Stéphane Hans1, Florian Scotte2, Caroline Hoffman1, Nicole Pelicier3, Madeleine Ménard1, Cécile Badoual4, Stéphane Oudard5, Martin Housset6, Daniel Brasnu1 1 APHP, Hôpital européen Georges-Pompidou, Service d’ORL, 20, rue Leblanc, 75015 Paris, France <stephane.hans@egp.aphp.fr> 2 Hôpital européen Georges-Pompidou, Unité de soins de support, Service d’oncologie, 75015 Paris, France 3 Hôpital européen Georges Pompidou, Service de psychiatrie et de psychologie de liaison, 75015 Paris, France 4 Hôpital européen Georges-Pompidou, Service d’anatomo-pathologie, 75015 Paris, France 5 Hôpital européen Georges-Pompidou, Service d’oncologie, 75015 Paris, France 6 Hôpital européen Georges-Pompidou, Service d’onco-radiothérapie, 75015 Paris, France

For early-stage T1-T2 glottic squamous cell carcinoma, transoral laser microsurgery (TLM) is the main surgical modality, with rates of local control and laryngeal preservation ranging from 85% to 100% and low morbidity. For extensive lesions, open conservation laryngeal surgery may enable wider resections than TLM but at costs of longer hospital stay and higher postoperative morbidity. Surgery provides results that are comparable to nonsurgical treatment options while reserving radiation therapy for recurrences or second primary cancers, particularly in younger patients. In the future, transoral robot-assisted surgery may enable more extensive transoral resections than laser alone, decreasing further the indications for open surgery.

185 Background: An in-patient unit for supportive care in oncology (USSO) was created in 2011 in the Georges Pompidou European Hospital. Its primary objective is to improve patient care and manage the complications of cancer as well as their specific treatment. Patients are previously screened by a cross disciplinary team at an early stage before complication. Methods: A prospective observational study was performed through a yearly evaluation of the unit’s activity from January 1st, 2011 to December 31st, 2013. Results: 594 patients were admitted in the unit during the three years period of study. Most of them (64.3%) came directly from home, with an increase of this rate along this period (59.4% to 67.6%). The early screening thereby rendered emergency admission from 17.7% (2011) to 6.5% (2013). The predominant diseases observed were head and neck cancer (42.4%) and lung cancer (23%), followed by breast (7.2%) and ovarian cancer (7.2%). The main grounds for hospitalization were state of health impairment 32%, pain 12.8%, and invasive procedures 11.8%, increasing from 2011 to 2013. Therefore, an interdisciplinary approach is the cornerstone of the unit with the daily collaboration of dieticians (for 90% of inpatients), social workers, psychologists, physiotherapists and pain specialists (34%, 46%, 56% and 50% of inpatients respectively). The average length of stay decreased from 2011 (10.2 days) to 2013 (8.3 days) and 58.4% of the patients were home discharged. With the help of a social worker, 12% of the patients were transferred to a recovery unit and 9.7% to a palliative care unit while 9% died in the unit. Conclusions: With the opening of the in-patient USSO, and the development of its interdisciplinary strategy, most of the patients recover faster and regain better health. Preventive care can accommodate a majority of patients coming from home and allows for ambulatory secured discharge. These positive results conducted to enhance the USSO’s beds capacity and supportive care development in order to improve cancer care organisation in the hospital as well as patient’s quality of life.

OBJECTIVES:To present the preliminary results of the qualiit of life and quality of swallowing in a series of 15 patien! treated with oropharyngectomy by transoral robotic-assisted (CTAR) (robot da Vinci, Intuitive Surgical ).MATERIALS AND METHODS:A prospective monocentric non-randomized study of 15 patients with cancer of the oropharynx. Were analyzed: demographics, quality of life questionnaires (QLQ-C30 and H&N 35 EORTC) and quality of swallowing questionnairex (MDADI, DHI and EAT 10) with an average of 1 year after the end of the treatment.RESULTS:Fifteen patients (10 males and 5 females), mean age of 65 years (47-73 years) were included. The tumours were classified as: cT1: 4; cT2: 10 cT3: 1. Five of the 15 patients received postoperative chemoradiotherapy as histo-pathological studies showed multiple metastatic cervical lymph nodes +/- capsular rupture. For the analysis of the quality of life and quality of swallowing, the patients were divided into two groups. Group A included patients who underwent CTARs and group B, patients operated by CTAR with adjuvant chemoradiotherapy. At 12 months of the procedure, all patients had a deglutition considered as normal without feeding tube nor tracheostomy. With the three scales used, the quality of swallowing was satisfactory for all patients. It was better for patients in group A than for patients in group B. In terms of quality of life, the EORTC QLQ-C30 scale showed our patients had a high rate of satisfaction scale in "health and overall quality of life". For the EORTC H&N35 questionnaire, mean scores for "specific symptoms" were also low except for the following three items "dry mouths", "sticky saliva" and "sexuality problem". The first two items were statistically more frequent (p = 0.02 and p = 0.001) in group B patients.CONCLUSION:After transoral robotic-assisted oropharyngectomy, patients have a good quality of life and swallowing. Postoperative chemoradio-therapy compromises the quality of swallowing. Multicentric studies are required to confirm these preliminary results.

La plasmocytose laryngée (PL), est une lésion bénigne rare à plasmocytes matures et polyclonaux, qu’il faut savoir distinguer du plasmocytome extramédullaire. Nous rapportons l’observation d’une patiente âgée de 59 ans, ayant une dysphonie chronique comme unique symptôme, chez qui une PL isolée à localisation laryngée a été découverte. Nous discutons la présentation histopathologique, les modalités thérapeutiques, et le pronostic de cette entité. La PL est une lésion bénigne et rare, dont le diagnostic est à évoquer devant une infiltration plasmocytaire polyclonale de la sous-muqueuse.

Laryngeal plasmacytosis (LP) is a rare benign lesion of mature polyclonal plasma cells, which should be differentiated from extramedullary plasmacytoma.Isolated laryngeal plasmacytosis was discovered in a 59-year-old woman, free of symptoms other than chronic hoarseness.Histological presentation, treatment modalities and prognosis are discussed.Laryngeal plasmacytosis is a rare benign lesion that must be considered in case of submucosal polyclonal plasma cell infiltrate.

BACKGROUND:Malignant tumours of the salivary glands (MSGT) are rare and pleomorphic entities. Patients with advanced disease may benefit from targeted therapy; however, specific targets for optimising and personalising treatments are yet to be identified.DESIGN:Immunohistochemistry for C-KIT, EGFR, HER2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was carried out and evaluated in terms of progression-free and overall survival. High throughput molecular screening of key oncogenes was done in 107 patients using routine diagnostic methods and Sequenom technology.RESULTS:Several therapy leads were identified, including high levels of HER2 and androgen receptors in salivary duct carcinomas, C-KIT in myoepithelial carcinomas and EGFR in mucoepidermoid carcinomas. Recurrent mutations involving downstream elements of the EGFR pathway were found in HRAS, notably in tumours with a myoepithelial component, and in other key oncogenes (KRAS/NRAS/PI3KCA/BRAF/MAP2K). On the other hand, <1% of samples had EGFR or HER2 mutations.CONCLUSION:Several tumour subtypes overexpressed targets of directed therapies suggesting potential therapy leads. Genotyping results suggest activation downstream of EGFR in 18 of the 107 samples that could be associated with low efficacy of EGFR inhibitors. Other molecules, such as PI3K/MEK or mTOR inhibitors, may have anti-tumour activity in this subgroup. The high mutation rate in HRAS highlights a novel key oncogenic event in MSGT.

The aim of the study was to examine the effects of resonant voice therapy (RVT) on the vocal resonance of trained Carnatic singers. The specific objectives were to evaluate the effects of resonant voice therapy on the auditory perceptual judgments and acoustic source and tract parameters before and after RVT on phonation and sung voice samples.Six vocally healthy trained Carnatic singers, three males and three females aged 18-25 years (M = 23; S.D = 2.09) participated in the study. All the participants were assigned to a 21-days-long Resonance Voice Therapy (RVT) training program. The participants' pre and post training phonation and sung samples were subjected to auditory perceptual analysis and acoustic analysis.The results revealed that the post training auditory perceptual ratings of the phonation task showed a statistically significant difference from the pre training scores (Z= 2.35; P = 0.019). While for the singing task, the post training perceptual ratings were not significantly different from the pre training perceptual rating scores (Z= 2.66; P = 0.08). A significant difference was observed between the pre and post training values for all the measured acoustic parameters of the phonation task. In singing task, though the fundamental frequency, third and fourth formant frequencies showed no significant difference in the pre and post training conditions (P > 0.05), the parameter of- difference between the first formant frequency and the fundamental frequency showed a significant decrease (P = 0.028).The effects of resonant voice production led to a high vocal economy, as evidenced from the improved source and filter acoustic parameters. Indication for formant tuning through vocal tract modifications, probably an enlarged pharyngeal area resulting in increased resonant voice quality in both phonation and singing tasks, is inferred from these results.

L’immunothérapie pourrait révolutionner la prise en charge des cancers des voies aérodigestives supérieures (VADS), principalement représentés par les carcinomes épidermoïdes (CE), qui sont le plus souvent traités de façon insatisfaisante. Les modifications du microenvironnement, multifactorielles, peuvent être corrélées au pronostic et à la réponse clinique aux immunothérapies. Cet article collige les données récentes de la littérature concernant les CEVADS, les carcinomes nasopharyngés indifférenciés non kératinisants (CNP) et les tumeurs malignes des glandes salivaires, principales potentielles cibles de ces immunothérapies. Les essais cliniques actuels semblent montrer une meilleure réponse clinique à un traitement par anti-PD-1 chez les patients dont le CE exprime fortement PD-L1. Cependant, certains de ces traitements ont été approuvés par la Food and Drug Administration sans présélection sur l’expression de PD-L1. L’identification de marqueurs est nécessaire, ainsi PD-L2, l’interféron-γ, les cytokines inflammatoires, le phénotype de transition épithéliale-myoépithéliale et le taux de mutations pourraient aider à anticiper la réponse au traitement. Les CNP induits par l’Epstein-Barr virus (EBV) expriment davantage PD-L1 que les carcinomes EBV-. Un taux de réponse de 22 % a été retrouvé avec un anti-PD-1 chez des patients PD-L1+. Peu d’études concernent les modifications du microenvironnement des carcinomes des glandes salivaires. Un taux de réponse de 11 % a été retrouvé avec un anti-PD-1 chez des patients PD-L1+, cette expression pouvant être hétérogène. La compréhension fine des mécanismes régulant les changements au sein du microenvironnement et des checkpoints immunitaires des carcinomes des VADS est nécessaire afin que les patients puissent bénéficier, au mieux, des nouvelles immunothérapies.Head and neck (HN) carcinomas (mostly represented by squamous cell carcinomas [SCC]) still have a poor prognosis, which could be dramatically improved with immunotherapy. Tumor's microenvironment changes, caused by many endogenous or exogenous events, can correlate with prognosis and therapeutic response. Here, we review recent data regarding HNSCC, nasopharyngeal carcinomas (NPC) and salivary gland malignant tumors, all three being potential target of immunotherapies. About half of HNSCC exhibit PD-L1 expression, this expression being upregulated in HPV-positive tumors. In recent clinical trials, a better therapeutic response to anti-PD-1 has been obtained in patients with higher PD-L1 expression. Food and Drug Administration (FDA) approved the use of these therapeutics without the screening of patients regarding PD-L1 status. Activation status, density and localisation of TIL as well as PD-L2, γ-interferon, inflammatory cytokines, epithelial-mesenchymal transition phenotype and mutational burden may all be potential therapeutic response markers. In Epstein-Barr Virus (EBV)-induced nasopharyngeal non-keratinizing cancer, PD-L1 is over-expressed compared to EBV negative-tumors. A 22 % response rate has been observed under anti-PD-1 treatment, among PD-L1-positive HNSCC patients. There is little data regarding microenvironment of salivary gland cancer. PD-L1 shows great heterogeneity in localisation, when expressed. A 11 % response rate has been obtained under anti-PD-1 treatment among PD-L1-positive NPC patients. A better understanding of immune checkpoint regulation processes needs to be achieved to allow patients with HN carcinomas to benefit from these promising immunotherapies.

Objective. The objective of this study was prospectively to assess the feasibility and safety of Transoral Robotic Surgery (TORS) in head and neck carcinomas and to report our learning curve and two year outcomes.Methods. Patients with oropharyngeal, hypopharyngeal and laryngeal tumors treated with TORS were prospectively included.We evaluated: the feasibility of TORS, robotic set-up time, transoral robotic surgery time, blood loss, surgical margins, tracheotomy, feeding tube, time to oral feeding and surgery-related complications and preliminary oncologic outcomes.Results. 50 patients were treated for 52 carcinomas. 49 patients underwent successful robotic resection for 51 carcinomas (98.9 %). One patient required conversion to open surgery due to massive bleeding. The mean robotic set-up time was 25 minutes (range : 15 to 100 minutes) and mean TORS operating time was 70 minutes (range : 20 to 150 minutes). Positive margin of resection was observed in three patients. A tracheotomy was performed in 4 patients. Twelve patients required a nasogastric tube and gastrostomy was performed in the three patients.Complications in the 30-day postoperative period included one pneumonia with aspiration, one alcohol withdrawal, one neck hematoma one neck fistula and one death related to sudden postoperative bleeding occurred on the 15th postoperative day in a patient with total pyriform sinus resection by TORS. The mean hospital stay was 8.4 days (3-29 days).Mean follow-up was 19 months. Four deaths occurred: postoperative (n = 1,2 %), an event linked to oncological (n = 3,6 %).Conclusions. Early-stage selected head and neck cancers can be treated by TORS avoiding the need for tracheotomy and allowing more rapid resumption of swallowing and a shorter hospital stay. Further studies are necessary to confirm these preliminary results and to provide oncological results.

5554 Background: Malignant salivary gland tumors are rare and pleomorphic entities (24 sub types, WHO 2005). Curative treatment relies on surgery sometimes completed by radiotherapy. Management of non-surgical, locally advanced or metastatic tumors is difficult as conventional chemotherapies are ineffective. Directed therapies may provide important benefits for these patients. The aim of this work was to assess the expression and prognostic value of directed therapy targets on salivary gland tumors and search for mutations within the key players of the EGFR pathway. Methods: Immunochemistry on formalin fixed paraffin embedded (FFPE) samples from 124 patients for c-KIT, EGFR, c-ERBB2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was performed and related to progression free interval and survival. DNA was extracted from FFPE samples and conditional for treatment mutations of EGFR/KRAS/BRAF were assessed. An additional high throughput screening for mutations of key oncogenic genes was performed. Results: EGFR was the most expressed marker, found across almost all histotypes. Expression of the other markers was heterogeneous but some potential therapy leads were suggested by high levels of C-ERBB2 and androgen receptors in salivary duct carcinomas or C-KIT over expression in myoepithetial carcinomas. Tumor grade and a high proliferation index (Ki67>20%) were associated with progression free interval and survival. None of the other marker was. No mutation was found in EGFR/KRAS/BRAF. 7% (7/104) of the tumors harbored a mutation at the codon 61 of HRAS. In epithelial and epithelial-myoépithélial carcinoma, the mutation rate reached 33%. Mutations of PI3K and p53 were the most frequently found in the broader screen. Conclusions: Several tumor subtypes expressed frequently some targets of directed therapies suggesting potential therapy leads. The EGFR/MAPK pathway seems intact suggesting a low efficacy of small kinase inhibitors such as erlotinib or gefitinib. The mutation of H-RAS, known to be important but not sufficient to trigger urothelial carcinoma, could be a key oncogenic event in tumors with a myoepithelial component.

The trans-oral approach allows direct access to pathologies of the anterior craniocervical junction. However, the classic midline incision of the posterior pharyngeal wall can be surgically burdensome and limits lateral exposure. We reviewed the medical records of nine patients undergoing the trans-oral approach. The sites of the pathology ranged from the clivus to C2, and surgical exposure ranged from the clivus to C3. Each operation utilized an inferiorly based flap. None of the patients experienced vascular or neurologic complications, and no patient had a cerebrospinal fluid fistula, pseudomeningocele, or meningitis postoperatively. The trans-oral approach with an inferiorly based flap can therefore be safely and effectively performed with minimal oropharyngeal and neurologic morbidity. Not only does a U-shaped flap allow adequate exposure from the lower half of the clivus to C3, a flap improves lateral exposure, provides a clear operating field, and allows superficial mucosal closure not directly overlying the operative field.

Les robots ont envahi le monde industriel et récemment médical. En chirurgie, après la mise au point de différents prototypes, Intuitive Surgical® a développé le robot chirurgical Da Vinci. Ce robot conçu pour la chirurgie abdominale s’est imposé en urologie au cours des années 2000. Les avantages de cette chirurgie minimale invasive assistée par robot (CMIR) sont multiples et sont décrits dans l’article. Les inconvénients sont dominés par le prix et l’absence de retour de force. En cancérologie des voies aérodigestives supérieures, les premières études de faisabilité chez des animaux, des mannequins et des cadavres datent de 2005, suivies en 2006 par les premières publications chez des patients. Les premières séries comprenant plus de 20 patients traités par CMIR ont permis de souligner la faisabilité pour les localisations suivantes : oropharynx, larynx supraglottique et hypopharynx. Ces études ne permettent pas de valider la technique de CMIR en terme carcinologique. La CMIR permet de diminuer le nombre de trachéotomies nécessaires, une réhabilitation de la déglutition plus rapide et une durée d’hospitalisation plus courte. Des améliorations techniques sont attendues. Des robots de nouvelle génération de volume plus réduit, plus ergonomiques, et donc plus adaptés aux voies aérodigestives supérieures (VADS) seront probablement disponibles.