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The REFCOR (French Network of Expertise in Head and Neck Cancers) aims to organize the optimal management of rare head and neck cancers. Its main recommendation is to be an active member of the network. That network allows transmission of information and helps for accurate diagnosis and treatment of patients. It also promotes research and clinical trials. [ABSTRACT FROM AUTHOR]

Summary Today's customary techniques for pharyngo-esophageal reconstruction are jejunum and radial forearm free flaps. In this type of reconstruction, the jejunum flap is considered as the reference, but when its harvesting is not possible, the radial forearm flap is used. Since perforator flaps have begun to be developed, the anterolateral thigh flap (ATF) has become increasingly prominent in pharyngo-esophageal reconstruction. The aim of our study was to describe the use of the anterolateral perforator flap in pharyngo-esophageal reconstruction (indications, harvesting method, flap design) and to discuss its advantages and drawbacks as regards oral feeding and esophageal speech. [ABSTRACT FROM AUTHOR]

Résumé: Objectif: Évaluer les résultats de la radiothérapie chez les patients atteints de carcinomes épidermoïdes du larynx avec atteinte sous-glottique. Patients et méthodes: Entre 1998 et 2012, 56 patients ont reçu une radiothérapie ou une radiochimiothérapie (63 %) sans ou avec chimiothérapie d’induction (37 %) dans notre établissement. Résultats: Le suivi médian était de 74mois. À cinq ans, les probabilités de survie globale, de survie sans progression et de survie spécifique étaient respectivement de 64 % (intervalle de confiance à 95 % [IC 95 %] : 48–90 %), 45 % (IC 95 % : 28 %–61 %) et 88 % (IC 95 % : 78 %–98 %), respectivement. Les probabilités de contrôle locorégional et de contrôle à distance à cinq ans étaient de 69 % (IC 95 % : 56–83) et 95 % (IC 95 % : 89–100). Il n’y avait pas de différence de survie globale ni de contrôle locorégionale en fonction des traitements reçus (radiothérapie/chimioradiothérapie contre chimiothérapie puis radiothérapie/chimioradiothérapie) ou en cas d’atteinte sous-glottique primitive. Un indice de performance de 1 ou plus et la présence d’adénopathie cervicale au moment du diagnostic étaient des facteurs pronostiques défavorables de survie globale en analyse multifactorielle (hazard ratio [HR] [IC 95 %], respectivement de 6,5 [1,3–34 ; p =0,03] et 11 [1,6–75 ; p =0,02]). La probabilité de contrôle locorégional des cancers de stades T3-T4 était plus basse (HR : 3,1 ; IC 95 % : 1,1–9,2, p =0,04) en analyse unifactorielle mais aucun facteur pronostique n’a été retrouvé dans l’analyse multifactorielle. Aucune différence de probabilité de contrôle locorégional n’a été observée en fonction du premier traitement reçu (p =0,3). La probabilité de préservation laryngée à cinq ans était de 88 % (IC 95 % : 78–98) pour l’ensemble des patients et 58 % en cas de cancer de stade T3. Les probabilités de préservation laryngée à cinq ans étaient de 91 % (IC 95 % : 79–100) et 83 % (IC 95 % : 66–100), respectivement chez les patients qui n’ont pas et ont reçu une chimiothérapie néoadjuvante. Conclusion: Cette analyse suggère que les résultats obtenus pour les cancers du larynx avec atteinte sous-glottique par la radiothérapie avec ou sans chimiothérapie seraient comparables à ceux obtenus pour les autres tumeurs laryngées. Des protocoles de préservation laryngée pourraient donc être proposés en cas d’atteinte sous-glottique, dans certains cas sélectionnés. D’autres études sont nécessaires pour préciser ces données préliminaires. [ABSTRACT FROM AUTHOR]

Abstract: The optimal timing and extent of neck dissection in the context of chemoradiation for head and neck cancer remains controversial. For some institutions, it is uncertain whether neck dissection should still be performed upfront especially for cystic nodes. For others, neck dissection can be performed after chemoradiation and can be omitted for N1 disease as long as a complete response to chemoradiation is obtained. The question is debated for N2 and N3 disease even after a complete response as the correlation between radiological and clinical assessment and pathology may not be reliable. Response rates are greater than or equal to 60% and isolated neck failures are less than or equal to 10% with current chemoradiation protocols. Some therefore consider that systematic upfront or planned neck dissection would lead to greater than or equal to 50% unnecessary neck dissections for N2-N3 disease. Positron-emission tomography (PET) scanning to assess treatment response and have shown a very high negative predictive value of greater than or equal to 95% when using a standard uptake value of 3 for patients with a negative PET at four months after the completion of therapy. These data may support the practice of observing PET-negative necks. More evidence-based data are awaited to assess the need for neck dissection on PET. Selective neck dissection based on radiological assessment and peroperative findings and not exclusively on initial nodal stage may help to limit morbidity and to improve the quality of life without increasing the risk of neck failure. Adjuvant regional radiation boosts might be discussed on an individual basis for aggressive residual nodal disease with extracapsular spread and uncertain margins but evidence is missing. Medical treatments aiming at reducing the metastatic risk especially for N3 disease are to be evaluated. [Copyright &y& Elsevier]

Nasal NK/T cell is a rare form of usually localized non-Hodgkin's lymphoma (NHL) which generally carries a poor prognosis when treated with conventional NHL chemotherapy protocols. We reviewed 20 consecutive localized stage I/II nasal NK/T cell lymphomas treated at our institution over a 29 year period. Median age was 44 (range 23-71). Front-line therapy was generally radiotherapy alone (35-70 Gy) before 1980 and combination chemotherapy after 1980. Six patients were treated with first-line radiotherapy and they achieved complete remission (CR). Two subsequently received combination chemotherapy. Five of those patients remained in complete remission, after 97+ to 277+ months. Twelve patients were treated with first-line chemotherapy including CHOP or CHOP-like regimen in seven cases, and COP in five cases. Only three of them achieved CR, five had partial response and four had progressive disease. Five of the seven patients treated with CHOP did not achieve complete remission. The nine patients who failed to achieve CR with chemotherapy subsequently received salvage radiotherapy but only two of them obtained CR. Finally, two patients were treated with alternated chemotherapy and radiotherapy and achieved CR, which persisted after 14+ and 26+ months. Median survival was not reached in patients who received front-line radiotherapy, and was 35 months in patients who received front-line chemotherapy. These findings confirm that chemotherapy gives a low complete remission rate in localized nasal NK/T cell lymphoma. By contrast, first-line radiotherapy seems to give favorable results, whereas its results are poorer when administered after resistance to chemotherapy. Whether the use of chemotherapy after radiotherapy, or alternated chemotherapy-radiotherapy regimens give better clinical results than radiotherapy alone will have to be evaluated prospectively in this type of NHL. [ABSTRACT FROM AUTHOR]

Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established. Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed. In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10−4), although, as in SNMM, it was not a significant prognostic predictor. Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control. • Head and neck mucosal melanoma is a rare neoplasm with poor prognosis due to its high metastatic potential. • Surgery remains the cornerstone of the therapeutic algorithm. • Postoperative radiotherapy is interesting for local control, both in oral cavity mucosal melanoma and sinonasal mucosal melanoma, even in early-stage tumours. • Nodal involvement is not a significant predictor of outcomes. • Combination with systemic therapies, such as anti–PD-1 immunotherapy, must be considered. [ABSTRACT FROM AUTHOR]

Summary Clear cell sarcomas (SCC), also called "soft-tissue melanoma", are rare and aggressive tumors that preferentially affect the lower limbs (tendons and fasciae) and which have also been described in head and neck localizations. Their clinical and immunohistochemical mimicry with melanoma makes it difficult to diagnose sarcomas. SCC treatment is mainly focused on large-scale resection surgery with adjuvant radiotherapy because of their low chemo-sensitivity and extreme lymphophilia. In case of head and neck localization, these treatments may lead to function and aesthetic sequelae thus requiring the use of modern techniques of reconstructive surgery. The authors describe the diagnosis, treatment and follow-up of large lingual SCC case using a DIEP free flap reconstruction according to an original technique developed in the department. Given the characteristics of patients with SCC (a high proportion of women between 20 and 40 years old) and its inherent qualities (low morbidity of the donor site, volume delivered and excellent plasticity), the fascio-cutaneous free flap type "DIEP" "taken according to the design of the" Cathedral triptych seems to be a viable choice among the range of reconstruction solutions. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate the reliability of sentinel node biopsy (SNB) in T1/T2 cN0 oral squamous cell carcinoma (OSCC), and compare recurrence-free time (RFT) and overall survival (OS) between patients undergoing SNB and neck dissection (ND).Patients and Methods: Patients with T1/T2 cN0 OSCC underwent SNB followed by systematic ND in the first cohort and SNB followed by selective ND in case of positive sentinel nodes (SN) in the second cohort.Results: A total of 229 patients were followed (first cohort 50, second cohort 179). SNs were successfully detected in 93.9% (215/229) of cases. Median follow-up was 5.6 years. Recurrence occurred in 38/215 patients, with isolated nodal recurrence in 18/215 patients. At 5 years, the rate of recurrence-free patients was 80.0% and the rate of patients without isolated nodal recurrence was 90.4%. Negative predictive value of SNB was 92.7%. No statistically significant difference was observed between the two groups regarding RFT and OS. In 83% (10/12) of ipsilateral isolated nodal recurrences, primary tumor was located in anterior part of oral cavity. Only 43% (3/7) of SN+ patients with nodal recurrence were eligible for salvage surgery, compared to 91% (10/11) of SN- patients. SNB resulted in fewer complications than ND (8% vs 28%, p < 0.0001).Conclusion: SNB is a reliable staging tool for T1/T2 cN0 OSCC, without adverse effect on patient survival and fewer complications. No late recurrences occurred in long-term follow-up. Close follow-up is mandatory for SN+ patients, who are at higher risk of nodal recurrence and have worse prognosis. [ABSTRACT FROM AUTHOR]

Background: Cetuximab, an anti-EGFR monoclonal antibody in combination with platinum and 5FU is the standard of care in first-line treatment of patients with recurrent head and neck squamous cell carcinoma (HNSCC), with an expected median outcome of 10months. For this population, development of efficacious and safer therapies is still needed.Case Report: A 62-year-old male with a first recurrence of human papillomavirus positive stage IVA (T3N2bM0) adenocarcinoma of the glossotonsillar sulcus not amenable to locoregional curative treatment was offered chemotherapy as part of the TPEx clinical trial. He was treated by cetuximab (loading dose 400mg/m2 on day 1 cycle 1, then 250mg/m2 weekly), and chemotherapy (cisplatin 75mg/m2 and docetaxel 75mg/m2, on day 1). Cycles were repeated every 21days for 4 cycles (TPEx regimen) with systematic granulocyte colony-stimulating factor support at each cycle. Bi-monthly maintenance cetuximab 500mg/m2 was then administered. The patient showed a clinical complete response according to RECIST 1.1 criteria after 5months maintenance, with progression-free survival of 25months. Relapses that followed were treated with stereotactic irradiation, radiofrequency ablation, cetuximab and paclitaxel. The patient is alive eleven years after cancer diagnosis and remains controlled for his disease, with a cumulative period of 59months of cetuximab administration (equivalence of 121 injections).Conclusion: This case report demonstrated that TPEx regimen, by synergistic interaction between taxanes and cetuximab, followed by bimonthly cetuximab maintenance may lead to patient complete remission within the first year of treatment. Furthermore, prolonged intermittent treatment with cetuximab seems to participate in the improved survival associated with preserved quality of life. Key favorable prognostic factors may be moderate tumor differentiation, oropharyngeal location, HPV p16 positive tumor status. [ABSTRACT FROM AUTHOR]

• SN is a safe and effective procedure for managing T1/T2 cN0 OSCC. • In 80% of cases, only SN were positive and neck dissection could be avoided. • The SN micrometastatic involvement is associated with only one positive SN. Sentinel node procedure (SN) is a standard procedure that has shown its safety and effectiveness for T1/T2 cN0 oral squamous cell carcinoma (OSCC), with completion neck dissection (CND) for patients with positive SN. The aim of this study was to characterize the nodal involvement in a cohort of SN + OSCC. Patients with T1/T2 cN0 OSCC with positive SN with CND were included in this single-center, prospective cohort study between 2000 and 2013. 54/301 patients had at least one positive SN. In 43/54 (80 %) cases, only the SN(s) were invaded; with only one SN involved (SN+=1) in 36/54 (67 %) cases. No predictive factors of nodal involvement in the CND were found considering the followings: SN micro/macrometastases, primary tumor's depth of invasion (DOI), perineural spread, lymphovascular involvement, primary tumor location, T stage and extranodal extension. The SN micrometastatic involvement (n = 22) was significantly associated with only one SN + CND- (p = 0.017). In the group of patients with unique micrometastatic involvement in the SN (n = 20/54), there was a higher isolated nodal recurrence free time (p = 0.017). 80% of T1/T2 cN0 OSCC with positive SN had no other lymph node metastases in the CND, questioning the potential benefits of this procedure. Predictive factors such as the size of the SN metastasis need to be tested to stratify the risk of positive non-SN lymph nodes leading to a personalized treatment, lowering the therapeutic morbidity while maintaining the oncologic safety. [ABSTRACT FROM AUTHOR]

Résumé Objectifs de l’étude Les carcinomes épidermoïdes de la cavité buccale du sujet jeune constituent une entité spécifique dont la prise en charge et le pronostic sont discutés. Nous avons effectué une analyse rétrospective des dossiers de l’ensemble des patients âgés de moins de 40 ans et pris en charge à Gustave-Roussy pour un carcinome épidermoïde de la cavité buccale entre 1999 et 2011. Méthodes Les caractéristiques des patients, des tumeurs, du traitement, et le devenir ont été enregistrés. Une analyse de survie par la méthode de Kaplan-Meier a été réalisée, ainsi qu’une analyse unifactorielle et multifactorielle à la recherche de facteurs pronostiques de la survie globale et la survie sans progression. Résultats Soixante-trois patients ont été identifiés. Le suivi médian était de 64 mois. La majorité des tumeurs siégeait au niveau de la langue mobile ( n = 54, 86 %). Au total 17 patients sont décédés, dont 15 du cancer traité. Les taux de survie globale et sans progression à 5 ans étaient de 80 % et 69 %. Les taux de survie sans rechute locale, régionale ou métastatique à 5 ans étaient de 80 %, 91 % et 89 %. En analyse multifactorielle, seule l’absence de chirurgie initiale était pronostique pour la survie globale ( hazard ratio [HR] : 13,5 [2,0 ; 90,5], p = 0,007), tandis que la consommation d’alcool (HR : 0,38 [0,15 ; 0,9], p = 0,03) et l’absence de chirurgie (HR : 9,8 [1,9 ; 50,9], p = 0,006) étaient associées à une diminution de la probabilité de survie sans progression. Un âge plus jeune (moins de 30 ans) n’était pas associé ni à la survie globale ni à celle sans progression. Conclusion Les taux de survie et de contrôle tumoral sont relativement élevés chez les sujets jeunes atteints de carcinome épidermoïde de la cavité buccale traités dans un centre tertiaire. L’identification préthérapeutique des sujets à risque de récidive est actuellement difficile. La balance entre risque de rechute et toxicité des traitements justifie la réalisation d’études supplémentaires, sur le plan clinique et pour le développement de biomarqueurs pronostiques. Purpose Squamous cell carcinomas of the oral cavity occurring in young people represent a specific entity. Its management and prognosis are controversial. We performed a retrospective chart review of all patients aged less than 40 years old and treated at Gustave-Roussy Cancer Centre for a squamous cell carcinomas of the oral cavity between 1999 and 2011. Methods Patients and tumour characteristics, type of treatment and follow-up data were collected. Survival data were analysed according to the methods of Kaplan-Meier and both univariate and multivariate analyses were performed to look for prognostic factors regarding overall survival and progression-free survival. Results Sixty-three patients were identified. Median follow-up was 64 months. Most of the tumours were initially located in the mobile tongue ( n = 54, 85.7%). Overall 17 patients had died, including 15 from the treated cancer. Overall and progression-free survival rates at 5 years were respectively 79.6% and 68.6%. The corresponding 5 years local, regional and metastatic relapse free survival rates were 80%, 91% and 89% respectively. In the multivariate analysis only the absence of initial surgery (hazard ratio [HR]: 13.5 [2.0; 90.5]; P = 0.007) was prognostic for overall survival, while alcohol abuse (HR: 0.37 [0.15; 0.9]; P = 0.03) and the absence of surgery (HR: 13.6 [2.5; 74.2]; P = 0.002) were associated with a decreased progression-free survival. A younger age (less than 30 year old) was not associated with the risk of recurrence or death. Conclusion Survival rates and tumour control probabilities are relatively high among young patients suffering from squamous cell carcinomas of the oral cavity treated at a tertiary centre. The early identification of patients at risk of relapse is currently difficult. The balance between recurrence and treatment toxicity warrants further studies, both on the clinical level and for the development of prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Objective:This study aimed to assess the influence of supra- and subglottic extensions and vocal fold mobility on outcome in a large monocentric cohort of 148 patients treated for tumour–node–metastasis stage T2N0 glottic carcinomas.Methods:In all, 107 glottic carcinoma patients had normal vocal fold mobility (T2aN0), and 41 had impaired vocal fold mobility (T2bN0). Treatment decisions were made by a multidisciplinary team.Results:Vocal fold mobility was associated with overall survival, disease-free survival, local control, larynx preservation and laryngectomy-free survival. For patients with T2a lesions, local control, laryngectomy-free survival and disease-free survival improved after surgery but overall survival did not. For patients with T2b lesions, local control, laryngectomy-free survival, disease-free survival and overall survival were all higher after surgery than after radiotherapy.Conclusion:This study highlights for the first time the importance of vocal fold mobility in treatment outcomes and is the first to assess its influence on survival. Updated tumour–node–metastasis classifications should consider the distinction between T2a and T2b lesions. [ABSTRACT FROM PUBLISHER]

Résumé: L’objectif de cette revue de la littérature était d’évaluer les pratiques en cas de métastases cervicales ganglionnaires sans primitif retrouvé, en termes d’irradiation des muqueuses et ganglionnaires et de les discuter afin de définir une stratégie personnalisée de sélection des volumes à irradier. Une recherche de la littérature a été réalisée avec les mots clés suivants : adénopathie cervicale, primitif inconnu, cancer voies aérodigestives supérieures, radiothérapie, curage, carcinome épidermoïde. Les adénopathies cervicales (carcinomes épidermoïdes dans plus des deux tiers des cas) de primitif inconnu après confirmation diagnostique font l’objet d’un bilan étiologique, une scanographie, une TEP-scanographie au (18F)-fluorodésoxyglucose (FDG), une panendoscopie et une amygdalectomie. Dans un certain nombre de situations cliniques, les métastases cervicales ganglionnaires sans primitif retrouvé sont traitées par curage et irradiation ganglionnaire et muqueuse non sélective étendue du nasopharynx à l’hypopharynx afin de contrôler la maladie ganglionnaire et de prévenir l’émergence d’un cancer primitif métachrone à partir d’un cancer infraclinique lors du diagnostic d’adénopathie. Il pourrait être justifié du fait de la morbidité majeure de proposer une sélection des volumes cibles ganglionnaires et muqueux par radiothérapie conformationnelle avec modulation d’intensité plutôt qu’une irradiation étendue systématique sur la base de quatre critères décisionnels essentiels : le niveau ganglionnaire, le stade ganglionnaire, le statut selon les papillomavirus humains (HPV) et le virus d’Epstein-Barr (EBV), les données immuno-histochimiques avec les variants histologiques. Il ne s’agit pas de proposer une recommandation en l’absence de niveau de preuve suffisant mais de repositionner le problème de ces irradiations pan-muqueuses, associées à une importante toxicité, et en conséquence de proposer une redéfinition sélective personnalisée des volumes cibles. Ces critères de décision devront être évalués prospectivement au regard de l’indice thérapeutique obtenu. [ABSTRACT FROM AUTHOR]

Summary: Purpose/objectives: To analyze the clinical features, treatment modalities and outcome of patients treated for a localized esthesioneuroblastoma (ENB). Materials and methods: Forty-three consecutive patients with biopsy proven ENB treated at two referral cancer centers between 1998 and 2010 were retrospectively reviewed. Results: Overall, 5 patients had stage A disease, 13 stage B, 16 stage C and 9 stage D according to the modified Kadish classification. Neo-adjuvant chemotherapy was performed in 23 patients leading to a 74 % response rate. Thirty-one patients were treated by surgery. Thirty-nine patients (90.6%) underwent radiation therapy. Twelve patients received bilateral cervical lymph node irradiation (LNI). After a median follow-up of 77months, the 5-year overall and progression free survival were 65% and 57%. Twelve patients (28%) had a locoregional relapse leading to 10 ENB-related deaths. The major prognostic factor was the modified Kadish stage with a 3-year survival for stage A–B, C and D of 100%, 48% and 22% respectively (p <0.0001). Two (9%) isolated cervical lymph node relapses occurred among staged B and C patients treated without elective LNI and none after elective or adjuvant LNI. Conclusion: The high risk of locoregional failure in ENB justifies the use of multimodal therapy. Induction chemotherapy leads to a high response rate. Elective LNI might prevent regional failure in locally advanced disease. [Copyright &y& Elsevier]

Objectifs: L’esthésioneuroblastome (ENB) est une tumeur rare développée aux dépend de l’épithélium de la cavité nasale supérieure et de l’ethmoïde. Nous avons revu l’expérience de l’Institut Gustave Roussy sur les ENB des enfants et adolescents. Matériels et Méthodes: Onze enfants et adolescents ont pris en charge sur une période de 20 ans. 9 patients ont reçu un traitement par chimiothérapie initiale suivie de chirurgie et de radiothérapie. Un patient a été traité par chirurgie et radiothérapie sans chimiothérapie ; un autre patient en rémission complète après chimiothérapie n’a pas eu de chirurgie avant la radiothérapie. Résultats: 10 patients étaient évaluables pour la réponse au traitement, parmi lesquels 7 ont été mis en rémission complète ou partiale par la chimiothérapie. Seul un patient a rechuté localement et sous forme métastatique 9 mois après le diagnostic. Il est décédé en quelques semaines. Les 10 autres sont vivants en première rémission. Avec un suivi médian de 8,8 ans (extrêmes : 9,9-16,4), la survie sans évènement et la survie globale à 5 ans sont de 91 % (95 % IC : 62 % – 98 %). Conclusions: Ces résultats montrent la chimiosensibilité des ENB et l’efficacité d’un traitement combinant chimiothérapie, chirurgie et radiothérapie. [Copyright &y& Elsevier]

This study sought to determine whether the presence of hypermethylated genes in the surgical margins can predict local recurrences in head and neck squamous cell carcinomas (HNSCCs). We prospectively collected tumour and surgical margin specimens from patients with HNSCCs who had undergone surgical resections. Quantitative methylation-specific PCR (QMSP) of CDKN2A, CCNA1 and DCC were performed in these specimens and correlated with clinical data. Of the 42 patients eligible for the study, 27 were hypermethylation informative for the above three genes. This latter group was associated with longer disease-free survivals (P=0.007) and longer time to disease-specific deaths (P=0.004). Multivariate analyses confirmed hypermethylation non-informative tumours as an independent prognosticating factor for disease-specific deaths (risk ratio 3.8, P=0.026). Quantitative MSP of the margins of 24 hypermethylation informative tumours revealed that 11 patients had molecularly positive margins, of which, five developed disease-specific events (DSEs, three local recurrences and two metastases), compared to none in patients with molecularly negative margins, after a median follow-up of 48 months. Log-rank analyses showed that molecularly positive margins were associated with shorter time to local recurrences and disease-specific deaths (P=0.03 and 0.01, respectively). This study demonstrated that QMSP of hypermethylated promoters in surgical margins predicted all the local recurrences in our series of HNSCC patients. We have also identified hypermethylation non-informative tumours as an independent predictor for the development of DSEs. [ABSTRACT FROM AUTHOR]

Oesopharyngeal brush (OPB) sampling with cytological analysis can yield exfoliated cells from asymptomatic tumours of the upper aero-digestive tract and the oesophagus. In this study, we compared cytological evaluation and molecular analysis for the detection of exfoliated cancer cells sampled with an OPB. A total of 56 patients with a known unique head and neck squamous cell carcinoma (HNSCC) and five healthy controls were enrolled prospectively. Exfoliated cells from these 61 patients were collected with an OPB before initial endoscopy. p53 mutations and UT 5085 microsatellite instability (MI) were analysed in the HNSCC tumour, lymphocytes and the corresponding OPB DNA samples. p53 mutations and UT5085 MI were detected in 31 out of 56 and 14 out of 56 HNSCC, respectively, but not in any of the five controls. Direct sequencing of p53 was able to detect mutations in OPB DNA in only two out of 29 patients harbouring a p53-mutated primary tumour. Microsatellite instability was detected in OPB DNA of 11 out of 13 informative (bandshift detected in tumour) patients, whereas cytological analysis detected abnormal cells in only six of the same 13 patients (P=0.03). In informative patients, all positive OPB samples at cytological analysis were also positive at molecular analysis of UT5085, and both analyses confirmed the two negative samples. Molecular analysis of OPB from eight uninformative patients and from five healthy controls were all negative. OPB sampling with MI-based molecular analysis could be efficient for early detection of recurrent HNSCC. This result prompts us to use other microsatellite markers in order to maximise the percentage of informative patients. [ABSTRACT FROM AUTHOR]

In vivo transfer of wild-type (wt) p53 gene via a recombinant adenovirus has been proposed to induce apoptosis and increase radiosensitivity in several human carcinoma models. In the context of combining p53 gene transfer and irradiation, we investigated the consequences of adenoviral-mediated wtp53 gene transfer on the cell cycle and radiosensitivity of a human head and neck squamous cell carcinoma line (SCC97) with a p53 mutated phenotype. We showed that ectopic expression of wtp53 in SCC97 cells resulted in a prolonged G1 arrest, associated with an increased expression of the cyclin-dependent kinase inhibitor WAF1/p21 target gene. A transient arrest in G2 but not in G1 was observed after irradiation. This G2 arrest was permanent when exponentially growing cells were transduced by Ad5CMV-p53 (RPR/INGN201) immediately after irradiation with 5 or 10 Gy. Moreover, levels of cyclins A2 and B1, which are known to regulate the G2/M transition, dramatically decreased as cells arrived in G2, whereas maximal levels of expression were observed in the absence of wtp53. In conclusion, adenoviral mediated transfer of wtp53 in irradiated SCC97 cells, which are mutated for p53, appeared to increase WAF1/p21 expression and decrease levels of the mitotic cyclins A2 and B1. These observations suggest that the G2 arrest resulted from a p53-dependent premature inactivation of the mitosis promoting factor. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m[SUP-2] by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1-9) per patient. The median cumulative dose was 449 mg m[SUP-2]. Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1-50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4-52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h[SUP-1] m[SUP-2] and an area under the curve of 6.00 μg ml[SUP-1] h[SUP-1])was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance. [ABSTRACT FROM AUTHOR]

Background: The standard of care for sinonasal malignancies is a large surgical resection followed by radiotherapy. Midfacial defects resulting from maxillectomy require a complex reconstruction procedure. Given their adaptability, chimeric flaps such as latissimus dorsi-scapular (LDS) free flaps appear to be a good option.Material& Methods: We performed a single-center retrospective study of consecutive patients with sinonasal cancers where a LDS free flap was used for reconstruction. We assessed the postoperative complications and the functional, aesthetic and oncologic outcomes.Results: Eighty-four patients were included. Primary tumors were staged as T4a in 68% of cases; 38.3% of the patients received induction chemotherapy and 82.7% received adjuvant radiotherapy. Based on our classification of midfacial and palatal defects, the majority of the patients (69%) had a type IIa with interruption of the three facial pillars. The orbital floor was removed in 55.9% of cases. The median follow-up was 45 months. Total flap necrosis with no possible revascularization occurred in 5.9% of cases. For the orbital reconstruction, a revision procedure was needed for necrosis and/or infection of the costal cartilage graft in eight cases (17%). More than 90% of the patients had no functional disorders regarding speaking, swallowing and chewing. Soft palate involvement was a prognostic factor of speech (p < 10-4) and swallowing (p = .005) disorders. Dental rehabilitation was realized in 70.2% of the patients. No severe complications were observed in the donor site, except for one seroma.Conclusion: A LDS free flap is a reliable technique for the reconstruction of complex midfacial defects. [ABSTRACT FROM AUTHOR]

Introduction et but de l’étude: Après chirurgie carcinologique des voies aéro-digestives supérieures (VADS), les patients présentent souvent une altération du statut nutritionnel. L’objectif de l’étude est de déterminer le paramètre nutritionnel le plus pertinent pour surveiller la renutrition par rapport à l’évolution de la masse maigre sèche (MMS), méthode considérée comme référence dans notre étude. Matériel et méthodes: Étude prospective, avec recueil des poids habituel (Ph), et initial avant la chirurgie (Pi) et de certains paramètres nutritionnels à la sortie (S1) et en consultation à 1, 3 et 6 mois (M1,M3,M6) : poids, taux plasmatiques d’Albuminémie (Alb), et de Transthyrétine (TTR), apports énergétiques, composants de l’organisme mesurés par impédancemétrie (Bodystat Quadscan 4000) : Masse Grasse (MG), Masse Maigre Sèche (MMS), secteur hydrique (H2O). Résultats: . Les résultats sont préliminaires chez 36 patients (33 H, âge moyen 62 ans). Les valeurs du poids moyen sont (en kg) : Ph : 72,3 (n=36), Pi : 66,3 (n=36), S1 : 64,4 (n=36), M1 : 64,5 (n=34), M3 : 66,1 (n=27) et M6 : 65,5 (n=17) (inférieur de 4,9 % par rapport au Ph). Toute variation du poids traduit une variation parallèle de la MMS, la corrélation est statistiquement significative (R2 0,54). Cette corrélation n’est pas retrouvée avec les paramètres biologiques : Alb et TTR. Si on considère l’évolution des composants corporels, par rapports au jour de sortie (tableau) et en fonction de la présence d’un traitement adjuvant, seule la différence d’évolution de la MMS est statistiquement significative p=0,007 Tableau 1[0,1-6]Évolution des composants corporels, par rapport aux valeurs du jour de sortieSans TA M1-S1Sans TA M3-S1Sans TA M6-S1Avec TA M1-S1Avec TA M3-S1Avec TA M6-S1Masse Maigre Sèche6,1 %23,1 %38,5 %5,2%-5,3%2,7%Masse Grasse5,7%20,4 %37,8 %4,2%5,2%16,4%Secteur Hydrique1,8%0,6%4,9%-1,3%-1,9%-4,0% Conclusions: Le poids, corrélé à la MMS, est le paramètre le plus pertinent à surveiller après chirurgie carcinologique des VADS. La MMS diminue, contrairement à la MG, au cours du traitement adjuvant. Le poids, après 6 mois de renutrition, ne revient pas à sa valeur habituelle. Il reste diminué de 9 %. [Copyright &y& Elsevier]

Objectifs Les carcinomes épidermoïdes de la cavité buccale touchent habituellement les personnes âgées de plus 50 ans ayant eu une intoxication alcoolotabagique. Chez les patients de moins de 40 ans, ils sont rares et leur pronostic n’est pas connu. L’objectif est de déterminer le pronostic du carcinome épidermoïde de la cavité buccale chez les patients jeunes. Patients et méthodes Étude rétrospective, monocentrique de type cas-témoin. Les patients inclus étaient atteints d’un carcinome épidermoïde de la cavité buccale traité à l’institut Gustave-Roussy (IGR) de 1999 à 2012. Les patients avaient moins de 40 ans. Les témoins étaient âgés de plus de 40 ans. Deux témoins ont été sélectionnés pour chaque cas et appariés sur le sexe, le TNM et la période de traitement. Résultats Cinquante-sept patients, 44 hommes et 13 femmes ( sex ratio de 3,4) ainsi que 114 témoins ont été inclus. L’âge médian était de 32 [19–39] ans pour les cas contre 53 [41–61] ans pour les témoins ( p < 0,0001). Vingt-six (456 %) cas n’avaient jamais fumé contre 9 (7,8 %) témoins ( p < 0,0001), 47 (82,5 %) cas n’avaient pas consommé d’alcool contre 31 (27,2 %) témoins ( p < 0,0001). Cinquante-trois (93 %) cas et 104 (91,2 %) témoins avaient eu un traitement chirurgical ( p = 0,69), 29 (51 %) cas avaient reçu une radiothérapie ou une chimioradiothérapie contre 60 (52,6 %) témoins. Les taux de contrôle locorégional à 5 ans étaient de 75 % chez les patients et de 73 % chez les témoins, ceux de survie spécifique à 5 ans respectivement de 79 % et 77 %, ( p = 0,7), ceux de survie globale à 5 ans de 76 % et 64 % ( hazard ratio : 0,56 [0,3 ; 1,0] ; p = 0,05). Conclusion Le taux de survie globale à 5 ans des patients de moins de 40 ans atteints d’un carcinome épidermoïde de la cavité buccale tend à être meilleur que celui des patients plus âgés, alors que celui de survie spécifique est similaire. [ABSTRACT FROM AUTHOR]

Focuses on the study regarding prognostic values of histological and biological factors in pharyngeal squamous cell carcinoma. Aim of the study; Use of these factors in clinical treatments of patients.