Gideon Bachar

MUCOSAL MELANOMAS OF THE HEAD AND NECK: THE PRINCESS MARGARET HOSPITAL EXPERIENCE

The aim of this study was to identify the prognostic variables in mucosal melanoma of the head and neck.

Solitary extramedullary plasmacytoma of the head and neck—Long-term outcome analysis of 68 cases

Head and neck solitary extramedullary plasmacytomas are rare plasma cell neoplasms. Literature review reveals only small numbers of reports. The objective was to review our experience with treating patients with this neoplasm.

Esthesioneuroblastoma: The Princess Margaret Hospital experience

Esthesioneuroblastoma is rare. The aim of the study was to review our experience and to evaluate the staging system and treatment that best correlates with the patient outcome.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research

Background:Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC.Methods:The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan–Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.Results:The OS was 49% for patients with LND⩽0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND⩽0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.Conclusion:This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Primary Tumor Staging for Oral Cancer and a Proposed Modification Incorporating Depth of Invasion: An International Multicenter Retrospective Study

IMPORTANCE The current American Joint Committee on Cancer (AJCC) staging system for oral cancer demonstrates wide prognostic variability within each primary tumor stage and provides suboptimal staging and prognostic information for some patients. OBJECTIVE To determine if a modified staging system for oral cancer that integrates depth of invasion (DOI) into the T categories improves prognostic performance compared with the current AJCC T staging. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 3149 patients with oral squamous cell carcinoma treated with curative intent at 11 comprehensive cancer centers worldwide between 1990 and 2011 with surgery ± adjuvant therapy, with a median follow-up of 40 months. MAIN OUTCOMES AND MEASURES We assessed the impact of DOI on disease-specific and overall survival in multivariable Cox proportional hazard models and investigated for institutional heterogeneity using 2-stage random effects meta-analyses. Candidate staging systems were developed after identification of optimal DOI cutpoints within each AJCC T category using the Akaike information criterion (AIC) and likelihood ratio tests. Staging systems were evaluated using the Harrel concordance index (C-index), AIC, and visual inspection for stratification into distinct prognostic categories, with internal validation using bootstrapping techniques. RESULTS The mean and median DOI were 12.9 mm and 10.0 mm, respectively. On multivariable analysis, DOI was a significantly associated with disease-specific survival (P < .001), demonstrated no institutional prognostic heterogeneity (I² = 6.3%; P = .38), and resulted in improved model fit compared with T category alone (lower AIC, P < .001). Optimal cutpoints of 5 mm in T1 and 10 mm in T2-4 category disease were used to develop a modified T staging system that was preferred to the AJCC system on the basis of lower AIC, visual inspection of Kaplan-Meier curves, and significant improvement in bootstrapped C-index. CONCLUSIONS AND RELEVANCE We propose an improved oral cancer T staging system based on incorporation of DOI that should be considered in future versions of the AJCC staging system after external validation.

Laryngeal and hypopharyngeal obstruction in sleep disordered breathing patients, evaluated by sleep endoscopy

The objectives of our study were to demonstrate the patterns and sites of the upper airway (UA) collapse in obstructive sleep apnea/hypopnea syndrome (OSAHS) patients, utilizing the sleep endoscopy technique, and to describe the technique and summarize our experience in a large series of patients. UA findings during sleep endoscopy with midazolam were examined prospectively in 55 surgical candidates with OSAHS. The uvulopalantine was the most common site of obstruction (89%), followed by the tongue base, hypopharynx and larynx (33% each), and nose (21%); 72% of the patients had multiple obstructions. There was a significant correlation between the number of obstructions and the respiratory distress index (RDI). Laryngeal obstruction was typically supraglottic. Hypopharyngeal obstruction involved concentric UA narrowing. Our findings emphasize the considerable rate of laryngeal and hypopharyngeal obstructions in patients with OSAHS and suggest that their misdiagnosis may explain at least part of the high surgical failure rate of UPPP for OSAHS patients. The number of obstruction sites correlates with respiratory distress index. Sleep endoscopy is safe and simple to perform.

Hyaluronan-grafted particle clusters loaded with Mitomycin C as selective nanovectors for primary head and neck cancers.

CD44, a well-documented cell surface receptor, is involved in cell proliferation, migration, signaling, adhesion, differentiation and angiogenesis, which are important properties for normal and cancerous cell function. We recently developed particle clusters coated with hyaluronan (termed gagomers; GAG), and showed that they can deliver the insoluble drug paclitaxel directly into CD44-over-expressing tumors in a mouse tumor model. Here, we tested primary head and neck cancers (HNC) and normal cells taken from the same patient, and found that although CD44 expression in both types of cells was high, GAGs bind only to the cancerous cells in a selective manner. We next formulated the anti cancer agent mitomycin C (MMC) in the GAGs. MMC-based chemoradiation is a potential treatment for HNC, however, due to patients toxicity, MMC is not part of the standard treatment of HNC. MMC encapsulation efficiency was about 70% with a half-life drug efflux of 1.2 ± 0.3 days. The Ex vivo study of the targeted MMC-GAG showed significant increase in the therapeutic effect on HNC cells (compared to free MMC), while it had no effect on normal cells taken from the same patient. These results demonstrate the specificity of the nanovectors towards head and neck cancers, which might be applicable as future therapy to many CD44-expressing tumors.

NODAL RATIO AS AN INDEPENDENT PREDICTOR OF SURVIVAL IN SQUAMOUS CELL CARCINOMA OF THE ORAL CAVITY

The association between nodal ratio and survival in oral cavity carcinomas has recently been proposed, but no prospective evaluations exist.

Outcome of oral tongue squamous cell carcinoma in patients with and without known risk factors.

BACKGROUND Tobacco smoking and high alcohol consumption are considered major risk factors of oral tongue squamous cell carcinoma. This study compared disease outcome between patients with and without known risk factors. METHODS Patients with oral tongue squamous cell carcinoma treated at two major medical centers from 1994 to 2008 were identified by cancer registry search. The medical files were reviewed for background-and-disease-related data, risk factors, and outcome. RESULTS The study sample consisted of 291 patients: 175 had a history of heavy tobacco smoking and alcohol abuse and 116 did not. Comparison of the patients without risk factors between the two centers yielded no differences in background features. Men accounted for 74% of the total patients with risk factors and comprised 77% of the risk-factor group. The risk-factor group was characterized by a significantly higher mean tumor grade (p=0.0001) and greater tumor depth of invasion (p=0.022) than the non-risk-factor group. The 5-year local and regional control rates were 85.3% and 74%, respectively, with no significant difference between the groups. The 5-year overall survival rate was 68% in the risk-factor group and 64% in the non-risk-factor group (p=NS). Separate analysis of patients aged <40 years at diagnosis revealed a worse overall (p=0.015) and disease-free survival (p=0.038) in those without risk factors. CONCLUSIONS The outcome of oral tongue carcinoma is similar in patients with and without risk factors. The worse prognosis in younger patients (<40 years) without risk factors suggests that the pathogenesis in these cases involves factors other than smoking and alcohol.

Invasive well-differentiated thyroid carcinoma: effect of treatment modalities on outcome.

OBJECTIVE: Well-differentiated thyroid carcinoma is considered an indolent malignant disease. Although rare, extrathyroidal invasion is associated with a worse prognosis and increased risk of morbidity. Management remains controversial, with some authors advocating conservative treatment with preservation of midline structures and others, aggressive extensive en bloc resection. The aim of this study was to report our 40-year experience with invasive thyroid carcinoma, with emphasis on the clinical characteristics and the effect of different treatment modalities on survival. STUDY DESIGN AND SETTING: A retrospective study including a file review of 1,200 patients with a diagnosis of well-differentiated thyroid carcinoma of whom 49 (5%) showed involvement of an adjacent structure (larynx, trachea and esophagus) (study group). Type of surgery, radiation treatment, radioiodine treatment, and patient demographics were evaluated. RESULTS: Compared to the rest of the patients, the study group was characterized by a higher rate of male patients (39% vs 25%), and older average age (58 vs 45 years). Average size of the primary tumor was 3.7 cm. Sixteen patients underwent radical surgery and 33 conservative surgery followed by radio-iodine treatment. Five-year survival and recurrence rates for the whole group were 78% and 52%, respectively. The only statistically significant factor for survival was large tumor size. Distant metastases developed in 46% of patients, all in the lungs. Ten of 14 deaths were due to distant metastases. External radiation, used in 52% of the patients, was associated with worse prognosis. CONCLUSION: Conservative procedures followed by radioiodine treatment are associated with similar survival rates as aggressive techniques, with less perioperative mortality and lower overall morbidity. SIGNIFICANCE: This study provides further evidence that in cases of invasive thyroid tumors the extent of the primary surgery seems to have no influence on survival. EBM rating: C-4