Dominique Chevalier

Induction Chemotherapy Followed by Either Chemoradiotherapy or Bioradiotherapy for Larynx Preservation: The TREMPLIN Randomized Phase II Study

PURPOSEnTo compare the efficacy and safety of induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) or bioradiotherapy (BRT) for larynx preservation (LP).nnnPATIENTS AND METHODSnPreviously untreated patients with stage III to IV larynx/hypopharynx squamous cell carcinoma received three cycles of ICT-docetaxel and cisplatin 75 mg/m(2) each on day 1 and fluorouracil 750 mg/m(2) per day on days 1 through 5. Poor responders (< 50% response) underwent salvage surgery. Responders (≥ 50% response) were randomly assigned to conventional radiotherapy (RT; 70 Gy) with concurrent cisplatin 100 mg/m(2) per day on days 1, 22, and 43 of RT (arm A) or concurrent cetuximab 400 mg/m(2) loading dose and 250 mg/m(2) per week during RT (arm B). Primary end point was LP at 3 months. Secondary end points were larynx function preservation (LFP) and overall survival (OS) at 18 months.nnnRESULTSnOf the 153 enrolled patients, 116 were randomly assigned after ICT (60, arm A; 56, arm B). Overall toxicity of both CRT and BRT was substantial following ICT. However, treatment compliance was higher in the BRT arm. In an intent-to-treat analysis, there was no significant difference in LP at 3 months between arms A and B (95% and 93%, respectively), LFP (87% and 82%, respectively), and OS at 18 months (92% and 89%, respectively). There were fewer local treatment failures in arm A than in arm B; salvage surgery was feasible in arm B only.nnnCONCLUSIONnThere is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone (French Groupe Oncologie Radiothérapie Tête et Cou [GORTEC] 2000-01 trial [Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma]). The protocol that can best compare with RT alone after ICT is still to be determined.

Galectin 7 (p53-induced gene 1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer.

BackgroundEighty percent of hypopharyngeal squamous cell carcinoma patients have advanced stages (III and IV) of the disease, and biological markers are required to predict high-risk head and neck squamous cell carcinoma patients in need of highly aggressive treatments after surgery to improve the survival rate. We analyzed the potential prognostic value of galectin 7 in a series of 81 stage IV hypopharyngeal SCCs because galectin 7 is an emerging marker involved in the epidermal development of pluristratified epithelia and in epidermal cell migration.MethodsThe immunohistochemical expression of galectin 7 was determined on a series of 81 stage IV hypopharyngeal SCCs and was compared with that of galectins 1 and 3.ResultsHigh levels of galectin 7 expression were associated with rapid recurrence rates and dismal prognoses in these 81 stage IV hypopharyngeal SCCs, a feature not observed with galectin 3 and one observed weakly, if at all, with galectin 1.ConclusionsThese data suggest that the immunohistochemical determination of galectin 7 expression in the case of high-risk hypopharyngeal cancers is a meaningful tool to identify patients who should benefit from aggressive postsurgical adjuvant therapy after surgery, including not only radiotherapy, but also chemotherapy.

Local Recurrence after CO2 Laser Cordectomy for Early Glottic Carcinoma

Objectives: To point out prognosis factors of local recurrence after endoscopic cordectomies for Tis, T1a, T1b, and T2 glottic squamous cell carcinomas.

Increased expression and altered intracellular distribution of adhesion/growth‐regulatory lectins galectins‐1 and ‐7 during tumour progression in hypopharyngeal and laryngeal squamous cell carcinomas

Aims: To examine the level of expression of the pleiotropic regulators galectins‐1 and ‐7 in relation to neoplastic progression of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas.

Schwannoma of the Sinonasal Tract A Clinicopathologic and Immunohistochemical Study of 5 Cases

CONTEXTnPeripheral nerve sheath tumors are soft tissue neoplasms rarely encountered in the nasal cavity and paranasal sinuses.nnnOBJECTIVEnTo describe the clinicopathologic and immunohistochemical features of a series of schwannomas of the sinonasal tract.nnnDESIGNnSurgical pathology files were searched for the diagnosis sinonasal schwannoma. All histologic documents and clinical data were reviewed. Immunohistochemistry was performed on paraffin-embedded tissue with antibodies to S100 protein, epithelial membrane antigen, CD34, and MIB-1. RESULSTS: Five cases of sinonasal schwannoma were retrieved; patients included 3 women and 2 men, aged 20 to 56 years. Three cases were located in the ethmoid sinus. Clinical symptoms were nonspecific (nasal obstruction, epistaxis, and anosmia). All tumors were treated with conservative surgical resection. Pathologic examination showed a spindle cell proliferation without encapsulation in all cases. No cytologic atypia was seen, and the mitotic activity was low (<3 mitotic figures/10 high-power fields). Immunohistochemistry showed diffuse positivity with S100 protein and negativity with CD34 and epithelial membrane antigen. MIB-1 staining was low (1%-5% of tumor cell nuclei stained). During the follow-up (median, 6 years), no recurrence or metastasis was observed.nnnCONCLUSIONSnSchwannoma is a very unusual tumor of the sinonasal tract and is associated with nonspecific symptoms. Histologically, sinonasal schwannomas differ from schwannomas of other locations by their lack of a peripheral capsule and possible ulceration of the epithelial covering. Sinonasal schwannomas are treated with conservative surgical resection and have an excellent prognosis.

Supraglottic hemilaryngopharyngectomy plus radiation for the treatment of early lateral margin and pyriform sinus carcinoma

Supraglottic hemilaryngopharyngectomy is a functional procedure suitable for the treatment of carcinoma of the upper part of the pyriform sinus and carcinoma of the lateral laryngeal margin. It consists of resection of the supraglottic hemilarynx and ipsilateral pyriform sinus.

Galectin-3 upregulation during tumor progression in head and neck cancer.

Objectives/Hypothesis: To examine the level of expression of galectin‐3 in relation to neoplastic progression of hypopharyngeal squamous cell carcinomas (HSCCs) and laryngeal squamous cell carcinomas (LSCCs).

Indications and Results of Anterior Mediastinal Tracheostomy for Malignancies

BACKGROUNDnThis study was designed to assess the early and long-term results, and determine suitable indications of anterior mediastinal tracheostomy, after radical resection for cervicothoracic malignancies.nnnMETHODSnFrom 1985 to 2009, 13 patients ranging in age from 40 to 75 years underwent an anterior mediastinal tracheostomy for malignancy, 2 as an isolated procedure, 5 with concomitant laryngectomy, and 6 with concomitant laryngopharyngoesophagectomy. The patients had subglottic carcinoma, proximal tracheal carcinoma invading the subglottic larynx (n = 6), stomal recurrence following laryngectomy (n = 4), esophageal carcinoma invading the proximal trachea (n = 2), or tracheal recurrence after conventional resection (n = 1). The postoperative course and outcome were assessed in all patients.nnnRESULTSnIn 5 patients, the postoperative course was uneventful. There were 2 in-hospital deaths, and 6 patients experienced nonfatal complications including three pharyngocutaneous fistulas, two pharyngogastric or pharyngocolic anastomotic leaks, and one pulmonary embolism. Satisfactory airway was achieved in 7 patients presenting with proximal obstruction, and ability to tolerate oral feeding, in 2 patients with esophageal carcinoma. The mean follow-up time for survivors was 89 months (range, 9 to 201 months). Patients with esophageal carcinoma or recurrence of tracheal carcinoma showed a poor outcome. In contrast, in the subgroup of patients with head and neck malignancy, 3-year and 5-year survival rates were 57% and 43%, respectively.nnnCONCLUSIONSnOur results and survival analysis from the literature suggest that suitable indications for anterior mediastinal tracheostomy are (1) carcinoma of the subglottic region or proximal trachea invading the subglottic larynx, (2) stomal recurrence after laryngectomy, and (3) well-differentiated thyroid carcinoma invading the trachea or recurrence.

Surgical management of sinonasal inverted papillomas through endoscopic approach

We defined a standardized approach to surgery of sinonasal inverted papillomas (IP) for adequate and safe resection. A cohort of 65 patients treated from January 1995 to December 2005 at a single institution was retrospectively analyzed (mean follow-up: 28xa0months; range 1–132). The extension of the tumor was evaluated on clinical findings and computed tomography (CT) scan and/or resonance magnetic imaging (RMI). External and endoscopic surgical approaches were compared according to tumor extension, rate of local recurrence. Univariate analysis was used to review the impact on disease-free survival of factors related to the histopathological findings and the treatment. Endoscopic (alone or combined with transantral approach) and external surgery were used in 46 patients (71%) and 19 patients, respectively. Endoscopic approach (34/46) was performed to control IP in the nasal fossa, the ostiomeatal complex, the sphenoid sinus. It was combined with Caldwell-Luc procedure (12/46) for tumor extent into the lateral part of the maxillary sinus. The mean time for recurrences to occur was 19xa0months with range of 5–35xa0months. The rate of local recurrence was 17.6% (6/34) in endoscopic approach alone, 8.3% in endoscopic approach combined with a Caldwell-Luc procedure and 15.8% (3/19) in external approach. Tumor extension, excision with safe margins, associated malignancy or dysplasia have no significant impact on disease-free survival regardless of surgical procedure. On the basis of imaging evaluation and peroperative view of tumor extent, we propose a surgical strategy in which endoscopic approach could be used on the first attempt by trained surgeons. RMI is very useful to determine acute extent of the disease.

Macrophage migration inhibitory factor in head and neck squamous cell carcinoma: clinical and experimental studies

PurposeThe present in vivo/in vitro study was undertaken in order to evaluate the importance of macrophage migration inhibitory factor (MIF) in the progression of head and neck squamous cell carcinoma (HNSCC).MethodsTumor tissue expression (MIF immunostaining) and plasma levels (ELISA) of MIF were determined in HNSCC patients and correlated with tumor recurrence and metastasis, and overall survival. Furthermore, the impact of MIF expression on cell proliferation and anticancer drug sensitivity was examined in murine squamous carcinoma cell line SCCVII after MIF knockdown (MIF-KD).ResultsAs revealed by quantitative analysis of MIF immunostaining, tumor progression was accompanied by an increase in mean optical density (MOD) and labeling index (LI). Likewise, an elevation of MIF serum levels was noted in HNSCC patients (nxa0=xa066) versus healthy individuals (nxa0=xa016). Interestingly, comparison of laryngeal carcinoma patients on the basis of MIF tissue expression (high expression, LIxa0≥xa047, versus low expression, LIxa0<xa047) disclosed a significant difference between disease-free survival curves for local and nodal recurrence, and overall survival curve. In vitro, MIF knockdown in murine SCCVII cells resulted in reduced cell proliferation and a decrease in cell motility. In mice inoculated with SCCVII cells, MIF-KD tumors grew more slowly and also appeared more sensitive to chemotherapy.ConclusionsBoth clinical observations and experimental data suggest that MIF plays a pivotal role in the progression of HNSCC.