Small scale dosimetry and modeling for salivary gland toxicity in thyroid cancer patients treated with ¹³¹I

Objectives: Salivary gland toxicity is a quality of life concern in radioiodine treatment of thyroid cancer. Clinically observed toxicity is inconsistent with absorbed doses (AD) to the salivary glands calculated by absorbed fraction methods, or even by personalized Monte Carlo-based voxelized 3-dimensional radiobiological dosimetry (3D-RD) calculations, which includes accounting for dose rate effects as well as contribution to AD from outside the salivary glands. Small scale anatomical modeling has been proven to reconcile discrepancies between whole organ AD values and clinically or pre-clinically observed toxicities.

Methods: Uptake in the salivary glands has been shown to be primarily confined to the epithelial striated ducts which contain sodium iodine symporters. Dimensions of typical striated duct cells were obtained from the literature and S-values for the striated cells for various isotopes of iodine and astatine (¹³¹I, ¹²⁴I, ¹²³I, ¹²⁵I, ²¹¹At) used in clinical or pre-clinical scenarios were calculated using GEANT4 Monte Carlo. Based on the fraction of occupancy of these cells within the salivary glands (5.1 %), a grid of striated cells placed randomly in spheres of increasing size was used to simulate decay of activity in these cells from which ratios of striated duct AD and acinar cell AD to whole organ AD were calculated for these same isotopes. Results were applied to the calculation of AD and biological effective dose (BED) to the striated ducts and acinar cells of the salivary glands of 5 patients treated for thyroid cancer using ¹³¹I therapy at the University of Duisburg-Essen.

Results: S-values for striated duct to striated duct as well as striated duct to acinar cells as a function of distance from the striated duct were calculated, as were S-values for contents (saliva) inside the tube formed by the striated ducts to the same target cells. The grid-based Monte Carlo results showed a ductal cell AD to salivary whole organ AD ratio of 3.5 - 3.3 for ¹³¹I and 14.6 for ²¹¹At dependent on salivary gland size (5 - 25 ml). BED for the striated ducts ranged from 3 - 25 Gy, as opposed to the 1-5 Gy calculated to the whole gland. Conclusions: This is a significant step in quantifying the discrepancy between clinically observed toxicity and predicted toxicity based on whole organ AD values and is based on small scale dosimetry, which has been shown to explain similar discrepancies in different cases, particularly alpha-particle dosimetry. This study shows that while the salivary glands may be considered as parallel organs for external beam radiation, the physiology for iodine uptake means that for radiodine therapy, they have a more complex structure.