Efficacy of radiotherapy and stereotactic radiosurgery as adjuvant or salvage treatment in atypical and anaplastic (WHO grade II/III) meningiomas. A systematic review and meta-analysis

Background. The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Published reports present aggregated and heterogeneous data, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to compare these two modalities systematically. Methods. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n=27; SRS n=15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n=26; SRS n=11); salvage regimens were described in 5 articles (RT n=1; SRS n=4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. Results. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7 cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with a grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p<0.001), and received subtotal resection (57 vs 27%, p=0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3 months, p=0.01). The recurrence rate was 38% in adjRT vs 25% in adjSRS (p=0.01), while mortality did not differ between the groups (20% vs 23%; p=0.80). The median time to recurrence was 1.5 times longer in RT group (p=0.30). 5y-LC was 55% in adjRT and 26% in adjSRS (p=0.01), while 5y-OS was 73% and 78% (p=0.62), and 5y-PFS was 62% and 40% in adjRT and adjSRS (p=0.008). No difference in the incidence of complications (24% vs 14%, p=0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p=0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5 months, p=0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p=0.54). Data on local and distant control were only available for salSRS. The 5y-OS was 49% and 83% (p=0.90), and the 5y-PFS was 39% and 50% in salRT and salSRS (p=0.66), respectively. Conclusions. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.