Surgery Followed by Salvage Stereotactic Radiosurgery vs Whole-Brain Radiotherapy for Four or Fewer Brain Metastases


Key Points

  • Salvage SRS was noninferior to WBRT in overall survival.
  • Intracranial progression-free survival was longer with WBRT.

In a Japanese phase III noninferiority trial (JCOG0504) reported in the Journal of Clinical Oncology, Kayama et al found that salvage stereotactic radiosurgery (SRS) was noninferior to whole brain radiation therapy (WBRT) for survival in patients with 1 to 4 resected brain metastases.

In the trial, 271 patients from 32 sites of the Japan Clinical Oncology Group Brain Tumor Study Group were randomized between January 2006 and May 2014 to undergo salvage SRS (n = 134) or WBRT (n = 137) within 21 days of surgery. Patients had to be aged 20 to 79 years old with an Eastern Cooperative Oncology Group performance status of 0 to 2 (3 if due only to neurologic deficits) and had to have a maximum of 4 surgically resected brain metastases with only 1 lesion > 3 cm in diameter.

Primary tumors were in the lung (~48%) and breast (~20%). The primary endpoint was overall survival.

Overall Survival

Median overall survival was 15.6 months in the SRS group vs 15.6 months in the WBRT group (hazard ratio [HR] = 1.05, 1-sided P for noninferiority = .027). Median intracranial progression-free survival was 10.4 months in the WBRT group vs 4.0 months in the SRS group (HR = 1.91, 95% confidence interval [CI] = 1.46–2.51).

Similar proportions of SRS vs WBRT patients had Mini-Mental Status Examination scores (42.5% vs 45.3%) and performance status scores (46.3% vs 46.0%) that did not worsen at 12 months. At 91 days post enrollment, grade 2 to 4 cognitive dysfunction was observed in 16.4% of patients in the WBRT group vs 7.7% of the SRS group (P = .048).

The investigators concluded, “Salvage SRS is noninferior to WBRT and can be established as a standard therapy for patients with four or fewer [brain metastases].”

The study was supported by grants from the National Cancer Center Research and Development Funds and from the Ministry of Health, Labor, and Welfare of Japan. Takamasa Kayama, MD, of the Department of Advanced Medicine, Yamagata University Faculty of Medicine, is the corresponding author for the Journal of Clinical Oncology article. 

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