Emile Reyt

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

PURPOSE To compare the efficacy and safety of induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) or bioradiotherapy (BRT) for larynx preservation (LP). PATIENTS AND METHODS Previously 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. RESULTS Of 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. CONCLUSION There 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.

Tumor-Specific Methylation in Saliva: A Promising Biomarker for Early Detection of Head and Neck Cancer Recurrence

Purpose: Our goal was to define tumor and saliva gene methylation profile of head and neck squamous cell carcinoma and to evaluate its prognostic significance and its biomarker potential for early detection of relapse. Experimental Design: We prospectively analyzed 11 genes by methylation-specific PCR on primary tumors, histologically normal adjacent mucosa, and saliva from 90 French patients at diagnosis and during follow-up as well as on 30 saliva specimens from control-matched patients with nonmalignant head and neck pathology. Five additional genes were analyzed on 50 tumors of the series. Results: Methylation of TIMP3, ECAD, p16, MGMT, DAPK, and RASSF1 was the most frequently observed in tumors and paired saliva samples were analyzed at diagnosis, with an excellent agreement between both samples. At least one of these six genes was methylated in >75% of the samples without additional positive samples when other genes were analyzed. Methylation profile was similar in newly diagnosed and second primary cancers. Aberrant methylation was not associated with a worse prognosis. Ninety percent of normal adjacent mucosa and all control saliva samples were negative. Twenty-two patients were followed after treatment; abnormal methylation was detectable in the saliva of five patients few months before clinical and 2-deoxy-2[18F]fluoro-d-glucose-positron emission tomography signs of relapse, allowing curable surgery. Saliva samples were negative for the 17 other patients: 16 were in remission and only 1 relapsed. Conclusions: Gene methylation in saliva is a promising biomarker for the follow-up and early detection of still curable relapses of head and neck squamous cell carcinoma patients.

Adenocarcinoma of Ethmoid: A GETTEC Retrospective Multicenter Study of 418 Cases

Objective: To determine risk factors and evaluate the treatment of ethmoid adenocarcinoma. Epidemiologic data were recorded and compared with the literature.

The pectoralis myofascial flap in pharyngolaryngeal surgery after radiotherapy

Pharyngocutaneous fistula after total laryngectomy remains a hardly inevitable complication. The predisposing factors are not clearly identified, but prior radiotherapy seems to increase the risk of fistulae. The purpose of this retrospective study was to determine the value of the pectoralis myofascial flap in pharyngeal reconstruction in post-radiotherapy total laryngectomy in order to decrease the risk of fistula formation. The charts of 60 consecutive patients who had undergone total laryngectomy or pharyngolaryngectomy after radiotherapy were analyzed. Twenty-one variables were recorded for each patient. The overall rate of fistula formation was 38% (23% when a pectoralis myofascial flap was used to cover the pharynx and 50% when no flap was used, P=0.06). The flap-related complications were exceptional. In the subgroup of patients with diabetes mellitus, a history of vascular disease or a poor nutritional status, the use of a flap reduced the fistula formation from 73 to 13% (P=0.018). The pectoralis myofascial flap covering the pharyngeal sutures in postradiotherapy laryngectomy is particularly useful in a selected group of patients (with diabetes mellitus, history of vascular disease or poor nutritional status).

Immunohistochemical detection of p53 protein in preneoplastic lesions and squamous cell carcinoma of the head and neck

Alterations in the p53 tumor suppressor gene are the most frequent genetic abnormalities in human cancers. The p53 protein is present in normal cells, and is assumed to induce G1 arrest or apoptosis in the presence of DNA lesion. The mutant protein lacks this property. Squamous cell carcinomas of the head and neck (SCCHN) are related to carcinogens in tobacco and alcohol, and provide a good model of multiple-step carcinogenesis in association with DNA damage and p53-related tumorigenesis. Stabilization of the mutant p53 protein allows immunohistochemical analyses (IHC) to be routinely used to demonstrate the mutant p53 protein in tissue samples, whereas normal p53 protein is undetectable. Ninety-nine squamous cell carcinomas, 8 in situ carcinomas, 31 preneoplastic lesions and 79 normal carcinogen-exposed mucosas of the head and neck from a total of 107 patients were examined for the expression of p53 tumor suppressor gene protein. Samples were collected before treatment, and stained with p53 specific mono- and polyclonal antibodies (DO-7, Pab 1801 and 240, CM1) using an indirect immunoperoxidase technique. Proliferating cell nuclear antigen (PCNA) provided semiquantitative estimates of proliferation. The main localizations were the pharynx (64/107) and the larynx (21/107). Positive IHC detection of p53 was observed in 9% of normal-appearing carcinogen-exposed mucosas, 37% of hyperplasias, 68% of dysplasias, 75% of in situ carcinomas, and 56/99 (56.5%) of primary tumor samples. Mucosas from 15 control patients under 10 years of age were negative. There was no correlation between p53 IHC and localization, differentiation or TNM staging.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized phase III trial comparing induction chemotherapy followed by radiotherapy to concomitant chemoradiotherapy for laryngeal preservation in T3M0 pyriform sinus carcinoma.

Conclusions. Conventional radiotherapy with concurrent cisplatin is significantly superior to induction cisplatin fluorouracil chemotherapy followed by radiotherapy in terms of laryngeal preservation in patients with T3 hypopharyngeal carcinoma. Despite a high rate of laryngeal preservation no survival benefit was recorded in this selected population. Objectives. To compare conventional radiotherapy with concurrent cisplatin to induction chemotherapy with cisplatin fluorouracil followed by conventional radiotherapy. The primary end point was the preservation of the larynx. The secondary end points included toxicity, causes of death, and survival rates. Patients and methods. Seventy-one adult patients with previously untreated resectable T3 pyriform sinus squamous cell carcinoma were enrolled in the multicenter prospective randomized phase III trial. They were evaluated for organ preservation, survival rates, and toxic reactions. Results. The rates of laryngeal preservation at 2 years were 68% for the induction chemotherapy (IC) group and 92% for the chemoradiotherapy (CR) group (p = 0.016). At 2 years, the event-free survival rates were 36% and 41% for the IC group and CR group, respectively.

Lemierre syndrome: study of 11 cases and literature review.

Lemierre syndrome is a rare but serious illness that associates throat infection and thrombosis of the internal jugular vein (IJV) or one of its tributaries with subsequent distant septic emboli. The purpose of our study was to review the pathogenesis, clinical presentation, and treatment of this disease.

A rationale for chemoradiation (vs radiotherapy) in salivary gland cancers? On behalf of the REFCOR (French rare head and neck cancer network)

BACKGROUND Salivary gland carcinomas constitute a heterogeneous group of tumors, with over 20 histological subtypes of various prognoses. The mainstay of treatment is surgery, with radiotherapy advocated for unresectable disease or postoperatively in case of poor prognostic factors such as high grade, locally advanced and/or incompletely resected tumors. Concurrent chemotherapy is sometimes advocated in routine practice based on criteria extrapolated from squamous cell carcinomas of the head and neck, on radioresistance of salivary gland tumors and on results obtained in the metastatic setting. The aim of this review was to identify situations where chemotherapy is advocated. MATERIAL AND METHODS A search of literature was performed with the following key words: parotid, salivary gland, neoplasm, cancer, malignant tumor, chemoradiation, chemotherapy, radiotherapy and treatment. Case report and studies published before 2000 were not included. RESULTS Platinum-based regimens were the most frequent. Other regimens were reported and seemed dependent on histology. The level of evidence for the concurrent delivery of chemotherapy with radiation therapy is supported by a low level of evidence. Prescribing chemotherapy mostly relies on poor prognostic factors similar to those used to indicate high dose radiotherapy. Protocols vary with histology. CONCLUSION The rationale for adding chemotherapy to radiotherapy remains to be demonstrated prospectively. Although the type of systemic treatments used may be adapted on histology, the strongest rationale remains in favor of cisplatin.

Syndrome de Lemierre : revue de la littérature

Objectifs Le but de notre travail etait de rappeler la pathogenie, la clinique et le traitementdu syndrome de Lemierre. Patients et methodes Il s’agit d’une etude retrospective (1998-2005) de quatre patients, trois hommes et une femme, d’un âge moyen de 22 ans (18-30). Tous les patientsont eu des prelevements bacteriologiques, une radiographie pulmonaire et un scanner injecte cervico-thoracique. Tous ont eu une antibiotherapie a large spectre d’une duree de 4 a 6 semaines. Trois ont necessite un traitement chirurgical. Une revue de la litterature apartir de la base de donnees informatisee Medline a ete realisee. Resultats Trois patients presentaient un abces para-amygdalien. Tous presentaient unethrombose de la veine jugulaire interne (VJI) ou une de ses branches. Il existait dans tous lescas des emboles septiques pulmonaires. Chez un patient etaient associees une arthrite etune mediastinite. Dans trois cas, du Fusobacterium (necrophorum — 2, nucleatum — 1) aete isole. Dans un cas, les prelevements bacteriologiques n’ont pas permis l’isolement d’ungerme. Un passage en reanimation medicale a ete necessaire pour un patient. L’evolution aete favorable dans tous les cas. Conclusions Le syndrome de Lemierre est une pathologie rare et grave qui touche lessujets jeunes non immunodeprimes. La pathogenie consiste en une thrombose septique dela VJI ou une de ses collaterales consecutive a un foyer infectieux le plus souvent oropharynge,a l’origine d’emboles septiques, generalement pulmonaires. Le traitement est avanttout medical, parfois chirurgical.

Near‐infrared fluorescence imaging‐guided surgery improves recurrence‐free survival rate in novel orthotopic animal model of head and neck squamous cell carcinoma

Appropriate animal models are required to test novel therapeutics for head and neck squamous cell carcinoma (HNSCC) such as near‐infrared (NIR) imaging‐guided surgery.