Initial Safety and Tumor Control Results from a “First-in-Human” Multicenter Prospective Trial Evaluating a Novel Alpha-Emitting Radionuclide for the Treatment of Locally Advanced Recurrent Squamous Cell Carcinomas of the Skin and Head and Neck

Abstract Purpose To report the feasibility and safety of Diffusing Alpha-emitter Radiation Therapy (DaRT), which entails the interstitial implantation of a novel alpha-emitting brachytherapy source, for the treatment of locally advanced and recurrent squamous cancers (SCC) of the skin and head and neck. Materials and Methods This prospective first-in-human, multi-center clinical study evaluated 31 lesions in 28 patients. The primary objective was to determine the feasibility and safety of this approach and the secondary objectives were to evaluate the initial tumor response and local progression-free survival. Eligibility criteria included all patients with biopsy-proven SCC of the skin and head and neck with either primary tumors or recurrent/previously treated disease by either surgery or prior external beam radiotherapy; 13 of 31 lesions (42%) had received prior radiotherapy (RT). Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE v 4.03). Tumor response was assessed at 30-45 days at a follow-up visit using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1). Median follow-up time was 1 year. Results Acute toxicity included mostly local pain and erythema at the implantation site followed by swelling and mild skin ulceration. For pain and Grade 2 skin ulcerations, 90% of patients had resolution within 3-5 weeks. Complete response (CR) to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 78.6%); six lesions (6/28, 21.4%) manifested a partial response (>30% tumor reduction). Among the 22 lesions with a CR, 5 (22%) developed a subsequent local relapse at the site of DaRT implantation at a median time of 4.9 months (range: 2.43-5.52 months). The 1-year local progression-free survival (PFS) probability at the implanted site was 44% overall (Confidence Interval, CI: 20.3-64.3%) and 60% (95% CI: 28.61-81.35%) for complete responders. Overall survival rates at 12 months post-DaRT implantation was 75% (95% CI: 46.14-89.99%) among all patients and was 93% (95% CI: 59.08-98.96%) among complete responders. Conclusions Alpha emitter brachytherapy using DaRT achieved significant tumor responses without Grade 3 or higher toxicities observed. Longer follow-up observations and larger studies are underway to validate these findings.