Background
MD Anderson post-operative SRS trial: Phase III, randomized, single-institution trial. 128 patients with 1–3 brain metastases and a single resection cavity randomized to SRS to the cavity vs observation. Enrolled 2009–2016. SRS dose: 12–16 Gy (based on cavity size). Patients could receive SRS for other BM simultaneously. Direct comparison of cavity SRS vs observation (not vs WBRT, unlike N107C).
Interventions and follow up
Arm A: SRS to resection cavity (12 or 16 Gy based on cavity diameter ≤3 cm vs >3 cm)
Arm B: Observation (with salvage SRS or WBRT at recurrence)
Primary endpoint: Local recurrence at the resection cavity
mFollow up: Median 11.1 month
Arm B: Observation (with salvage SRS or WBRT at recurrence)
Primary endpoint: Local recurrence at the resection cavity
mFollow up: Median 11.1 month
Results
12-month local recurrence (cavity): 15.7% (SRS) vs 43.2% (observation), HR 0.31 (95% CI 0.14–0.70), P<.001
OS: No significant difference (HR 0.98, P=.92)
Distant brain recurrence: No significant difference
Functional independence: No significant difference
OS: No significant difference (HR 0.98, P=.92)
Distant brain recurrence: No significant difference
Functional independence: No significant difference
Adverse events
Main adverse events: Grade 3+ neurologic toxicity: 2% SRS vs 0% observation. Leptomeningeal carcinomatosis: 8% SRS vs 4% observation (not statistically significant). Radionecrosis: not separately reported. Fatigue, headache more common with SRS.
Conclusions
SRS to the surgical cavity reduced 12-month local recurrence by 68% (HR 0.31, P<.001) compared with observation alone, without improving OS or functional outcomes. SRS to the resection cavity is an effective local therapy that reduces local relapse and the need for WBRT salvage, while avoiding the neurocognitive harm of upfront WBRT.
Key Limitations
Key Limitations: Single-institution study with inherent center-specific selection bias and technical expertise advantages. Trial was designed when whole-brain RT was still common — observation arm patients could receive salvage WBRT, confounding the comparison. Small N (128) limits power for secondary endpoints. Local recurrence is a surrogate endpoint — OS equivalence means recurrence was managed effectively with surveillance and salvage.
Clinical Context
The Mahajan trial and Alliance N107C (Brown 2017) together constitute the two major RCTs supporting SRS to the cavity as standard of care after BM resection. Both showed local control benefit without OS improvement and with cognitive preservation (though Mahajan only implied this vs WBRT). Combined with the N107C LMC data (17% LMC with SRS), the field is working to optimize cavity contouring margins, timing of post-op SRS, and identification of LMC risk factors.
References