Acetylated tubulin (AT) as a prognostic marker in squamous cell carcinoma of the head and neck.

Acetylated tubulin (AT) expression has been proposed as a marker for sensitivity to taxane chemotherapy. We wanted to explore AT as a prognostic marker in squamous cell carcinoma of the head and neck (SCCHN). We assessed AT expression in archival tissue from our institutional tissue bank of primary SCCHN specimens. We also examined AT expression on pre-therapy tissues of patients with SCCHN receiving induction chemotherapy with docetaxel, cisplatin and 5FU (TPF IC). AT expression was assessed on archival cases of SCCHN with (N = 63) and without (N = 82) locoregional lymph node metastases (LNM). The predominant tumor site was oral cavity (52 %). Immunohistochemistry staining was based on staining intensity and percentage of tumor cells stained to create a weighted index (WI). A total of nine patients who received TPF IC were evaluable for response by RECIST and also had pre-therapy tissues available. A significant independent correlation between AT and tumor grade (p = 0.001) and primary location (p = 0.008) was noted. There was a trend of higher AT in patients with presence of LNM (p = 0.052) and a trend in improved OS for patients with an AT WI below the median compared to those above the median for patients with no LNM (p = 0.054). For patients treated with induction TPF, we observed an inverse correlation between AT expression and response to TPF IC (p = 0.0071). AT expression is correlated with tumor grade and primary site. There was an observed trend correlating AT with presence nodal metastases. The observed inverse correlation with response to taxane based chemotherapy needs validation in a larger sample size.

Chemoprevention of head and neck cancer by simultaneous blocking of epidermal growth factor receptor and cyclooxygenase-2 signaling pathways: preclinical and clinical studies.

PURPOSE: We investigated the efficacy and underlying molecular mechanism of a novel chemopreventive strategy combining EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) with cyclooxygenase-2 inhibitor (COX-2I). EXPERIMENTAL DESIGN: We examined the inhibition of tumor cell growth by combined EGFR-TKI (erlotinib) and COX-2I (celecoxib) treatment using head and neck cancer cell lines and a preventive xenograft model. We studied the antiangiogenic activity of these agents and examined the affected signaling pathways by immunoblotting analysis in tumor cell lysates and immunohistochemistry (IHC) and enzyme immunoassay (EIA) analyses on the mouse xenograft tissues and blood, respectively. Biomarkers in these signaling pathways were studied by IHC, EIA, and an antibody array analysis in samples collected from participants in a phase I chemoprevention trial of erlotinib and celecoxib. RESULTS: The combined treatment inhibited head and neck cancer cell growth significantly more potently than either single agent alone in cell line and xenograft models, and resulted in greater inhibition of cell-cycle progression at G1 phase than either single drug. The combined treatment modulated the EGFR and mTOR signaling pathways. A phase I chemoprevention trial of combined erlotinib and celecoxib revealed an overall pathologic response rate of 71% at time of data analysis. Analysis of tissue samples from participants consistently showed downregulation of EGFR, pERK, and pS6 levels after treatment, which correlated with clinical response. CONCLUSION: Treatment with erlotinib combined with celecoxib offers an effective chemopreventive approach through inhibition of EGFR and mTOR pathways, which may serve as potential biomarkers to monitor the intervention of this combination in the clinic. Clin Cancer Res; 19(5); 1244-56. ©2013 AACR.

Cervical tracheal resection: new lessons learned.

BACKGROUND: Cervical tracheal stenosis can be a difficult condition to manage. Depending on the etiology, location, and extent of the stenosis, tracheal or cricotracheal resection may be required. Intraoperative decisions may predict outcome. METHODS: We performed a retrospective chart review of all patients undergoing cervical tracheal or cricotracheal resection from April 2000 through March 2008. RESULTS: One hundred and five patients underwent 108 tracheal or cricotracheal resections. Median age was 65 years (range, 15 to 78); 68% were women. Indication for operation included postintubation tracheal stenosis (38), idiopathic (31), tracheostomy stenosis (19), invasive thyroid cancer (9), and other (8). Median length of trachea resected was 2.7 cm (range, 1.5 to 6.0 cm); 48 patients (46%) underwent extended cricotracheal resections. Twenty-six patients (25%) had an intraoperative chin stitch placed. Hospital stay was a median of 4 days (range, 2 to 33). Operative mortality was (1%); 1 patient died of myocardial infarction on postoperative day 3. Four patients (4%) had hoarseness or vocal cord immobility. Median follow-up was 36 months (range, 1 to 79). Eighteen patients (17%) required dilation postoperatively. Seven patients (7%) required tracheostomy; 2 (2%) are tracheostomy dependent. Three patients (3%) underwent a re-resection for recurrent stenosis. Multivariate analysis of indication for resection, type of resection, length of resection, anastomotic technique, and use of chin stitch did not predict the need for postoperative dilation, tracheostomy, or reoperation. CONCLUSIONS: Cervical tracheal resection can be performed safely with low morbidity and mortality. Only 5% of patients required a long-term tracheostomy or re-resection for recurrent tracheal stenosis. Specific intraoperative decisions did not predict long-term success.

Prognostic accuracy of computed tomography findings for patients with laryngeal cancer undergoing laryngectomy.

PURPOSE: The indications for upfront laryngectomy in the management of laryngeal cancer are a functionless larynx and extralaryngeal extension. Practically, clinicians rely on imaging to predict which patients will have T4 disease. Our goal was to review the accuracy of preoperative computed tomography (CT) scanning in determining the necessity for initial laryngectomy for advanced laryngeal cancer. PATIENTS AND METHODS: In total, 107 consecutive untreated laryngectomy specimens with high-quality, preoperative CT imaging interpreted by our neuroradiologists were reviewed. Radiographic findings, including sclerosis, invasion, penetration, extralaryngeal spread, and subglottic extension were correlated with pathologic findings. CT images were not reinterpreted, since our purpose was to assess the original interpretations. RESULTS: CT imaging reported 23 cases of thyroid cartilage penetration and 27 cases of extralaryngeal spread. Pathology reported 12 cases of thyroid cartilage invasion, 29 cases of penetration, and 45 cases of extralaryngeal disease. CT imaging identified 17 (59%) of 29 cases of pathologically documented thyroid cartilage penetration and 22 (49%) of 45 cases of pathologically documented extralaryngeal spread. Pathologically proven extralaryngeal spread without thyroid cartilage penetration occurred in 18 (40%) of 45 cases. The positive predictive values for thyroid cartilage penetration and extralaryngeal spread were 74% and 81%. Sclerosis was of limited value in predicting thyroid cartilage invasion or penetration. Cricoid or arytenoid destruction predicted for thyroid cartilage penetration at rates of 57% and 63%. CONCLUSION: CT imaging has clear limitations when deciding whether there is thyroid cartilage penetration or extralaryngeal spread of advanced laryngeal cancer. Extralaryngeal spread without thyroid cartilage penetration was more common than expected. Alternate methods of pretreatment assessment are needed.