Abstract

Abstract BACKGROUND Radiotherapy is often used as a postoperative treatment for WHO Grade 2 (G2) and Grade 3 (G3) meningioma. However, there is limited data on the long-term outcomes following radiotherapy for these patients. The present study aims to evaluate the outcomes of intermediate and high-risk meningioma patients treated with radiotherapy. MATERIAL AND METHODS A retrospective analysis was conducted on all G2 and G3 meningioma patients treated at our centre with fractionated radiotherapy from 2012 to 2021. Clinical status at follow up was updated to 20 March 2023. Those who received stereotactic radiosurgery or were re-irradiated were excluded. Univariate Cox Regression modelling was conducted to assess association of progression, progression-free survival (PFS) and overall survival (OS) with clinical variables. RESULTS Forty-three patients were included in the analysis, 25 (58.2%) female. 39 patients had G2 and 4 G3 meningioma. Median age was 60 (range 11-80) years. Median follow-up was 72 months. At the time of radiotherapy, most (n= 34) had an ECOG performance status (PS) of 0-1. The dose fractionation was 50.4Gy (n=2), 54Gy (n=20) or 59.4Gy(n=1) in 1.8Gy fractions, or 60Gy(n=20) in 2Gy fractions. The PFS was 76.7% (95%CI:64.1,89.4) at 3 years and 64.3% (95%CI:49.8,78.9) at 5 years. OS was 79.1% (95% CI:66.9,91.2) at 3 years and 74.0% (95% CI:60.8,87.3) at 5 years. For the lower dose subgroup (50.4/54Gy), 3 and 5-year PFS rates were 86.4% (95% CI: 72.0,100) and 72.7% (95% CI:54.1,91.3), while 3 and 5-year OS rates were both 86.4% (95% CI:72.0,100). For the higher dose subgroup (59.4/60Gy), 3 and 5-year PFS rates were 66.7% (95% CI:46.5,86.8) and 55.0% (95% CI: 32.8,77.2), while 3 and 5 year OS were 71.4% (95% CI: 52.1,90.8) and 59.9% (95% CI: 38.1,81.8). All survival times were calculated from radiotherapy end date. Effect of dose (low vs high), age (either continuous or categorical as <60 vs ≥60), gender, WHO grade and PS were examined in univariate Cox regression for relationship to each of progression free status at last assessment, PFS and OS. No factor was statistically significant for progression free status or PFS. For OS, we found a significant association of worse OS with higher doses (59.4/60Gy), Hazard ratio (HR) 3.749 (95%CI: 1.18,11.9), p=0.025, and a borderline significance for age ≥60, HR 3.056 (95%CI:0.995,9.39), p=0.051. At the end of follow-up, 18 patients were alive without progression (16 G2, 2 G3), 8 were alive with progression (all G2), 10 had died with progression (9 G2, 1 G3) and 7 had died without progression (6 G2, 1 G3). CONCLUSION The worse OS in the higher dose group likely relates to clinical risk factors beyond WHO grade. There is a need for clinical trials to improve outcomes for intermediate and high risk meningioma. This may require better risk stratification by use of molecular markers, dose escalation or dose painting of high risk sub volumes and when possible targeted agents.

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