Long-Term Follow-Up Evaluation of Efficacy in Alpha-Emitting Radiation Therapy on Recurrent and Locally Advanced Squamous Cell Carcinomas in Multi-Center Clinical Study

Abstract

<h3>Purpose/Objective(s)</h3> Diffusing Alpha-emitter Radiation Therapy (DaRT) represents a novel method to deliver alpha particles intratumorally via the decay of Radium-224. Early results demonstrated the feasibility, safety, and efficacy of DaRT with an associated 100% overall response rate at six weeks and a favorable toxicity profile. The purpose of the study was to report the long-term tumor control outcomes of DaRT for the treatment of locally advanced and recurrent squamous cancers (SCC) of the skin and head and neck. <h3>Materials/Methods</h3> This retrospective study evaluated the outcomes of patients with histologically-confirmed SCC of the skin and head and neck who either previously failed or were medically unfit for definitive therapy. For this study, 28 lesions in 23 patients were eligible and treated per protocol. Treatment was delivered via a percutaneous interstitial technique with placement of the radioactive DaRT to encompass the tumor volume with margin. Tumor control was assessed using serial radiographic imaging or clinical assessments. The median follow-up time was 28 months following treatment. <h3>Results</h3> Complete response to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 79%); 6 lesions (6/28, 21%) manifested a partial response. Among the 22 lesions with a CR, 9 (41%) developed a subsequent local relapse at the site of DaRT implantation at a median time of 6.2 months (range: 2.8-35.4 months). The 2-year local progression-free survival (PFS) probability at the implanted site was 50% (95% Confidence Interval, CI: 28-68%) for complete responders. The 2-year overall survival rates post-DaRT implantation was 65% (95% CI: 42%-81%) among all patients and was 77% (95% CI: 50%-91%) among complete responders. <h3>Conclusion</h3> Despite prior therapy among these recurrent, locally advanced tumors, Ra-224 DaRT treatment was well tolerated and associated with excellent 2-year tumor control outcomes. A pivotal US trial for marketing approval is already underway.