Is the human brain elastic enough to recover from the side effects of radiation treatment for brain tumors?
Scientists have long thought the brain is permanently damaged when the radiation that kills brain tumors also damages nearby healthy brain cells. It has been acknowledged by medical professionals that patients suffer permanent cognitive and psychological problems as a result.
However, researchers in a new Johns Hopkins University School of Medicine study appearing in the journal Stem Cells. say they believe they’ve uncovered possibilities for replacing the cells and restoring patients’ former capabilities. They are optimistic after studying the effects of radiation on the subventricular zone (SVZ), the main producer of stem or precursor nerve cells involved in brain repair, of young male mice.
A small animal radiation research platform, which simulates the focused radiation used to treat human tumors, delivered the radiation. Some weeks after radiating the mice, the researchers intentionally damaged their myelin sheath — the protective covering of nerves in the brains of mice and humans — with an injury similar to that found in multiple sclerosis patients.
Afterward, the mice reactivated cells that remained in their SVZs after radiation, plus generated new stem cells that appeared to migrate to the injured myelin to begin repair work. Oligodendrocytes, the cells that form myelin, were found at the damaged sites. The SVZs also repopulated within a year.
Dr. Alfredo Quiñones-Hinojosa, professor of neurosurgery at the Johns Hopkins University School of Medicine and co-author of the study, said in a statement, “These mice have brain damage, but that doesn’t mean it’s irreparable. The brain has some innate capabilities to regenerate, and we hope there is a way to take advantage of them.” He went on to say, “If we can let loose this potential in humans, we may be able to help them recover from radiation therapy, strokes, brain trauma, you name it.”
On the down side, Quiñones-Hinojosa said, the radiation resistance of cells in the SVZ may also explain why glioblastoma, the most lethal and aggressive form of brain cancer, is so difficult to treat with radiation.
Dr. Steven Brem, professor and co-director of the Penn Brain Tumor Center at the University of Pennsylvania, said during a recent interview that the study uses good science and focuses on a hot topic — neurocognitive repair. He said 130 brain tumors have been classified by the World Health Organization, and while the causes of these brain tumors remain unclear, the long-term survival rates after treatment have improved.
So a growing concern is the quality of patients’ lives after treatment: Brem said, “It’s true that many patients get radiation and their tumors get controlled, and they live normal lives. And they’re OK and they’re happy, and they’re crying and they’re grateful for the wonderful care they’re getting at the hospital. But, they’re forgetting where they parked their car.”
Brem added that his colleague, Dr. Christina Meyers, co-authored a study in the Journal of Clinical Oncology showing that 35 percent of patients had a significant decline in neurocognitive functioning when treated with whole-brain radiation therapy for metastatic brain cancer.
Besides whole-brain radiation, tumors are treated with more focused radiation therapies, such as proton beam and stereotactic radiation. Brem said focused radiation causes far fewer problems, albeit “not a complete elimination.”
Other standard brain tumor treatments are surgery and chemotherapy.
The next challenge is whether the study’s results can be replicated in people. Brem noted that “there’s hundreds of therapies that work for stroke and spinal cord injury and head injury and brain tumors in mice” but are not applicable to humans.
Other promising findings in Brem’s own research focus on new drugs and vaccines. Brem says he believes these medications will be used in combination with radiation therapy, not replace it. “Radiation works.”
Dr. Peter Le Roux, co-director of the Brain and Spine Center at Lankenau Medical Center, stressed that the study’s findings are preliminary. While the cells in the SVZ of mice replicated and migrated after radiation, it’s still unknown if the oligodendrocytes at the damaged sites could actually form new myelin. Previous research has shown that stem cells may look like replacements, “but they don’t make the correct fiber growths and integrate with the other cells.”
Le Roux said scientists discovered that the human brain could generate new cells only about 30 years ago. According to the National Institute of Neurological Disorders and Stroke website, some neurosurgeons still believe the development of new nerve cells is an unproven theory. When deciding which type of radiation to give a patient, doctors take into account the size, shape and location of a tumor, plus the age and health of the patient. Asked about cognitive side effects, Le Roux replied, if the correct protocols are followed, most people in their “20s, 30s, 40s, 50s, if you radiate them, they’re going to tolerate it. You’re not going to find something noticeable unless you go really searching for it.”
While there’s much ongoing research, Le Roux said, there’d be more advances in the treatment of brain tumors and trauma if researchers received more funding. Jason Westenberger, 29, is on the planning committee of the Brain Tumor Society’s Race for Hope in Philadelphia. He said most of the race’s money goes toward research. Westenberger began fundraising seven years ago when his cousin, Marty, was diagnosed with a deadly glioblastoma multiforme brain tumor at the age of 18. Marty died a year later. Westenberger added, “Little did I know I would be fighting for my life to be up there at the race in 2010.”
In 2010, Westenberger was diagnosed with a craniopharyngioma brain tumor, a benign yet aggressive tumor found near the pituitary gland. The tumor was treated with surgery and stereotactic radiation because it had calcified around his pituitary gland and stalk. His surgeon feared that if he removed the calcification surgically, he might cut Westenberger’s pituitary stalk and his memory would be gone.
The radiation worked. And today Westenberger has his mind set on what he has to do to make sure the Race for Hope proceeds.
For more information about Race for Hope, go to www.braintumorcommunity.org .
Lynne Blumberg is a freelance writer who lives and tries to stay healthy in Philadelphia. This article appeared originally in the special section, "Fighting Cancer."