S. Vergez

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.

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.

The Role of Radiation Therapy in Pediatric Mucoepidermoid Carcinomas of the Salivary Glands

OBJECTIVE To investigate the role of radiation therapy in rare salivary gland pediatric mucoepidermoid carcinoma (MEC). STUDY DESIGN A French multicenter retrospective study (level of evidence 4) of children/adolescents treated for MEC between 1980 and 2010 was conducted. RESULTS Median age of the 38 patients was 14 years. Parotid subsite, low-grade, and early primary stage tumors were encountered in 81%, 82%, and 68% of cases, respectively. All except 1 patient were treated by tumoral surgical excision, and 53% by neck dissection (80% of high grades). Postoperative radiation therapy and chemotherapy were performed in 29% and 11% of cases. With a median 62-month follow-up, overall survival and local control rates were 95% and 84%, respectively. There was 1 nodal relapse. Lower grade and early stage tumors had better survival. Postoperative radiation therapy and chemotherapy were associated with similar local rates. Patients with or without prior cancer had similar outcomes. CONCLUSIONS Pediatric salivary gland MEC carries a good prognosis. Low-intermediate grade, early-stage tumors should be treated with surgery alone. Neck dissection should be performed in high-grade tumors. Radiation therapy should be proposed for high grade and/or advanced primary stage MEC. For high-grade tumors without massive neck involvement, irradiation volumes may be limited to the primary area, given the risk of long-term side effects of radiation therapy in children. Pediatric MEC as second cancers retain a similar prognosis. Long-term follow-up is needed to assess late side effects and second cancers.

Brachytherapy in lip carcinoma: long-term results.

PURPOSE The aim of this study was to evaluate the effectiveness of low-dose-rate brachytherapy for local control and relapse-free survival in squamous cell and basal cell carcinomas of the lips. We compared two groups: one with tumors on the skin and the other with tumors on the lip. PATIENTS AND METHODS All patients had been treated at Claudius Regaud Cancer Centre from 1990 to 2008 for squamous cell or basal cell carcinoma. Low-dose-rate brachytherapy was performed with iridium 192 wires according to the Paris system rules. On average, the dose delivered was 65 Gy. RESULTS 172 consecutive patients were included in our study; 69 had skin carcinoma (squamous cell or basal cell), and 92 had squamous cell mucosal carcinoma. The average follow-up time was 5.4 years. In the skin cancer group, there were five local recurrences and one lymph node recurrence. In the mucosal cancer group, there were ten local recurrences and five lymph node recurrences. The 8-year relapse-free survival for the entire population was 80%. The 8-year relapse-free survival was 85% for skin carcinoma 75% for mucosal carcinoma, with no significant difference between groups. The functional results were satisfactory for 99% of patients, and the cosmetic results were satisfactory for 92%. Maximal toxicity observed was Grade 2. CONCLUSIONS Low-dose-rate brachytherapy can be used to treat lip carcinomas at Stages T1 and T2 as the only treatment with excellent results for local control and relapse-free survival. The benefits of brachytherapy are also cosmetic and functional, with 91% of patients having no side effects.

Langerhans Cell Histiocytosis of the Thyroid is a Rare Entity, but an Association with a Papillary Thyroid Carcinoma is Often Described

Comments on “Langerhans cell histiocytosis of the lung and thyroid, co-existing with papillary thyroid cancer” Jamaati HR, Shadmehr MB, Saidi B, Khosravi A, Arab M, Mohammadi F. Endocr Pathol 20:133–136, 2009 and “Incidental langerhans cell histiocytosis of thyroid: case report and review of the literature” Foulet-Roge A, Josselin N, Guyetant S, Gardet JJ, Besancon A, Saint-Andre JP, Fabiani B. Endocr Pathol 13:227–233, 2002. We read with great interest the contributions of Jamaati et al. and Foulet-Roge et al. respectively entitled “Langerhans cell histiocytosis of the lung and thyroid, co-existing with papillary thyroid cancer” and “Incidental langerhans cell histiocytosis of thyroid: case report and review of the literature” [1, 2]. We have had a similar case of coexistent thyroid Langerhans cell histiocytosis (LCH) and papillary thyroid carcinoma (PTC). A 29-year-old male patient presented with a huge neck mass, immobile, and compressive, involving the trachea, the pharynx, the left jugular vein and the left carotid sheath. Bone (mandible), lung, skin and hypothalamo-pituitary LCH lesions had been documented for 6 years, and clinical stability had been obtained with corticosteroids. The transpharyngeal biopsies performed during a panendoscopy revealed a PTC with positive immunostaining for TTF1, HBME1 and CK19. Associated LCH involvement was diagnosed by the presence of Langerhans cells reactive to CD1a and S100 protein (Fig. 1). The cytological examination of a blind transcutaneous thyroid fine needle aspiration biopsy and other surgical biopsies isolated only the LCH section and a lymphocytic thyroiditis. A surgical resection of this advanced disease could not be considered and a multidisciplinary panel proposed a medical treatment (Prednisone 40 mg/day). Given that there was no response 6 months later, chemotherapy with Vinblastine (Velbe® 6 mg/m every 2 weeks) produced a stabilization over 14 months. Then, due to a severe increase in size and the extension from the oropharynx to the mediastinum in a vertical axis and from the cervical rachis to the subcutaneous tissues in a horizontal axis, a treatment with Cladribine was initiated (Leustatin® 0.1 mg/kg/day over 5 days every 2 months). After 7 months without a response, the treatment was stopped and changed to Imatinib (Gleevec® 100 mg/day for 1 month and then 400 mg/day). Three months after the beginning of this targeted therapy and 3 years after the appearance of the cervical mass, a dramatic dyspnea caused by the compression and the infiltration of the trachea occurred. A tracheostomy under local anaesthesia was carried out in difficult technical conditions. Despite this attempt, acute pulmonary distress resulted in the death of the patient. The family refused an autopsy. S. Vergez (*) Department of Head and Neck Surgery, University-Hospital Rangueil-Larrey, 24 chemin de Pouvourville, 31059 Toulouse Cedex 9, France e-mail: vergez.s@chu-toulouse.fr

Preclinical and Clinical Evidence that Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography with Computed Tomography Is a Reliable Tool for the Detection of Early Molecular Responses to Erlotinib in Head and Neck Cancer

Purpose: There is a clinical need to identify predictive markers of the responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Deoxy-2-[18F]fluoro-d-glucose positron emission tomography with computed tomography (18FDG-PET/CT) could be a tool of choice for monitoring the early effects of this class of agent on tumor activity. Experimental Design: Using models of human head and neck carcinoma (CAL33 and CAL166 cell lines), we first tested in vitro and in vivo whether the in vivo changes in 18FDG-PET/CT uptake were associated with the molecular and cellular effects of the EGFR-TKI erlotinib. Then, the pathologic and morphologic changes and the 18FDG-PET/CT uptake before and after erlotinib exposure in patients were analyzed. Results: Erlotinib strongly inhibited extracellular signal-regulated kinase-1/2 (ERK-1/2) phosphorylation both in the preclinical models and in patients. Western blotting, immunofluorescence, and immunohistochemistry showed that erlotinib did not modify Glut-1 expression at the protein level either in cell line models or in tumor tissue from mouse xenografts or in patients. Phospho-ERK-1/2 inhibition was associated with a reduction in 18FDG uptake in animal and human tumors. The biological volume was more accurate than the standardized uptake value for the evaluation of the molecular responses. Conclusion: These results show that the 18FDG-PET/CT response is a reliable surrogate marker of the effects of erlotinib in head and neck carcinoma. Clin Cancer Res; 16(17); 4434–45. ©2010 AACR.

Clinical outcomes with transoral robotic surgery for supraglottic squamous cell carcinoma: Experience of a French evaluation cooperative subgroup of GETTEC

Transoral, minimally invasive, organ preservation surgeries are increasingly used to treat laryngopharyngeal carcinomas to avoid the toxicity associated with combined chemoradiotherapy (CRT) regimens. This study investigated the efficiency, safety, and functional outcomes of using transoral robotic surgery (TORS) to perform supraglottic laryngectomy (SGL).

Initial staging of squamous cell carcinoma of the oral cavity, larynx and pharynx (excluding nasopharynx). Part I: Locoregional extension assessment: 2012 SFORL guidelines.

OBJECTIVES To set out good practice guidelines for locoregional extension assessment of squamous cell carcinoma of the head and neck (excluding nasopharynx, nasal cavities and sinuses). MATERIALS AND METHODS A critical multidisciplinary review of the literature on locoregional extension assessment of squamous cell carcinoma of the head and neck was conducted, applying levels of evidence in line with the French health authoritys (HAS) literature analysis guide of January 2000. CONCLUSION Based on the levels of evidence of the selected articles and on work-group consensus, graded guidelines are set out for clinical, endoscopic and imaging locoregional extension assessment of head and neck cancer.

A comparative immunohistochemistry study of diagnostic tools in salivary gland tumors: usefulness of mammaglobin, gross cystic disease fluid protein 15, and p63 cytoplasmic staining for the diagnosis of mammary analog secretory carcinoma?

BACKGROUND Mammary analog secretory carcinoma (MASC) of the salivary gland has been recently described according to morphological, immunohistochemical, and molecular (ETV6-NTRK3 translocation) similarities with the mammary secretory carcinoma. The most important differential diagnostic considerations of MASC are low-grade adenocarcinoma not otherwise specified (NOS), cystadenocarcinoma, and acinic cell carcinoma (AciCC). These tumors may share an overlapping morphology with MASC, and additional immunohistochemical studies are required to reinforce the diagnosis. Mammaglobin, GCDFP-15, and p63 staining have been reported in MASC. Our study was designed to check the specificity of these antibodies in MASC compared to other frequent tumors of salivary glands. METHODS A series of 62 salivary gland tumors [10 MASCs, 5 adenocarcinomas NOS and 2 cystadenocarcinomas with MASC features and without ETV6 rearrangement, one low-grade cribriform cystadenocarcinoma (LGCCC), 9 AciCCs, 10 MECs, 10 adenoid cystic carcinomas (AdeCCs), 5 polymorphous low-grade adenocarcinomas (PLGAs), and 10 pleomorphic adenomas (PAs)] was analyzed by immunohistochemistry with mammaglobin, GCDFP-15, and p63 antibodies. RESULTS Positivity for mammaglobin was observed in all MASCs, cystadenocarcinomas, LGCCC, and PLGAs, in some adenocarcinomas NOS, PAs, and MECs, rarely in AciCCs and never in AdeCCs. Positivity for GCDFP-15 was observed in most of the tumor types except in AdeCCs. Interestingly, cytoplasmic positivity for p63 was observed in most of MASCs and PLGAs while rarely in adenocarcinomas NOS and PAs, and never in the other tumor types. CONCLUSION Our study revealed the usefulness of mammaglobin and p63 cytoplasmic staining to define which tumors are worth to be screened for ETV6 rearrangement.

Endoscopic vs Transfacial Resection of Sinonasal Adenocarcinomas

Objectives. Compare the survival and the complication rates of 2 comparable groups of patients who underwent either endoscopic or transfacial resection of a sinonasal adenocarcinoma. Study Design. Historical cohort study. Setting. Tertiary referral center. Subjects and Methods. Twenty-four patients with sinonasal adenocarcinomas who recently underwent an endoscopy (the ENDO group, 1999-2009) were compared with 24 patients who underwent a lateral rhinotomy procedure (the LR group, 1993-2007). The present retrospective study included patients who would have had an endoscopic resection in 2011. Results. The groups were comparable in terms of age and sex (P = .49), as well as tumor stages; 43 of the 48 patients had undergone postoperative radiotherapy. There were 13 T1-T2 and 11 T3-T4 tumors in the ENDO group compared with 12 T1-T2 and 12 T3-T4 tumors in the LR group (P = .77). The mean length of follow-up was 38 months for the ENDO group and 89 for the LR group. The overall survival and recurrence-free rates were not significantly different (P = .3 and P = .87, respectively). The median duration of hospitalization was significantly shorter in the ENDO group than in the LR group (4 vs 8 days, P < .0001). The rate of early complications was identical in both groups (12.5%). Conclusion. The endoscopic approach is a safe and effective treatment in selected sinonasal adenocarcinoma cases. The early oncological outcome and morbidity associated with the endoscopic approach were comparable with a transfacial approach. Hospitalization was significantly reduced by the endoscopic approach. Although the endoscopic approach is less invasive, it requires an optimal preoperative imaging protocol and an experienced surgical team.