Preventing Cognitive Decline After Brain Cancer Treatment

Halting the immune response could prevent cognitive decline related to brain cancer treatment, according to recent research from the University of California, San Francisco (UCSF).

The National Cancer Institute estimates that there will be nearly 24,000 new cases of brain cancer diagnosed this year. Radiation is one of the most common and effective treatments for brain cancer, though it could potentially come with severe cognitive impairments down the line.

“Radiation treatment has a significant effect on cognitive function in both children and adults,” study co-author Nalin Gupta, M.D., Ph.D., chief of pediatric neurological surgery at UCSF Benioff Children's Hospital, said.

After realizing that brain irradiation — not necessarily the tumor itself — is the likely culprit of post-treatment cognitive decline, researchers created a mouse model to better understand how to best prevent this effect. They realized that when mice are given an agent to block CSF-1R, a gene that activates the brain’s immune system, before undergoing radiation, they were less likely to experience mental deterioration.

“Pharmacological inhibition of CSF-1R has shown advantages in preventing cranial irradiation-induced cognitive defects in tumor-free models, prolonging survival in glioma-bearing mice and delaying the recurrence of glioma after radiotherapy,” researchers wrote in the study published in the journal eLife.

The researchers tested single-agent and combinations of three different types of treatment in mice with glioma: CSF-1R inhibition, fractioned whole-brain irradiation (fWBI) and diphtheria toxin (DR) receptor treatment.

CSF-1R inhibition alone resulted in no survival improvement, while CSF-1R inhibition plus fWBI showed significantly improved survival over CSF-1R inhibition, but not over fWBI alone. DT alone resulted in a higher survival benefit than fWBI alone, but when the two treatment methods were combined, they resulted in an even higher efficacy of tumor growth inhibition and a 46-day average survival. When all three methods were combined, there was no statistically significant improved survival. One month after treatment, both survival and recognition memory performance were measured.

“However, strikingly, memory deficits were detected only in mice that received fWBI not in non-irradiated tumor-bearing mice,” researchers wrote. “Finally, we demonstrated that CSF-1R inhibitor treatment was able to prevent fWBI-induced memory loss in glioma-bearing animals.”

These findings lay the groundwork for future studies examining how CSF-1R inhibition could prevent cognitive decline. But, there is still a long way to go before this treatment will be used in humans, especially since the mutation combination seen in many of the study mice is rarely seen in people with glioma.

“These differences in genetic and molecular features may affect the inflammatory microenvironment of the tumor, and, in turn, influence cognitive outcomes measured in the study,” researchers wrote. “Further studies using genetically modified mouse glioma models that faithfully recapitulate molecular features in glioma patients would help clarify this concern.”