Interim report of the JROSG99-1 multi-institutional randomized trial, comparing radiosurgery alone vs. radiosurgery plus whole brain irradiation for 1-4 brain metastases.

1506 Background: Stereotactic radiosurgery (SRS) is effective treatment for brain metastases when the number is 4 or less, however the role of upfront whole brain irradiation (WBI) combined with SRS has not been well known. METHODS Eligibility criteria include pathologically confirmed systemic cancer, number of brain metastases 4 or less, and size of brain metastases 3 cm or less. Patients were randomly assigned to either SRS alone arm or SRS+WBI arm after the stratification according to the primary tumor site (lung vs. others), extracranial tumor status (active vs. inactive), and number of brain metastases (1 vs. 2-4). Primary endpoint is survival rate. Secondary endpoint includes cause of death, free from new brain metastases rate, KPS preservation (≥ 70%) rate, local tumor control, and late radiation morbidity (RTOG score). Results were analyzed according to the intention-to-treat basis. RESULTS The planned accrual number of each arm was 85 patients. The reported accrual number for this interim analysis was 61 patients in SRS alone arm and 59 patients in SRS+WBI arm. The median follow-up duration was 6 months (range, 1-40). The mean marginal radiation dose of radiosurgery was 21.8 Gy in SRS alone arm and 16.6 Gy in SRS+WBI arm. The schedule of WBI was 30 Gy in 10 fractions. The actuarial 1-year survival rate was 26% in SRS alone arm and 39% in SRS+WBI arm(log-rank, p=0.58).Death was attributed to neurologic causes in 9 patients in SRS arm and 6 patients in WBI+SRS arm(χ-square, p=0.48). Actuarial 1-year KPS-preservation (KPS ≥ 70%) rate were 25% in SRS alone arm and 37% in WBI+SRS arm(log-rank, p=0.54). Actuarial 6-months free from new brain metastases rate was 49% in SRS alone arm and 82% in SRS+WBI arm(log-rank, p=0.003). Actuarial 1-year local tumor control rate was 70% in SRS alone arm and 88% in SRS+WBI arm(log-rank, p=0.019). Grade 3,4 late radiation morbidity was observed in 1 patient in each arm. CONCLUSIONS Although survival benefit was not confirmed, the use of upfront WBI combined with SRS is superior to SRS alone regarding the free from new brain metastases rate and local tumor control rate. No significant financial relationships to disclose.