RADT-45. THE MULTICENTER SOPRANO STUDY: OUTCOMES OF PATIENTS WITH IDH-MUTATED WHO GRADE 2 AND 3 GLIOMA TREATED WITH PROTON OR PHOTON RADIOTHERAPY

Abstract BACKGROUND Concerns were raised about an observed increase in treatment-related effects in patients treated with proton radiotherapy for glioma. This study compares next-intervention free survival in IDH-mutated WHO grade 2 and 3 glioma patients treated with proton or photon radiotherapy within the same time period. METHODS Patients treated consecutively in 2018-2022 with either protons or photons for IDH-mutated WHO grade 2 and 3 glioma were included from eight centers in the Netherlands and one in Belgium. All patients received standard-of-care radiotherapy and adjuvant chemotherapy. The primary outcome was Next Intervention Free Survival (NIFS; new treatment for either tumor progression or therapy effects). Additional endpoints were overall survival (OS), progression free survival (PFS), and pseudoprogression free survival (PsPFS; any new transient contrast-enhancing lesion after radiotherapy). All analyses were corrected for baseline factors in Cox regressions. RESULTS The total cohort comprised 373 patients with IDH-mutated glioma: 256 WHO grade 2, and 117 WHO grade 3, 216 received proton radiotherapy, and 157 received photon radiotherapy. The median follow-up time is 44.2 months. The NIFS in the entire cohort had an HR of 3.07 (p<0.01), in favor of photons. For WHO grade 2 glioma, no significant differences were seen in any of the outcomes. For WHO grade 3 glioma results were: NIFS HR=5.0 (p<0.01), OS HR=5.0 (p<0.01), PFS HR=4.0 (p<0.01) and PsPFS HR=3.1 (p<0.01), all favoring photons. In WHO grade 3 glioma, 5-year OS and PFS were 59.2% and 34.1% for protons, and 83.9% and 79.1% for photons, respectively. CONCLUSIONS In patients with IDH-mutated WHO grade 3 glioma, proton radiotherapy was associated with a higher rate of subsequent interventions, for either tumor progression or treatment effects, compared to photon radiotherapy. Additionally, we observed poorer OS and PFS, and increased rates of pseudoprogression after proton therapy. Further dosimetric and molecular analyses are warranted and ongoing.