Variable relative biological effectiveness (RBE) in proton therapy of gliomas


Variable relative biological effectiveness (RBE) in proton therapy of gliomas

Eulitz, J.; Raschke, F.; Seidlitz, A.; Hahn, C.; Permatassari, F.; Lutz, B.; Schulz, E.; Karpowitz, C.; Grey, A.; Engellandt, K.; Löck, S.; Troost, E. G. C.; Krause, M.; Lühr, A.

Purpose:

Currently, there is an intense debate on the need to consider variable clinical relative biological effectiveness (RBE) in proton therapy. Here, the variability of the clinical RBE is studied for late radiation-induced brain injuries (RIBI) observed after proton therapy in WHO grade 2-3 glioma patients.

Methods: In total, 42 patients out of a consecutive WHO grade 2-3 glioma patient cohort that received (adjuvant) proton radio(chemo)therapy between 2014 and 2017, were eligible for analysis. RIBI lesions (symptomatic or clinically silent) were diagnosed and delineated on T1-weighted magnetic resonance imaging with contrast agent scans obtained in the first two years of follow-up. Correlation of RIBI location and occurrence with simulated dose (D), proton linear energy transfer (LET, dose-averaged) and variable RBE dose parameters were tested in voxel- and in patient-wise logistic regression analyses, respectively. Additionally, anatomical and clinical parameters were considered and model performance was estimated through cross-validated area-under-the-curve (AUC) values.

Results: In 23 patients, 69 RIBI lesions were diagnosed. RIBI location and occurrence were significantly correlated with D×LET and variable RBE dose in voxel- and patient-wise regression analysis with cross-validated AUC values of 0.90 (95% confidence interval: 0.90-0.90) and 0.83 (0.60-1.00), respectively, when incorporating the periventricular region and tumor histology in the analysis. Models without D×LET and constant RBE revealed AUC values of 0.88 (0.88-0.88) and 0.78 (0.51-1.00), respectively.

Conclusions: Models with variable RBE performed substantially better in predicting occurrence and location of RIBI when compared to fixed RBE models. The obtained clinical evidence for a variable proton RBE suggests its consideration in proton treatment planning of brain tumors.

Keywords: Variable proton RBE; Glioma; Radiation-induced brain injury; Periventricular region; LET

  • Invited lecture (Conferences) (Online presentation)
    59th Annual Conference of the Particle Therapy Co-Operative Group, 04.-07.06.2021, Dresden (Online), Germany

Permalink: https://www.hzdr.de/publications/Publ-32077
Publ.-Id: 32077