Practical Dosimetry in the Treatment of Head-and-Neck Squamous Cell Carcinoma by Diffusing Alpha-Emitters Radiation Therapy (" Alpha DaRT")

Diffusing Alpha-emitters Radiation Therapy is a brachytherapy modality based on the coverage of solid tumors by alpha emitting atoms, released into the tumor following the decay of Ra-224. This parent isotope is securely fixed on thin metallic sources, which are arranged in the volume of the tumor in a prescribed geometric pattern. This pattern is designed to assure that the entire tumor volume receives a radiation dose exceeding the minimum level required to assure the killing of the malignant cells. In the course of clinical trials treating head-and-neck squamous cell carcinoma, a practical treatment planning approach was developed and implemented. It is based on the quantitative characterization of the diffusion process in pre-clinical experiments on nude mice bearing human SCC tumors and on the in-vitro experiments on cell survival under irradiation. A further central premise is that the diffusion length of the alpha-emitters in healthy tissue is much smaller than in cancerous tissue. Consequently, Alpha DaRT sources are arranged along lines forming a rectangular grid with a constant 5 millimeter spacing. The sources span the entire tumor volume, with occasional placement in adjacent healthy tissue as required. A Ra-224 activity of 2 microcuries (74 kBq) per centimeter of seed is providing a dose exceeding 12 Gy over the entire volume. The two key parameters - grid spacing and activity concentration - are correlated; a more sparse source arrangement requires higher Ra-224 activity per unit length. The alpha related safety is inherent in the modality. However, since some beta and gamma radiation is associated with the decay chain, it is instructive to estimate the expected dose both to the vicinity of the tumor and to distant organs. A simple physical model provides an upper limit of the dose. The upper limit of the exposure on the tumor edge is 0.02 A/V 2/3 Gy, and in the patient's body 0.0003 AxW 1/3 , where A is the administered 224 Ra activity in microcurie, V is the total volume of the tumor in cm 3 and W is the weight of the patient in kg.