Background
Alliance N107C/CEC·3: Phase III, randomized, multicenter trial. 194 patients with 1–4 brain metastases who had undergone gross total resection randomized to SRS to the surgical cavity vs WBRT (30 Gy/12 fractions). First RCT to directly compare post-operative SRS (cavity) vs WBRT. Primary endpoints: OS and cognitive deterioration-free survival (CDFS).
Interventions and follow up
Arm A: SRS to surgical cavity (dose: 12–20 Gy based on cavity diameter)
Arm B: WBRT 30 Gy in 12 fractio
Primary endpoint: Overall survival and cognitive deterioration-free survival
mFollow up: Median 11.1 month
Arm B: WBRT 30 Gy in 12 fractio
Primary endpoint: Overall survival and cognitive deterioration-free survival
mFollow up: Median 11.1 month
Results
OS: Median 12.2 months (SRS) vs 11.6 months (WBRT), HR 1.07 — not significantly different
Cognitive deterioration at 6 months: 52% (SRS) vs 85% (WBRT), P<.001
1-year local tumor control: 80% (SRS) vs 87% (WBRT)
1-year intracranial failure (any site): SRS had more distant brain failures, but comparable neurologic death rates
Cognitive deterioration at 6 months: 52% (SRS) vs 85% (WBRT), P<.001
1-year local tumor control: 80% (SRS) vs 87% (WBRT)
1-year intracranial failure (any site): SRS had more distant brain failures, but comparable neurologic death rates
Adverse events
Main adverse events: Leptomeningeal carcinomatosis: 17% (SRS) vs 3% (WBRT) — higher with SRS, P=.007. Grade ≥3 cognitive toxicity: 0% (SRS) vs 28% (WBRT), P<.001. Radionecrosis: 4.9% (SRS) vs 5.8% (WBRT) — similar.
Conclusions
Post-operative SRS to the surgical cavity preserved cognition significantly better than WBRT (52% vs 85% cognitive failure at 6 months) without compromising OS. The trade-off was higher distant brain failure and leptomeningeal carcinomatosis with SRS. SRS to the cavity has become the standard of care after BM resection based on this trial.
Key Limitations
Key Limitations: Higher rate of leptomeningeal carcinomatosis with SRS (17% vs 3%) is a concerning safety signal, particularly for patients with posterior fossa tumors, intraventricular resection, or specific histologies. Cavity SRS requires precise targeting and accounts for cavity changes over time. Distant brain failures with SRS require intensive MRI surveillance. Patients with poor performance status or expected short survival may not benefit from the cognitive preservation of SRS.
Clinical Context
Alliance N107C established SRS to the surgical cavity as the new standard of care, replacing WBRT after BM resection. ASCO 2022 and NCCN guidelines now recommend SRS to the cavity for most patients with resected BM. Optimal cavity margin and timing of SRS post-surgery remain areas of research. WBRT remains an option for patients with multiple BM, poor prognosis, or inadequate follow-up capacity. This trial should be considered alongside Mahajan (MD Anderson) post-op SRS RCT (same conclusion).
References