Relating proton LETd to biological response of parotid and submandibular glands using PSMA-PET in clinical patients

Background and purpose: A recent study investigated the use of PSMA-PET in monitoring loss of secretory cells in salivary glands of head and neck cancer (HNC) patients. Previously, a dose–effect relation has been formulated to the PSMA-PET uptake in salivary glands. The aim of this study was to derive a proton RBE model from the PSMA-PET uptake in salivary glands after proton therapy of HNC patients. Materials and methods: Six patients treated with proton therapy were included. These patients received a PET-CT scan using ⁶⁸Ga (N = 1) or ¹⁸F (N = 5) PSMA before treatment (baseline) and one month after the last fraction (follow-up). Physical dose (D), D·LET_d and the follow-up PSMA-PET scan were deformed to the baseline PET-CT using deformable image registration. Parotid and submandibular gland delineations were adjusted to include voxels which had an uptake of ≥ 5 g/ml in the baseline PSMA-PET scan. Results: The average RBE-LET slope was 0.075 [0.009; 0.125] (keV/μm)^-1 (mean [95 %CI]) for parotid and submandibular glands combined. When analyzing parotid or submandibular glands separately the RBE-LET curve slope varies with two and five patients showing a positive RBE-LET slope when only analyzing parotid or submandibular glands respectively. Conclusion: Our study did not find clear evidence of an increased RBE in parotid and submandibular glands with increasing LET_d. On average an LET_d effect was observed, however our sample size was too small to clearly define an RBE-LET relation. A larger cohort scanned at later time intervals could shed more light on this issue.