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.

Inflammation following invasive procedures for Warthin's tumour: A retrospective case series.

OBJECTIVE: To determine the risk of inflammation associated with fine-needle aspiration during evaluation of Warthin's tumour. DESIGN: Retrospective case series. SETTING: Tertiary medical centre. PARTICIPANTS: All patients who underwent fine-needle aspiration followed by parotidectomy between 1992 and 2009 for the diagnosis/evaluation of a parotid gland tumour. MAIN OUTCOME MEASURE: Rate of fine-needle-aspiration-related parotitis in patients with Warthin's tumour or other parotid pathologies. RESULTS: A total of 593 parotidectomies were performed in 553 patients during the study period, 96 (16.2%) for Warthin's tumour (study group) and 497 for other parotid-related pathologies (control group). Parotid gland inflammation following fine-needle aspiration was observed in 16 cases in the study group (16.7%) and eight (1.6%) in the control group (P<.001). On multivariate regression analysis, parotitis following fine-needle aspiration was more common in patients with Warthin's tumour than other parotid-related pathologies even after adjustment for possible confounders (P<.007). Signs of inflammation were noted during surgery in six cases in the study group (6.3%) and none in the control group (P<.001); respective rates of postoperative inflammation (wound infection) were 1.04% and 3.3% (P=NS). Management of parotitis consisted of hospitalisation and systemic antibiotic therapy. CONCLUSIONS: Warthin's tumour is associated with a tenfold higher risk of inflammation compared to other parotid tumours following invasive procedures. Clinicians should be alert to this complication in order to initiate proper treatment and patients must be properly counselled.

Elective neck dissection during salvage total laryngectomy--a beneficial prognostic effect in locally advanced recurrent tumours.

OBJECTIVES: Elective neck dissection during salvage laryngectomy is controversial. The goal of our study was to evaluate the effect of elective neck dissection during salvage laryngectomy in patients with locally advanced disease at recurrence. DESIGN: Multicentre, retrospective study. SETTINGS: Two tertiary medical centres. PARTICIPANTS: Eighty-seven patients treated by salvage laryngectomy. MAIN OUTCOME MEASURES: Disease-Free and Overall Survival. RESULTS: Fifty-seven patients underwent salvage total laryngectomy for locally advanced recurrent squamous cell carcinoma of the larynx, and 30 patients underwent salvage laryngectomy for limited recurrent disease. Elective lateral neck dissection was performed in 48 patients. The groups were similar in age, sex, initial TNM stage and pre-operative treatment. Survival analysis showed that both disease-free survival and overall survival were improved in patients with locally advanced disease who underwent elective neck dissection. This beneficial effect was not demonstrated in patients with limited disease at recurrence. Multivariate analysis showed that the extent of the recurrent disease as well as elective neck dissection was associated with improved disease-free survival and overall survival. CONCLUSIONS: Elective neck dissection during salvage total laryngectomy seems to improve survival in patients with advanced local disease at recurrence. The role of neck dissection in the treatment of smaller tumours awaits further studies.

Resolved sudden hearing loss as a presenting symptom of retrocochlear lesion.

OBJECTIVE: To determine whether acoustic neuroma-induced sudden hearing loss is associated with hearing recovery and, if so, to characterize its clinical, audiometric and imaging manifestations. METHODS: The files of 72 patients with sudden hearing loss evaluated between 1989 to 2001 were reviewed. All patients underwent pure tone audiometry, acoustic reflex and auditory brain revoked response (ABR) test. Magnetic resonance imaging (MRI) was performed followed by a second hearing test after one month. The findings were compared between patients with and without evidence of tumors on imaging, and between patients with tumors with and without recovery. RESULTS: Twenty-five patients (35%) had a diagnosis of acoustic tumor. Of these, six (24%) recovered hearing after one month. Five of them had small intracanicular tumors and one had a small extracanicular tumor. There was variability in the hearing loss. Five had a pathological ABR and one had normal ABR. CONCLUSIONS: We conclude that recovery from hearing loss does not exclude acoustic tumors and these patients therefore require full evaluation including MRI.