This is the delicate dance of countless brain cancer surgeries — slicing out enough of the bulky tumor without slashing away healthy tissue. Detecting that fine line is one reason the disease is so tough to conquer, doctors say.
The family of Joseph “Beau” Biden III, son of Vice President Joe Biden, has not yet revealed the specific type of brain cancer that killed the 46-year-old father and Iraq veteran on Saturday. In all, there are more than 120 forms of brain tumors.
This much is known: Biden had a brain lesion removed in 2013 at M.D. Anderson Cancer Center in Houston. And last week, the former attorney general of Delaware was receiving treatment at Walter Reed National Military Medical Center in Bethesda, Maryland, where he died.
The Washington Post further reported that Biden’s brain tumor may have been a glioblastoma. These aggressive masses grow from the star-shaped cells, or astrocytes, that compose the brain’s gluey, supportive tissue.
They represent about 15 percent of all primary brain tumors. And they pose a particularly tricky surgical challenge because glioblastomas usually have finger-like tentacles that creep deeper into the brain, often near sectors that manage our coordination and language, according to the American Brain Tumor Association (ABTA).
For adults with more aggressive glioblastomas who receive chemotherapy and radiation, the median survival is just over 14 months. In all, brain cancers kill nearly 14,000 Americans annually, ABTA reports.
“Glioblastoma patients who have a near complete resection [of the tumor], even if there is microscopic disease, have a significantly better outcome than patients who have an incomplete resection,” said Dr. Jim Olson, a pediatric brain cancer expert at Fred Hutchinson Cancer Research Center.
“But it does seem very important to get the bulky disease out. And part of the reason for that is when there is bulky tumor, the tumor finds ways to protect itself against chemotherapy or radiation therapy,” Olson said.
Lighting up the cancer
Olson’s trailblazing work, however, is providing — literally — a bright dash of hope in this area. He pioneered the concept of targeting tumors with fluorescent dye to help surgeons discern malignant growths from normal tissue.
In 2014, the Food and Drug Administration approved an investigational drug application for Tumor Paint BLZ-100, a molecule discovered and first developed by scientists at Fred Hutch, Seattle Children’s Hospital and the University of Washington.
Now, nine patients have been enrolled at hospitals in Los Angeles and Brisbane, Australia, to test tumor paint in gliomas — a general term used to describe any tumor that starts in the gluey tissue of the brain, including glioblastomas.
“We’re midway through our first brain tumor patient trial in LA and Australia,” Olson said. “My understanding is, so far, the glioblastomas have lit up with the tumor paint and the normal brain has not lit up with the tumor paint. So it’s behaving in patients as we hoped it would.
“The tumor paint is intended to be part of strong, local control of the disease,” Olson said.
Renowned brain cancer researcher and neurosurgeon Dr. Eric Holland is also aiming for better ways to treat brain cancers.
If Biden was diagnosed with a glioblastoma, that tumor type carries several potentially lethal obstacles to successful treatment, said Holland, senior vice president and director of the Human Biology Division at Fred Hutch and director of Solid Tumor Translational Research.
“They cannot be fully removed surgically because they infiltrate the brain,” Holland said. “The [anti-cancer] drugs do not get in very effectively because of the blood-brain barrier. And the tumor cells are inherently very resistant to therapy in the first place.”
'We can ask questions'
But as with Olson’s tumor paint innovations, Holland’s ongoing work is providing hope in this tricky realm. He oversees a genetic and clinical database that will help drive more effective treatments for all tumors, including brain cancers.
Hutch Integrated Data Repository and Archive, or HIDRA, which is currently under construction, will combine clinical records with tumor genetics and molecular data with the aim of eventually helping doctors choose the best targeted treatment.
HIDRA links a patient’s clinical data — personal history, diagnosis, treatment, response to treatment — with his or her tumor’s genetic data, and then integrates it with information from thousands of patients. Ultimately, when someone is diagnosed, a physician will be able to enter the patient’s information and place them in a “neighborhood” of patients with similar characteristics to see which treatments were most effective for others with similar cancers, and determine which treatments were most effective based on these comparisons.
“We can ask questions, like what did we do differently for some patients in this neighborhood that affected their outcome? Eventually, HIDRA will help oncologists make actual decisions about patient care,” said Holland in a previous interview.
Holland is helping direct this effort to combine records from Fred Hutch and its Cancer Consortium partners (UW Medicine, Seattle Children’s and Seattle Cancer Care Alliance) to build a single database to help researchers find these patterns. HIDRA will also collect molecular data from tumors, such as those stored in NWBioTrust’s tissue bank. The first web-based application designed to query and visualize this wealth of data is Argos, which launched in March as a service for Consortium members researching brain, gastrointestinal, head and neck and thoracic cancers, with more tumors sites to come.
Holland, who also directs the Alvord Brain Tumor Center at UW Medicine, said his immediate goal is to help patients’ live longer and better. He hopes the database will help steer oncologists on the best ways to do that. For someone who doesn’t have much time left, even an extra six months can mean a lot.
“We can ask questions and get answers,” he said.
And there is still more hopeful news on this long-stubborn front.
Fred Hutch's Drs. Hans-Peter Kiem and Jennifer Adair are pioneering a gene-therapy-based strategy to allow glioblastoma patients to receive a drug to sensitize their brain tumors to chemotherapy while simultaneously protecting healthy blood cells from chemo's wider toxicity.
In their study, the researchers are providing blood stem cells with a gene that shields them from the chemo. By doing that - and sensitizing the tumor - they were able to achieve more-effective chemotherapy dosing with fewer side effects for patients. They are currently testing this strategy in a clinical trial of glioblastoma patients and are seeing, they say, highly encouraging results.
"This has shown success and promise for glioblastoma," Kiem said. "Our two-year survival rate is significantly better than in historical patients with similar, high-risk features."
Bill Briggs was a former Fred Hutch News Service staff writer as well as a contributing writer for NBCNews.com and TODAY.com. As a staff writer for The Denver Post, he was part of the newspaper's team that earned the Pulitzer Prize for coverage of the Columbine High School massacre. He authored two books, including "The Third Miracle: An Ordinary Man, a Medical Mystery, and a Trial of Faith."
Dr. Sabrina Richards, a staff writer at Fred Hutchinson Cancer Research Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a Ph.D. in immunology from the University of Washington, an M.A. in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her atsrichar2@fredhutch.org.
Solid tumors, such as those of the brain, are the focus of Solid Tumor Translational Research, a network comprised of Fred Hutchinson Cancer Research Center, UW Medicine and Seattle Cancer Care Alliance. STTR is bridging laboratory sciences and patient care to provide the most precise treatment options for patients with solid tumor cancers.
