Long-Term Quality-of-Life and Cognition Outcomes in Patients Receiving SRS vs WBRT for Resected Brain Metastasis

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In an analysis from a Canadian/U.S. phase III trial (Alliance N107C/CEC.3) reported in JAMA Oncology, Palmer et al found that use of stereotactic radiosurgery (SRS) vs whole-brain radiotherapy (WBRT) among patients who had undergone resection of one brain metastasis was associated with better cognitive function and quality of life among those surviving > 1 year; WBRT was associated with better intracranial disease control. 

Study Details

The study population consisted of patients with one to four brain metastases who had undergone resection of one metastasis and were randomly assigned to undergo SRS or WBRT. Patients in the WBRT group received SRS for unresected metastases. As stated by the investigators, the previously reported findings of the trial “suggest that use of SRS in patients with limited brain metastasis after surgical resection provide acceptable local tumor control with less cognitive decline compared with WBRT.”

The current analysis included 27 patients who received SRS alone and 27 who received WBRT who were evaluable and remained alive at > 1 year from random assignment. Patients were assessed for cognitive function; quality of life; and intracranial tumor control at 3, 6, 9, and 12 months.

Key Findings

Proportions of patients with cognitive deterioration in the SRS group vs the WBRT group were 37% vs 89% at 3 months, 46% vs 89% at 6 months, 48% vs 81% at 9 months, and 62.5% vs 91% at 12 months.

A decline of at least two standard deviations (SDs) in one or more cognitive test(s) was observed in 22% of patients in the SRS group vs 70% of the WBRT group at 3 months, 19% vs 46% at 6 months, and 20% vs 50% at 9 months.

Among all patients, a two-SD decline in at least two cognitive tests was associated with worse 12-month quality of life scores in emotional well-being, functional well-being, general, additional concerns, and total scores.

Overall quality of life and functional independence favored SRS for categorical change at all time points. However, improvements over time in the quality-of-life domains of physical well-being, social and emotional well-being, fatigue, and functional well-being were observed in the WBRT group.

Proportions of patients with total intracranial control in the SRS group vs WBRT group were 88.9% vs 100%, 70.4% vs 92.6%, and 40.7% vs 81.5% at 3, 6, and 12 months (overall P = .003).

The investigators concluded, “In the current study, cognitive function and quality of life following radiotherapy for brain metastasis in long-term survivors was generally superior in the SRS arm compared with the WBRT arm…. The association of late cognitive deterioration with WBRT was clinically meaningful. A significant decline in cognition (two SD) was associated with overall quality of life. However, intracranial tumor control was improved with WBRT. This study provides detailed insight into cognitive function over time in this patient population.”

Joshua D. Palmer, MD, of The James Cancer Center at The Ohio State University, Columbus, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit

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