Evaluation of particle radiotherapy for the re-irradiation of recurrent intracranial meningioma

Abstract

BackgroundWith the advance of modern irradiation techniques, the role of radiotherapy (RT) for intracranial meningioma has increased significantly throughout the past years. Despite that tumor’s generally favorable outcome with local control rates of up to 90% after ten years, progression after RT does occur. In those cases, re-irradiation is often difficult due to the limited radiation tolerance of the surrounding tissue. The aim of this analysis is to determine the value of particle therapy with its better dose conformity and higher biological efficacy for re-irradiating recurrent intracranial meningioma. It was performed within the framework of the “clinical research group heavy ion therapy” and funded by the German Research Council (DFG, KFO 214).MethodsForty-two patients treated with particle RT (protons (n = 8) or carbon ions (n = 34)) for recurrent intracranial meningioma were included in this analysis. Location of the primary lesion varied, including skull base (n = 31), convexity (n = 5) and falx (n = 6). 74% of the patients were categorized high-risk according to histology with a WHO grading of II (n = 25) or III (n = 6), in the remaining cases histology was either WHO grade I (n = 10) or unknown (n = 1). Median follow-up was 49,7 months.ResultsIn all patients, re-irradiation could be performed safely without interruptions due to side effects. No grade IV or V toxicities according to CTCAE v4.0 were observed. Particle RT offered good overall local control rates with 71% progression-free survival (PFS) after 12 months, 56,5% after 24 months and a median PFS of 34,3 months (95% CI 11,7–56,9). Histology had a significant impact on PFS yielding a median PFS of 25,7 months (95% CI 5,8–45,5) for high-risk histology (WHO grades II and III) while median PFS was not reached for low-risk tumors (WHO grade I) (p = 0,03). Median time to local progression was 15,3 months (Q1-Q3 8,08–34,6). Overall survival (OS) after re-irradiation was 89,6% after 12 months and 71,4% after 24 months with a median OS of 61,0 months (95% CI 34,2–87,7). Again, WHO grading had an effect, as median OS for low-risk patients was not reached whereas for high-risk patients it was 45,5 months (95% CI 35,6–55,3).ConclusionRe-irradiation using particle therapy is an effective method for the treatment of recurrent meningiomas. Interdisciplinary decision making is necessary to guarantee best treatment for every patient.

Clinical Outcomes of Recurrent Intracranial Meningiomas Treated with Proton Beam Reirradiation

“…The lower rate of radiographic radiation injury observed in the current study is consistent with the prevalence reported by the Heidelberg group for reRT with particle therapy [21] and the prevalence reported by colleagues in our institution who studied risk of temporal lobe necrosis for PBRT reRT of skull base head and neck cancers [32].…”

“…Our series is hypothesis generating for prognosticating the patients who might benefit most from PBRT: those with longer interval between prior RT and reRT and those with initially grade I tumors. The finding that grade I histology portends improved prognosis following reRT has been recapitulated in other small series [9,[21][22][23]. This consistent finding suggests that full-dose reRT is unlikely to be sufficient for durable long-term response in patients with grade II-III disease, and future prospective efforts may need to consider novel combinations of RT with systemic agents to overcome a relatively radioresistant histology.…”

“…For example, most patients had skull base lesions where reoperation carries significant risk of complications [20]. The Heidelberg Ion Therapy Center recently published its experience using particle therapy for reRT of 42 patients with recurrent meningioma [21]. In that analysis, 81% of patients received carbon ion therapy and only 8 patients received PBRT and the outcomes are pooled across particles.…”

Particle therapy tumour outcomes: An updated systematic review

“…Seven studies examining re-irradiation for recurrent disease were identified across five different subsites, [51][52][53][54][55][56][57] including a recent systematic review 58 of 16 studies across broad indications. The level and quality of evidence was low as the majority of studies are retrospective, with small sample size, limited follow-up duration and do not directly compare results to photon-based re-irradiation.…”

Dose-Limiting Organs at Risk in Carbon Ion Re-Irradiation of Head and Neck Malignancies: An Individual Risk-Benefit Tradeoff

“…The potential for severe early and late side effects after CIR depends primarily on the location of the tumor. In particular, re-irradiation of tumors that have infiltrated the base of the skull result in higher doses applied to dose-limiting OAR, such as the brainstem and temporal lobes [22]. Furthermore, simultaneous systemic therapies lead to a significant increase in treatment-related toxicities [1,2].…”