thorium-x and Carcinoma--Squamous-Cell

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

The objective of this study was to examine the combined effect of diffusing alpha-emitter radiation therapy (DART) together with the chemotherapeutic agent cisplatin on tumor development.. BALB/c mice bearing squamous cell carcinoma tumors were treated with radium 224 ((224)Ra-)-loaded stainless steel wires, releasing short-lived, alpha-emitting atoms from their surface. A concomitant regimen of cisplatin doses (5 mg/kg per dose) was given intravenously for the evaluation of the combined effect. Animals were monitored for tumor growth and survival.. First, the authors observed that alpha particles and cisplatin inhibited SQ2 cell proliferation in vitro and promoted apoptosis. Treatment of tumor-bearing mice indicated that, when a regimen of 2 separate doses of cisplatin was given concomitantly with a single intratumoral (224)Ra-loaded wire, there was moderate tumor growth inhibition relative to what was observed from each treatment alone. When tumors were treated with 2 radioactive wires positioned near the tumor base and a similar drug administration, the growth arrest effect intensified, and there also was a significant increase in survival rates. The combined treatment reduced both local tumor growth and metastatic spread to the lungs.. Antitumor activity and overall survival of metastatic tumor-bearing mice were improved significantly by the combined treatment. These results highlight the potential benefit of alpha radiation-based radiotherapy in combination with chemotherapeutic drugs for anticancer treatment.

Topics: Alpha Particles; Animals; Apoptosis; Brachytherapy; Carcinoma, Squamous Cell; Cell Line, Tumor; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Radiation; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Radium; Survival Rate; Thorium; Xenograft Model Antitumor Assays