Gene expression profiling on pre- and post-erlotinib tumors from patients with head and neck squamous cell carcinoma.

BACKGROUND: The purpose of our work was to identify genomic predictive markers of erlotinib response in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Tumor tissue biopsies were collected before and after treatment for 39 patients. We analyzed genomic expression of the tumors using microarrays to (1) identify genes differentially expressed in baseline samples in patients who were responders vs nonresponders, (2) characterize erlotinib's effect on gene expression, and (3) identify the pharmacodynamic marker of erlotinib. RESULTS: Gene expression profiles found no statistically significant differentially expressed genes between responders and nonresponders. An exploratory analysis by combining statistical criteria allowed us to identify genes differentially expressed in nonresponders compared to responders and genes whose expression was modified during erlotinib treatment. Finally, the search of pharmacodynamic markers identified cyclin-dependent kinase 2-interacting protein (CINP) as a potential marker of erlotinib efficacy because its expression decreased only in patients who were responders to the treatment. CONCLUSION: This study provides candidate genes potentially involved in erlotinib response in HNSCC.

Initial multi-institutional experience with transoral robotic surgery.

OBJECTIVE: To assess the initial experience for transoral robotic surgery (TORS), as observed in the French TORS group. STUDY DESIGN: A multi-institutional prospective cohort study. SETTING: Seven tertiary referral centers. SUBJECTS AND METHODS: One hundred thirty consecutive patients who were scheduled for a TORS between October 2008 and March 2011 were included. The operative times, conversion rates, morbidity, and alternatives were described. The serious adverse effects encountered were analyzed, and recommendations for avoiding them are specified. RESULTS: Most of the patients (65%) had a laryngeal (supraglottic) and/or hypopharyngeal resection. Thirty-nine of the 130 patients receiving TORS would have had a transoral laser resection as their alternative surgery. The tumor exposure was suboptimal in 26% of the cases. Six of the 130 patients needed conversion to an open approach. There were 15 postoperative hemorrhages and 2 deaths due to posthemorrhage complications in patients with significant comorbidities at 9 and 18 days after the surgery. The median setup and procedure times were 52 ± 46 and 90 ± 92 minutes, respectively. The learning curve was characterized by better selection and management of potential patients. CONCLUSION: The visualization offered by the robotic assistance allowed transoral resections of tumors that were difficult to resect or unresectable by laser surgery. Self-assessment of surgical exposure and a decrease in the need to convert to an open procedure over time suggested improvement in TORS-related surgical skills. Nevertheless, strict patient selection is essential. Even with a minimally invasive approach, some patients will need a tracheostomy for safety reasons.

Transoral minimally invasive robotic surgery for carcinoma of the pharynx and the larynx: a new approach.

Partial laryngectomy is an old but well-accepted surgical treatment for selected carcinomas of the larynx. Actually, the transcervical approach remains the most popular even if the transoral laser approach is useful in some cases. Transoral robotic surgery is a new promising surgical procedure in head and neck oncology as an alternative to conventional surgery with decreased morbidity. The aim of this study is a description of the state of the art by a review of the literature. We emphasize limits and future prospects on this topic with a special focus on dependability.

Postoperative radiotherapy in head and neck mucosal melanoma: a GETTEC study.

OBJECTIVE: to report patterns of failure according to treatment modality, with an emphasis on the role of postoperative radiotherapy in patients with localized head and neck mucosal melanoma (HNMM) treated during a 28-year period in a multi-institutional setting. DESIGN: retrospective review. SETTING: french medical institutions. PATIENTS: a total of 160 patients with nonmetastatic HNMM treated from 1980 through 2008. INTERVENTIONS: treatment modality consisted of surgery alone (hereinafter, S group) (n = 82 patients) or with postoperative radiotherapy (hereinafter, SRT group) (n = 78). Patients and tumor characteristics were similar in the 2 groups. There was a nonsignificant trend (P = .11) for more locally advanced tumor stage (38.9%) in the SRT group compared with the S group (24.5%). RESULTS: patients in the S group had an increased probability of locoregional recurrence as a first event (55.6%) compared with those in the SRT group (29.9%; P < .01). After adjusting for tumor stage (T1/T2 vs T3/T4), the subdistribution hazard ratio of locoregional relapse was 0.31, (95% confidence interval [CI], 0.15-0.61; P < .01).The rate of distant metastasis as a first event was significantly higher in the SRT group (40.6%) compared with the S group (19.9%; P = .01). Regardless of their treatment, patients who had a locoregional relapse during follow-up had an increased risk of subsequent distant metastasis (hazard ratio, 3.07; 95% CI, 1.65-5.67) and death (hazard ratio, 3.01; 95% CI, 1.91-4.78). CONCLUSIONS: this large retrospective study suggests that postoperative radiotherapy improves the locoregional control of HNMM. The higher rate of distant metastasis was due to more advanced disease in the SRT group.

Population pharmacokinetics of erlotinib and its pharmacokinetic/pharmacodynamic relationships in head and neck squamous cell carcinoma.

UNLABELLED: A clinical study was conducted to determine the safety and efficacy of neoadjuvant erlotinib treatment in patients with head and neck squamous cell carcinoma [Thomas F, Rochaix P, Benlyazid A, et al. Pilot study of neoadjuvant treatment with erlotinib in non-metastatic head and neck squamous cell carcinoma. Clin Cancer Res 2007;13:7086-92]. The aim of the present analysis was to explore the impact of several covariates on the pharmacokinetics of erlotinib and its main metabolite (OSI-420) and to determine PK/PD relationships. PATIENTS AND METHODS: Plasma concentrations of erlotinib and OSI-420 of 42 patients were analysed using the NONMEM program to evaluate the impact of patients' covariates on erlotinib pharmacokinetics. The presence of single nucleotide polymorphisms (SNP) in ABCB1 (2677G>T/A and 3435C>T), ABCG2 (421C>A) and CYP3A5 (6986G>A) was investigated. Pharmacokinetic/pharmacodynamic relationships between plasma drug exposure (AUC) and early drug response or toxicity were also studied. RESULTS: The covariates retained to predict erlotinib clearance were ALAT (alanine amino transferase), age and ABCG2 polymorphism. A significant link between drug exposure and the grade of skin rash was observed but early response to treatment was not correlated to the erlotinib AUC. CONCLUSIONS: Erlotinib treatment may present criteria justifying dose individualisation but further studies, including more patients, are necessary to define the modalities of this adaptation.

Pilot study of neoadjuvant treatment with erlotinib in nonmetastatic head and neck squamous cell carcinoma.

PURPOSE: To determine the safety and efficacy of erlotinib given as neoadjuvant treatment in patients with head and neck squamous cell carcinoma (HNSCC). Further objectives were to identify markers of response to erlotinib and to assess the pharmacodynamic effects of erlotinib in tumor cells. EXPERIMENTAL DESIGN: Patients with locally advanced nonmetastatic HNSCC were treated with erlotinib 150 mg daily pending surgical management. Tumor samples were collected before and after erlotinib treatment and were analyzed using immunohistochemistry. Epidermal growth factor receptor copy number was determined in tumors using CISH analysis. RESULTS: Between November 2003 and December 2005, 35 patients were included in the study. Neoadjuvant treatment with erlotinib in HNSCC patients was well tolerated and did not necessitate modification to routine surgical procedures. Among 31 evaluable patients, erlotinib was given for a median of 20 days. At the time of surgery, tumor shrinkage was observed in nine patients (29%). Immunohistochemistry analyses were done for 31 patients and showed a decrease in phosphorylated tyrosine residues and phosphorylated erk immunostaining after erlotinib treatment. In a retrospective analysis, baseline p21(waf) expression in the basal-like cell layer was statistically positively correlated with clinical response to treatment. Epidermal growth factor receptor copy number did not correlate with response to erlotinib. CONCLUSION: Neoadjuvant treatment of HNSCC with erlotinib was well tolerated. Baseline p21(waf) expression was associated with response to erlotinib and so might be useful as a tool to select patients for erlotinib therapy in this setting.

Ameloblastic carcinoma of the maxilla: case report and review of the literature.

MATERIAL AND METHODS: A case of ameloblastic carcinoma of the maxilla arising in a 90-year-old patient is presented along with a review of 65 other cases of the international literature. RESULTS: The median age was 44 years with a predominance of men (42/66). The maxilla was concerned in almost one third of cases (21/66). Twenty patients died of disease after a median time of 60 months. Fifteen patients died with metastatic spread in the lung, brain, or bones; the others were due to a local recurrence. The specific survival rate was 68.7% at 5 years. CONCLUSION: Ameloblastic carcinoma is a rare entity of odontogenic tumors that exhibits malignant histologic features in the primary site. Specific mortality, estimated at 31.3% at 5 years, was generally due to a metastatic spread.