A Secondary Analysis of The N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group) Randomized Clinical Trial Key Points Question What is the long-term association of brain radiotherapy (whole-brain radiotherapy [WBRT] or stereotactic radiosurgery [SRS]) with quality of life (QOL) and cognition outcomes for patients with limited brain metastasis following surgical resection?
Findings This secondary analysis of a randomized phase 3 clinical trial found that more patients declined in 1 or more cognitive tests by 2 standard deviations (SDs) with WBRT than with SRS at 3, 6, and 9 months. A 2 SD decline in at least 2 cognitive tests was associated with worse QOL.
Meaning Late cognitive effects of WBRT are clinically meaningful and significant, and a significant decline in cognition (2 SD) was associated with worsening overall QOL; this study provides detailed insight into cognitive function over time in this patient population.
Abstract Importance Long-term outcomes of radiotherapy are important in understanding the risks and benefits of therapies for patients with brain metastases.
Design, Setting, and Participants This secondary analysis of a randomized phase 3 clinical trial included 48 institutions in the US and Canada. Adult patients with 1 resected brain metastases but limited to those with 1 to 4 brain metastasis were eligible. Unresected metastases were treated with SRS. Long-term survivors were defined as evaluable patients who lived longer than 1 year from randomization. Patients were recruited between July 2011 and December 2015, and data were first analyzed in February 2017. For the present study, intracranial tumor control, cognitive deterioration, QOL, and cognitive outcomes were measured in evaluable patients who were alive at 12 months from randomization and reanalyzed in June 2017. Interventions Stereotactic radiosurgery or WBRT.
Main Outcomes and Measures Intracranial tumor control, toxic effects, cognitive deterioration, and QOL.
Results Fifty-four patients (27 SRS arm, 27 WBRT arm; female to male ratio, 65% vs 35%) were included for analysis with a median follow-up of 23.8 months. Cognitive deterioration was less frequent with SRS (37%-60%) compared with WBRT (75%-91%) at all time points. More patients declined by 2 or more standard deviations (SDs) in 1 or more cognitive tests for WBRT compared with SRS at 3, 6, and 9 months (70% vs 22%, 46% vs 19%, and 50% vs 20%, respectively). A 2 SD decline in at least 2 cognitive tests was associated with worse 12-month QOL in emotional well-being, functional well-being, general, additional concerns, and total scores. Overall QOL and functional independence favored SRS alone for categorical change at all time points. Total intracranial control for SRS alone vs WBRT at 12 months was 40.7% vs 81.5% (difference, -40.7; 95% CI, -68.1% to -13.4%), respectively. Data were first analyzed in February 2017.
Conclusions and Relevance The use of SRS alone compared with WBRT resulted in less cognitive deterioration among long-term survivors. The association of late cognitive deterioration with WBRT was clinically meaningful. A significant decline in cognition (2 SD) was associated with overall QOL. However, intracranial tumor control was improved with WBRT. This study provides detailed insight into cognitive function over time in this patient population.
Trial Registration ClinicalTrials.gov Identifier: NCT01372774; ALLIANCE/CCTG: N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group)