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Background Ultrasound imaging has recently benefited from the introduction of a new 70 MHz transducer able to provide high-resolution images, i.e. ultra-high-frequency ultrasound (UHFUS). Aim To study the morphological features of basal cell carcinomas (BCCs) and measure BCC thickness by means of UHFUS examination. Methods In this retrospective multicentric study, 171 consecutive patients underwent UHFUS examination between November 2018 and May 2019 for suspected BCC. Diagnosis was confirmed by histopathology. A series of morphological parameters including echogenicity, structure, borders, shape composition (presence of intralesional structures) were investigated along with objective measurements such as thickness (maximum distance between the surface of the epidermis and the deepest part of the tumour) and width. Results In total, 117 BCCs from 93 patients were examined, including superficial (n = 13; 11.1%), nodular (n = 64; 54.7%), infiltrative (n = 18; 15.4%), mixed subtypes (n = 20; 17.1%) and other subtypes (n = 2; 1.7%). The most frequently observed UHFUS parameters included: hypoechoic signal (n = 80; 68.4%, P < 0.001), homogeneous structure (n = 76, 65.0%, P = 0.01), well-defined borders (n = 77, 65.8%, P < 0.001) and elongated shape (n = 71, 60.7%, P < 0.001). An excellent correlation was found between the BCC thickness measured by UHFUS and the value estimated by histology (interclass correlation ≥ 0.80). Conclusion UHFUS is a new rapid and easy noninvasive skin imaging technique able to provide data on the dimensions and morphology of BCCs in real time and at the bedside. These characteristics mean UHFUS has a number of possible applications, ranging from presurgical mapping to the detection of disease recurrence and treatment monitoring.

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.

Supplemental Figures S1 - S7 Supplemental Tables S1 - S17

Inherent immune suppression represents a major challenge in the treatment of human cancer. The extracellular matrix molecule tenascin-C promotes cancer by multiple mechanisms, yet the roles of tenascin-C in tumor immunity are incompletely understood. Using a 4NQO-induced oral squamous cell carcinoma (OSCC) model with abundant and absent tenascin-C, we demonstrated that tenascin-C enforced an immune-suppressive lymphoid stroma via CCL21/CCR7 signaling, leading to increased metastatic tumors. Through TLR4, tenascin-C increased expression of CCR7 in CD11c+ myeloid cells. By inducing CCL21 in lymphatic endothelial cells via integrin α9β1 and binding to CCL21, tenascin-C immobilized CD11c+ cells in the stroma. Inversion of the lymph node-to-tumor CCL21 gradient, recruitment of T regulatory cells, high expression of anti-inflammatory cytokines, and matrisomal components were hallmarks of the tenascin-C–instructed lymphoid stroma. Ablation of tenascin-C or CCR7 blockade inhibited the lymphoid immune-suppressive stromal properties, reducing tumor growth, progression, and metastasis. Thus, targeting CCR7 could be relevant in human head and neck tumors, as high tenascin-C expression and an immune-suppressive stroma correlate to poor patient survival.

PDF file, 31K, Description of mean median min and max values for each biomarker.

Purpose: Intermediate/high-risk operated patients with head and neck cancer may benefit from the addition of EGF receptor (EGFR) inhibitor gefitinib to chemoradiation. This study was designed to assess improved outcomes and identify predictive biomarkers.Experimental Design: Patients provided informed consent for tumor biomarker analyses and, when eligible, were further enrolled in the therapeutic CARISSA multicenter randomized phase II trial of postoperative irradiation with cisplatin + gefitinib (GORTEC 2004-02-NCT00169221).Results: Seventy-nine patients were included in the biomarker study, whereas 27 did not meet prerequisites for randomization between gefitinib and placebo. Two-year disease-free survival (DFS) rate was 65.0% and did not differ between randomized patients treated with gefitinib or placebo (P = 0.85). The similarity of DFS curves between nonrandomized patients (n = 27), randomized patients without gefitinib (n = 27), and randomized patients receiving gefitinib (n = 25), and similar histoclinical parameter distributions for all groups, allowed us to conduct statistical analyses on the entire population. On multivariate analysis, elevated expression of PAK1 by Western blotting, CD31 and membranous insulin-like growth factor 1 receptor (IGF1R) both by immunohistochemistry was significantly associated with shorter DFS. There was a significant interaction between IGF1R and gefitinib. Gefitinib abolished the prognostic discriminative power of high IGF1R expression; patients with elevated IGF1R expression benefited from gefitinib whereas those with low IGF1R fared worse.Conclusion: Gefitinib treatment affords no significant clinical benefit on DFS in an unselected population of patients with head and neck cancer. Our results point to the potential advantage of personalizing treatment for gefitinib based on tumoral IGF1R expression. This should foster confirmatory analyses in trials involving EGFR-targeting agents. Clin Cancer Res; 18(18); 5123–33. ©2012 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.

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.

Nutritional support during radiotherapy is crucial to tolerating and completing oropharyngeal squamous cell carcinoma (OPSCC) treatment. The impact of HPV status on nutritional support is debated. The objective was to evaluate the rate of Reactive Feeding Tube (RFT) use and determine its prognostic factors during definitive radiotherapy for OPSCC. All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. The impact of tumor p16 status on the risk of RFT was assessed through multivariate analyses. Among the 543 patients, 103 patients required an RFT (19.0%). The use of RFT differed between centers (5% to 32.4%). In multivariate analysis, only tongue base involvement and concurrent chemotherapy were significantly associated with RFT (OR = 2.18 and 3.7, respectively). Tongue base involvement and concomitant chemotherapy were prognostic factors for RFT. HPV status was not a prognostic factor for enteral nutrition during radiotherapy for OPSCC.

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.

Background: The aims of this study were to compare the survival outcomes of salvage vs. primary total laryngectomy (TL) in patients with locally advanced laryngeal or hypopharyngeal carcinoma and to determine their predictive factors. Methods: Overall (OS), cause-specific (CSS) and recurrence-free survival (RFS) of primary vs. salvage TL were compared in univariate and multivariate analysis taking into account other potential predictive factors (tumor site, tumor stage, comorbidity level etc.). Results: A total of 234 patients were included in this study. Five-year OS was 53% and 25% for the primary and salvage TL groups, respectively. Multivariate analysis confirmed the independent negative impact of salvage TL on OS (p = 0.0008), CSS (p < 0.0001) and RFS (p < 0.0001). Hypopharyngeal tumor site, ASA score ≥ 3, N-stage ≥ 2a and positive surgical margins were the main other predictors of oncologic outcomes. Conclusions: Salvage TL is associated with significantly worse survival rates than primary TL highlighting the need for careful selection of patients who are candidates for larynx preservation. The predictive factors of survival outcomes identified here should be considered in the therapeutic decision-making, especially in the setting of salvage TL, given the poor prognosis of these patients.

Background: The aims of this study were to evaluate the clinical outcomes and their predictive factors in locally advanced hypopharyngeal cancer (HC) patients included in a docetaxel-cisplatin-fluorouracil induction chemotherapy (ICT)-based larynx preservation (LP) program. Methods: Between 2005 and 2021, 82 patients with a locally advanced resectable HC who received ICT in an LP program were included in this retrospective study. The predictors of oncologic and swallowing outcomes were determined in univariate and multivariate analyses. Results: The three- and five-year overall survival (OS) rates were 67 and 54%, respectively. The T4 tumor stage was the only predictive factor of poor response to ICT (p = 0.03). In multivariate analysis, a T stage = 4 (p = 0.02), an ICT cycle number < 3 (p = 0.003) and the absence of a response to ICT (p = 0.03) were significantly associated with worse OS. A low body mass index before therapy (p = 0.003) and enteral nutrition during therapy (p = 0.005) were significantly associated with severity of dysphagia 6 months after treatment. Conclusions: The T stage, number of ICT cycles performed and response to ICT are the main predictors of oncologic outcomes. Patients with T4 HC are poor candidates for LP and should be referred to immediate radical surgery.

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.

International audience; Background: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival.Patients and methods: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015.Results: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis.Conclusion: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

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.

International audience; Background: Adenoid cystic carcinoma (ACC) accounts for 1% of malignant head and neck tumours [1] and 10% of salivary glands malignant tumours. The main objective of our study is to investigate the prognostic factors influencing the event-free survival (EFS) of patients with ACC. Patients and methods: A multicentre prospective study was conducted from 2009 to 2018. All 470 patients with ACC whose survival data appear in the REFCOR database were included in the study. The main judgement criterion was EFS. Both a bivariate survival analysis using log-rank test and a multivariate using Cox model were performed using the R software. Results: Average age was 55 years. Females accounted for 59.4% of the cohort. The body mass index (BMI) was normal in 86% of cases. Tumours were located in minor salivary glands in 60% of cases. T3/T4 stages represented 58%; 89% of patients were cN0. histological grade III was observed on 21% of patients. The EFS and overall 5-year survival rates were 50% and 85%, respectively. After adjustment, the most significant pejorative prognostic factors were age >= 65 years (hazard ratio [HR] = 1.67), BMI

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.

Inherent immune suppression represents a major challenge in the treatment of human cancer. The extracellular matrix molecule tenascin-C promotes cancer by multiple mechanisms, yet the roles of tenascin-C in tumor immunity are incompletely understood. Using a 4NQO-induced oral squamous cell carcinoma (OSCC) model with abundant and absent tenascin-C, we demonstrated that tenascin-C enforced an immune-suppressive lymphoid stroma via CCL21/CCR7 signaling, leading to increased metastatic tumors. Through TLR4, tenascin-C increased expression of CCR7 in CD11c+ myeloid cells. By inducing CCL21 in lymphatic endothelial cells via integrin α9β1 and binding to CCL21, tenascin-C immobilized CD11c+ cells in the stroma. Inversion of the lymph node-to-tumor CCL21 gradient, recruitment of T regulatory cells, high expression of anti-inflammatory cytokines, and matrisomal components were hallmarks of the tenascin-C–instructed lymphoid stroma. Ablation of tenascin-C or CCR7 blockade inhibited the lymphoid immune-suppressive stromal properties, reducing tumor growth, progression, and metastasis. Thus, targeting CCR7 could be relevant in human head and neck tumors, as high tenascin-C expression and an immune-suppressive stroma correlate to poor patient survival.

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.

Locoregional relapse in previously irradiated region for head and neck tumours is associated with a bad locoregional and distant prognosis. Reirradiation might be exclusive, or feasible in addition with surgery and/or chemotherapy, according to histopronostic factors. Data show that reirradiation is feasible with some severe toxicity due to the bad prognosis of this situation. Hyperfractionnated regimen with split course or normofractionnated regimen without split course are possible with similar efficacy. If tumour size is small, stereotactic ablative radiotherapy may be considered, and if the treatment centre has proton therapy, it could be proposed because of better organs at risk sparing. There is no standard regarding reirradiation schedules and several trials have to be done in order to determine the best technique. Nevertheless, it is agreed that a total dose of 60Gy (2Gy per fraction) is needed. Other trials testing the association with new systemic agents have to be performed, among them agents targeting the PD1/PD-L1 axis.

Objective To analyze postoperative course, oncologic and functional results and prognostic factors of transoral-transcervical oropharyngeal cancer surgery without mandibulotomy, associated to radial forearm free-flap reconstruction. Material and methods Retrospective analysis of computerized medical records of all patients who underwent this type of surgery in our institution between 2004 and 2014. Predictive factors of oncologic and functional results were investigated on univariate and multivariate analyses. Results Forty-four patients (37 male, 7 female; mean age, 62.3 ± 9.3 years) were included. Three-year overall, disease-specific and recurrence-free survival was 90%, 92% and 79%, respectively. Functional scores were satisfactory (normal or slight impairment) for feeding, speech and oral opening functions in 86%, 93% and 100% of cases, respectively. ASA score ≥ III had significantly negative impact on overall survival (P = 0.005) and on feeding (P = 0.01) and speech (P = 0.01). Conclusion Transoral-transcervical oropharyngeal cancer surgery without mandibulotomy provided excellent oncologic and functional outcomes; it is an advantageous alternative to the conventional conservative transmandibular oropharyngectomy.

To analyze the impact of tumor p16 status and other clinical factors on the therapeutic decision-making process in patients with oropharyngeal squamous cell carcinoma (OPSCC).We conducted a multicenter retrospective study (GETTEC collaborative study group) enrolling all OPSCC patients with a determined p16-status considered eligible for surgery between 2009 and 2014. The impact of p16-status and other clinical factors on the therapeutic decision was evaluated in multivariate analysis.A total of 476 patients were enrolled in the study, including 244 cases (51%) of p16-positive OPSCC. Overall, 223 (47%) patients underwent primary surgery, and 184 (83%) of them received postoperative radiotherapy ± chemotherapy. More patients with p16-positive OPSCC tended to undergo non-surgical treatment than did patients with p16-negative OPSCC (p = 0.10). Multivariate analysis showed that 5 factors significantly influenced therapeutic management of the patients: T-stage ≥ 3 (towards a non-surgical strategy; p 0.001), N-stage ≥ 2a (non-surgical strategy; p = 0.02), tumor involvement of the glosso-tonsillar sulcus (surgical strategy; p = 0.002), tumor extension to the oral cavity (surgical strategy; p 0.009) and the center of care (p 0.001). The rate of patients directed towards a surgical strategy varied between 9% and 74% depending on the center.There was a non-significant trend to recommend patients with p16-positive OPSCC for non-surgical treatment. Center of care, tumor stage and tumor anatomical subsite and extensions were the main determinants of the treatment choice.

The aims of this study were to evaluate clinical outcomes and to determine their predictive factors in patients with oral cavity squamous cell carcinoma (OCSCC) invading the mandibular bone (T4) who underwent primary radical surgery and fibula free-flap reconstruction. Between 2001 and 2013, all patients who underwent primary surgery and mandibular fibula free-flap reconstruction for OCSCC were enrolled in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analysis. 77 patients (55 men and 22 women, mean age 62 ± 10.6 years) were enrolled in this study. Free-flap failure and local and general complication rates were 9, 31, and 22 %, respectively. In multivariate analysis, ASA score (p = 0.002), pathologic N-stage (p = 0.01), and close surgical margins (p = 0.03) were independent predictors of overall survival. Six months after therapy, oral diet, speech intelligibility, and mouth opening functions were normal or slightly impaired in, respectively, 79, 88, and 83 % of patients. 6.5 % of patients remaining dependent on enteral nutrition 6 months after therapy. With acceptable postoperative outcomes and satisfactory oncologic and functional results, segmental mandibulectomy with fibula free-flap reconstruction should be considered the gold standard primary treatment for patients with OCSCC invading mandible bone. Oncologic outcomes are dependent on three main factors: ASA score, pathologic N-stage, and surgical margin status.

Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer worldwide. Treatments including surgery, radio- and chemo-therapies mostly result in debilitating side effects. Thus, a more accurate evaluation of patients at risk of recurrence after radio/chemo treatment is important for preserving their quality of life. We assessed whether the Telomeric Repeat-binding Factor 2 (TERF2) influences tumor aggressiveness and treatment response. TERF2 is over-expressed in many cancers but its correlation to patient outcome remains controversial in OSCC. Our retrospective study on sixty-two patients showed that TERF2 overexpression has a negative impact on survival time. TERF2-dependent survival time was independent of tumor size in a multivariate analysis. In vitro, TERF2 knockdown by RNA interference had no effect on cell proliferation, migration, senescence and apoptosis. Instead, TERF2 knockdown increased the expression of cytokines implicated in inflammation and angiogenesis, except for vascular endothelial growth factor. TERF2 knockdown resulted in a decrease vascularization and growth of xenograft tumors. Finally, response to erlotinib/Tarceva and cetuximab/Erbitux treatment was increased in TRF2 knocked-down cells. Hence, TERF2 may represent an independent marker of survival for OSCC and a predictive marker for cetuximab/Erbitux and erlotinib/Tarceva efficacy.

To evaluate oncologic and functional outcomes and prognostic factors in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program in daily clinical practice. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngo-laryngectomy, treated by docetaxel (75 mg/m(2), day 1), cisplatin (75 mg/m(2), day 1) and 5-fluorouracil (750 mg/m(2)/day, day 1-5) (TPF)-ICT (2-3 cycles) for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Prognostic factors of oncologic (overall, cause-specific and recurrence-free survival: OS, SS and RFS) and functional (dysphagia outcome and severity scale, permanent enteral nutrition, larynx preservation) outcomes were assessed in univariate and multivariate analyses. A total of 53 patients (42 men and 11 women, mean age 58.6 ± 8.2 years) were included in this study. Grade 3-4 toxicities were experienced by 17 (32 %) patients during ICT. The rate of poor response (response

Objectives To evaluate the clinical outcomes of total pharyngolaryngectomy (TPL) in the elderly and to analyze the impact of age on postoperative complications and oncologic and functional outcomes. Methods We conducted a retrospective review of the medical records of all patients who underwent TPL for a laryngeal or hypopharyngeal squamous cell carcinoma, between 2000 and 2015. The impact of advanced age (>70 years) on clinical outcomes was assessed in univariate and multivariate analyses. Results A total of 245 patients (mean age = 66.4 years) were enrolled in this study including 91 (37%) patients aged over 70 years. In patients aged over 70 years, local and general complication rates were 36% and 10%, respectively. Five-year overall, cause-specific and recurrence-free survival rates were 36%, 52% and 31%, respectively. Satisfactory swallowing (swallowing score ≥ 1; i.e. no enteral feeding) and speech (speech score ≥ 1; i.e. intelligible speech) functions were recovered by 94% and 70% of elderly patients. In multivariate analysis, older age had no significant impact on postoperative complications, oncologic outcomes and swallowing function. Compared to younger patients, elderly patients achieved significantly lower speech scores (p = 0.05). Conclusion TPL is associated with favorable clinical outcomes in patients aged over 70 years and can therefore be considered a reliable therapeutic option. However, compared to younger patients, a lower level of recovery regarding speech function is expected in the elderly, and particular attention should be paid to the postoperative speech rehabilitation program in this population of patients.

Objectives/Hypothesis Recent preclinical and clinical studies on head and neck squamous cell carcinoma (HNSCC) revealed synergistic effects when combining anti-EGFR agents with conventional chemotherapeutic drugs. Activation of the PI3-kinase/AKT/mTOR signaling pathway has been identified as an important mechanism implicated in tumor progression and resistance to EGFR inhibitors. The aim of this study was to investigate the effects of combining the mTOR inhibitor temsirolimus (Tem) with the anti-EGFR agent cetuximab (Cet) and conventional chemotherapeutic drugs (cisplatin and fluorouracil (C/F)) on an orthotopic model of HNSCC. Study Design Preclinical in vivo study. Methods We evaluated the anti-tumor efficacy (measured tumor volume) of Tem, Cet, and C/F, administered alone or in combination. Investigations were performed using a human HNSCC cell line, CAL33, injected into the mouth floor of nude mice. Results As compared with the control, the combination of Tem and Cet led to the highest tumor inhibition and induced almost complete tumor growth arrest (P = 0.001). Tem significantly enhanced the impact of the Cet-C/F combination on tumor growth (P < 0.001). The highest inhibitory effects of treatments on cell proliferation (Ki67 labeling), MAPK (pP42/44 labeling), and PI3K/AKT/mTOR (pS6R labeling) signaling pathways were found with the Tem-Cet association. Conclusion In this orthotopic HNSCC model, the combination of Tem with Cet produced synergistic effects on tumor growth. These results were corroborated by a strong inhibition of both MAPK and PI3K-mTOR signaling pathways. Level of Evidence N/A. Laryngoscope, 126:E156–E163, 2016

A significant proportion of patients with locally advanced hypopharyngeal cancer could not be managed by larynx-sparing therapy. T4 stage is one of the main predictive factors of oncologic and functional outcomes.To analyze the therapeutic management of patients with locally advanced hypopharyngeal cancer in clinical practice and to report oncologic and functional outcomes.This was a retrospective study of all patients treated for a locally advanced hypopharyngeal squamous cell carcinoma between 2001 and 2012 at our institution.A total of 100 patients were included in this study. Induction chemotherapy (CT) followed by radiotherapy (RT) ± CT, primary RT + CT, and primary total pharyngolaryngectomy (TPL) comprised the initial therapeutic management for 54, 24, and 20 patients, respectively. Two patients received only supportive care. Overall survival (OS) and cause-specific survival (SS) were 50% and 60% at 3 years, respectively. In the group of patients referred for induction CT, the 3-year OS and SS were 58% and 70%, respectively. In multivariate analysis, T stage (p = 0.05) and ASA score (p = 0.02) were significant predictive factors of OS. T4 tumor stage had a pejorative impact on swallowing function after therapy (p = 0.006). The rate of patients alive, disease-free, and with a functional larynx at 2 years was 23%.

Functional interplay between tumour cells and their neoplastic extracellular matrix plays a decisive role in malignant progression of carcinomas. Here we provide a comprehensive data set of the human HNSCC-associated fibroblast matrisome. Although much attention has been paid to the deposit of collagen, we identify oncofetal fibronectin (FN) as a major and obligate component of the matrix assembled by stromal fibroblasts from head and neck squamous cell carcinomas (HNSCC). FN overexpression in tumours from 435 patients corresponds to an independent unfavourable prognostic indicator. We show that migration of carcinoma collectives on fibrillar FN-rich matrices is achieved through αvβ6 and α9β1 engagement, rather than α5β1. Moreover, αvβ6-driven migration occurs independently of latent TGF-β activation and Smad-dependent signalling in tumour epithelial cells. These results provide insights into the adhesion-dependent events at the tumour–stroma interface that govern the collective mode of migration adopted by carcinoma cells to invade surrounding stroma in HNSCC., Tumour microenvironment influences the migration of cancer cells. Here the authors analyse the proteomic constitution of the extracellular matrix and identify a role for fibronectin in regulating the collective migration of squamous cell carcinoma cells.

Objectives Overexpression of epidermal growth factor receptor (EGFR) and angiogenic factors is associated with the progression of androgen-independent prostate cancer (AIPC). We examined the effects of vandetanib, an inhibitor of vascular endothelial growth factor (VEGFR), EGFR, and rearranged during transfection (RET) tyrosine-kinase activities, alone or combined with docetaxel, on PC3 docetaxel-sensitive (PC3wt) or docetaxel-resistant (PC3R) AIPC cell growth in vivo and in vitro. Methods Mice bearing PC3wt or PC3R tumors were treated for 3 weeks with vandetanib (25 or 50 mg/kg/d p.o., 5 d/wk), docetaxel (10 or 30 mg/kg i.p., 1 d/wk), or their combination (low or high doses). Xenograft tumors were analyzed for expression of Ki-67, EGFR, VEGFR2, and production of VEGFA. Results On PC3wt, vandetanib at both doses stimulated tumor growth, whereas docetaxel at both doses exerted strong growth-inhibiting effects. The low-dose vandetanib-docetaxel combination resulted in tumor growth similar to that of control, whereas the high-dose combination induced a significant antiproliferative effect. In contrast, on PC3R, the low-dose of vandetanib had no effect on tumor growth, whereas the high-dose of vandetanib significantly inhibited tumor growth. Docetaxel at both doses exerted moderate and transient antitumor effects. The combination of high-dose vandetanib with high-dose docetaxel resulted in antiproliferative effects, which were lower than expected from the sum of individual drug effects. Importantly, tumor analyses revealed overexpression of the EGFR/VEGFR pathways in PC3R relative to PC3wt. Conclusion Present results suggest that vandetanib should not be associated with docetaxel in treatment-naive or docetaxel-resistant prostate cancer (CaP). The use of high-dose vandetanib alone may warrant further investigation in patients with docetaxel-resistant AIPC overexpressing VEGFR/EGFR pathways.

The objective of this study was to evaluate the potential detection of circulating tumor cells (CTCs) using the CellSearch (CS) Assay™ in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and then to identify the clinical factors predictive of the presence of CTCs. The presence and number of CTCs were determined using the CS system before treatment, and in 10 healthy individuals (control group). The CS system was able to successfully identify the presence of CTCs in 8 of 49 patients (16 %) before therapy. No CTC was found in the control group. CTCs were detected before therapy in 1 of 19 patients (5 %) with N0 tumor and in 7 of 30 patients (23 %) with N1-2c tumor (p = 0.12; Fisher's exact test). CTCs were identified in a relatively low proportion of patients with locally advanced HNSCC.

Resume Objectif L’objectif principal de notre etude etait de determiner les facteurs pronostiques cliniques et histologiques des cancers localement avances de la cavite buccale traites par chirurgie premiere. Methodes Nous avons mene une etude retrospective portant sur l’ensemble des patients ayant eu une chirurgie premiere avec reparation par lambeaux libres, pour un carcinome epidermoide localement avance de la cavite buccale, dans notre institution, entre 2000 et 2010. Les survies globales, specifiques et sans recidive locoregionale ont ete determinees par la methode de Kaplan-Meier. Les facteurs pronostiques cliniques et histologiques ont ete recherches en analyses uni- (tests du Log Rank) et multivariees (modeles de Cox). Resultats Au total, 149 patients (102 hommes et 47 femmes), d’âge moyen egal a 61,3 ± 12,1 ans ont ete inclus dans notre etude. Les survies globales, specifique et sans recidive locoregionale etaient respectivement de 55, 68 et 71 % a cinq ans. L’âge, la comorbidite et la taille tumorale (sur coupes histologiques) ont ete correles de facon statistiquement significative a la survie globale (p Conclusion Les principaux facteurs pronostiques retrouves dans notre etude etaient a la fois cliniques comme l’âge et la comorbidite des patients et histologiques comme la taille tumorale mesuree sur coupes anatomo-pathologiques, l’envahissement osseux et les limites d’exerese chirurgicale.

Background Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described, and the evidence of a functional impact on gene expression is still limited. Methods We performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours. Results We identified novel differentially methylated CpGs and regions associated with viral infection that are independent of the anatomic site. In particular, most hypomethylated regions were characterized by a marked loss of CpG island boundaries, which showed significant correlations with expression of neighbouring genes. Moreover, a subset of only five CpGs in a few hypomethylated regions predicted HPV status with a high level of specificity in different cohorts. Finally, this signature was a better predictor of survival compared with HPV status determined by viral gene expression by RNA sequencing in The Cancer Genome Atlas cohort. Conclusions We identified a novel epigenetic signature of HPV infection in HNSCCs which is independent of the anatomic site, is functionally correlated with gene expression and may be leveraged for improved stratification of prognosis in HNSCCs. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0419-z) contains supplementary material, which is available to authorized users.

The aim of this study was to assess the impact of the different subtypes of patient comorbidities on the outcomes of head and neck microvascular reconstruction. A total of 423 patients who underwent head and neck free flap reconstruction in our institution between 2000 and 2010 were included in this retrospective study. The impact of the different subtypes of patient comorbidities (as defined by the Kaplan-Feinstein Index) and other global health status-related factors on free flap success, local and general complications, postoperative mortality and length of stay was assessed in univariate and multivariate analysis. We found no correlation between patient comorbidities and free flap failure. In multivariate analysis, we demonstrated a significant correlation between tobacco consumption (p = 0.04) and local complications. Gastro-intestinal comorbidity (p = 0.005) and malnutrition (p = 0.02) were associated with a higher risk of fistula formation. Diabetes mellitus (p = 0.003), gastro-intestinal (p = 0.02), systemic (p = 0.02) and cardiac comorbidities (p = 0.03) were significant predictors of medical complications. We concluded that the different subtypes of patient comorbidities were relevant predictors of complications in head and neck microvascular reconstruction.

Summary Objective The objective of this study was to evaluate the prognostic impact of tumour multifocality in papillary thyroid microcarcinoma (PTMC). Methods All patients who underwent total thyroidectomy and central neck dissection for PTMC in our institution between 1990 and 2007 were included in this retrospective study. Statistical correlations between tumour multifocality and various clinical or pathological prognostic parameters were assessed by univariate and multivariate analyses. Results A total of 160 patients (133 women and 27 men; mean age: 47.8 ± 13.7 years) were included in this study. Tumour multifocality was demonstrated in 59 (37%) patients. Central neck metastatic lymph node involvement was identified in 46 (28%) patients. No statistical correlation was demonstrated between tumour multifocality and the following factors: age, gender, tumour size, extension beyond the thyroid, metastatic central neck lymph node involvement and risk of recurrence. A tumour diameter greater than 5 mm was associated with a higher risk of recurrence (P = 0.008). Conclusion Tumour multifocality does not appear to have a prognostic impact in PTMC.

Resume Objectif Le but de notre etude est d’evaluer l’impact pronostique de la multifocalite tumorale dans le cadre des microcarcinomes papillaires (MCP) de la glande thyroide. Methodes Nous avons mene une etude retrospective portant sur l’ensemble des patients operes d’une thyroidectomie totale avec evidement du compartiment central (ECC) pour un MCP entre 1990 et 2007 au sein de notre institution. Nous avons recherche en analyses uni- et multivariees une correlation statistique entre la multifocalite tumorale et divers parametres cliniques et histologiques determinants du pronostic. Resultats Au total, 160 patients (133 femmes et 27 hommes) d’âge moyen egal a 47,8 ± 13,7 ans ont ete inclus dans notre etude. Une multifocalite tumorale a ete retrouvee chez 59 (37 %) patients. Un envahissement ganglionnaire du compartiment central a ete identifie chez 46 (28 %) patients. Il n’a pas ete retrouve de correlation statistique entre la multifocalite tumorale et les facteurs suivants : âge, sexe, taille tumorale, extension extrathyroidienne, envahissement ganglionnaire initial du compartiment central et risque de recidive. Une taille tumorale superieure a 5 mm a ete associee a un risque plus eleve de recidive (p = 0,008). Conclusion La multifocalite tumorale ne semble pas avoir d’impact pronostique dans les MCP de la glande thyroide.

Background Radiotherapy (RT) is the standard treatment for uveal melanoma. However it can cause damage to the retina and optic nerve. This study examined the in vitro and in vivo effects of the anti-VEGF monoclonal antibody bevacizumab associated with radiotherapy (RT) on tumor growth and tumor proliferation and vasculature on OCM-1 human uveal melanoma cell line. Methods The anti-proliferative effects of bevacizumab, RT and their combination were tested both in vitro (OCM-1 cells co-cultured with HUVEC cells in Transwell plates) and in vivo (OCM-1 tumor xenografts in nude mice). In addition, treatment effects in vitro on VEGF secretion, as well as treatment effects in vivo on tumor proliferation (Ki67 labelling), tumor vasculature (VEGFR2 labelling) and VEGF tumoral concentration were analyzed. Results Bevacizumab given alone had a significant impact on tumor growth in vivo (and moderate effects in vitro). The bevacizumab-RT combination had additive effects in vitro (tumor cell proliferation) and in vivo (tumor growth), which translated into a significant decrease in Ki67 expression, VEGFR2 labelling and VEGF tumoral content. Conclusions The bevacizumab-RT combination could be a promising clinical option to explore for the management of human uveal melanoma, since it may allow RT dose reduction without loss of antitumor efficacy.

Resume Introduction Les schwannomes cervicaux sont des tumeurs benignes des nerfs peripheriques developpees exclusivement a partir des cellules de Schwann. L’atteinte du nerf sympathique cervical est relativement rare, et les auteurs en rappellent, a partir d’un cas, les signes radiologiques evocateurs ainsi que les caracteristiques histologiques. Le traitement de ces tumeurs est chirurgical. Presentation du cas Une patiente de 56 ans consultait pour une masse laterocervicale superieure gauche isolee, ancienne, mais accompagnee d’une gene pharyngee recente. Une tomodensitometrie cervicale mettait en evidence une masse vascularisee au temps retarde, retrostylienne refoulant l’axe jugulocarotidien en avant. Un examen cytologique non contributif conduisait a realiser une exerese chirurgicale de la masse par voie de cervicotomie. Il s’agissait d’une tumeur retro-jugulocarotidienne developpee aux depens du nerf sympathique cervical. L’analyse histopathologique concluait a un schwannome. Les suites operatoires etaient marquees par un syndrome de Claude-Bernard-Horner. Conclusion Le schwannome du sympathique cervical est une tumeur benigne rare, qui doit etre evoquee devant toute masse laterocervicale isolee. La tomodensitometrie preoperatoire est un examen de choix indispensable pour evoquer le diagnostic. Le traitement est chirurgical, afin de confirmer le diagnostic histologique. Un syndrome de Claude-Bernard-Horner postoperatoire confirme souvent l’atteinte du sympathique cervical.

Summary Background: Cetuximab (Cet), an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is a standard of care in advanced head and neck (HN) cancer when combined with irradiation or cisplatin. The TPF association combining docetaxel (T), cisplatin (P) and fluorouracil (F) has become a chemotherapy of reference in the management of HN tumors. The aim of the study was to evaluate the anti-tumor activity of the association of Cet with TPF. In addition, the potential benefit from adding bevacizumab (Bev), an anti-VEGF monoclonal antibody, was examined. Methods: Investigations were performed on CAL33 human head and neck cancer cell line (high content of EGFR) injected as an orthotopic xenograft into the mouth floor of nude mice. The anti-tumor efficacy of Cet (2.5 mg/kg), Bev (20 mg/kg) and of TPF (at the MTD: T 20 mg/kg, P 6 mg/kg, F 17 mg/kg), administered alone or in combination on day 3 and day 10 after tumor cell injection, was assessed on day 12 (animal sacrifice for ethical reasons, 10 animals per treatment group). Tumor volume, tumor histology, tumor cell proliferation (Ki67, immunochemistry) and apoptosis (Bcl2, immunochemistry) were examined. Results: As compared to controls, TPF–Cet and TPF–Cet–Bev had a significant impact on tumor volume and histological response. The highest efficacy was observed with the TPF–Cet combination. The effects of the TPF–Cet–Bev association were not significantly different from those observed with TPF–Cet. Data were corroborated by a diminution in Ki67 labeling and Bcl2 expression. Conclusion: The association of Cet with TPF can be considered a beneficial clinical option in advanced HN cancer patients.

The impact of cervical lymph node metastases and the optimal surgical management of the neck in patients with papillary thyroid carcinoma (PTC) remain controversial. The objectives of this retrospective study were to determine, in patients with PTC, the predictive factors and the impact on tumor recurrence rate of cervical lymph node involvement, and to evaluate the oncologic results and the morbidity of central neck dissection (CND). We reviewed the records of patients who had undergone surgical treatment for PTC at our institution between 1990 and 2000. A total of 368 patients (86 men and 282 women) were included in this study. Young age (p = 0.02), tumor size (p = 0.001) and extrathyroidal tumor extension (p = 0.003) were significant predictive factors of cervical lymph node metastatic involvement (multivariate analysis). Initial metastatic cervical lymph node involvement was identified as an independent risk factor of tumor recurrence (multivariate analysis, p = 0.01). Metastatic lymph node(s) were found in prophylactic CND specimens in 31% of the patients. CND increased the risk of postoperative hypocalcemia (p = 0.008) and of permanent hypoparathyroidism (p = 0.002). In conclusion, cervical lymph node metastatic involvement at the time of initial surgery is an independent risk factor of tumor recurrence. CND provided an up-staging of more than 30% of patients with a clinically N0 neck, but was associated with significant morbidity regarding parathyroid function.

We previously reported on head and neck tumor xenografts that the tumor regression induced by a triple combination of irradiation (RT), anti-EGFR and anti-angiogenic therapies was followed, after treatment arrest, by tumor re-growth characterized by activation of the AKT signaling pathway. Since mTOR is the main AKT-related messenger, the aim of this study was to add the mTOR inhibitor temsirolimus to a tri-therapy with RT plus anti-EGFR and anti-angiogenic drugs in order to improve anti-tumor effects. The human head and neck cancer cell line CAL33 (over-expressing EGFR and secreting VEGF-A) was xenografted in nude mice. Treatment (20 mice per treatment group) was administered for 2 weeks and consisted of either vehicle (control), temsirolimus (5mg/kg i.p. five times a week), tri-therapy with RT (6 Gy three times a week) combined with cetuximab (0.5mg/kg i.p. five times a week) and bevacizumab (5mg/kg i.p. five times a week) or the temsirolimus-tri-therapy association. The time to reach a tumor volume of 2000 mm(3) was significantly different between the four treatment groups (Log Rank p0.0001), with a median of 29.5, 44.5, 67.0 and 70.0 days for control, temsirolimus, tri-therapy and combination groups, respectively. The combination of temsirolimus plus tri-therapy produced the longest growth-inhibiting effects (tri-therapy versus combination, p=0.01). No significant interaction was observed between temsirolimus and the tri-therapy, suggesting that temsirolimus, on the one hand, and RT-cetuximab-bevacizumab, on the other, exert additive effects on tumor growth inhibition. These decreases observed on tumor growth were corroborated by the parallel decreases observed on tumor proliferation (Ki67) and on anti-apoptotic markers (Bcl2). These results suggest that temsirolimus exhibits synergistic antiproliferative effects when administered in combination with irradiation, anti-EGFR and anti-angiogenic therapies in head and neck cancer patients.

Resume Objectif Evaluer la fiabilite de la reconstruction cervicofaciale par lambeau libre chez le sujet âge. Patients et methodes Il s’agit d’une etude retrospective, portant sur l’ensemble des patients ayant beneficie d’une chirurgie reconstructive cervicofaciale par lambeau libre, entre 2000 et 2010, dans notre institution. Au total, 418 patients (301 hommes et 117 femmes) ont ete inclus dans notre etude dont 95 etaient âges de plus de 70 ans (âge moyen = 60,2 ± 11,6 ans). L’impact de l’âge sur le taux d’echec du lambeau, la survenue de complications locales et generales ont ete recherchees en analyse univariee et multivariee. Resultats L’âge avance n’avait pas d’impact sur le taux d’echec du lambeau et la survenue de complications locales. En revanche, le taux de complications generales etait significativement plus eleve chez les patients âges (analyse multivariee : p = 0,007). Ce taux etait egalement significativement plus eleve chez les patients presentant une comorbidite elevee (analyse multivariee : p = 0,001). Les patients ayant beneficie d’une pharyngolaryngectomie totale circulaire ont presente significativement plus d’echec du lambeau (p = 0,005) et plus de complications locales (p = 0,001) que les autres patients, en analyse multivariee. Conclusion Les lambeaux libres representent une technique fiable et sans danger chez le sujet âge. Une selection rigoureuse des patients candidats a ce type de chirurgie est neanmoins necessaire en se basant principalement sur les comorbidites associees.