generate immune cells integral to creating cancer vaccines

August 14, 2018
For the first time, Mount Sinai researchers have identified a way to make large numbers of immune cells that can help prevent cancer reoccurrence, according to a study published in August in Cell Reports.

Chemicals found in vegetables prevent colon cancer in mice

August 14, 2018
Chemicals produced by vegetables such as kale, cabbage and broccoli could help to maintain a healthy gut and prevent colon cancer, a new study from the Francis Crick Institute shows.

Ovarian cancer genetics unravelled

August 14, 2018
Patterns of genetic mutation in ovarian cancer are helping make sense of the disease, and could be used to personalise treatment in future.

Lymphatic vessels unexpectedly promote the spread of cancer metastases

August 14, 2018
Lymphatic vessels actively contribute to the spread of cancer metastases from various organs. This unexpected realisation is the result of a joint study by researchers from ETH Zurich and the University Hospital Zurich as ...

Stress hormone is key factor in failure of immune system to prevent leukemia

August 14, 2018
The human stress hormone cortisol has been identified by scientists at the University of Kent as a key factor when the immune system fails to prevent leukemia taking hold.

Medically underserved women in the Southeast rarely receive BRCA tests

August 14, 2018
Medically underserved women in the Southeast diagnosed with breast cancer or ovarian cancer missed out on genetic testing that could have helped them and their relatives make important decisions about their health, according ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.