thorium-x and Head-and-Neck-Neoplasms

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.. 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.. 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.. 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.

Topics: Aged; Aged, 80 and over; Alpha Particles; Brachytherapy; Carcinoma, Squamous Cell; Erythema; Feasibility Studies; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Pain, Procedural; Photography; Pilot Projects; Progression-Free Survival; Prospective Studies; Radium; Safety; Skin Neoplasms; Skin Ulcer; Thorium; Time Factors; Treatment Outcome

Diffusing alpha-emitters radiation therapy ('DaRT') is a new cancer-treatment modality, which enables treating solid tumors by alpha particles. The treatment utilizes implantable seeds embedded with a low activity of radium-224. Each seed continuously emits the short-lived alpha-emitting daughters of radium-224, which spread over several mm around it, creating a 'kill region' of high alpha-particle dose. DaRT is presently tested in clinical trials, starting with locally advanced and recurrent squamous cell carcinoma (SCC) of the skin and head and neck, with promising results with respect to both efficacy and safety. This work aims to provide a simple model which can serve as a zero-order approximation for DaRT dosimetry, allowing for calculating the macroscopic alpha particle dose of a point source, as a basis for more realistic source geometries. The model consists of diffusion equations for radon-220, lead-212 and bismuth-212, with the other short-lived daughters in local secular equilibrium. For simplicity, the medium is assumed to be homogeneous, isotropic and time-independent. Vascular effects are accounted for by effective diffusion and clearance terms. To leading order, the alpha particle dose can be described by simple analytic expressions, which shed light on the underlying physics. The calculations demonstrate that, for a reasonable choice of model parameters, therapeutic alpha-particle dose levels are obtained over a region measuring 4-7 mm in diameter for sources carrying a few [Formula: see text]Ci of radium-224. The model predictions served as the basis for treatment planning in the SCC clinical trial, where treatments employing DaRT seeds carrying 2 [Formula: see text]Ci of radium-224 and spaced 5 mm apart resulted in  ∼[Formula: see text] complete response of the treated tumors with no observed radiation-induced toxicity. The promising results of the SCC clinical trial indicate that in spite of its approximate nature, the simple diffusion-based dosimetry model provides a quantitative starting point for DaRT treatment planning.

Topics: Alpha Particles; Bismuth; Brachytherapy; Diffusion; Dose Fractionation, Radiation; Head and Neck Neoplasms; Humans; Kinetics; Lead Radioisotopes; Radioisotopes; Radiometry; Radium; Radon; Squamous Cell Carcinoma of Head and Neck; Thorium

Topics: Alopecia Areata; Carcinoma, Basal Cell; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasms, Radiation-Induced; Radiotherapy; Radium; Scalp; Skin Neoplasms; Thorium