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.

Purpose Our purpose was 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 of the skin and head and neck. Methods and Materials This prospective first-in-human, multicenter 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 squamous cancers of the skin and head and neck with either primary tumors or recurrent/previously treated disease by either surgery or prior external beam radiation therapy; 13 of 31 lesions (42%) had received prior radiation therapy. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. Tumor response was assessed at 30 to 45 days at a follow-up visit using the Response Evaluation Criteria in Solid Tumors, version 1.1. Median follow-up time was 6.7 months. 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 to 5 weeks. Complete response to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 78.6%); 6 lesions (6/28, 21.4%) manifested a partial response (>30% tumor reduction). Among the 22 lesions with a complete response, 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 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 were 75% (95% CI, 46.14%-89.99%) among all patients and 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

Chemical Composition and Microhardness of Human Enamel Treated with Fluoridated Whintening Agents. A Study in Situ

BACKGROUND: Dental whitening has been increasingly sought out to improve dental aesthetics, but may cause chemical and morphological changes in dental enamel surfaces. OBJECTIVE: Assess in situ the effects of high-concentration hydrogen peroxide with and without fluoride on human dental enamel using the ion chromatography test (IC) and the Knoop hardness test (KHN). MATERIAL AND METHODS: Nineteen enamel specimens were prepared using third human molars. These specimens were fixed on molars of volunteers and were divided into groups: OP38-Opalescence Boost PF38%, PO37-Pola Office 37.5% and CO-Control group. For chemical analysis (n= 3), the dentin layer was removed, keeping only the enamel, which was subjected to acidic digestion by microwave radiation. It was necessary to perform sample dilutions for the elements fluorine (F), calcium (Ca) and phosphorus (P) for quantification using the IC test. The KHN (n= 5) was performed before and after the treatments. Five indentations were made, separated by 100 µm, for each specimen using a load of 25 gf for 5 seconds in the microdurometer. The data were analyzed using ANOVA with a 5% significance level. RESULTS: The OP38 group had the largest concentrations of F, Ca and P ions. The PO37 group showed the lowest concentrations of F and Ca ions. The average KHN was not significantly different between the OP38 and PO37 groups. CONCLUSION: Enamel whitened with hydrogen peroxide containing fluoride had greater concentrations of F, Ca and P ions. The presence of fluoride in the whitening agent did not influence the enamel microhardness