Hippocampal avoidance during whole-brain radiotherapy reduces cognitive toxicity risk
Click Here to Manage Email Alerts
Hippocampal avoidance during whole-brain radiotherapy with memantine for brain metastases appeared to better preserve cognitive function and improve patient-reported outcomes, according to results of a randomized phase 3 study published in Journal of Clinical Oncology.
Researchers observed no difference in intracranial PFS and OS with hippocampal avoidance whole-brain radiotherapy (HA-WBRT) vs. standard WBRT, each with memantine.
“[This trial] provides physicians with the information needed to offer patients a safer alternative to standard whole-brain radiotherapy,” Paul D. Brown, MD, radiation oncologist at Mayo Clinic, said in a press release. “Hippocampal avoidance whole-brain radiotherapy with memantine should be a standard of care that providers offer to patients with brain metastases who are seeking whole-brain radiotherapy.”
WBRT has long been an important treatment for patients with brain metastases due to its ability to palliate symptoms, improve intracranial control and reduce risk for death from neurologic causes. Cognitive deterioration after therapy, however, has prompted concerns about WBRT toxicity.
Brown and colleagues sought to determine if a more targeted approach using intensity-modulated radiotherapy would decrease toxicity without affecting clinical outcomes. The researchers randomly assigned 518 patients (median age, 61.5 years; range, 20-91) with brain metastases to either HA-WBRT with memantine (n = 261) or WBRT with memantine (n = 256)
Time to cognitive function failure, defined as decline using the reliable change index on at least one of a series of cognitive tests, served as the primary endpoint.
OS, intracranial PFS, toxicity and patient-reported symptom burden served as secondary endpoints.
Median follow-up was 7.9 months.
Results showed significantly lower risk for cognitive failure among patients in the HA-WBRT group compared with those in the WBRT group (adjusted HR = 0.74; 95% CI, 0.58-0.95).
The difference reflected less deterioration in executive function at 4 months in the HA-WBRT group (23.3% vs. 40.4%; P = .01), as well as less deterioration in learning (11.5% vs. 24.7%; P = .049) and memory (16.3% vs. 33.3%; P = .02) at 6 months.
Researchers observed no significant differences in OS, intracranial PFS or toxicity.
At 6 months, patients in the HA-WBRT group reported less fatigue (P = .04), less difficulty remembering things (P = .01) and less difficulty speaking (P = .049), according to all data, and less interference of neurologic symptoms in daily activities (P = .008) and fewer cognitive symptoms (P = .01), according to inputed data, compared with those in the WBRT group.
“Hippocampal avoidance during whole-brain radiotherapy in this trial leads to a 26% relative reduction in cognitive toxicity risk following treatment,” Vinai Gondi, MD, director of research and education at Northwestern Medicine Chicago Proton Center and co-director of the brain tumor center at Northwestern Medicine Cancer Center Warrenville, said in a press release. “This is the first definitive and most important clinical evidence that the hippocampus is important in determining the negative effects that radiotherapy can have on cognitive function.”
These results should be a welcome practice-changing update, especially considering the known harms of WBRT and the large number of patients who receive this treatment every year, Joseph P. Weiner, MD, radiation oncologist at Rutgers Cancer Institute of New Jersey, wrote in an accompanying editorial.
“Additional future trials are needed to expand on HA in other situations, such as partial brain irradiation for the treatment of primary benign neoplasm or the utility of hippocampal dosing for patients who undergo radiosurgery,” Weiner wrote. “Although the results of the current study indicate a reduction of neurocognitive toxicity from WBRT, there is still detriment to patients who undergo this treatment. Recent reports have questioned the benet of WBRT compared with best supportive care, and additional research is needed to assess whether select patients can completely avoid WBRT.” – by John DeRosier
Disclosures: Brown reports honoraria from UpToDate. Gondi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Weiner reports no relevant financial disclosures.
Collapse
Brown PD, et al. J Clin Oncol. 2020;doi:10.1200/JCO.19.02767.
Weiner JP. J Clin Oncol. 2020;doi:10.1200/JCO.19.03359.
Read more about
Click Here to Manage Email Alerts