Prognostic value of tumor mutational burden in patients with oral cavity squamous cell carcinoma treated with upfront surgery.

BACKGROUND: Oral cavity is the most prevalent site of head and neck squamous cell carcinomas (HNSCCs). Most often diagnosed at a locally advanced stage, treatment is multimodal with surgery as the cornerstone. The aim of this study was to explore the molecular landscape of a homogenous cohort of oral cavity squamous cell carcinomas (OCSCCs), and to assess the prognostic value of tumor mutational burden (TMB), along with classical molecular and clinical parameters. PATIENTS AND METHODS: One hundred and fifty-one consecutive patients with OCSCC treated with upfront surgery at the Institut Curie were analyzed. Sequencing of tumor DNA from frozen specimens was carried out using an in-house targeted next-generation sequencing panel (571 genes). The impact of molecular alterations and TMB on disease-free survival (DFS) and overall survival (OS) was evaluated in univariate and multivariate analyses. RESULTS: Pathological tumor stage, extranodal spread, vascular emboli, and perineural invasion were associated with both DFS and OS. TP53 was the most mutated gene (71%). Other frequent molecular alterations included the TERT promoter (50%), CDKN2A (25%), FAT1 (17%), PIK3CA (14%), and NOTCH1 (15%) genes. Transforming growth factor-ß pathway alterations (4%) were associated with poor OS (P = 0.01) and DFS (P = 0.02) in univariate and multivariate analyses. High TMB was associated with prolonged OS (P = 0.01 and P = 0.02, in the highest 10% and 20% TMB values, respectively), but not with DFS. Correlation of TMB with OS remained significant in multivariate analysis (P = 0.01 and P = 0.005 in the highest 10% and 20% TMB values, respectively). Pathological tumor stage combined with high TMB was associated with good prognosis. CONCLUSION: Our results suggest that a high TMB is associated with a favorable prognosis in patients with OCSCC treated with upfront surgery.

Morbidity and mortality revue of the French group of transoral robotic surgery: a multicentric study.

Transoral robotic assisted surgery (TORS) represents an innovative endoscopic therapeutic alternative in the treatment of head and neck tumors. Many publications favor this surgery, especially in terms of functional results. The aim of this study was to investigate the TORS morbidity and mortality and to identify the risk factors for complications. It is a multicenter retrospective study. All head and neck tumor patients treated by TORS were included in the study over a period of 5 years (2009-2014). The studied parameters were the intraoperative and post-operative complications including hemorrhage, fistula, tracheotomy, aspiration pneumonia and death. The parameters were correlated with age, tumor location, tumor stage, endoscopic exposure and patient's co-morbidities. 178 patients were included in the study. Malignant tumors classified as T1 were found in 169 cases (n = 51), T2 (n = 100), T3 (n = 16) and T4 (n = 2). The tumor locations were distributed as follows: larynx (n = 84), oropharynx (n = 51), and hypopharynx (n = 43). Fifty-three patients followed post-radiation therapy. We observed 12 intraoperative complications including 6 hemorrhage, 3 pharyngeal fistulas and 3 external surgical conversions. Postoperatively, we detected 33 hemorrhage, 27 aspiration pneumonia, 9 tracheostomy, 2 pharyngostomes, 2 cervical spondylitis and 2 deaths. The risk factors identified were (i) anticoagulant and/or antiplatelet therapy for hemorrhage, (ii) tumoral stage and the laryngeal location for aspiration pneumonia and (iii) laryngeal location for tracheostomy. Higher age over 65 years has been identified as a risk factor for all post-operative complications. TORS is a safe technique for the treatment of head and neck tumors. We identified some risk factors for complications which should systematically be studied in order to reduce its morbidity.

Cervical lymph node metastases and T1 squamous cell carcinoma of the lips.

OBJECTIVE: The occurrence of cervical lymph node metastasis is a major prognostic factor for head and neck squamous cell carcinoma (SCC) of the lip. This study focuses on patients with T1 stage tumours,in order to describe the prevalence of metastatic lymphadenopathies. METHODS: A multicenter retrospective study was performed in three tertiary care referral centers and included 59 patients surgically treated for T1 stage SCC of the lips from January 1996 to December 2006. This surgical treatment concerned the tumour, with cervical neck dissection when lymph node metastasis was suspected. RESULTS: Cervical lymph node metastasis was found and histologically proven in 7 patients (11.9% of the cases, pN+ group; 95% confidence interval, 3.6 to 20.2%) during follow-up, never at the time of diagnosis. Metastasis appeared 13.3 ± 7.9 months (min. 5.3 months, max. 29.1 months) after the initial treatment and involved the IB level in all cases. Tumour progression was significantly longer in the pN+ group compared to patients with no lymph node metastases (sN-group). The pN+ group also had a significantly higher proportion of poorly or moderately differentiated tumours, and a significant decrease in overall survival, disease-free survival, and disease-specific survival. CONCLUSION: Lymph node metastasis occurs in roughly 12% of T1 stage SCC of the lips, and the management of neck lymph node areas is necessary. A randomized trial is needed to determine the proportion of occult lymph node metastases in T1N0 patients and the impact of this therapeutic procedure on survival.

Guidelines update: Post-treatment follow-up of adult head and neck squamous cell carcinoma: Screening for metastasis and metachronous esophageal and bronchial locations.

OBJECTIVE: The present article is an update of the guideline of the French Society of Otorhinolaryngology and Head and Neck Surgery (SFORL) on the post-treatment follow-up of adult head and neck squamous cell carcinoma concerning screening for metastasis and metachronous esophageal and bronchial locations. METHODS: A multidisciplinary work-group was entrusted with a review of the literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the work-group members' own experience. These were then reviewed by an editorial group independent of the work-group. A coordination meeting then finalized the guidelines. Guidelines were graded A, B, C or "expert opinion" according to decreasing level of evidence.

Guidelines of the French Society of Otorhinolaryngology (SFORL), short version. Diagnosis of local recurrence and metachronous locations in head and neck oncology.

Surveillance is fundamental to the management of head and neck cancer. The present guidelines of the French ENT society (SFORL) were drawn up by a group of experts in the field, and are intended to specify the modalities of management, based on a review of the literature and, where data are lacking, to provide expert opinion. The present paper deals with guidelines for the diagnosis of local and regional recurrence and metachronous head and neck locations. Locoregional recurrence usually occurs within 3 years of primary treatment and is mainly related to the characteristics of the primary tumor and the treatment measures taken. Laryngeal location, safe primary resection margins, low level of lymph node invasion, unimodal primary treatment and early diagnosis of recurrence are factors of good prognosis. Systematic imaging surveillance may be considered for patients for whom a curative technique exists and when surveillance is difficult. The role of PET-scanning remains to be determined. Metachronous locations are frequent, even in the late course; prolonged surveillance is appropriate. The best preventive measure is cessation of alcohol abuse and smoking. Patient education is primordial.

French Society of ENT (SFORL) guidelines for care pathway organization in head and neck oncology (short version). Early management of head and neck cancer.

Early management in oncology is based on coordination and high-quality exchange between the various health-care partners. The present guidelines are based on a literature search with levels of evidence. Treatment waiting time can be optimized by performing assessment as early as possible (Expert opinion), to limit the interval (ideally, less than 4 weeks) between first consultation and data collection. In the first specialist consultation, diagnostic work-up should be scheduled and the data required for management should be determined (Grade B). Work-up may be conducted on a day-care basis or with conventional admission (Expert opinion). The patient's medico-social context should be taken into account from the outset, with social work involvement whenever necessary (Expert opinion). Pain and nutritional management should be planned for (Grade A) and realistic therapeutic education be provided (Expert opinion). Community-hospital teamwork for supportive care should be optimized (Expert opinion). Management should be early and multidisciplinary, to shorten delay between diagnosis and treatment initiation.

Guidelines (short version) of the French Otorhinolaryngology - Head and Neck Surgery Society (SFORL) on patient pathway organization in ENT: The therapeutic decision-making process.

OBJECTIVES: The authors present the guidelines of the French Otorhinolaryngology - Head and Neck Surgery Society (SFORL) for patient pathway organization in head and neck cancer, and in particular for multidisciplinary team meetings. The present article concerns the therapeutic decision-making process. METHODS: A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. RESULTS: It is recommended that: an organ specialist should contribute to all multidisciplinary meetings on head and neck cancer; all members of the multidisciplinary meeting should have specific knowledge in head and neck cancer; any referring physician who does not follow the multidisciplinary meeting's advice should justify that decision; there should be sufficient time to prepare, discuss and sum up the cases dealt with in the multidisciplinary team meeting.

Rapidly progressive bilateral postmeningitic deafness in children: Diagnosis and management.

OBJECTIVES: To determine the diagnostic approach to severe or profound bilateral postmeningitic deafness and to propose management guidelines. MATERIAL AND METHODS: A retrospective review of five patients (two adolescents and three infants) with rapidly progressive severe bilateral deafness following an episode of meningitis managed between 2004 and 2010. RESULTS: The two adolescents presented Neisseria meningitidis meningitis and the three infants presented Streptococcus pneumoniae meningitis. Acquired bilateral deafness was diagnosed by audiometry an average of 68.8 days (range: 9-210) after the episode of meningitis. Behavioural audiological testing, adapted to age and state of health, was performed in all patients. Deafness was confirmed by Auditory Brainstem Response tests. All five patients were assessed by computed tomography (CT) and magnetic resonance imaging (MRI) within ten days. T2-weighted MRI sequences showed endolymph changes in four patients. CT scan demonstrated ossification in only one patient. Bilateral cochlear implant was performed in all patients, with complete electrode array insertion for eight implants and partial insertion for two implants (20 and 21 out of 22 electrodes inserted). Good results were obtained with cochlear implants in four cases. CONCLUSIONS: Bilateral deafness can occur immediately or several months after bacterial meningitis, regardless of the micro-organism responsible, justifying screening by behavioural audiological testing adapted to age for two years following bacterial meningitis. Auditory Brainstem Response testing can confirm audiometric findings. When severe or profound bilateral deafness is observed, MRI must be performed urgently to detect endolymph inflammation or ossification. Early bilateral cochlear implantation is recommended in the presence of ossification.

BRAF mutation in papillary thyroid carcinoma: predictive value for long-term prognosis and radioiodine sensitivity.

OBJECTIVES: BRAF pV600E mutation is the most common oncogenic event and the most specific mutation for papillary thyroid carcinoma (PTC). Many studies over the last decade have shown a direct relationship between BRAF mutation and aggressive tumour characteristics, resulting in poor prognosis. However, several recent studies have suggested that BRAF mutation is not associated with poor prognosis of PTC. The present study was designed to evaluate the association between BRAF mutation with clinicopathological factors and tumour recurrence. MATERIAL AND METHODS: In this retrospective study, BRAF mutation status was examined by direct sequencing on paraffin-embedded tumour specimens from 46 patients undergoing surgery for PTC in our institution from 1985 to 2000. The relationship between BRAF mutation and gender, advanced age, extrathyroid extension, multifocal tumour, cervical lymph node metastasis, tumour size and advanced pT stage of PTC and its predictive role for the risk of tumour recurrence were investigated with a median follow-up of 10.1 (±6.5)years. RESULTS: BRAF mutation was detected in 20 of the 46 patients (43.5%) included in the study. No statistically significant correlation was demonstrated between the presence of BRAF mutation and the various clinicopathological factors studied. No significant difference in tumour recurrence rate or radioiodine sensitivity was observed between the two subgroups: mutant BRAF and wild-type BRAF. CONCLUSION: Although BRAF mutation appears to play a role in local tumour progression, it is not a risk factor for poor prognosis or tumour recurrence in PTC.

Sialendoscopy: a new diagnostic and therapeutic tool.

BACKGROUND: Sialendoscopy is a recently developed minimally invasive diagnostic and therapeutic procedure for the management of obstructive diseases of the salivary glands. This report describes our early experience with this new tool and compares our results with the literature data. MATERIAL AND METHODS: This was a retrospective analysis of the 33 first cases treated at a teaching hospital from October 2009 to June 2011. RESULTS: The success rate for diagnostic sialendoscopy was 94%. Sialolithiasis was found in 19 cases and salivary duct stenosis in 11; no canal anomaly was found in two cases. The success rate for stone removal was 79%, while treatment of strictures failed in four cases. Longer surgical experience led to shorter operating times and improved indications as well as better therapeutic outcomes. There were no complications. CONCLUSION: Sialendoscopy is a safe technique that can easily be learned by surgeons familiar with endoscopic surgery. However, practical experience is needed to reduce operating times, lower failure rates and determine its precise indications.

Management of voice prosthesis leakage with Blom-Singer large esophage and tracheal flange voice prostheses.

INTRODUCTION: Voice rehabilitation after total laryngectomy is a major socio-economic challenge. Voice rehabilitation can be achieved by voice prostheses, which provide rapid patient satisfaction. Enlarged tracheo-oesophageal puncture is a frequent complication and can be difficult to manage. MATERIAL AND METHOD: A prospective study was conducted from November 2010 to October 2011 on 28 Blom-Singer large oesophageal and tracheal flange voice prostheses placed in 18 patients with enlarged tracheo-oesophageal puncture causing leakage around the voice prosthesis. RESULT: Leakage around the voice prosthesis resolved in all patients with a mean prosthesis lifespan of 95 days. The patients considered voice quality to be similar to that obtained with the initial voice prosthesis. CONCLUSION: The Blom-Singer large oesophageal and tracheal flange voice prosthesis is a useful solution for the management of periprosthetic leakage ensuring similar voice quality and an identical lifespan to that of other voice prostheses.

Acquired cholesteatoma in children: strategies and medium-term results.

OBJECTIVES: To assess paediatric cholesteatoma surgical management strategies, residual disease and recurrence rates and especially the medium-term auditory impact. MATERIAL AND METHODS: Retrospective study of 22 cases of acquired middle ear cholesteatoma selected from a series of 77 children under the age of 16 operated for cholesteatoma between 1st January 2000 and 31st December 2003 on the basis of the following criteria: first-line surgical management with postoperative follow-up greater than four years. Surgical strategies, preoperative and postoperative (at 1 year and at the final visit) audiograms and residual disease and recurrence rates were analysed. RESULTS: A canal wall up tympanoplasty was performed in 82% of cases as first-line procedure and a canal wall down tympanoplasty was performed in 32% of cases. Residual cholesteatoma was observed in 9% of cases and recurrent disease was observed in 18% of cases. The mean preoperative hearing loss was 26dB with an air-bone gap of 23dB with values of 26dB and 20dB respectively at the end of follow-up. CONCLUSION: The majority of children were operated by two-stage canal wall up tympanoplasty. Long-term hearing results remained stable and close to preoperative values. The recurrence rate (residual disease and relapse) was low (27%), as reported in the literature.

Management of the neck in the setting of definitive chemoradiation: is there a consensus? A GETTEC study.

BACKGROUND: The management of the neck remains controversial in the definitive chemoradiation setting of advanced N2-3 head and neck squamous cell carcinoma. Most published data favor omission of neck dissection (ND) after complete response for N2-3 or selective ND for residual disease METHODS: We studied the patterns of care in the French-Belgian Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC) through a questionnaire-based survey. RESULTS: Eighteen percent of institutions never performed up-front ND, 20% rarely, 40% sometimes, 14% often, and 8% systematically. Induction chemotherapy was indicated in 30% of the cases, and most ND were performed either between induction and radiation or after chemoradiation for residual disease. Response to chemoradiation was assessed by computed tomographic scan and positron emission tomography in 72% of cases. Selective ND was more common than radical ND. CONCLUSIONS: Omission of ND based on computed tomographic scan and positron emission tomography-based complete response to chemoradiation is the most common strategy for advanced nodal disease among centers. However, neck management strategies vary among institutions, and some institutions continue advocating systematic ND before irradiation. The new treatment options and the changing epidemiology, namely docetaxel-based induction chemotherapy and human papilloma virus-related head and neck squamous cell carcinoma having better response profiles and prognosis, are adding to the nonconsensual approach. The best therapeutic index in terms of neck management remains to be defined in this evolving context.

Acute mastoiditis in children: 10 years experience in a French tertiary university referral center.

Acute mastoiditis have been increasingly reported in the last decade, with bacteriologic modifications and new therapeutic guidelines. This study is a retrospective review of 36 children hospitalized for acute mastoiditis in a French tertiary university referral center from 1999 to 2009, to assess incidence, bacteriology of pathogens and management. There were 10 periosteitis and 26 subperiosteal abscesses. There was a trend toward increased incidence over the past 10 years. The mean age of the patients was 31.8 months. A total of 63.2% children received 7.2 days antibiotic prior to hospitalization for acute otitis media, with sensitive pathogens in 80%. The pathogens were Streptococcus pneumoniae (36.1%), S. pyogenes A (13.9%), Staphylococcus coagulase-negative (13.9%), Pseudomonas aeruginosa (8.3%), Fusobacterium necroforum (8.3%) and Haemophiluss influenzae (2.8%). Cultures were negative in 16.7%. All patients received intravenous antibiotics. Eleven patients underwent bilateral myringotomy with or without tympanostomy tubes. Mastoidectomy was performed in 24 patients. Decrease in the length of hospitalization and delay from admission to surgery were significantly correlated. We observed a trend in the increase of acute mastoiditis at our center. The pathogens were dominated by S. pneumoniae. F. necroforum and P. aerguginosae were pathogens found in children over 2 years of age. Mastoidectomy was performed in 92.3% of subperiostal abscesses. However, there has been a trend toward conservative nonsurgical treatment in recent reported studies and further prospective studies are warranted to evaluate the long-term sequelae.

Basaloid squamous cell carcinoma of the head and neck: report of 18 cases.

OBJECTIVE: To evaluate the clinical course and pathological characteristics of basaloid head and neck squamous cell carcinoma. METHOD: Retrospective study of 18 cases of basaloid head and neck squamous cell carcinoma. Epidemiological, clinical and histological data were analysed and the Kaplan-Meier test used to estimate survival rates. RESULTS: The majority of lesions were at an advanced stage. These lesions were primarily localised in the larynx, hypopharynx and oropharynx. Routine pre-therapeutic assessment of squamous cell carcinoma was performed. Pathological diagnosis was difficult, although immunostaining was extremely useful. Positive staining for KL1, MNF 116 and 34ßE12 and negative immunostaining for chromogranin and synaptophysin were also important factors in obtaining a definitive diagnosis. In the majority of cases, treatment involved surgery and radiotherapy. The five-year survival rate was 5 per cent. CONCLUSION: Basaloid squamous cell carcinoma is an uncommon head and neck lesion, with a challenging histological diagnosis. These lesions must be carefully monitored due to their aggressive course, and require multimodality treatment.

[Thyroid differenciated carcinoma in children. Study from Normandy]. / Cancers thyroïdiens différenciés de l'enfant. l'expérience normande.

OBJECTIVE: Definition of a strategy for the management of thyroid differenciated carcinoma in children. DESIGN AND SETTING: Retrospective cohort study from the Normandy area in France. METHOD: Analysis of the medical records of 13 children and adolescents (age > 15 years), presenting with thyroid differenciated carcinoma in three Normandy French hospitals from 1994 to 2006, to determine the clinical features and treatment of the disease. RESULTS: X of the patients were male and y were female, with a mean age at presentation of 11 years. Most frequently symptom was solitary nodes in the thyroid gland (69%). Most frequent histological type was papillary cancer (92%). Size of tumor was > 4 cm in 23% of cases. Children had undergone surgery with total thyroidectomy, radio-iodine treatment and suppressive hormonotherapy. We observed 46% post surgery complications. All patients were alive and none developed a recurrence. CONCLUSION: Thyroid differenciated carcinoma in children and adolescents were more agressif with most frequently metastasis and recurrence than thyroid differenciated carcinoma of adults. Pronostic is good with 90% of survival at 20 years. We propose a coherent plan of treatment: 1. Thyroidectomy with cervical central lymph node dissection (group VI) completed bilateral selected head neck dissection compartments (groups IIa, III, IV) if macroscopic lymph node metastases in lateral cervical compartment. 2. Postoperative radioiodine is done in all tumor > T1N0 and completed with hormonotherapy.

[CT scan, MR imaging and anatomopathologic correlation in the glottic carcinoma T1-T2]. / Corrélation TDM, IRM et anatomopathologique dans les cancers glottiques T1-T2.

OBJECTIVES: Endoscopy and imaging are necessary to diagnose glottis carcinoma. Today, CT scan is the gold standard but MR imaging should be more sensitive for neoplastic invasion detection. The purpose of this study was to determine which exam to perform (CT scan or MRI) for neoplastic invasion. MATERIAL AND METHODS: This prospective study span a 18 months period. Seven patients with glottis carcinoma (TI-T2) underwent CT and MR imaging before surgery. Findings at imaging and pathologic examination were compared. RESULTS: Both CT and MR imaging were interesting, more specific (90%) than sensitive (74%). The anterior commissure, ventricles, subglottis, thyroid and arytenoid cartilages are the more difficult area analyzing. CONCLUSION: CT imaging stays the gold standard. MR imaging is more effective on second intention to refine the data. Indications are being improved, with complete cure and more preserved laryngealfunctions.