Repeated brain radiation no safer than 1-dose therapy

man receives radiation therapy

Repeated radiation therapy used to target brain tumors may not be as safe for healthy cells as previously assumed.

A new study shows the treatment can kill important support cells in the brain and may cause as much, if not more damage, than single-dose radiation therapy.

“This study suggests that conventional repeated radiation treatments offer no significant benefit to brain tumor patients,” says Kerry O’Banion, professor of neuroscience at the University of Rochester Medical Center. “It also shows that certain cell populations in the brain are vulnerable to radiation and this may help explain why so many brain cancer patients experience cognitive problems after treatment.”

Radiation therapy is used to treat cancerous tumors in the brain and elsewhere in the body because of its ability to control cell growth. It works by damaging the DNA of cancerous tissue, a process that ultimately leads to cellular death.  Rapidly dividing cancer cells are particularly vulnerable to radiation therapy.

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In order to spare the healthy tissue the radiation beam passes through on its way to the tumor, physicians use shaped beams that are aimed from several angles and intersect at the tumor. This approach delivers the highest dose to the tumor while limiting radiation exposure to other cells.

The radiation is also typically delivered in a series of modest doses—a process called fractionation—over a period of several weeks or months, an approach that is believed to be more effective in sparing healthy cells from damage than applying the radiation in a single large dose.

While many of the cells found in the adult brain, most notably neurons, do not have the capacity to self-renew, the brain is also home to a population of cells that continue to divide and grow.  Specifically a cell called the oligodendrocyte progenitor (OPC), which is responsible for producing myelin, the fatty tissue that insulates the connections between nerve cells and is critical for the conduction of signals between cells in the central nervous system.

Rethink protocols

Because these cells continue to divide, even in the adult brain, OPCs are susceptible to the same mechanism that radiation employs to kill cancer cells.

For the study, published in the International Journal of Radiation Oncology, Biology, Physics, researchers conducted a series of experiments with mice.

The animals received modest doses of radiation in their brains over a period of time. The researchers observed that the initial doses of radiation killed off some of the OPCs. However, when this occurred, the surviving OPCs became more active, essentially trying to make up for the loss of the other cells. This in turn made the remaining OPC cells even more vulnerable to subsequent doses of radiation, killing them off in larger numbers.

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When OPCs are destroyed the brain losses the ability to maintain and refresh its supply of myelin, or white matter, which was observed in the mice during the experiments. This impairs the ability of neurons to effectively communicate with each other, leading to cognitive dysfunction.

“These studies indicate that reducing the volume of the brain exposed to radiation is necessary to minimize white matter damage and the need to potentially revisit protocols for delivering radiation therapy in the brain,” says Jacqueline Williams, professor of environmental medicine and radiation oncology.

The University of Rochester, the National Institute of Allergy and Infectious Diseases, the Toxicology Training Program, and the Schmitt Program in Integrative Neuroscience funded the work.

Source: University of Rochester

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