P07.10.A CLINICAL OUTCOMES OF SPOT-SCANNING PROTON BEAM THERAPY FOR IDH-MUTANT CNS WHO GRADE 2 AND 3 GLIOMA
Authors: Pelak M J , Lütgendorf-Caucig C , Flechl B , Mock U , Mozes P , Fossati P , Georg P , Fussl C , Surböck B , Mumot M , Stock M , Wolfsberger S , Urbanic Purkart T , Calabek-Wohinz B , Hug E 
Published: September 2023

Abstract

BACKGROUND
The latest WHO brain tumour classification puts utmost emphasis on prognostic significance of isocitrate dehydrogenase (IDH) mutation. IDH-wildtype tumours are now automatically considered CNS WHO grade 4 and associated with poor prognosis. On the contrary, patients with IDH1/2-mutant tumours have a favourable outcome. A high chance of long-term survival justifies the use of proton beam therapy (PBT) in these patients as it reduces unnecessary dose to unaffected brain and, consequently, late side effects. The data on outcomes specific for IDH-mutant tumours, in particular CNS WHO grade 3, remains limited. In this study we analysed the results of PBT in patients with IDH-mutant glioma of both CNS WHO grade 2 and 3 treated at our institution.

MATERIAL AND METHODS
The analysis included 30 patients enrolled in MedAustron prospective registry study (NCT03049072), who were diagnosed with CNS WHO Grade 2 and 3 glioma with IDH1/2 mutation. The median patient age was 38.8 years (range: 20.3 - 77.9) and male to female ratio was 16:14. The median time from last surgery to PBT was 91 days. CNS WHO grade 2 tumours (n =17) were treated with 54-54.04 Gy RBE total dose in 27-30 fractions and CNS WHO grade 3 tumours (n = 13) received 59.6-60 Gy RBE in 30-33 fractions. Fifteen (50%) and 24 (80%) of patients received temozolomide-based concomitant and adjuvant chemotherapy, respectively. Follow-up including MRI was obtained at 3, 6 and 12 months post PBT completion and then annually.

RESULTS
The median follow-up was 46.1 months (range: 13-69). Actuarial 3-year PFS of the whole cohort was 84.7% (95%CI: 64.1%-94%) and OS was 95.8% (95%CI: 73.9%-99.4%). At latest follow-up, 14 out of 17 patients with CNS WHO grade 2 (82.4%) and 8 out of 13 CNS WHO grade 3 tumours (61.5%) remained progression-free. Two patients died due to disease progression. This corresponded to actuarial 3-year PFS and OS of 86.8% (95%CI: 56.6%-96.6%) and 91.7% (95%CI: 53.9%-98.8%) for CNS WHO grade 2 and 83.3% (95%CI: 48.2%-95.5%) and 100% for CNS WHO grade 3 tumours, respectively. No risk factors of death and disease progression could be identified. Specifically, no significant differences were observed between CNS WHO grade 2 and 3 tumours for neither OS nor PFS (p = 1.0 and p = 0.32, respectively). The average time to progression in patients with treatment failure was 35.3 months. Only one patient (3.3%) developed grade ≥ 3 toxicity (G3 transient seizures). Radiation-induced brain lesions (RIBL) were identified in 11 patients (36.7%), out of which 10 (90.9%) remained asymptomatic. The median time to RIBL onset was 11.48 months and median duration in patients in whom RIBL eventually resolved was 14.8 months.

CONCLUSION
Our clinical data demonstrate that PBT is a safe and effective treatment of IDH-mutant glioma. Due to favourable and comparable outcomes of both grade 2 and 3 IDH-mutant tumours it is a valuable therapeutic option for both patient groups.