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ObjectiveIndeterminate thyroid nodules (ITN) are common and often lead to (sometimes unnecessary) diagnostic surgery. We aimed to evaluate the performance of two machine learning methods (ML), based on routinely available features to predict the risk of malignancy (RM) of ITN.DesignMulti-centric diagnostic retrospective cohort study conducted between 2010 and 2020.MethodsAdult patients who underwent surgery for at least one Bethesda III-V thyroid nodule (TN) with fully available medical records were included. Of the 7917 records reviewed, eligibility criteria were met in 1288 patients with 1335 TN. Patients were divided into training (940 TN) and validation cohort (395 TN). The diagnostic performance of a multivariate logistic regression model (LR) and its nomogram, and a random forest model (RF) in predicting the nature and RM of a TN were evaluated. All available clinical, biological, ultrasound, and cytological data of the patients were collected and used to construct the two algorithms.ResultsThere were 253 (19%), 693 (52%), and 389 (29%) TN classified as Bethesda III, IV, and V, respectively, with an overall RM of 35%. Both cohorts were well-balanced for baseline characteristics. Both models were validated on the validation cohort, with performances in terms of specificity, sensitivity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve of 90%, 57.3%, 73.4%, 81.4%, 84% (CI95%: 78.5%-89.5%) for the LR model, and 87.6%, 54.7%, 68.1%, 80%, 82.6% (CI95%: 77.4%-87.9%) for the RF model, respectively.ConclusionsOur ML models performed well in predicting the nature of Bethesda III-V TN. In addition, our freely available online nomogram helped to refine the RM, identifying low-risk TN that may benefit from surveillance in up to a third of ITN, and thus may reduce the number of unnecessary surgeries.

Although it is the gold standard for assessing the malignancy of thyroid nodules (TNs) preoperatively, the cytological analysis of fine-needle aspiration cytology (FNAC) samples results in 20–30% of cases in indeterminate lesions (ITNs). As two-thirds of these lesions will appear benign after diagnostic surgery, improved preoperative diagnostic methods need to be developed. In this pilot study, we evaluate if the metabolomic profiles of liquid-based (CytoRich®) FNAC samples of benign and malignant nodules can allow the molecular diagnosis of TNs. We performed untargeted metabolomic analyses with CytoRich® FNAC in a monocentric retrospective study. The cohort was composed of cytologically benign TNs, histologically benign or papillary thyroid carcinomas (PTCs) cytologically ITNs, and suspicious/malignant TNs histologically confirmed as PTCs. The diagnostic performance of the identified metabolomic signature was assessed using several supervised classification methods. Seventy-eight patients were enrolled in the study. We identified 7690 peaks, of which 2697 ions were included for further analysis. We selected a metabolomic signature composed of the top 15 metabolites. Among all the supervised classification methods, the supervised autoencoder deep neural network exhibited the best performance, with an accuracy of 0.957 (0.842–1), an AUC of 0.945 (0.833–1), and an F1 score of 0.947 (0.842–1). Here, we report a promising new ancillary molecular technique to differentiate PTCs from benign TNs (including among ITNs) based on the metabolomic signature of FNAC sample fluids. Further studies with larger cohorts are now needed to identify a larger number of biomarkers and obtain more robust signatures.

Background: Many classifications exist to select patients with “high-risk” head and neck cutaneous squamous cell carcinoma (HNCSCC). Objective: To compare the performance of the Brigham and Women’s Hospital (BWH) classification with the performance of the American Joint Committee on Cancer 8th Edition (AJCC8), the Union for International Cancer Control 8th Edition (UICC8), and the National Comprehensive Cancer Network (NCCN) classifications. Methods: In this single-center retrospective study, HNCSCC resected in a tertiary care center were classified as “low-risk” or “high-risk” tumors according to the four classifications. Rates of local recurrence (LR), lymph node recurrence (NR), and disease-specific death (DSD) were collected. The performance of each classification was then calculated in terms of homogeneity, monotonicity, and discrimination and compared. Results: Two hundred and seventeen HNCSCC from 160 patients, with a mean age of 80 years, were included. For predicting the risk of any poor outcome and risk of NR, the BWH classification had the best specificity and positive predictive value. However, its concordance index was not significantly higher than that of the AJCC8 and UICC8 classifications. The NCCN classification was the least discriminant. Conclusions and Relevance: This study suggests that the BWH classification is the most appropriate for predicting the risk of poor outcomes in patients with HNCSCC when compared with the NCCN, UICC8, and AJCC8 classifications.

Quantification of organotypic invasion assay screening.

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In squamous cell carcinoma (SCC), tissue invasion by collectively invading cells requires physical forces applied by tumor cells on their surrounding extracellular matrix (ECM). Cancer-related ECM is composed of thick collagen bundles organized by carcinoma-associated fibroblasts (CAF) within the tumor stroma. Here, we show that SCC cell collective invasion is driven by the matrix-dependent mechano-sensitization of EGF signaling in cancer cells. Calcium (Ca2+) was a potent intracellular second messenger that drove actomyosin contractility. Tumor-derived matrix stiffness and EGFR signaling triggered increased intracellular Ca2+ through CaV1.1 expression in SCC cells. Blocking L-type calcium channel expression or activity using Ca2+ channel blockers verapamil and diltiazem reduced SCC cell collective invasion both in vitro and in vivo. These results identify verapamil and diltiazem, two drugs long used in medical care, as novel therapeutic strategies to block the tumor-promoting activity of the tumor niche.Significance: This work demonstrates that calcium channels blockers verapamil and diltiazem inhibit mechano-sensitization of EGF-dependent cancer cell collective invasion, introducing potential clinical strategies against stromal-dependent collective invasion.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/18/5229/F1.large.jpg. Cancer Res; 78(18); 5229–42. ©2018 AACR.

Hypopharyngeal cancer (HC) is an aggressive and life-threatening malignancy that requires a complex multimodal treatment. The aims of the present study were to analyze, in locally advanced HC patients, the oncologic and swallowing outcomes and their predictive factors according to the therapeutic strategy.All patients with locally advanced HC (T3/T4, N0-3, M0) treated at our institution between 2000 and 2020 were included in this retrospective study. Patients were classified in 3 groups according to the therapeutic strategy: primary radical surgery (RS), induction chemotherapy (ICT) or definitive (chemo)-radiation therapy ((C)RT). Predictive factors of oncologic outcomes (overall, cause-specific and recurrence-free survival: OS, CSS and RFS) and swallowing outcome (dysphagia outcome and severity scale: DOSS) were investigated in univariate and multivariate analysis.A total of 217 patients were included in this study (RS: 40; ICT: 106; (C)RT: 71). 5-year OS, CSS and RFS rates were 36, 38 and 32%, respectively. ICT was associated with improved oncologic and swallowing outcomes in univariate analysis. After multivariate analysis, patient age ≥ 70 years (p = 0.0002) was the only factor significantly associated with a worse OS, whereas patient age ≥ 70 years (p = 0.002) and N stage ≥ 2 (p = 0.01) were significantly associated with a worse CSS. Comorbidity level (KFI ≥ 2; p = 0.01) and N stage (≥ 2; p = 0.02) were significantly associated with worse swallowing outcomes.In selected locally advanced HC patients, an ICT-based therapeutic strategy offers acceptable oncologic and functional outcomes. Patient age, N stage and comorbidity level are the main determinants of oncologic and functional outcomes.

Background: Health-related quality of life (HRQoL) is an important outcome in oncology. In our previous work, the specific questionnaire to evaluate the HRQoL for thyroid cancer, the THYCA-QoL, has been translated into French. In this work we aimed to validate the psychometric properties of the French version of the THYCA-QoL questionnaire (F-THYCA-QoL). Methods: The F-THYCA-QoL is composed of 24 items and is divided into 7 dimensions and 6 single items. The F-THYCA-QoL and QLQ-C30 of the European Organisation for Research and Treatment of Cancer (EORTC) were mailed to thyroid cancer patients undergoing surgery. Data from responders obtained was used to test acceptability, reliability and validity of the F-THYCA-QoL questionnaire. Results: Among contacted patients, 280 patients of the University Institute of Face and Neck of Nice responded to the questionnaire between January 2015 and January 2019. The low number of missing data (0.007%) showed a good acceptability of the questionnaire. Six of the 7 items exhibited a good internal consistency with a Cronbach’s alpha ≥ 0.70. No floor or ceiling effects were observed. Factorial validity was demonstrated for 5 scales out of 7, using a multitrait-multimethod analysis and an exploratory factor analysis. Criterion validity assessed between the F-THYCA-QoL and QLQ-C30 was satisfactory. Conclusion: The F-THYCA-QoL questionnaire is a reliable and valid assessment tool that used with the EORTC QLQ-C30 allows to evaluate the HRQoL of thyroid cancer patient in France.

Resume Introduction Le but de cette etude etait de traduire en francais les 24 items du questionnaire THYCA-QoL evaluant la qualite de vie des patients atteints de cancers de la thyroide puis d’en etudier les proprietes psychometriques. Materiels et methodes Le THYCA-QoL est un questionnaire specifique d’evaluation de la qualite de vie des patients operes d’un cancer de la thyroide. Il se compose de 24 items (sept dimensions et six questions isolees). La traduction a ete realisee selon les recommandations de l’EORTC. Pour chaque item, la validation de la version traduite, a fait l’objet d’un consensus d’experts. Resultats Toutes les questions originales du questionnaire ont pu etre adaptees en francais. Le questionnaire traduit, nomme THYCA-QoL-fr, a ete teste sur 60 patients (65 % de femmes) d’âge moyen 54,5 ans. Les questions ont ete bien acceptees et comprises, aucune donnee manquante n’a ete reportee. Huit patients (13 %) ont propose une modification d’un item du questionnaire. Aucun effet de saturation (planche, plafond) n’a ete detecte. La structure interne etait comparable a celle du questionnaire original. Les coefficients α de Cronbach variaient de 0,53 pour la dimension oro-pharyngee a 0,88 pour la dimension vocale. Le diagramme des valeurs propres mettait en evidence les sept dimensions de la version originale. Conclusion THYCA-QoL-fr est le premier questionnaire specifique d’evaluation de la qualite de vie des patients operes d’un cancer de la thyroide en langue francaise. Les premiers resultats psychometriques exploratoires confirment la similarite des qualites psychometriques de cette adaptation francaise du THYCA-QoL.

International audience; Background: The aim of this study was to assess the impact of the initial therapeutic strategy on oncologic outcomes in patients with HPV-positive OPSCC.Methods: All p16-positive OPSCCs treated from 2009 to 2014 in 7 centers were retrospectively included and classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Univariate, multivariate propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS).Results: 382 patients were included (surgical group: 144; non-surgical group: 238). Five-year OS, DSS and RFS were 89.2, 96.8 and 83.9% in the surgical group and 84.2, 87.1 and 70.4% in the non-surgical group, respectively. These differences were statistically significant for DSS and RFS after multivariate analysis, but only for RFS after propensity score matching analysis.Conclusion: In p16+ OPSCC patients, upfront surgery results in higher RFS than definitive radiotherapy ± chemotherapy but does not impact OS.

Resume Introduction L’objectif de cette etude est d’evaluer les resultats fonctionnels de la reconstruction mandibulaire par lambeau libre osseux en termes de deglutition, de la parole et de l’esthetique. Materiel et methodes Enquete transversale multicentrique incluant 134 patients operes d’une reconstruction mandibulaire par lambeau libre osseux sur 9 centres entre 1998 et 2016, avec un recueil minimum de 6 mois. Un questionnaire standardise a recueilli les caracteristiques des patients et du traitement realise. Les criteres de jugement etaient : perte de poids, ouverture buccale, gastrostomie, type de regime alimentaire, reprise de l’alimentation orale et score DHI. L’impact des caracteristiques des patients sur ces criteres a ete recherche par analyse uni/multivariee. Resultat Quatre-vingt-dix patients/134 etaient operes pour cancer, majoritairement par lambeau fibulaire (80 %). Quatre-vingt quatorze pour cent des reconstructions etaient des succes primaires. Soixante et onze pour cent des patients etaient en contexte post-radique. Quatre-vingt-huit pour cent des patients avaient une exerese linguale limitee. Quatre-vingt-dix-sept pour cent des patients ont repris une alimentation orale. Quatre-vingt-neuf pour cent des patients ont une voix intelligible. Quatre-vingt-six pour cent evaluent leur aspect esthetique comme moyen ou bon. Neuf pour cent des patients ont beneficie d’une rehabilitation prothetique. La radiotherapie et l’etendue de l’exerese linguale influencent significativement la fonction de deglutition (p = 0,04 ; p = 0,03 respectivement). La radiotherapie et l’extension a l’oropharynx influencent significativement la dependance a une gastrostomie (p = 0,04 ; p = 0,02 respectivement). Conclusion Les patients reconstruits par lambeau libre osseux retrouvent en majorite une alimentation orale. Plus de 80 % d’entre eux sont satisfaits en termes d’elocution et d’esthetique. Cependant, le taux de rehabilitation dentaire reste faible et les complications frequentes.

Introduction Although Human Papilloma Virus (HPV)-driven oropharyngeal cancer (OPC) prognosis is significantly better than that of other head and neck cancers, up to 25% of cases will recur within 5 years. Data on the pattern of disease recurrence and efficiency of salvage treatment are still sparse. Material and method Observational study of all recurrent OPCs diagnosed, following a curative intent treatment, in seven French centers from 2009 to 2014. p16 Immunohistochemistry was used to determine HPV status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival was examined using Kaplan–Meier and multivariate Cox regression modeling. Results 350 recurrent OPC patients (246 p16-negative and 104 p16-positive patients). The site of recurrence was more frequently locoregional for p16-negative patients (65.4% versus 52.9% in p16-positive patients) and metastatic for p16-positive patients (47.1% versus 34.6% in p16-patients, p = 0.03). Time from diagnosis to recurrence did not differ between p16-positive and p16-negative patients (12 and 9.6 months, respectively, p-value = 0.2), as the main site of distant metastasis (all p-values ≥0.10). Overall and relapse-free survival following the first recurrence did not differ according to p16 status (p-values from log-rank 0.30 and 0.40, respectively). In multivariate analysis, prognosis factors for overall survival in p16-negative patients were distant metastasis (HR 2.11, 95% CI 1.30–3.43) and concurrent local and regional recurrences (HR 2.20, 95% CI 1.24–3.88). Conclusion With the exception of the initial site of recurrence, the pattern of disease relapse and the efficiency of salvage treatment are not different between p16-positive and negative OPCs.

NK cells and tissue-resident innate lymphoid cells (ILCs) are innate effectors found in the skin. To investigate their temporal dynamics and specific functions throughout the development of cutaneous squamous cell carcinoma (cSCC), we combined transcriptomic and immunophenotyping analyses in mouse and human cSCCs. We identified an infiltration of NK cells and ILC1s as well as the presence of a few ILC3s. Adoptive transfer of NK cells in NK cell‒ and ILC-deficient Nfil3−/− mice revealed a role for NK cells in early control of cSCC. During tumor progression, we identified a population skewing with the infiltration of atypical ILC1 secreting inflammatory cytokines but reduced levels of IFN-γ at the papilloma stage. NK cells and ILC1s were functionally impaired, with reduced cytotoxicity and IFN-γ secretion associated with the downregulation of activating receptors. They also showed a high degree of heterogeneity in mouse and human cSCCs with the expression of several markers of exhaustion, including TIGIT on NK cells and PD-1 and TIM-3 on ILC1s. Our data show an enrichment in inflammatory ILC1 at the precancerous stage together with impaired antitumor functions in NK cells and ILC1 that could contribute to the development of cSCC and thus suggest that future immunotherapies should take both ILC populations into account.

The selection of patients for the constitution of a cohort is a major issue for clinical research (prospective studies and retrospective studies in real life). Our objective was to validate in real life conditions the use of a Deep Learning process based on a neural network, for the classification of patients according to the pathology involved in a head and neck surgery department. 24,434 Electronic Health Records (EHR) from the first visit between 2000 and 2020 were extracted. More than 6000 EHR were manually classified in ten groups of interest according to the reason for consultation with a clinical relevance. A convolutional neural network (TensorFlow, previously reported by Hsu et al.) was then used to predict the group of patients based on their pathology, using two levels of classification based on clinically relevant criteria. On the first and second level of classification, macro-average performances were: 0.95, 0.83, 0.85, 0.97, 0.84 and 0.93, 0.76, 0.83, 0.96, 0.79 for accuracy, recall, precision, specificity and F1-score versus accuracy, recall and precision of 0.580, 580 and 0.582 for Hsu et al., respectively. We validated this model to predict the pathology involved and to constitute clinically relevant cohorts in a tertiary hospital. This model did not require a preprocessing stage, was used in French and showed equivalent or better performances than other already published techniques.

Local or metastatic relapse following surgery, radiotherapy, and cisplatin is the leading cause of death in patients with head and neck squamous cell carcinoma (HNSCC). Our study shows overexpression of c-MET and AXL in HNSCC cells and patients resistant to radiotherapy and cisplatin. We demonstrate that cabozantinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), c-MET, and AXL, decreases migration, invasion, and proliferation and induces mitotic catastrophe and apoptotic cell death of naive and radiotherapy- and cisplatin-resistant HNSCC cells. Cabozantinib inhibits the growth and metastatic spread of experimental HNSCC in zebrafish and the growth of experimental HNSCC in mice by blocking tumor cell proliferation and angiogenesis. The efficacy of cabozantinib is also confirmed on viable sections of surgically removed specimens of human HNSCC and on a patient who relapses after five lines of treatment. These results suggest that cabozantinib is relevant for the treatment of patients with HNSCC after relapse under radiotherapy and cisplatin.

Resume Introduction La dysphagie est un motif frequent de consultation. Les diverticules pharyngo-œsophagiens sont une des etiologies frequentes, dont le diverticule de Zenker. Plus rare, elle peut egalement etre la cause d’un diverticule pharynge iatrogene, apparaissant a la suite d’une chirurgie rachidienne par voie cervicale anterieure. Observations Ce travail rapporte le cas d’un homme de 51 ans, opere d’une discopathie cervicale par voie anterieure il y a une dizaine d’annees et qui se plaint d’une dysphagie chronique et de fausses routes invalidantes. Apres la realisation d’un transit pharyngo-œsophagien et d’une endoscopie digestive, on diagnostique la presence d’un diverticule pharynge anterolateral au contact des plaques de vissage cervicales. Discussion Le diverticule pharynge differe du diverticule de Zenker par sa localisation et son origine. Il apparait de maniere precoce ou retardee apres la chirurgie orthopedique du rachis. Son traitement est chirurgical, par voie endoscopique ou externe par abord cervical. Dans notre cas, un traitement adapte a permis une regression totale des symptomes sans complications sous couvert d’une surveillance stricte postoperatoire.

Introduction Dysphagia is a common presenting complaint and can often be due to pharyngoesophageal diverticulum, including Zenker's diverticulum. Iatrogenic pharyngeal diverticulum, occurring after anterior cervical spine surgery, is a rare cause of dysphagia. Case report We report the case of a 51-year-old man, with a history of anterior cervical fusion about ten years previously, who complained of chronic dysphagia and disabling episodes of aspiration. Anterolateral pharyngeal diverticulum in contact with the cervical screw plates was diagnosed on barium swallow and upper gastrointestinal endoscopy. Discussion Pharyngeal diverticulum differs from Zenker's diverticulum in terms of its position and its origin. It may occur early or late after anterior cervical spine surgery. Treatment consists of endoscopic or open surgery via a neck incision. In our case, appropriate treatment allowed complete resolution of the patient's symptoms with no complications following rigorous postoperative surveillance.

Objectives To assess the functional results of oromandibular reconstruction by free bone flap, in terms of swallowing, speech and esthetics. Materials and methods A transverse multicenter study included 134 patients reconstructed by free bone flap between 1998 and 2016, with more than 6 months’ follow-up, in 9 centers. A standardized questionnaire collected data on patients and treatment. Study endpoints comprised: weight loss, mouth opening, gastrostomy dependence, type of feeding, and DHI score. The impact of patient baseline characteristics on these functional criteria was explored by uni/multivariate analysis. Results Ninety of the 134 patients had cancer. Fibula flap was mainly used (80%). 94% of reconstructions were primary successes. 71% of patients had pre- or post-operative radiation therapy. 88% had less than 50% lingual resection. 97% recovered oral feeding. 89% had intelligible speech. 86% judged their esthetic appearance as good/average. 9% had dental prosthetic rehabilitation. Radiation therapy and extensive lingual resection significantly impacted swallowing function (P = 0.04 and P = 0.03, respectively). Radiation therapy and oropharyngeal extension significantly increased gastrostomy dependence (P = 0.04 and P = 0.02, respectively). Conclusion Oromandibular reconstruction by free bone flap enabled return to oral feeding in most cases. More than 80% of patients were satisfied with their result in terms of speech and esthetics. However, the rate of dental rehabilitation was low and the rate of complications was high.

Local or metastatic relapses following surgery, radiotherapy and chemotherapy (cisplatin) are the leading causes of death of patients with head and neck squamous cell carcinoma (HNSCC). In the current study, we showed that acquired resistance to radiotherapy and cisplatin of HNSCC cells and patients depends on overexpression of c-MET and AXL. Cabozantinib, a VEGFR, c-MET and AXL inhibitor, decreased migration, invasion and proliferation, and induced mitotic catastrophe and apoptotic cell death of naive and radiotherapy- and cisplatin-resistant HNSCC cells.Cabozantinib inhibited the growth of experimental HNSCC in mice by inhibiting tumor cell proliferation and angiogenesis. Cabozantinib inhibited the growth and the metastatic spread of experimental HNSCC in zebrafish. The efficacy of cabozantinib on experimental models of HNSCC was further confirmed on viable sections of surgically removed specimens of human HNSCC. These results suggest that cabozantinib is highly relevant for the treatment of HNSCC patients following relapses on radiotherapy and cisplatin.

International audience; Objectives: To assess the factors associated with long-term quality of life (QoL) and patient concerns in elderly oral or oropharyngeal cancer (OOPC) patients after oncologic surgery and free-flap reconstruction. Methods: Patients aged over 70 years who were still alive and disease-free at least 1 year after surgery were enrolled in this cross-sectional multicentric study. Patients completed the EORTC QLQ-C30, -H&N35 and -ELD14 QoL questionnaires, and the Hospital Anxiety and Depression Scale (HADS). Patient needs were evaluated using the Patient Concerns Inventory (PCI). Factors associated with these clinical outcomes were determined in univariate and multivariate analysis. Results: Sixty-four patients were included in this study. Long-term QoL, functioning scales and patient autonomy were well-preserved. Main persistent symptoms were fatigue, constipation and oral function-related disorders. Salivary and mastication/swallowing problems were the main patient concerns. The mean number of patient concerns increased with the deterioration of their QoL. Psychological distress (HADS score ≥ 15) and patient frailty (G8 score

The aim of this study was to determine the impact and cost-effectiveness of virtual surgical planning during fibula free flap mandibular reconstruction on peri- and postoperative data. We conducted a retrospective cohort study from January 2012 to December 2016 in four French university centres. Three hundred fibula free flaps for mandibular reconstruction were performed in 294 patients. Surgeries were planned in 29.7% of cases (n = 89). There was no significant difference in the rate of negative-margins excision, median length of hospital stay, operative time, and early complications between planned and non-planned surgeries. Morphological analysis revealed a higher rate of centred occlusion in planned patients (satisfactory alignment of interincisal points: Planned 65.5% vs Non-Planned 33.3%, p = 0.006). In mandibular reconstruction by fibula free flap, the additional cost generated by virtual surgical planning does not seem to be balanced by savings resulting from a shorter operative course, a reduced hospital stay, or a reduction in postoperative complications. However, virtual surgical planning may provide a higher rate of centred occlusion. Long-term benefits should be assessed by further studies.

International audience; Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk of synchronous primary neoplasia (SPN) which could impact their management. The aims of this study were to evaluate the risk and distribution of SPN in OPSCC patients according to their HPV (p16) status, the predictive factors of SPN and the impact of SPN on therapeutic strategy and oncologic outcomes.Material and methods: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. Univariate analyses were conducted using Chi-2 and Fisher exact tests. For multivariate analyses, all variables associated with a p ≤ 0.10 in univariate analysis were included in logistic regression models.Results: Among the 1291 patients included in this study, 75 (5.8%) displayed a SPN which was preferentially located in the upper aerodigestive tract, lung and esophagus. Comorbidity level (p = 0.03), alcohol (p = 0.005) and tobacco (p = 0.01) consumptions, and p16 tumor status (p < 0.0001) were significant predictors of SPN. In multivariate analysis, p16+ status was significantly associated with a lower risk of SPN (OR = 0.251, IC95% [0.133;0.474]). Patients with a SPN were more frequently referred for non-curative treatment (p = 0.02). In patients treated with curative intent, there was no impact of SPN on the therapeutic strategy (surgical vs. non-surgical treatment). We observed no overall survival differences between patients with or without SPN.Conclusion: P16 tumor status is the main predictive factor of SPN in OPSCC patients. This study provides crucial results which should help adapt the initial work-up and the global management of OPSCC patients.

The aim of this study was to translate into French the 24 items of the THYCA-QoL questionnaire used in thyroid cancers and then to study its psychometric properties.The THYCA-QoL is a specific questionnaire for evaluating the quality of life of patients undergoing thyroid cancer surgery. It consists of 24 items and is divided into seven dimensions and six isolated questions. The translation has been carried out according to the recommendations of the EORTC. Validation of the translated version was obtained by finding a consensus of experts for each of the items.All the original questions of the questionnaire have been adapted into French. The translated questionnaire, named THYCA-CoL-fr, was tested on 60 patients (65 % female), mean age 54.5 years. All questions were well accepted and understood and no missing data were reported. Eight patients (13 %) proposed an item correction to the questionnaire. No attenuation effects (floor or ceiling) were detected. The internal structure was comparable to the original questionnaire: Cronbach α coefficients varied from 0.53 for the oropharyngeal dimension to 0.88 for the voice dimension. The scree-plot highlighted the seven dimensions of the English version.THYCA-QoL-fr is the first specific French language questionnaire to evaluate the quality of life in thyroid cancer patients undergoing surgery. These first exploratory psychometric results confirmed the conceptual similarity of the French translation and the English version.

To assess patient needs and concerns after head and neck squamous cell carcinoma (HNSCC) treatment and their possible correlations with long-term quality of life (QoL) and to examine the potential impact of psychological distress on these results.Alive and disease-free HNSCC patients at least 1 year after treatment were enrolled in this cross-sectional multicentric study and completed the EORTC QLQ-C30 and HN35 QoL questionnaires, the head and neck cancer-specific patient concerns inventory (PCI-HN) questionnaire and the hospital anxiety and depression scale (HADS). Correlations between QoL outcomes and patient needs and concerns were investigated using Spearman's correlation tests.Seventy-two patients were enrolled in the study. Fear of cancer recurrence was the main patient concern followed by dental, salivary, fatigue, speech, and eating problems. The leading patient needs in terms of consultation were to be referred to the surgeon, the speech, and swallow therapist and the oral rehabilitation team. The number of patient concerns correlated negatively (r .40) with functioning scales score and positively (r .40) with general and head and neck symptoms. Psychological distress was the main determinant of QoL outcomes (p .0001). We found a significant impact of gender (p = .002) on the number of patient concerns, and of patient age (p = .003) on the number of staff members selected by patients.Identification of patient needs and concerns along with multidisciplinary management of persistent symptoms and psychological distress seem essential steps towards improving QoL of HNSCC patients.

Resume Dans le contexte de la pandemie de COVID-19, des conseils specifiques semblent necessaires concernant la prise en charge des patients atteints de cancers ORL. La regle est de limiter au maximum le flux de patients afin de reduire les risques de contamination par le virus SARS-Cov-2 aussi bien des patients que du personnel soignant, particulierement expose en ORL. L’objectif est de limiter le risque de perte de chance pour le patient et d’anticiper le flux de patients atteints de cancers a traiter a la fin de l’epidemie, en tenant compte du degre d’urgence, de la lourdeur de la chirurgie, du risque de contamination de l’equipe soignante (tracheotomie) et de la situation locale (saturation ou non de l’hopital et des services de reanimation).

Background Dihydropyrimidine dehydrogenase (DPD) status is an indicator of a marked risk for toxicity following fluoropyrimidine (FP)-based chemotherapy. This notion is well-established for low DPD status but little is known about the clinical impact of high DPD activity. This study examined the possible link between high intrinsic lymphocytic DPD activity and overall survival, progression free survival and response to FP-based treatment in patients treated in our institution. Methods Lymphocytic DPD activity was assessed in a group of 136 patients receiving FP-based chemotherapy from 2004 to 2016. There were 105 digestive (77.2%), 24 breast (17.6%) and 7 head and neck cancers (5.2%). Cox or logistic regression models were applied with adjustment on all confounding factors that could modify OS, PFS or response. All models were stratified on the three cancer locations. A cut-off for DPD activity was assessed graphically and analytically. Results An optimal cut-off for DPD activity at 0.30 nmol/min/mg protein was identified as the best value for discriminating survivals and response. In multivariate analysis, individual lymphocytic DPD activity was significantly related to overall survival (p = 0.013; HR: 3.35 CI95%[1.27–8.86]), progression-free survival (p p = 0.033; HR: 0.33 CI95%[0.12–0.92]) with a marked detrimental effect associated with high DPD activity. Conclusions DPD status screening should result in a two-pronged approach with FP dose reduction in case of low intrinsic DPD and, inversely, an increased FP dose for high intrinsic DPD. In a context of personalized FP-based treatment, this innovative strategy needs to be prospectively validated.

In this article, we aimed to discuss the role of total laryngectomy (TL) in the management of patients with larynx cancer (LC) in the era of organ preservation. Before the 1990s, TL followed by radiotherapy (RT) was the standard treatment for patients with locally advanced LC. Over the last 30 years, various types of larynx preservation (LP) programs associating induction or concurrent chemotherapy (CT) with RT have been developed, with the aim of treating locally advanced LC patients while preserving the larynx and its functions. Overall, more than two-thirds of patients included in a LP program will not require total laryngectomy (TL) and will preserve a functional larynx. However, despite these advances, the larynx is the only tumor site in the upper aero-digestive tract for which prognosis has not improved during recent decades. Indeed, none of these LP protocols have shown any survival advantage compared to primary radical surgery, and it appears that certain LC patients do not benefit from an LP program. This is the case for patients with T4a LC (extra-laryngeal tumor extension through the thyroid cartilage) or with poor pretreatment laryngeal function and for whom primary TL is still the preferred therapeutic option. Moreover, TL is the standard salvage therapy for patients with recurrent tumor after an LP protocol.

Introduction Therapeutic management of oropharyngeal squamous cell carcinomas (OPSCC) is still debated. Since the role of HPV was demonstrated, few studies have focused on HPV-negative OPSCC. The aim of our study was to assess the impact of therapeutic strategy (surgical vs. non-surgical) on oncologic outcomes in patients with HPV-negative OPSCC. Material and method All p16-negative OPSCCs treated from 2009 to 2014 in 7 tertiary-care centers were included in this retrospective study and were classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Patients not eligible for surgery (unresectable tumor, poor general-health status) were excluded. Univariate, multivariate and propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). Results Four hundred seventy-four (474) patients were included in the study (surgical group: 196; non-surgical group: 278). Five-year OS, DSS and RFS were 76.5, 81.3 and 61.3%, respectively, in the surgical group and 49.9, 61.8 and 43.4%, respectively, in the non-surgical group. The favorable impact of primary surgical treatment on oncologic outcomes was statistically significant after multivariate analysis. This effect was more marked for locally-advanced than for early-stage tumors. Propensity score matching analysis confirmed the prognostic impact of primary surgical treatment for RFS. Conclusion Therapeutic strategy is an independent prognostic factor in patients with p16-negative OPSCC and primary surgical treatment is associated with improved OS, DSS and RFS. These results suggest that surgical strategy is a reliable option for advanced stage OPSCC.

Resume Objectifs Analyser dans les cancers du plan glottique envahissant la commissure anterieure (CA) les resultats carcinologiques et fonctionnels de la laryngectomie supra-cricoidienne (LSC) avec crico-hyoido-epiglotto-pexie (CHEP), en determiner les facteurs predictifs, et comparer ces resultats avec ceux publies avec les autres therapeutiques disponibles. Materiel et methodes Etude retrospective portant sur l’ensemble des patients traites par LSC avec CHEP pour un carcinome epidermoide glottique envahissant la CA, dans notre institution, entre 2000 et 2014. La qualite de la deglutition a ete evaluee grâce au score Dysphagia Outcomes and severity Scale (DOSS). Resultats Cinquante-trois patients ont ete inclus dans cette etude. Les survies globale, specifique et sans recidive etaient de 86, 95 et 80 % a 3 ans, respectivement. Nous avons constate 5 cas de recidive locale (9 %), tous traites par laryngectomie totale. Le tabagisme etait le seul facteur influencant de facon significative la survie sans recidive (p = 0,02). Le score DOSS moyen etait de 5,5 ± 0,9. Un score DOSS ≥ 6 (alimentation orale normale) a ete atteint par 59 % des patients. Le stade T (≥ 2, p = 0,04) etait le seul facteur ayant un impact significatif pejoratif sur le score DOSS. Conclusion Dans les cancers glottiques envahissant la CA, la LSC avec CHEP permet d’obtenir le controle local dans plus de 90 % des cas, ce qui est superieur aux resultats publies pour la chirurgie endoscopique ou la radiotherapie externe. Cependant, contrairement aux LSC, un rattrapage des recidives locales par un traitement conservateur est souvent possible apres chirurgie endoscopique. Ainsi, les taux de survie sans laryngectomie totale obtenus par la LSC avec CHEP et par la chirurgie endoscopique sont, au final, comparables.

The proportion of elderly patients with head and neck cancer is increasing. However, predictive factors of postoperative outcomes are insufficiently explored in this population. In this study, we aimed to determine predictive factors of postoperative outcomes in elderly patients undergoing head and neck free-flap reconstructive surgery in order to determine criteria on which patient selection could be based.All patients aged 65 years or over who underwent head and neck free-flap reconstructive surgery at our institution, between 2000 and 2016, were included in this retrospective study. Predictive factors of postoperative outcomes were investigated in uni- and multivariate analysis.Two-hundred patients were included in the study. Older age (70,75 or 80 yrs) had no significant impact on postoperative outcomes. Free flap failure local and general complications rates were 11%, 34% and 43%, respectively. Oromandibular reconstruction (p = 0.04) was significantly associated with free flap failure and salvage surgery (p = 0.04) with local complications. A high comorbidity level (Charlson Comorbidity Index score ≥ 4; p = 0.02) was associated with a higher risk of general complications. A G8 (Geriatric 8 questionnaire) score 15 (p = 0.004), a high comorbidity level (Kaplan-Feinstein Index score ≥ 2; p = 0.04) and oromandibular reconstruction (p = 0.04) were associated with poor swallowing function at 6 months.Head and neck free flap reconstruction should be offered to fit (G8 score ≥ 15) elderly patients without severe comorbidities (KFI 2 or CCI 4), particularly when oral/pharyngeal soft-tissue reconstruction is planned.

International audience; Introduction: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival.Material and methods: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan-Meier analysis.Results: Among the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group.Conclusion: P16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients.

Introduction : Peri implantitis can be identified by classic clinical and radiographic signs. The aim of this case was to show an original exophytic lesion appeared 8 years after the implantation in the mandibular symphysis. Observations : The patient has been implanted on symphyseal site 8 years ago. The lesion was exophytic and located around mobile implant in right mandible. First curative surgical resection was performed under local anesthesia, combined with explantation of mobile implants. Histhopathological exam identified a giants cells granuloma. A second surgical removal was necessary under general anesthesia because of a severe recurrence. Discussion : The goal of this clinical case was to emphasize the possible correlation between inflammatory peri implantits context and giants cells granuloma. Others techniques could be used to manage this case.

MicroRNAs (miRs) participate in tumor growth and dissemination by regulating expression of various target genes. MiR-223-3p is suspected of being involved in head and neck squamous cell carcinoma (HNSCC) growth although its precise role has not been elucidated. In this study, we showed that miR-223-3p is present in biopsies of HNSCC patients and that its presence is correlated with high neutrophil infiltrate. We found that overexpression of miR-223-3p slightly increased proliferation of the CAL27 squamous carcinoma cell line both in vitro and in vivo. Moreover, miR-223-3p induced CAL27 apoptosis in an orthotopic xenograft mouse model, counteracting the proliferative effect and resulting in no impact on overall tumor growth. We analyzed the effect of miR-223-3p overexpression on signaling pathways and showed that it induced pERK2, pAKT and AKT, consistent with an increase in cell proliferation. In addition, we found that miR-223-3p reduced the STAT3 level correlating with increased cell apoptosis and inhibited vasculature formation. In HNSCC tissues, miR-223-3p expression was inversely correlated to CD31, highlighting the relationship between miR-223 and vessel formation. Finally, we studied the effect of miR-223-3p on response to selected anticancer agents and showed that cells expressing miR-223-3p are more resistant to drugs, notably cetuximab. In conclusion, our study is the first to show the antiangiogenic properties of miR-223-3p in HNSCC patients and to question whether expression levels of miR-223-3p can be evaluated as an indicator of eligibility for non-treatment of HNSCC patients with cetuximab.

Resume Objectifs Les objectifs de cette etude etaient d’evaluer les resultats carcinologiques et fonctionnels de la laryngectomie ou pharyngo-laryngectomie totale (PLT) premiere pour cancer du larynx ou de l’hypopharynx avec extension tumorale extra-laryngee (T4), ainsi que de determiner les facteurs predictifs de ces resultats. Materiel et methodes Analyse retrospective des dossiers informatises de tous les patients ayant beneficie d’une (P)LT premiere pour un carcinome epidermoide du larynx ou de l’hypopharynx de stade T4 dans notre institution entre 2000 et 2014. Les facteurs predictifs des resultats carcinologiques et fonctionnels ont ete recherches en analyse univariee et multivariee. Resultats Au total, 63 patients (58 hommes et 5 femmes) d’âge moyen egal a 68,8 ± 9,7 ans ont ete inclus dans cette etude. Les survies globale et specifique etaient de 69 % et 80 % a 3 ans et de 56 % et 69 % a 5 ans respectivement. En analyse multivariee, le sexe feminin ( p p = 0,006) et la presence d’emboles vasculaires ( p = 0,006) avaient un impact significatif pejoratif sur la survie globale. Six mois apres la fin du traitement, 90 % des patients avaient retrouve une alimentation orale autonome et 83 % de ceux appareilles d’une prothese phonatoire avaient recupere une voix intelligible. Conclusion La (P)LT premiere reste le traitement de reference des cancers de stade T4 du larynx et de l’hypopharynx. Elle permet d’obtenir des resultats carcinologiques et fonctionnels satisfaisants.