Molecular mediators of metastasis in head and neck squamous cell carcinoma

BACKGROUND: The presence of regional metastasis in patients with head and neck squamous cell carcinoma (HNSCC) is a common and adverse event associated with poor prognosis and high mortality. Although significant improvements in standard therapies have increased the efficacy of local tumor management, the high incidence of tumor recurrence has resulted in limited improvements in overall survival rates. Understanding the molecular mechanisms that mediate HNSCC invasion and metastasis may enable identification of novel therapeutic targets for the prevention and management of tumor dissemination. METHODS: A literature review was performed. RESULTS: Several biologic mediators and mechanisms that have been implicated in HNSCC metastasis, such as cell adhesion molecules, proteolytic enzymes, growth factor signaling, metastasis suppressor genes, and chemokine receptors were reviewed. CONCLUSIONS: Prevention of HNSCC metastasis is an important clinical objective that requires an increased understanding of the molecular mechanisms of tumor invasion and dissemination.     

Distant metastases after definitive radiotherapy for squamous cell carcinoma of the head and neck

PURPOSE: To analyze parameters that influence the risk of distant metastases after definitive radiotherapy. METHODS: Between 1983 and 1997, 873 patients were treated with definitive radiotherapy and had follow-up for 2 years or more. Univariate and multivariate analyses were performed to evaluate risk factors that might influence the risk of distant metastases. RESULTS: The 5-year distant metastasis-free survival rate was 86%. Univariate analyses revealed that the risk of distant metastases was significantly influenced by gender (p =.0092), primary site (p =.0023), T stage (p <.0001), N stage (p <.0001), overall stage (p <.0001), level of nodal metastases in the neck (p <.0001), histologic differentiation (p =.0096), control above the clavicles (p <.0001), and time to locoregional recurrence (p <.0001). Multivariate analysis of freedom from distant metastases revealed that gender (p =.0390), T stage (p <.0001), N stage (p =.0060), nodal level (p <.0001), and locoregional control (p <.0001) significantly influenced this end point. Multivariate analysis revealed that gender (p =.0049), T stage (p <.0001), N stage (p <.0001), and locoregional control (p <.0001) significantly influenced cause-specific survival. CONCLUSIONS: The risk of distant metastases after definitive radiotherapy is 14% at 5 years and is significantly influenced by gender, T stage, N stage, nodal level, and locoregional control.     

Efficacy of neck treatment in patients with head and neck squamous cell carcinoma

BACKGROUND: Treatment of head and neck squamous cell carcinoma (HNSCC) addresses the primary tumor and the lymphatic drainage. Modalities for the neck are neck dissection and/or radiation therapy. In most cases, the neck is treated by the modality that seems more appropriate for the primary. The aim of this study was to analyze the results of the neck treatments either by neck dissection alone, by radiation therapy alone or by neck dissection followed by radiation therapy. METHODS: This was a retrospective chart analysis of 699 patients treated for a previously untreated HNSCC. The primary endpoint was recurrence at the treated neck. RESULTS: Two hundred eighty-one (40%) patients underwent primary neck irradiation, 219 (31%) neck dissection alone, and 199 (29%) neck dissection followed by adjuvant irradiation. The 5-year regional control rates after neck dissection alone were 83% for pN0, 75% for pN1, 60% for pN2a, 59% for pN2b, and 50% for pN2c; after radiation alone, 89% for cN0, 87% for cN1, 40% for cN2a, 60% for cN2b, and 48% for cN2c; and after neck dissection with adjuvant radiation, 86% for pN0, 96% for pN1, 100% for pN2a, 88% for pN2b, and 88% for pN2c. CONCLUSIONS: Radiation or neck dissection alone are efficient to control early neck disease. For advanced N2/3 neck disease, neck dissection followed by adjuvant radiation is highly efficient, whereas primary radiation results in a high number of regional failures. The literature suggests planned neck dissection to improve regional control for these patients.     

Current philosophy in the surgical management of neck metastases for head and neck squamous cell carcinoma

Neck dissection is an important treatment for metastases from upper aerodigestive carcinoma; an event that markedly reduces survival. Since its inception, the philosophy of the procedure has undergone significant change from one of radicalism to the current conservative approach. Furthermore, nonsurgical modalities have been introduced, and, in many situations, have supplanted neck surgery. The refinements of imaging the neck based on the concept of neck level involvement has encouraged new philosophies to evolve that seem to benefit patient outcomes particularly as this relates to diminished morbidity. The purpose of this review was to highlight the new paradigms for surgical removal of neck metastases using an evidence‐based approach. © 2014 Wiley Periodicals, Inc. Head Neck 37: 915–926, 2015     

Risk stratification for metastasis from cutaneous squamous cell carcinoma of the head and neck

Background: The purpose of the study was to develop a system of risk stratification, based on clinical and histological factors that would aid prediction of metastasis from cutaneous squamous cell carcinoma (SCC) of the head and neck. Method: The method used was a retrospective case control study comparing clinical and histological parameters of 78 patients who developed metastasis with 92 patients who did not develop metastasis over a 5‐year period. Results: The two ‘absolute’ (highest) risk factors for development of metastatic disease are poor histological differentiation and perineural/lymphovascular infiltration. The three ‘relative’ risk factors are moderate histological differentiation, diameter ≥20 mm and Clark level 5. Risk stratification: High‐risk lesions have either one of the absolute risk factors or all three of the relative risk factors with a predicted incidence of metastasis of 37%. Intermediate risk lesions have two of three relative risk factors and a predicted incidence of metastasis of 5%. Low‐risk lesions have one or none of the relative risk factors and a predicted incidence of meatstasis of 0.3%. Conclusion: Ongoing management of patients with histo‐pathologically proven invasive SCC of the head and neck should be based upon risk stratification for metastasis.