P09.03.B ONCOLOGIC AND PATIENT-REPORTED OUTCOMES OF PENCIL-BEAM-SCANNING PROTON BEAM THERAPY FOR CNS WHO G2 AND G3 IDH1-MUTANT GLIOMA: A SINGLE INSTITUTION EXPERIENCE

Abstract BACKGROUND Patients with CNS-WHO G2 and G3 IDH-mutant glioma commonly achieve long survival after chemoradiotherapy. Proton beam therapy (PBT) can be used for this group to reduce the dose to uninvolved brain and, consequently, late toxicity involving mostly deterioration of neurocognitive functioning. In the present study we analyzed the disease control and patient-reported outcomes (PROs) from our institution. MATERIAL AND METHODS This prospective observational study included 30 patients with IDH1/2-mutant CNS-WHO G2 and G3 glioma treated with pencil beam scanning PBT between 2017 and 2021. The total dose was 54.04 Gy (RBE)/28 fractions for G2 and 60 Gy (RBE)/30 fractions for G3 disease. 25 patients (83.6%) received concomitant and/or adjuvant chemotherapy. PROs included quality of life (QoL) questionnaires (EORTC QLQ-C30 and EORTC QLQ-BN20) and a battery of neurocognitive tests: Hopkins verbal learning test - revised, trail making test and controlled oral word association. The assessments were routinely performed at baseline, end of treatment, at 3, 6, 12 months post PBT and afterwards annually. RESULTS The median follow-up was 62.5 months (range: 33.8 - 85.6). The actuarial 5-year progression-free and overall survival were 65.8% and 89.7%, respectively. The presence of MGMT promoter methylation corresponded to reduced risk of progression (HR = 0.24, 95%CI: 0.06-0.9, p = 0.034) and death (HR = 0.05, 95%CI: 0.005-0.56, p = 0.015). No other significant clinical risk factors were identified, including the tumor grade. The rates of acute and late ≥G3 complications were 6.6% and 0%, respectively. For QoL assessment, statistically significant longitudinal differences were seen in form of improvement of social functioning (Χηι2 = 17.8, p = 0.037) and future uncertainty (Χηι2 = 23.35, p = 0.006) as well as hair loss (Χηι2 = 27.9, p = 0.001) and itchy skin (Χηι2 = 17.22, p = 0.045), where after an expected initial symptom increase throughout the treatment, a full resolution was subsequently seen. No significant longitudinal changes were seen for neurocognitive assessment with high p-values of all scales (0.48 - 0.86) indicating a stable course of neurocognitive functioning. CONCLUSION Proton therapy is an effective and safe treatment modality of IDH1/2-mutant grade 2 and 3 glioma. It offers satisfactory disease control and does not lead to any long-term decline of quality of life and neurocognitive functioning. Comparable results for grade 2 and 3 tumors suggest that the reimbursement schemes should routinely involve both of these groups.