Stereotactic Radiosurgery vs Whole-Brain Radiotherapy for Resected Metastatic Brain Disease


Key Points

  • In patients with resected brain metastasis, stereotactic radiosurgery survival vs whole-brain radiotherapy was associated with a reduced risk of cognitive impairment.
  • There was no difference between the two treatments in terms of overall survival.

In the phase III NCCTG N107C/CEC.3 trial, stereotactic radiosurgery to the surgical cavity reduced cognitive deterioration and was associated with similar overall survival vs whole-brain radiotherapy in patients with resected brain metastasis. These results were reported by Brown et al in The Lancet Oncology.

Study Details

In the open-label trial, 194 adult patients from 48 sites in the United States and Canada were randomized between November 2011 and November 2015 to receive postoperative stereotactic radiosurgery at 12 to 20 Gy in a single fraction, with the dose determined by surgical cavity volume (n = 98), or whole-brain radiotherapy at 30 Gy in 10 daily fractions or 37.5 Gy in 15 daily fractions of 2.5 Gy (n = 96). Patients had to have one resected brain metastasis and a resection cavity < 5.0 cm in maximal extent.

Randomization was stratified by age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment center. The co-primary endpoints were cognitive deterioration–free survival and overall survival in the intention-to-treat population. Cognitive deterioration was defined as a decrease > 1 standard deviation from baseline in ≥ 1 of 6 well-established standardized cognitive tests.

Cognitive Deterioration and Overall Survival

Median follow-up was 11.1 months. Median cognitive deterioration–free survival was 3.7 months in the stereotactic radiosurgery group vs 3.0 months in the whole-brain radiotherapy group (hazard ratio [HR] = 0.47, P < .0001). The incidence of cognitive deterioration at 6 months was 52% among 54 evaluable patients vs 85% among 48 evaluable patients (P < .00031). Median overall survival was 12.2 months vs 11.6 months (HR = 1.07, P = .70).

Adverse Events

Grade ≥ 3 adverse events that were considered related to treatment occurred in 12% of the stereotactic radiosurgery group and 18% of the whole-brain radiotherapy group. The most common were fatigue (2%) and dyspnea (2%) in the stereotactic radiosurgery group and cognitive disturbance (5%), hearing impairment (4%), dehydration (3%), and nausea (2%) in the whole-brain radiotherapy group.

The investigators concluded: “Decline in cognitive function was more frequent with [whole-brain radiotherapy] than with [stereotactic radiosurgery], and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, [stereotactic radiosurgery] should be considered one of the standards of care as a less toxic alternative to [whole-brain radiotherapy] for this patient population.”

The study was funded by the National Cancer Institute.

Paul D. Brown, MD, of the Department of Radiation Oncology, Mayo Clinic, Rochester, is the corresponding author of The Lancet Oncology article.

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