As reported in the Journal of Clinical Oncology by Brown et al, the phase III NRG Oncology CC001 trial has shown superior cognitive function outcomes with hippocampal avoidance using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) for the treatment of adult patients with brain metastases.
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In the trial, 518 patients were randomly assigned between July 2015 and March 2018 to receive hippocampal avoidance WBRT plus memantine (n = 261) or WBRT plus memantine (n = 257). Most patients (58%) had primary lung cancer. The primary endpoint was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests used in assessment.
Key Findings
The median follow-up for surviving patients was 7.9 months. Overall, the risk of cognitive failure was significantly lower in the hippocampal avoidance WBRT group vs the WBRT group (adjusted hazard ratio [HR] = 0.74, 95% confidence interval = 0.58–0.95, P = .02). The difference favoring the hippocampal avoidance WBRT group was primarily attributable to reduced deterioration in executive function at 4 months (23.3% vs 40.4%, P = .01) and reduced deterioration in learning (11.5% vs 24.7%, P = .049) and memory (16.4% vs 33.3%, P = .02) at 6 months.
KEY POINTS
- The difference favoring the hippocampal avoidance WBRT group was primarily attributable to reduced deterioration in executive function at 4 months, and reduced deterioration in learning and memory at 6 months.
- At 6 months, the hippocampal avoidance WBRT group reported less fatigue, less difficulty with remembering things, less difficulty with speaking, less interference of neurologic symptoms in daily activities, and fewer cognitive symptoms.
Treatment groups did not differ significantly with regard to overall survival (median = 6.3 vs 7.6 months, HR = 1.13, P = 0.31) and intracranial progression-free survival (median = 5.0 vs 5.3 months, HR = 1.14, P = .21). No significant difference in grade ≥ 3 toxicity was observed (61.7% vs 58.8%, P = .53).
At 6 months, the hippocampal avoidance WBRT group reported less fatigue (P = .04), less difficulty with remembering things (P = .01), less difficulty with speaking (P = .049), less interference of neurologic symptoms in daily activities (P = .008), and fewer cognitive symptoms (P = .01).
The investigators concluded, “Hippocampal avoidance WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial [progression-free survival] and [overall survival], and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the hippocampal avoidance region.”
Paul D. Brown, MD, of the Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
