Full Cognitive Recovery After Brain RT Possible for Many

About 40% of patients with brain metastases who experienced cognitive decline after brain radiation therapy regained full cognitive function within 6 months following treatment, a new analysis found. 

Barring full cognitive recovery, roughly three quarters of patients showed improvement on at least one cognitive test, even if they initially failed that test after radiation, according to research presented at the American Society for Radiation Oncology (ASTRO) 2024 annual meeting. 

The findings underscore that neurocognitive decline after brain radiation is “not necessarily permanent,” lead researcher Hua-Ren Cherng, MD, with University of Maryland Medical Center, Baltimore, said during a presentation at the meeting. 

The study also found that patients were more likely to recover from these cognitive side effects if they received highly targeted radiation treatments, such as stereotactic radiosurgery and hippocampal-sparing methods, vs conventional whole-brain radiation. 

“This analysis has the potential to impact how we council our patients on the expectation of long-term impact of our therapies, something that is increasingly meaningful as our patients with brain metastasis live longer,” Stephanie E. Weiss, MD, chief of the Division of Neurologic Oncology, Fox Chase Cancer Center, Philadelphia, who wasn’t involved in the study, told Medscape Medical News. 

Top Concern: Will My Brain Recover? 

About 200,000 patients with cancer are diagnosed with brain metastases annually in the US. Neurocognitive changes following brain radiation therapy remain significant concerns for these patients, especially those receiving whole-brain radiation therapy (WBRT). 

Despite reductions in rates of neurocognitive failure with more targeted radiation techniques, including stereotactic radiosurgery and hippocampal-avoidance WBRT, a significant number of patients still experience neurocognitive issues following radiation therapy. However, data are lacking on the potential for cognitive recovery in these patients. 

To investigate, Cherng and colleagues conducted a pooled analysis of three large phase 3 randomized controlled trials that compared WBRT vs different types of conformal radiation techniques in patients with brain metastases. 

Cognitive outcomes were the primary endpoint in all three trials. Two of the trials compared WBRT vs stereotactic radiosurgery, and the third compared standard WBRT vs hippocampal-avoidance WBRT.

Analyses focused on 288 patients who experienced neurocognitive failure, defined as a 1–standard deviation decrease from baseline in at least one of six cognitive tests. 

Full cognitive recovery was defined as no longer exhibiting neurocognitive failure on any cognitive test, whereas recovery on individual tests was defined as at least a 1–standard deviation improvement on a previously failed cognitive test.

Of the 288 patients with cognitive decline after brain radiation, 38% fully recovered by 6 months and 42% by 12 months. Among a subset of patients who continued cognitive testing for 2 years following brain radiation, two thirds demonstrated sustained cognitive recovery.

Nearly 80% of patients showed improvement on at least one previously failed cognitive test, Cherng noted. 

The likelihood of full cognitive recovery was significantly greater for patients who received more targeted radiation techniques. 

The cumulative incidence of full cognitive recovery was higher among patients who received stereotactic radiosurgery compared to WBRT (hazard ratio [HR], 2.68) and those who received stereotactic radiosurgery alone compared with stereotactic radiosurgery plus WBRT (HR, 2.35). 

There was a trend toward a significant increase in the cumulative incidence of full cognitive recovery with hippocampal-avoidance WBRT vs WBRT (HR, 1.68; 95% CI, 0.98-2.87). Age, histology, and performance status were not significant predictors of cognitive recovery. 

A meta-analysis of the three trials confirmed that patients who received more targeted therapies “fared a lot better than patients who received traditional whole brain radiation,” Cherng reported. 

These findings may help radiation oncologists counsel patients about their likelihood of meaningful cognitive improvement after brain radiation and underscore that the cognitive impairments experienced following brain radiation are “potentially reversible,” Cherng told attendees. 

Offering perspective on the study, Lia Halasz, MD, chair of the ASTRO CNS Resource Panel, said one of the “truly gratifying” parts of her career has been seeing patients with brain metastases live longer over time. 

“Radiation to the brain has been very important in helping my patients live longer. But understandably, radiation therapy does come with some cognitive decreases, which is very concerning to people,” said Halasz, with Fred Hutchinson Cancer Center, University of Washington, Seattle. 

“We all know as physicians, anecdotally, that a lot of times this does pass, but we didn’t necessarily have the data to know how often it happens, which is why I am excited about this analysis, because it’s something I can bring into my clinic and really help patients understand what they may go through,” she said. 

This study was supported by the National Cancer Institute. Cherng and Weiss have no relevant disclosures.