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A genetically modified poliovirus can help some patients fight off a deadly form of brain cancer, researchers say.
The experimental treatment appears to have prolonged survival in a small group of patients with glioblastoma who faced a poor prognosis, as standard treatments had failed, according to researchers at Duke University.
"I've been doing this for 50 years and I've never seen results like this," says Dr. Darell Bigner, Emeritus Director of Preston's Robert Tisch Brain Tumor Center at the Duke Cancer Institute, which helps to develop the treatment.
But researchers and other brain cancer doctors warn that research is at a very early stage. In the study, only 21 percent of patients experienced prolonged survival. Much more follow-up research is needed to better evaluate and, hopefully, improve the effectiveness of treatment, say the researchers.
"We have to be careful," says Annick Desjardins, a neuro-oncologist from Duke who helped lead the study. "But we have long-term survivors, we see something we do not normally see with glioblastoma patients."
Dr. David Reardon, Clinical Director of the Neuro-Oncology Center at Boston's Dana-Farber Cancer Institute, says Duke's group results could be "a significant and solid step forward" for non-alternative patients.
"Unfortunately, for most patients, this will not be the answer yet," says Reardon, who worked at Duke but was not involved in the new research. "I fear that all patients and families who have devastating glioblastoma disease believe that poliovirus is the cure, unfortunately the patients who benefit from it reflect a relatively small percentage of the population.
Duke's results were published online Tuesday by the New England Journal of Medicine coincide with their presentation at the 22nd International Conference on Brain Tumor Research in Norway.
Glioblastoma is the most common and most aggressive malignant brain tumor in adults. It's the cancer that killed former Senator Edward Kennedy, D-Mass., And the former son of Vice President Joe Biden, Beau. Senator John McCain, R-Ariz., Fights glioblastoma.
Duke researchers decided to try to use a genetically modified version of the poliovirus, which can cause a devastating form of paralysis, because of the virus's ability to infect cells of the nervous system.
Scientists have removed one of the virus's genes to prevent it from causing polio and have replaced this gene with a virus from a harmless virus known as rhinovirus, which normally causes colds .
The modified virus was then injected directly into patients' brain tumors with a tube inserted through a hole in their skull. The modified virus retains the ability to infect and kill tumor cells in the brain, and also appears to trigger the patient's own immune system cells to attack tumors, say the researchers.
Between 2012 and 2017, the researchers treated 61 patients, testing various doses of the modified virus to determine which was the safest and most effective.
There are significant risks. The treatment can cause dangerous swelling in the brain that can lead to seizures and other complications, the researchers found. A patient suffered from a potentially fatal blood clot in the brain that required surgery.
But overall, the median survival time was 12.5 months for patients treated with poliovirus, compared with 11.3 months for a similar group of patients treated in the past, the researchers report. And from two years after treatment, the survival rate of both groups began to diverge, according to the researchers.
After 24 months, 21% of patients treated with the virus survived, compared to 14% of the historical comparison group. After three years, 21 percent of patients treated with poliovirus survived, compared with 4 percent of the other group, according to the researchers.
Two patients have survived for more than six years, says Bigner. One has survived more than five years.
"You simply do not see that percentage of long-term survivors with this disease," says Bigner. "Those who have survived for more than two years are in remission, and we expect them to continue to be long-term survivors."
Other researchers have praised the results.
"We are extraordinarily encouraged by what we see with these data," says Mitchel Berger, president of neurosurgery at the University of California at San Francisco and director of his center for brain tumors. "It's phenomenal."
But some cancer doctors warn against comparing results for patients receiving viral treatment to what would have happened to similar patients in the past, which could lead to misleading conclusions.
Duke researchers began a follow-up study combining treatment with a chemotherapy drug to try to improve the results. They also plan to combine treatment with other drugs, including some called checkpoint inhibitors, to harness the immune system to fight cancer.
In addition, researchers plan to try the approach on children with brain cancer, as well as other types of cancer, including melanoma and breast cancer. "We think we will be able to increase the results even more significantly," says Bigner.
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