Patient-reported outcomes, neurocognitive functioning and oncologic results of pencil-beam-scanning proton beam therapy for CNS WHO G2 and G3 IDH1-mutant diffuse adult glioma: A single institution experience

Purpose: Patients with isocitrate dehydrogenase (IDH)-mutant diffuse glioma achieve long survival after chemoradiation therapy. Proton beam therapy (PBT) can be used for this group to potentially reduce the late neurologic and cognitive complications. In the present study, we analyzed the patient-reported outcomes (PROs), objective neurocognitive (NC) functioning, and oncologic results of Central Nervous System World Health Organization (CNS WHO) G2 and G3 diffuse adult glioma treated with PBT in our institution. Methods and Materials: This prospective observational study included 30 patients with IDH1/2-mutant CNS WHO G2 and G3 astrocytoma and oligodendroglioma treated with pencil-beam-scanning PBT between 2017 and 2021. The total dose was 54.04 Gy relative biologic efficacy (RBE)/28 fractions for G2 and 60 Gy (RBE)/30 fractions for G3 disease. PROs and NC testing were performed at baseline, end of treatment 3, 6, and 12 months post end of treatment, and afterward annually. PROs included quality of life (QoL) questionnaires: European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and EORTC QLQ-BN20, and NC tests included Hopkins verbal learning test—revised, trail making test, and controlled oral word association. Results: The median follow-up was 62.5 months (range, 33.8-85.6). In QoL analysis, significant trends toward fewer symptoms were seen for future uncertainty (ß = –0.14, P = .036) and constipation (ß = –0.18, P = .005); the latter temporarily coinciding with completion of chemotherapy. As for NC scales, the results of controlled oral word association verbal fluency testing showed a significant longitudinal improvement (ß = 0.07, P < .001). Other QoL and NC scales showed an unchanged status over time. The estimated 5-year progression-free and overall survival were 65.8% and 89.7%, respectively. The presence of O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation corresponded to reduced risk of progression (hazard ratio, HR = 0.24, 95% CI, 0.06-0.9, P = .034) and death (HR = 0.05, 95% CI, 0.005-0.56, P = .015). Conclusions: Proton therapy is a safe and effective treatment for IDH1/2-mutant diffuse glioma with no apparent detrimental effect on QoL and NC functioning in this prospective cohort.