Background
Phase III, randomized, multicenter RTOG trial. 333 patients with 1–3 newly diagnosed brain metastases randomized to WBRT alone vs WBRT + SRS boost. Enrolled Jan 1996–Jun 2001. Stratified by number of metastases and extracranial disease status. Standard WBRT was 37.5 Gy/15 fractions; SRS boost dose: 15–24 Gy based on lesion size.
Interventions and follow up
Arm A: WBRT 37.5 Gy in 15 fractions + SRS boost (15–24 Gy based on lesion diameter)
Arm B: WBRT 37.5 Gy in 15 fractions alone
Primary endpoint: Overall survival
mFollow up: Not reported (enrollment ended Jun 2001)
Arm B: WBRT 37.5 Gy in 15 fractions alone
Primary endpoint: Overall survival
mFollow up: Not reported (enrollment ended Jun 2001)
Results
OS (single BM): 6.5 vs 4.9 months (WBRT+SRS vs WBRT alone), P=.0393
KPS stability at 6 months: 43% vs 27%, P=.03 (all patients)
OS (2-3 BM): No significant difference
Local control: Improved with SRS boost (HR ~0.5, favorable for SRS group)
KPS stability at 6 months: 43% vs 27%, P=.03 (all patients)
OS (2-3 BM): No significant difference
Local control: Improved with SRS boost (HR ~0.5, favorable for SRS group)
Adverse events
Main adverse events: No significant increase in acute grade ≥3 toxicities with SRS boost. Late necrosis rates not separately reported in primary publication. SRS acute toxicity (headache, nausea) manageable.
Conclusions
Adding an SRS boost to WBRT improved OS for patients with single unresectable brain metastasis (6.5 vs 4.9 months) and improved functional autonomy (KPS) for all patients. No OS benefit was seen for 2-3 BM, though there was a functional benefit. This trial established WBRT+SRS as standard for single unresectable BM.
Key Limitations
Key Limitations: OS benefit in single BM is modest (~1.6 months) and was based on a subset analysis, not a pre-specified primary endpoint for this subgroup. No neurocognitive testing — neurocognitive harm of WBRT not addressed. Modern practice increasingly omits WBRT altogether (using SRS alone) based on JROSG 99-1, Chang MD Anderson, N0574, and N107C data showing equivalent or superior outcomes with SRS alone. The WBRT+SRS standard has largely been superseded for patients with favorable prognosis.
Clinical Context
RTOG 9508 supported WBRT+SRS for single unresectable BM for years. Current practice in 2025 typically offers SRS alone (without WBRT) for 1-4 BM in patients with good performance status and controlled systemic disease, based on cognitive preservation data (Chang 2009, N0574 2016). WBRT is now largely reserved for poor-prognosis patients, extensive multiple BM, or leptomeningeal disease.
References
References: Andrews DW et al, Lancet 2004 (RTOG 9508)