Oncological Outcomes, Long-Term Toxicities, Quality of Life and Sexual Health after Pencil-Beam Scanning Proton Therapy in Patients with Low-Grade Glioma

SIMPLE SUMMARY: Low-grade glioma are primary brain tumors mostly with IDH mutations, usually occurring in young patients, with a clinically good prognosis. Here, we analyzed patients with these tumors who were treated with proton therapy at our institution from 1999 to 2022. Among 89 patients included in our study, a favorable long term overall survival rate of 89% at four years was observed. Severe treatment-related side effects were rare and of low-grade. The global quality of life remained constant and comparable to the general population during proton therapy and during the first six years of follow-up thereafter. Sexual satisfaction as a domain of sexual health was comparable to a reference population. These results indicate that proton therapy for patients with low-grade glioma results in favorable oncological and patient-reported outcomes. ABSTRACT: Purpose: To assess oncological outcomes, toxicities, quality of life (QoL) and sexual health (SH) of low-grade glioma (LGG) patients treated with pencil-beam scanning proton therapy (PBS-PT). Material and methods: We retrospectively analyzed 89 patients with LGG (Neurofibromatosis type 1; n = 4 (4.5%) patients) treated with PBS-PT (median dose 54 Gy (RBE)) from 1999 to 2022 at our institution. QoL was prospectively assessed during PBS-PT and yearly during follow-up from 2015 to 2023, while a cross-sectional exploration of SH was conducted in 2023. Results: Most LGGs (n = 58; 65.2%) were CNS WHO grade 2 and approximately half (n = 43; 48.3%) were located in the vicinity of the visual apparatus/thalamus. After a median follow-up of 50.2 months, 24 (27%) patients presented with treatment failures and most of these (n = 17/24; 70.8%) were salvaged. The 4-year overall survival was 89.1%. Only 2 (2.2%) and 1 (1.1%) patients presented with CTCAE grade 4 and 3 late radiation-induced toxicity, respectively. No grade 5 late adverse event was observed. The global health as a domain of QoL remained stable and comparable to the reference values during PBS-PT and for six years thereafter. Sexual satisfaction was comparable to the normative population. Conclusions: LGG patients treated with PBS-PT achieved excellent long-term survival and tumor control, with exceptionally low rates of high-grade late toxicity, and favorable QoL and SH.