Re-irradiation for recurrent intracranial meningiomas: Analysis of clinical outcomes and prognostic factors.

PURPOSE: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities. MATERIALS AND METHODS: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/ß = 2 for brain tissue and α/ß = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis. RESULTS: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (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) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-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 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively). CONCLUSIONS: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice.

Multisession stereotactic radiosurgery for large vestibular schwannomas.

OBJECT: Microsurgery is not the only option for larger vestibular schwannomas (VSs); recent reviews have confirmed the feasibility and efficacy of radiosurgery for larger VSs. This study illustrates the outcomes of a series of large VSs after multisession stereotactic radiosurgery (SRS). METHODS: A series of 33 VSs larger than 8 cm(3) (range 8-24 cm(3), mean 11 cm(3), median 9.4 cm(3)) were treated using the CyberKnife from 2003 to 2011 with the multisession SRS technique in 2-5 fractions (14-19.5 Gy). Five patients had undergone surgical removal and 5 had ventriculoperitoneal shunts. Nine patients were eligible for but refused surgery. Twelve patients were older than 70 years and 5 were younger than 40 years. Two female patients had neurofibromatosis. RESULTS: The follow-up period ranged from 12 to 111 months (median 48 months); radiological growth control was achieved in 94% of cases: 19 tumors (58%) displayed no size variation or reduction in tumor diameter; 12 (36%), after a transient enlargement, presented with arrested growth or shrinkage. Seven patients had a volume reduction of more than 50%. Two patients (6%) needed debulking and 2 were treated with ventriculoperitoneal shunts. Actuarial progressionfree survival rates at 1 year and 5 years were 97% and 83%, respectively. Hearing was retained in 7 of the 8 patients with serviceable baseline hearing. Adverse events were limited to 1 case each of vertigo, tongue paresthesia, and trigeminal neuralgia. CONCLUSIONS: The good control rate obtained with multisession SRS deepens the controversy of the radiobiology of VSs and may extend the indication of radiation therapy (fractionated or SRS) for large VSs to include patients without symptoms of mass effect. The limited number of cases and short follow-up period do not provide sufficient support for widespread application of multisession SRS in young patients. Further studies with multisession SRS are warranted.