Treatment of squamous cell carcinoma by alpha radiation-based brachytherapy (Alpha DaRT)

The first clinical trial in humans with skin and oral cavity squamous cell carcinoma was performed in order to evaluate the effect of a unique intra-tumoral alpha radiation based tumor ablation treatment termed Diffusing Alpha emitters Radiation Therapy (DaRT). DaRT relies on alpha particles and thus, effective against hypoxic tumors. DaRT seeds can be produced with various intensities, sizes and shapes and enable custom designed seeds .In our prior animal studies, we demonstrated the effectiveness of the treatment in mice for many tumors. In this first Human study we evaluated its role for Skin and oral Cavity Squamous cell Carcinoma. A Radium-224 loaded sources (DaRT seeds) were inserted into solid tumors and released by recoil short-lived alpha-emitting atoms (Rn-220, Po-216, Pb-212, Bi-212, Po-212, Tl-208). These atoms disperse in the tumor, and spray it with highly destructive alpha radiation. The decay products diffuse in the tumor mass to a distance of at least 5 mm. Thus, a sizable fraction of the tumor is irradiated by alpha particles, and because of their short half-life, only small amounts of the isotopes disperse in the body. A feasibility and safety clinical study is ongoing and currently were treated 13 patients at the Rabin Medical Center (Israel) . Patients with gamma radiation resistant recurrent histopathological confirmed skin or head and neck SCC, and tumor size ≤ 5 centimeters in the longest diameter, were enrolled. Treatment was delivered based on a CT-simulation pre-treatment plan. The Ra-224 Alpha DaRT Seeds were inserted under local anesthesia using a specially designed Alpha DaRT Applicator. The seeds (1 cm long and 0.7 mm in diameter) each carrying a dose of 2 μCi were placed 6 millimeters from each other. CT was used to check the position of the radioactive seeds. Two to four weeks after implantation the seeds were removed, and six weeks after treatment CT was performed to assess the effect of treatment. Blood tests and urinalysis were performed during the treatment. The Age of the patients ranged between 70 to 94 (median 81). Six patients had recurrent oral cavity SCC and seven diagnosed with aggressive skin SCC. All were treated within radiation failure fields(Radiation dosage >60 Gy).With a median follow up of 5 month, All tumors responded to the treatment; 9 tumors had a complete response, three tumors showed a partial response, and one tumor is still under observation. No major toxicity was noted. The areas around the treated tumors were not necrotic and no radionecrosis developed. In this feasibility and safety human study we demonstrated that alpha particles based DaRT exhibit enhanced radiobiological potential. The treatment was effective against radio-resistant SCC tumors without major toxicity.