CNS
Two meningioma datasets bookend the dose-intensity question: FIRESTORM adds a retrospective IPD signal for escalation; RTOG 0539 provides the field's longest prospective benchmarks.
FIRESTORM
ForHigh-risk meningioma (WHO grade 2 or recurrent), post-resection (mostly subtotal
TL;DR5-yr PFS 65.8% vs 38.8%, HR 0.40 favoring dose-escalated RT in high-risk meningioma; retrospective IPD meta-analysis.
8 details 3 trials watching
Methods
- 🔍 IPD meta-analysis, 7 institutions, N=248 (59 DE-RT, 189 SD-RT); DE-RT = BED ≥79.2 Gy (≡66 Gy/33 fr)
- 🔍 75.8% WHO grade 2; 41.5% recurrent; 75.2% subtotal resection
Results
- 📊 5-yr PFS: DE-RT 65.8% vs SD-RT 38.8%; 3-yr PFS 86.4% vs 55.6% (log-rank P=.0022)
- 📐 MVA: HR 0.40 (95% CI 0.24-0.69), P=.001; IPTW-adjusted HR 0.45 (95% CI 0.24-0.83), P=.01
Critique
- ⚠️ Radionecrosis higher with DE-RT
- Any grade RN: 33.9% DE-RT vs 13.2% SD-RT, P=.001
- Grade 3+ RN: 5.1% vs 3.2% (not significant)
- ⚠️ Retrospective non-randomized design; selection bias in who received dose escalation not fully eliminated by IPTW
- ⚠️ DE-RT arm small (N=59); 3:1 imbalance limits subgroup stability
- ⚠️ No OS endpoint reported in source
Open questions
- Does OS benefit accompany the PFS gain with dose-escalated RT?
- Does a prospective RCT confirm superiority of dose-escalated RT? n=90 · primary completion 2028-12 · prospective proton dose escalation, 5y RFS endpointrecruiting Somatostatin Receptor PET Imaging to Guide Radiotherapy Dose Escalation in High Risk Meningiomas. Phase NAn=53 · primary completion 2037-12 · prospective dose escalation guided by SSTR-PET in high-risk
- Which pts carry highest radionecrosis risk from dose escalation? recruiting Somatostatin Receptor PET Imaging to Guide Radiotherapy Dose Escalation in High Risk Meningiomas. Phase NAn=53 · primary completion 2037-12 · SSTR-PET-guided contouring to limit OAR dose escalation risk
📚 Sources · 📄 1 paper
Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM)
Abstract
Purpose: We performed an individual patient−level meta-analysis of high-risk meningiomas to compare the outcomes of dose-escalated radiation therapy (DE-RT) versus standard-dose postoperative radiation therapy (SD-RT).<br/>Methods and Materials: A total of 7 institutions participated. DE-RT was defined as treatment with a biologically effective dose of ≥79.2 Gy (equivalent of 66 Gy in 33 fractions). We compared progression-free survival (PFS) with DE-RT versus SD-RT via Kaplan-Meier analysis and log-rank t tests, a Cox proportional hazards multivariable model, and propensity score analyses with inverse probability of treatment weighting (IPTW). We also compared incidences of central nervous system radionecrosis (RN) with DE-RT versus SD-RT.<br/>Results: The analysis included 248 patients with high-risk meningioma (59 received DE-RT and 189 received SD-RT). One hundred and eighty-eight cases (75.8%) were World Health Organization grade 2, and 103 cases (41.5%) were recurrent meningiomas. Extent of resection was subtotal resection in 182 of 248 (75.2%). Three- and 5-year PFS rates were 62.8% (95% CI, 55.8%-69.0%) and 45.0% (95% CI, 37.3%-52.3%), respectively. DE-RT was associated with superior PFS rates (P = .0022), with 3-year (86.4% vs 55.6%) and 5-year (65.8% vs 38.8%) PFS rates favoring DE-RT. On multivariable analysis, DE-RT was associated with superior PFS (hazard ratio, 0.40; 95% CI, 0.24-0.69; P = .001). On IPTW, DE-RT continued to be associated with superior PFS (hazard ratio, 0.45; 95% CI, 0.24-0.83; P = .01). A greater incidence of any grade RN was observed following DE-RT (20 of 59; 33.9%) versus SD-RT (25 of 189; 13.2%) (P = .001) but with similar grade 3 or greater RN events (DE-RT 5.1% vs SD-RT 3.2%).<br/>Conclusions: DE-RT resulted in superior PFS for patients with high-risk meningiomas over SD-RT without an increase in severe toxicities.
NRG Oncology RTOG 0539 NCT00895622
ForWHO grade 1-3 meningioma, post-resection (GTR or STR), newly-diagnosed or recurr
TL;DR10-yr PFS 85.2%, 72.2%, 42.5% for low/intermediate/high-risk meningioma with risk-adapted observation or RT (median f/u ~12yr).
vs leading data
- Long-term benchmarks for future trials; ROAM/EORTC-1308 is ongoing randomised RT vs obs for grade 2
7 details 3 trials watching
Methods
- 🔍 Prospective phase 2, N=165 eligible (244 consented); risk-stratified by WHO grade, resection extent, recurrence status
- 🔍 Low: grade 1 GTR/STR → obs; intermediate: recurrent grade 1 or new grade 2 post-GTR → 54 Gy; high: new grade 2 post-STR, grade 3, or recurrent grade 2/3 → 60 Gy
- 🔍 Median PFS not reached in low- and intermediate-risk cohorts
Results
- 📊 10-yr outcomes by risk group
Risk Group Rx n 10-yr PFS 10-yr OS 10-yr prog. incidence Low Observation 60 85.2% 94.1% 8.9% (3.2–18.2%) Intermediate 54 Gy/30fx 52 72.2% 84.7% 21.2% (10.8–33.9%) High 60 Gy/30fx 53 42.5% 51.1% 39.3% (25.8–52.5%)
Critique
- ⚠️ G3+ RT-attributed toxicity
- Intermediate-risk: 9.6% (5/52 pts)
- High-risk: 15.1% (8/53 pts)
- ⚠️ Non-randomized: risk allocation deterministic, not randomised; no RT vs obs head-to-head for intermediate group
- ⚠️ WHO 2021 molecular criteria not applied; risk stratification reflects histologic grading (WHO 2007/2016)
Open questions
- RT vs observation for intermediate-risk meningioma: no randomised data recruiting Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery Phase 3n=163 · primary completion 2027-06 · phase 3 RCT: adjuvant RT vs obs, resected grade II
- Optimal RT dose for WHO grade 3 meningioma beyond 60 Gy n=90 · primary completion 2028-12 · proton escalation 60/68/72 Gy(RBE), grade II/IIIrecruiting Somatostatin Receptor PET Imaging to Guide Radiotherapy Dose Escalation in High Risk Meningiomas. Phase NAn=53 · primary completion 2037-12 · SSTR-PET guided dose escalation, grade III/recurrent II
- Role of WHO 2021 molecular grading in meningioma risk stratification
📚 Sources · 📄 1 paper
Long-Term Analysis of NRG Oncology RTOG 0539: A Phase II Trial of Observation for Low-Risk Meningioma and Radiotherapy for Intermediate- and High-Risk Meningioma
Abstract
NRG Oncology RTOG 0539 was a prospective phase II trial of risk-adapted radiotherapy for patients with WHO grade 1-3 meningioma. Low-risk (group 1, n = 60) was defined as a grade 1 tumor after gross total resection or subtotal resection (GTR/STR) and prospectively monitored. Intermediate-risk (group 2, n = 52) was defined as recurrent grade 1 or newly diagnosed grade 2 tumor after GTR and treated with radiotherapy (54 Gy). High-risk (group 3, n = 53) included a newly diagnosed grade 2 tumor after STR, newly diagnosed grade 3 tumor, or recurrent grade 2 or 3 tumor and treated with radiotherapy (60 Gy). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The median follow-up times for the low-, intermediate-, and high-risk cohorts were 12.1, 12.0, and 11.1 years, respectively. The 10-year PFS and OS rates for the low-, intermediate-, and high-risk cohorts were 85.2% and 94.1%, 72.2% and 84.7%, and 42.5% and 51.1%, respectively. Five patients (9.6%) and eight patients (15.1%) had a grade 3+ toxicity attributed to radiotherapy in the intermediate- and high-risk cohorts, respectively. The long-term outcomes using this risk-adapted approach support observation for low-risk patients, inform radiotherapy patient selection and practice standards for intermediate- and high-risk patients, and provide comparative benchmarks for future trials.