Clinical Outcomes and Dosimetric Predictive Factors in Patients Undergoing Reirradiation for Recurrent Meningiomas

Abstract

Re-irradiation (reRT) of intracranial meningiomas is often limited by radiation tolerance of the surrounding normal tissue and the risk of side effects. Aim of this retrospective study is to report outcomes, toxicity and prognostic factors of reRT in a large cohort of patients with recurrent meningiomas (RM) treated with different RT techniques. A multi-institutional database of intracranial meningioma patients who recurred after prior radiation treatment was collected. Patients underwent reRT with one of the following techniques: radiosurgery (SRS), multi-fraction stereotactic radiotherapy (f-SRT), proton therapy (PT), Intensity-Modulated radiotherapy (IMRT) and External Beam radiotherapy (EBRT). Biologically Equivalent Doses in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for surrounding normal tissue and tumor were estimated for each RT course, assuming an a/b = 2 for brain tissue and a/b = 4 for meningioma. Progression-free survival (PFS) was the primary outcome measure. Secondary outcomes were overall survival (OS) and treatment-related toxicity, according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Kaplan-Meier curves were used to estimate the effect of several parameters on PFS and on OS; Cox regression models assessed predictors of PFS and OS. Between 2003 and 2021, 181 patients (pts) were included. They were re-treated with SRS (n = 75; 41.4%), f-SRT (n = 63; 34.8%), PT (n = 31; 17.1%) and conventional radiotherapy (n = 12; 6.7%). 78 pts were identified with WHO Grade I disease, 65 pts with Grade II and 10 pts had Grade III disease. 28 pts without histologic sampling were included among Grade I patients for further analysis. Median age at re-irradiation was 62 (range 20-89) and median KPS 90 (range 60-100). After a median follow-up of 4.6 years (IQR 1.7-6.8), 3-year PFS was 51.6% and 3-year OS 72.5%. At univariate analysis Ki67 >5% (HR 2.81, 95% CI 1.48-5.34, p = 0.002) and WHO grade > I (HR 3.08, 95% CI 1.80-5.28, p< 0.001) were correlated with worse PFS, whereas f-SRT (HR 0.32, 95% CI 0.19-0.55, p<0.001), longer time to reRT (HR 0.37, 95% CI 0.21-0.67, p = 0.001) and higher tumor BED (HR 0.45 95% CI 0.27-0.76, p = 0.003) favorably correlated with PFS. At multivariate Cox analysis only f-SRT, time to reRT and tumor BED kept their statistically significant prognostic impact on PFS (HR 0.36, 95% CI 0.21-0.64, p<0.001; HR 0.38, 95% CI 0.20-0.72, p = 0.003 and HR 0.47 95% CI 0.26-0.83, p = 0.01, respectively). In addition, larger tumor GTV had a statistically significant higher risk of acute and late toxicity (p = .0.004 and p = 0.005, respectively). Reirradiation of RM progressing after previous RT seems to be feasible, with encouraging outcomes and an acceptable toxicity profile. Prognostic factors in the treatment-algorithm have been identified and should be adopted in clinical daily practice.