284 - Cognitive Function and Quality of Life in Patients with Lower Grade Gliomas Treated with Proton Radiation Therapy: A Phase II Study
Presenter(s)
J. M. Slater1, N. Horick2, L. B. Nachtigall3, M. W. Parsons4, N. A. Tritos3, A. Faje3, J. Dietrich3, B. C. Fullerton5, J. C. Sherman3, I. S. Wang3, T. Botticello3, K. S. Oh6, B. Y. Yeap2, and H. A. Shih7; 1Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 2Department of Biostatistics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 3Massachusetts General Hospital, Boston, MA, 4Pappas Center for Neuro-Oncology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, 5Massachusetts Eye and Ear Institute, Boston, MA, 6Harvard Medical Center, Boston, MA, 7Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Purpose/Objective(s): Lower grade gliomas (LGGs) are primarily diagnosed in younger adults, with many patients achieving long-term survival. Given the potential for treatment-related toxicities affecting neurocognitive and neuroendocrine function, optimizing therapy is crucial. Proton therapy, due to its unique physical properties, offers the potential for reduced toxicity compared to conventional photon therapy. This study evaluates the efficacy and safety of proton therapy in LGG patients, with a focus on neurocognitive, neuroendocrine, and quality-of-life (QOL) outcomes.
Materials/Methods: This single-arm, prospective phase 2 trial enrolled 60 patients with WHO grade 1-2 gliomas or IDH-mutant grade 3 gliomas requiring radiotherapy. Proton therapy was delivered at 54 Gy(RBE) for grade 1-2 gliomas and 59.4 Gy(RBE) for IDH-mutant grade 3 gliomas. Progression-free survival (PFS) was the primary endpoint, with secondary endpoints including overall survival (OS), neurocognitive function, neuroendocrine function, and QOL. Neurocognitive assessments were performed at baseline and biennially for up to seven years. Neuroendocrine function was monitored via serum hormone analysis, and QOL was measured using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Toxicity was evaluated per CTCAE v4.0 criteria.
Results: Median follow-up was 7.0 years. Five-year PFS and OS were 79.1% (95% CI: 66.1%-87.6%) and 85.6% (95% CI: 73.2%-92.5%), respectively. Molecular subgroup analysis showed superior outcomes in IDH-mutant, 1p/19q co-deleted oligodendrogliomas (5-year PFS: 100%) compared to IDH-mutant, non-codeleted astrocytomas (73.9%) and IDH-wildtype gliomas (62.5%). Neurocognitive assessment revealed minimal decline, with only 6% meeting criteria for cognitive impairment at 5 years. Neuroendocrine dysfunction was rare (5.3%), with only one case attributed to radiation exposure. QOL analyses showed a transient decline at six months, with subsequent recovery and stability; at five years, 15% of patients reported a clinically meaningful decline. The safety profile was favorable, with no late grade 3 toxicities and one grade 4 case of biopsy-proven radionecrosis (1.7%).
Conclusion: Proton therapy for LGG demonstrates high efficacy, excellent PFS, and a favorable toxicity profile, preserving neurocognitive and neuroendocrine function while maintaining QOL. These findings support proton therapy as an optimal treatment modality for LGG patients, warranting further investigation in comparative trials.