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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.

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.

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.

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.

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.

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.

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.

The aims of this retrospective study were to evaluate prosthetic voice restoration by tracheoesophageal puncture (TEP) in laryngectomized patients and to identify clinical factors correlated with functional outcomes. Between 2000 and 2008, 103 patients who underwent total laryngectomy or pharyngolaryngectomy (TPL) were included in our study. Functional outcomes were recorded 6 months postoperatively, and results were scored from 0 to 2 for oral diet and speech intelligibility. Lifetime of voice prosthesis and early and late complications were recorded. The impact of several clinical factors on functional outcomes, prosthetic valve lifetime and complications was assessed in univariate analysis. A total of 87 patients (84%) underwent TEP and speech valve placement (79 primary and 8 secondary punctures). Hypopharyngeal tumors (P = 0.005), circular TPL (P = 0.003) and use of a pectoralis major myocutaneous flap (P = 0.0003) were significantly associated with secondary TEP. Successful voice rehabilitation was obtained by 77 of 82 evaluable patients (82%). A high level of comorbidity (ASA scoreor = 3; P = 0.003) was correlated to speech rehabilitation failure. The median device lifetimes were 7.6 and 3.7 months for Provox I and II speech valves, respectively. Minor leakage around the valve occurred in 26% of the patients. Late complications occurred in 14 patients (16%) including: severe enlargement of the fistula (n = 3), prosthesis displacement (n = 7) and granulation tissue-formation (n = 4). In conclusion the use of voice prosthesis showed a high success rate of vocal rehabilitation with an acceptable complication rate.

The mathematical relationship between the dose to the parotid glands and salivary gland production needs to be elucidated. This study, which included data from patients included in a French prospective study assessing the benefit of intensity-modulated radiotherapy (RT), sought to elaborate a convenient and original model of salivary recovery.Between January 2001 and December 2004, 44 patients were included (35 with oropharyngeal and 9 with nasopharyngeal cancer). Of the 44 patients, 24 were treated with intensity-modulated RT, 17 with three-dimensional conformal RT, and 2 with two-dimensional RT. Stimulated salivary production was collected for/=24 months after RT. The data of salivary production, time of follow-up, and dose to parotid gland were modeled using a mixed model. Several models were developed to assess the best-fitting variable for the dose level to the parotid gland.Models developed with the dose to the contralateral parotid fit the data slightly better than those with the dose to both parotids, suggesting that contralateral and ipsilateral parotid glands are not functionally equivalent even with the same dose level to the glands. The best predictive dose-value variable for salivary flow recovery was the volume of the contralateral parotid gland receiving40 Gy.The results of this study show that the recommendation of a dose constraint for intensity-modulated RT planning should be established at the volume of the contralateral parotid gland receiving40 Gy rather than the mean dose. For complete salivary production recovery after 24 months, the volume of the contralateral parotid gland receiving40 Gy should be33%. Our results permitted us to establish two convenient tools to predict the saliva production recovery function according to the dose received by the contralateral parotid gland.

Post-operative outcomes of salvage surgery for recurrent oropharyngeal squamous-cell carcinoma (OPSCC) were acceptable. Pathologic overall, T- or N-stage and patient comorbidities were the main predictors of patient clinical outcomes.To evaluate post-operative outcomes of salvage surgery in patients with recurrent OPSCC and to determine their predictive factors.This study retrospectively reviewed the electronic medical records of all patients who underwent salvage surgery for recurrent OPSCC, between 2000-2013, in our institution. Overall survival (OS) and cause-specific survival (SS) were determined by Kaplan-Meier analysis. Predictive factors of post-operative outcomes were investigated by using univariate and multivariate analyses.A total of 34 patients were included in this study. Local and general post-operative complication rates were 26% and 27%, respectively. A high level of comorbidity (Kaplan Feinstein Index: KFI ≥ 2) was the only factor associated with a higher risk of local (p = 0.03) and general (p = 0.04) complications. OS and SS rates at 3 years were 48% and 61%, respectively. In multivariate analysis, pathologic overall stage ≥ III was a significant predictor of OS (p = 0.02) and pathologic T-stage ≥ 3 was a significant predictor of SS (p = 0.01). Mean pre-operative and post-operative DOSS (dysphagia outcome and severity scale) scores were 4.4 and 3.9, respectively.

The objective of the study is to evaluate the nutritional status and determine its impact on clinical outcomes in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program without prophylactic feeding-tube placement. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngolaryngectomy, treated by docetaxel, cisplatin and 5-fluorouracil (TPF)-ICT for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Patients’ nutritional status was closely monitored. Enteral nutrition was used if and when a patient was unable to sustain per-oral nutrition and hydration. The impact of nutritional status on clinical outcomes was investigated in univariate and multivariate analysis. A total of 53 patients (42 men and 11 women, mean age = 58.6 ± 8.2 years) were included in this study. Six (11.3 %) patients had lost more than 10 % of their usual body weight before therapy. Compared with patients’ usual weight, the mean maximum patient weight loss during therapeutic management was 8.7 ± 4.5 kg. Enteral nutrition was required in 17 patients (32 %). We found no influence of the tested nutritional status-related factors on response to ICT, toxicity of ICT, overall, cause-specific and recurrence-free survival, and on post-therapeutic swallowing outcome. Maximum weight loss was significantly associated with a higher risk of enteral tube feeding during therapy (p = 0.03) and of complications (grade ≥3, p = 0.006) during RT. Without prophylactic feeding-tube placement, approximately one-third of the patients required enteral nutrition. There was no significant impact of nutritional status on oncologic or functional outcomes.

Importance Cetuximab was recently proposed for advanced cutaneous squamous cell carcinomas (cSCC); however, its efficacy is inconsistent and identification of predictive biomarkers for response is necessary. Objective To search for somatic mutations of the HRAS, KRAS, NRAS, BRAF, and EGFR genes in patients with advanced cSCC treated with cetuximab; and to investigate the efficacy and tolerance of cetuximab according to these mutations. Design, Setting, and Participants A multicentric and retrospective study of 31 patients (22 men, 9 women) with histologically confirmed advanced cSCC carried out in 1 department of dermatology and 2 departments of medical oncology in France between January 2008 and December 2014. The median age of participants was 86 years (range, 48-96 years). Interventions Mutational status was determined by pyrosequencing method, allelic discrimination, or Sanger sequencing. Patients were treated by single-agent cetuximab. Main Outcomes and Measures The primary end point was the incidence of somatic mutations of the RAS, BRAF, and EGFR genes and association of cetuximab efficacy with these mutations was investigated by using Fisher test. Secondary end points were the disease control rate (DCR) at week 6, the progression free-survival (PFS), overall survival (OS), and safety profile of cetuximab. Results Thirty-one samples of cSCC from 31 patients were analyzed. Only 2 RAS mutated samples (6.5%) were identified. The first harbored a NRAS point mutation (c.35G>A) in codon 12, resulting in a p.G12D substitution. The second sample presented a HRAS point mutation (c.38G>T) in codon 13, resulting in a p.G13V substitution. No mutation of KRAS, BRAF, and EGFR genes at the investigated loci was found. Two patients with NRAS and HRAS mutations showed a partial and complete response to cetuximab, respectively. The mean duration of follow-up was 19 months. At week 6, the disease control rate was 67.8%. The median OS was 13 months and the median PFS was 9 months. All patients could continue cetuximab treatment without dose reduction. Conclusions and Relevance Even in elderly patients with advanced cSCC, cetuximab was efficacious and well-tolerated. This suggests that cetuximab is certainly warranted in the treatment of advanced cSCC. However, it is also important to identify tumor specific mutations that may determine response to treatment and prognosis for the disease. We have identified here that the incidence of RAS, BRAF, and EGFR mutations is low in cSCC.

Surgery for oral or oropharyngeal cancer with free-flap reconstruction is associated with moderate but persistent functional and quality of life (QoL) problems. Patient age, tumor stage, tumor site, and radiotherapy were the main predictors of functional outcome.To evaluate long-term functional outcomes and QoL, and to determine their predictive factors in patients with oral or oropharyngeal cancer after oncologic surgery and free-flap reconstruction.Patients who underwent surgery with free-flap reconstruction for oral or oropharyngeal cancer between 2000 and 2009 who were alive at least 1 year after therapy were included in this study. Patients completed the Voice Handicap Index (VHI-10) questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaires QLQ-C30 and HN35. Swallowing was evaluated using the Dysphagia Outcome and Severity Scale (DOSS) and by flexible fiberoptic laryngoscopy.Sixty-four patients were included in the study. VHI-10 mean score was 11.2 ± 9 and its predictive factors were T stage (p = 0.005) and tumor involvement of the tongue base (p = 0.01). The mean DOSS score was 4 ± 0.8. Age (p = 0.008), gender (p = 0.04), and radiotherapy (p = 0.001) were the main predictive factors of the DOSS score.

Background: To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours. Methods: This prospective multicentric study involved 251 stage I–III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12–13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4–9), CpG island methylation phenotype status, ploidy, S-phase, LOH. Results: The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P

The aims of this study were to evaluate long-term quality of life (QoL) and to determine its predictive factors after oncologic surgery and free flap reconstruction in patients with oral or oropharyngeal cancer. Patients treated at our institution between 2000 and 2009, who are alive and disease-free at least 1 year after therapy, completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific H&N35 module. Eighty patients were included in our study. Global QoL score was 69.3 ± 22.7%. Global QoL and general symptoms were correlated with T stage, whereas head and neck symptoms were correlated with T stage and tumor involvement of the tongue base. Emotional and social functioning scales, and resumption of professional activity were significantly associated with global QoL. In conclusion, T stage, tumor involvement of the tongue base, professional status and emotional and social functions were the main determinants of QoL in our study.

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.

Objective The primary objective of this study was to determine the clinical and pathological prognostic factors in locally advanced oral cavity cancers treated by primary surgery. Methods All patients treated by primary surgery with free-flap reconstruction for locally advanced oral cavity squamous cell carcinoma in our institution between 2000 and 2010 were included in this retrospective study. Overall, cause-specific and locoregional disease-free survivals were determined by Kaplan-Meier analyses. Clinical and histological prognostic factors were assessed by univariate (Log Rank tests) and multivariate (Cox models) analyses. Results A total of 149 patients (102 men and 47 women; mean age = 61.3 ± 12.1 years) were included in the study. Five-year overall, cause-specific and locoregional disease-free survivals were 55%, 68% and 71%, respectively. Age, comorbidity and tumour size (histological evaluation) were significantly correlated with overall survival (P

This was the first study to specifically demonstrate the validity of ablative surgery and free flap reconstruction for elderly patients with oral or oropharyngeal cancer in terms of oncologic and functional outcomes.The aim of our study was to evaluate the impact of advanced age on oncologic and functional outcomes after ablative surgery and free flap reconstruction in patients with oral or oropharyngeal cancer.We conducted a retrospective review of the medical records of all patients who underwent ablative surgery and reconstruction with free flap for primary oral or oropharyngeal cancer at our institution between 2000 and 2009. The impact of advanced age (≥70 years) on oncologic and functional outcomes was assessed in univariate and multivariate analyses.Advanced patient age had a worse impact on overall (p = 0.006), specific (p = 0.02) and disease-free (p = 0.03) survival in univariate analysis, but had only a worse impact on overall survival (p = 0.03) in multivariate analysis. In the elderly patients, overall, specific and disease-free survival rates at 5 years were 43%, 51% and 49%, respectively. There was no significant difference in functional outcomes between elderly and young patients.

To evaluate quality of life (QOL) after radial forearm free flap (RFFF) reconstruction of the oral cavity and oropharynx in head and neck cancer patients.Prospective study.Academic, tertiary referral centre.Between January 2004 and May 2005, 47 patients underwent immediate RFFF reconstruction of the oral cavity and oropharynx following ablative surgery for a previously untreated head and neck cancer and were initially included in this study. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Head and Neck Cancer Quality of Life Questionnaire were completed before surgery and at 6 and 12 months thereafter.QOL scores obtained at the three assessment dates. Predictive factors of QOL scores at 6 months researched among the following: age, gender, comorbidity, radiotherapy, tumour stage, and tumour site.Global QOL remained stable over time. Social and role functioning scores deteriorated significantly after treatment. Social eating and speech difficulties, trismus, and salivary problems increased significantly in the postoperative period and were among the main complaints of our patients.Despite some functional impairment, global QOL was preserved after RFFF reconstruction following extensive ablative surgery in patients with oral and oropharyngeal cancer.

Radical ablative surgery and radial forearm free flap (RFFF) reconstruction provide promising oncologic and functional results in patients with oral or oropharyngeal cancer.To assess the postoperative outcomes and the oncologic and functional results, with their main predictive factors, after radical ablative surgery and RFFF reconstruction for patients with oral or oropharyngeal cancer.Between 2000 and 2006, we prospectively analyzed the postoperative, oncologic and functional outcomes of all previously untreated patients who underwent this type of surgery.A total of 132 patients were enrolled in this study. There were three RFFF failures. The rate of surgical complications was 20%. The 5-year locoregional control and overall survival rates were 68% and 52%, respectively. Advanced age, high comorbidity index, elevated overall stage and tumoral involvement of the inner part of the cheek were correlated with a lower overall survival rate. A good functional result was obtained for oral diet, speech, mouth opening and aesthetic outcome in 87%, 80%, 86% and 88% of the patients, respectively. High comorbidity index, large flap surface, radiotherapy and tumoral involvement of the mobile tongue were significant predictors of poorer functional or aesthetic outcomes.

Objectives: This prospective study was designed to evaluate quality of life (QOL) after free-flap head and neck reconstruction. Study Design: Prospective study. Methods: Between January 2004 and December 2005, a total of 95 patients underwent microvascular reconstruction of the head and neck at our Institution (Centre Antoine-Lacassagne, Nice, France) and were initially included in this study. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Head and Neck Cancer Quality of Life Questionnaire were completed before surgery, and at 6 and 12 months thereafter. Sixty-five patients completed the questionnaires on at least two of the assessment dates. Predictive factors of Quality of Life (QOL) scores at 6 months were researched among the following: age, sex, comorbidity, radiotherapy, tumor recurrence, tumor stage, and type of surgery. Results: Global QOL remained stable over time. Physical, social, and role functioning deteriorated significantly after treatment. Pain decreased markedly. Social eating, senses, and speech difficulties increased significantly at 6 months, but stabilized between 6 and 12 months. Problems concerning mouth opening and social contact augmented progressively until the 12th postoperative month. Sex, type of surgery, and radiotherapy were the main factors influencing QOL 6 months after treatment. Conclusions: Despite some functional impairments, global QOL was preserved after major head and neck ablative surgery and microvascular free-flap reconstruction.

SummaryObjectiveTo evaluate the reliability of free-flap head and neck reconstruction in the elderly.Material and methodsAll patients who underwent free-flap head and neck reconstruction in our institution between 2000 and 2010 were included in this retrospective study. In all, 418 patients (301 men and 117 women) were enrolled, including 95 patients aged 70 years or older (mean age=60.2±11.6 years). The impact of age on free-flap failure and local and general complication rates was assessed on univariate and multivariate analysis.ResultsAdvanced age had no impact on free-flap failure and local complications rate but was correlated with a higher risk of general complications (multivariate analysis: P=0.007). A high level of comorbidity also had a significant impact on the general complications rate (multivariate analysis: P=0.001). Patients who underwent circular total pharyngolaryngectomy showed elevated risk of free-flap failure (P=0.005) and local complications (P=0.001) on multivariate analysis.ConclusionFree-flap reconstruction of the head and neck is safe and reliable in the elderly. Nevertheless, meticulous patient selection, mainly based on the level of comorbidity, is necessary.

Objective The present study describes the clinical, radiological and histological features of laryngeal chondrosarcoma, on the basis of two clinical cases, and discusses management. Case studies Two male patients, aged 63 and 51 years, presented with low-grade chondrosarcoma revealed respectively by a mass in the lateral neck and by laryngeal dyspnea. CT showed a tumoral process with calcification, developed from the thyroid and cricoid cartilage, respectively. The first patient underwent partial and the second total laryngectomy. Discussion Chondrosarcoma is diagnosed on the basis of combined clinical, radiological and histological signs. Differential diagnosis with chondroma may be difficult, especially in grade-1 chondrosarcoma. Conclusion Laryngeal chondrosarcoma is a rare tumor. Management is basically surgical. Prognosis is generally good, depending essentially on histologic grade.