For decades, a deadly type of childhood cancer has eluded the best tools of science. Now doctors have made progress with an unusual treatment: Dripping millions of copies of the virus directly into children's brains to infect their tumors and stimulate an attack by the immune system.
A dozen children treated this way lived more than twice as long as similar patients in the past, doctors reported Saturday at the American Association for Cancer Research Conference and in the New England Journal of Medicine.
Although most of them eventually died of the disease, some of them are alive and well a few years after treatment - something virtually unheard of in this situation.
"This is the first step, a critical step," said study leader Dr. Gregory Friedman, a childhood cancer specialist at the University of Alabama at Birmingham.
"Our goal is to improve this," perhaps by trying it when patients are first diagnosed or by combining it with other treatments to boost the immune system, he said. Patients in the study received an experimental approach after they failed other treatments.
The study involved gliomas, which account for 8% to 10% of brain tumors in children. They are usually treated with surgery, chemotherapy, or radiation, but they often recur. Once they do, survival averages just under six months.
In such cases, the immune system lost its ability to recognize and attack cancer, so scientists were looking for ways to make the tumor a fresh target. They turned to the herpes virus, which causes herpes and spurs a strong immune system response. A suburban Philadelphia company called Treovir has developed a treatment by genetically modifying the virus so that it infects only cancer cells.
Through tiny tubes inserted into the tumors, doctors gave the altered virus to 12 patients, ages 7 to 18, whose cancer worsened after routine treatment. Half also received a single dose of radiation, which is believed to help spread the virus.
Eleven showed evidence in tests of images or tissue samples that the treatment worked. The median survival was just over a year, more than twice as long as seen in the past. As of last June-a a cut-off for analyzing these results – four were still alive at least 18 months after treatment.
The tests also showed high levels of specialized immune system cells in their tumors, suggesting that the treatment recruited the help needed from the body to attack the disease.
No major safety concerns were observed, although there were several procedure-related complications and mild side effects, including nausea, vomiting, diarrhea, and fatigue.
Jake Koestler received treatment when he was 12.
"Everything went very well. He lived for a year and four months after that, "long enough to celebrate his bar mitzvahs, go with his family to Hawaii and see his brother be born," said his father, Josh Koestler, a financial services executive from Livingston, New Jersey.
Jake died on April 11, 2019, but "we have no regrets whatsoever" about attempting treatment, said Koestler, who with his wife founded a foundation, Trail Blazers for Children, for further research.
"This is a devastating disease for these patients and their families," and early results show that treating the virus helps, but they need to be tested in a larger study that doctors are planning, said Dr. Anthony Ribas, a cancer specialist at the University of California, Los Angeles, and president of the conference group.
Friedman said research is continuing in adults as well, and plans are in the works for other types of childhood brain tumors. U.S. government grants and several foundations paid for the study, and several doctors have financial ties to Treovir.
Only one similar viral therapy is currently approved in the United States-Imlygic, also a modified herpes virus, for the treatment of melanoma, the most serious type of skin cancer.