RADT-85. PHASE II STUDY OF PROTON THERAPY FOR LOWER GRADE GLIOMAS: SURVIVAL AND TOXICITY OUTCOMES

Abstract BACKGROUND Lower grade gliomas (LGGs) are associated with long survival and frequently affect young adults; as such, treatment-related toxicities and quality of life are of particular concern. Proton therapy may reduce the risks of these toxicities by minimizing radiation exposure to healthy brain and pituitary tissue. This study evaluates the safety and efficacy of proton therapy in LGG patients, focusing on neurocognitive, neuroendocrine, and quality-of-life (QOL) outcomes. METHODS A single-institution, prospective phase 2 trial enrolled 60 patients with WHO grade 1-2 gliomas or IDH-mutant grade 3 gliomas. Proton therapy was delivered to a dose of 54 Gy(RBE) or 59.4 Gy(RBE) based on tumor grade. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), neurocognitive and neuroendocrine function, and QOL. Neurocognitive testing occurred at baseline and biennially utilizing clinical trials’ battery composite (CTBC). QOL was assessed using the FACT-Brain questionnaire. Toxicities were graded per CTCAE v4.0. RESULTS The median follow-up was 7.0 years, 5-year PFS and OS were 79.1% and 85.6%, respectively. PFS was highest in IDH-mutant, 1p/19q co-deleted gliomas (100%) and lowest in IDH-wildtype tumors (62.5%). The incidence of neurocognitive decline at 5 years was 6%. Neuroendocrine dysfunction occurred in 5.3%, with only one case attributed to radiation. QOL decline peaked at 6 months with 29% showing clinically meaningful decline, then improved and remained stable at approximately 15% from years 2 to 7. No late grade 3 toxicities were observed; one case of grade 4 radionecrosis occurred. CONCLUSIONS Proton therapy for LGG provides effective disease control with modest long-term toxicity. These findings support its use as a standard radiation modality and highlight the need for comparative trials with photon therapy.