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

Radiother Oncol. 2024 Apr 7;195:110271. doi: 10.1016/j.radonc.2024.110271. Online ahead of print.

Desideri I(1), Morelli I(2), Banini M(1), Greto D(3), Visani L(3), Nozzoli F(4), Caini S(5), Della Puppa A(6), Livi L(1), Perini Z(7), Zivelonghi E(8), Bulgarelli G(8), Pinzi V(9), Navarria P(10), Clerici E(10), Scorsetti M(10), Ascolese AM(11), Osti MF(11), Anselmo P(12), Amelio D(13), Minniti G(14), Scartoni D(13).

Author information:

(1)Department of Experimental and Clinical Biomedical sciences "Mario Serio", University of Florence, Florence, Italy. (2)Department of Experimental and Clinical Biomedical sciences "Mario Serio", University of Florence, Florence, Italy. Electronic address: ilaria.morelli@unifi.it. (3)Radiation Oncology Unit, Careggi University Hospital, Florence, Italy. (4)Histopathology and Molecular Diagnostics, Careggi University Hospital, Florence, Italy. (5)Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy. (6)Neurosurgical Clinical Department of Neuroscience, Psychology, Pharmacology and Child Health, Careggi University Hospital, Florence, Italy. (7)CyberKnife Unit, Ospedale S. Bortolo, Vicenza, Italy. (8)Unit of Stereotactic Neurosurgery, Department of Neurosciences, Hospital Trust of Verona, Verona, Italy; Physic Department, Department of Neurosciences, Hospital Trust of Verona, Italy. (9)Radiotherapy Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy. (10)Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Milan, Italy. (11)Radiotherapy Department, St. Andrea Hospital, Sapienza University of Rome, Rome, Italy. (12)Radiotherapy Oncology Centre, Santa Maria Hospital, Terni, Italy. (13)Proton Therapy Center, 'S. Chiara' Hospital, Azienda Provinciale per i Servizi Sanitari, Trento, Italy. (14)Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.

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/β = 2 for brain tissue and α/β = 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.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.radonc.2024.110271 PMID: 38588920

Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.