Background
Phase II, prospective, single-arm, risk-stratified multi-cohort trial (RTOG 0539). Three risk groups: low-risk (observation only) — newly diagnosed, completely resected (Simpson 1–3) WHO grade I; intermediate-risk (N=56 evaluable) — STR WHO grade I, recurrent WHO grade I, or new WHO grade II; high-risk (N=56 evaluable) — WHO grade III (anaplastic) or recurrent/progressive WHO grade II.
Interventions and follow up
Arm A (low-risk): Observation only
Arm B (intermediate-risk): RT 54 Gy in 30 fractions
Arm C (high-risk): RT 60 Gy in 30 fractions (no chemotherapy); 3D conformal or IMRT with mandatory image guidance
Primary endpoint: 3-year PFS per cohort (vs historical benchmarks)
mFollow up: Intermediate median 55 months; high-risk median 50.4 months
Arm B (intermediate-risk): RT 54 Gy in 30 fractions
Arm C (high-risk): RT 60 Gy in 30 fractions (no chemotherapy); 3D conformal or IMRT with mandatory image guidance
Primary endpoint: 3-year PFS per cohort (vs historical benchmarks)
mFollow up: Intermediate median 55 months; high-risk median 50.4 months
Results
Intermediate-risk 3-yr PFS: 93.8% (95% CI 83.6–97.9%)
Intermediate-risk 5-yr PFS: 83.2%
High-risk 3-yr PFS: 58.8% (prespecified benchmark 55% — met)
High-risk 3-yr OS: 72.5%
Intermediate-risk 5-yr PFS: 83.2%
High-risk 3-yr PFS: 58.8% (prespecified benchmark 55% — met)
High-risk 3-yr OS: 72.5%
Adverse events
Intermediate-risk grade ≥3 late toxicity: 4%
High-risk grade ≥3 late toxicity: 25% (most common neurocognitive and cranial neuropathies)
Grade 5 toxicity: None in either cohort
High-risk grade ≥3 late toxicity: 25% (most common neurocognitive and cranial neuropathies)
Grade 5 toxicity: None in either cohort
Conclusions
RTOG 0539 established risk-stratified RT benchmarks for meningioma. Intermediate-risk tumors achieved 3-year PFS of 93.8% with 54 Gy; high-risk tumors achieved 3-year PFS of 58.8% with 60 Gy, meeting the prespecified efficacy threshold. One of the only prospective multiinstitutional datasets for meningioma RT.
Key Limitations
Single-arm, non-randomized — efficacy judged against historical benchmarks, not a concurrent control. Modest cohort sizes (N=56 each). Heterogeneous risk-group composition (mixed grades and recurrence status). No molecular stratification. Local central pathology review limited; chemotherapy not assessed.
Clinical Context
Provides the principal prospective evidence supporting risk-adapted adjuvant RT in meningioma: observation for completely resected grade I, 54 Gy for intermediate-risk, 60 Gy for high-risk. Informs current ASTRO/EANO management approaches; molecular and dosing questions are being addressed by ongoing trials (e.g., ROAM/EORTC-1308, NRG-BN003).