Modeling absorbed alpha particle dose from diffusing alpha-emitters radiation therapy in changing tissue volumes

Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a promising new radiation therapy modality for treating bulky tumors. ²²⁴Ra-carrying sources are inserted intratumorally, producing a therapeutic alpha-dose region with a total size of a few millimeter via the diffusive motion of ²²⁴Ra's alpha-emitting daughters. Clinical studies of Alpha DaRT have reported 100% positive response (30%-100% shrinkage within several weeks), with post-insertion swelling in close to half of the cases. While dosimetry recommendations informed by the effects of edema are standard in some radiation therapy modalities, the effect of edema and tumor shrinkage on the absorbed dose delivered by Alpha DaRT is still unknown.

The aim of this work is to develop a simple model for Alpha-DaRT dose deposition in a time-dependent tissue volume in order to study the effect of geometrical changes in source location due to edema and tumor shrinkage on the delivered alpha particle dose.

We perform FEM-based dose deposition modeling for a single Alpha-DaRT source inside shrinking and swelling tissues. Gradual volume change models were used for shrinkage and swelling, and an additional immediate volume gain model was also used for "worst case" swelling. Volume change rates were estimated from source location data from serial scans acquired at time of insertion and removal for seven patients treated using Alpha DaRT. We calculate absorbed dose profiles under both the high- and low-diffusion regimes described by the Diffusion-Leakage model.

Changes in tissue volume can lead to over- or underestimation of the calculated absorbed dose. In the low-diffusion regime, gradual tissue shrinkage can result in an increase of 100% and gradual swelling can result in a 35% decrease in absorbed dose compared to a calculation in static tissue. Although immediate post-insertion swelling can reduce the absorbed dose by close to 65% for very closely spaced sources, in all cases analyzed the final absorbed dose continues to exceed the 10 Gy target. These effects are less severe in the high-diffusion regime.

These results indicate that tissue swelling and shrinkage can have a non-negligible effect on the tumor absorbed dose. Further study of tissue dynamics during Alpha-DaRT treatment will be necessary for improvements in dosimetry practice.