Simple SummaryMeningiomas are one of the most common primary brain tumors. The current standard therapy for symptomatic or growing lesions includes surgery and/or radiotherapy. Pencil Beam Scanning Proton Therapy (PBS PT) is an alternative to conventional radiotherapy with unique dose deposition pattern and improved conformality. In this retrospective study, we assess the clinical outcome including the quality of life (QoL) of patients with intracranial meningiomas treated with PBS PT between 1997 and 2022 at the Centre for Proton Therapy of the Paul Scherrer Institute. In 200 patients, we observed a high local control and survival, especially in patients with grade 1 tumors as well as a low rate of high-grade toxicity and stable QoL over the years after treatment. This study shows that PBS PT is an adequate alternative to conventional radiotherapy in meningioma treatment.AbstractThe aim of this study was to assess the clinical outcome, including QoL, of patients with intracranial meningiomas WHO grade 1–3 who were treated with Pencil Beam Scanning Proton Therapy (PBS PT) between 1997 and 2022. Two hundred patients (median age 50.4 years, 70% WHO grade 1) were analyzed. Acute and late side effects were classified according to CTCAE version 5.0. Time to event data were calculated. QoL was assessed descriptively by the EORTC-QLQ-C30 and BN20 questionnaires. With a median follow-up of 65 months (range: 3.8–260.8 months) the 5 year OS was 95.7% and 81.8% for WHO grade 1 and grade 2/3, respectively (p< 0.001). Twenty (10%) local failures were observed. Failures occurred significantly (p< 0.001) more frequent in WHO grade 2 or 3 meningioma (WHO grade 1:n= 7, WHO grade 2/3:n= 13), in patients with multiple meningiomas (p= 0.005), in male patients (p= 0.005), and when PT was initiated not as upfront therapy (p= 0.011). There were no high-grade toxicities in the majority (n= 176; 88%) of patients. QoL was assessed for 83 (41.5%) patients and for those patients PT did not impacted QoL negatively during the follow-up. In summary, we observed very few local recurrences of meningiomas after PBS PT, a stable QoL, and a low rate of high-grade toxicity.