PurposeTo compare retrospectively outcome after photon radiotherapy alone, radiochemotherapy with temozolomide (TMZ), and carbon ion radiotherapy in patients with high-grade gliomas and to generate a hypothetical outcome curve for C12 and TMZ. Patients and methodsPatients treated within a Phase I/II Trial with a carbon ion boost were compared retrospectively with randomly chosen patients treated with photons or photons in combination with TMZ in a retrospective analysis. Per treatment group, 16 patients with anaplastic astocytoma (AA), and 32 patients with glioblastoma (GBM) were included. Treatment outcome with focus on progression-free survival (PFS) and overall survival (OS) was analyzed. ResultsMedian OS for patients with GBM was 9months with RT, 14months with RCHT group, and 18months in the C12 group. There was no significant difference between the C12 and the RCHT group. For patients with AA, median OS was 13months for RT, 39months for RCHT, and 35months after C12. The difference from RCHT to C12 was not significant. Median PFS for patients with GBM was 5months in the RT group, 6months in the RCHT group, and 8months in the C12 group. There was a significant difference between the RCHT group and the C12 group. For AA, median PFS was 15months with RT, 6months with RCHT, and 34 with C12. Comparing subgroups, C12 was significantly different from RCHT. Based on the significant OS increase from RT to RCHT, and from RT to C12, we projected the potential increase in outcome when combined C12 and TMZ would have been applied. A generated hypothetical curve based on the abovementioned outcome as well as preclinical examinations suggests there might be a benefit from the addition of C12 in patients with high-grade gliomas. ConclusionsThis exploratory retrospective study suggests a potential benefit of carbon ions in patients with high-grade gliomas. This hypothesis is now being evaluated prospectively in GBM within the randomized CLEOPATRA clinical trial.