"Reinnervated Serratus free flap, for a functional outcome in tongue reconstruction: a surgical technique video".

The current benchmark for tongue reconstruction following the excision of locally advanced tumors involves the utilization of free skin or fasciocutaneous flaps, such as anterolateral thigh flap or forearm free flap. They facilitate the volumetric reconstruction of the tongue, leveraging passive mobility from the remaining native tongue tissue. The challenge in tongue reconstruction surgery persists in achieving functional restoration through adequate volume and optimized mobility, using tissue that is both adapted and comparable to native tissue. While the free serratus muscle flap has been described for various indications, its application in tongue reconstructions remains underexploited. Specifically, in cases of locally advanced tumors affecting the mobile tongue, typically within the junctional area and without extension to the floor of the mouth nor to the tip of the tongue, the serratus free flap has shown great results. Reinnervation of the flap is achieved connecting the thoracodorsal nerve to the descending branch of the XII nerve. This technique facilitates functional tongue reconstruction, promoting rapid mucosal epithelialization and reinnervation, which, in turn, preserves muscle volume and sustains adequate trophicity without fibrosis. Regarding these considerations, the pure muscle serratus free flap emerges as a valuable and effective alternative in tongue reconstruction. Notably, there is a dearth of step-by-step operative technique descriptions for this indication in the existing literature. We present a video demonstrating the surgical technique, showcasing procedures as performed at Tenon Hospital (Paris, France).

Twelve years after: The french national network on rare head and neck tumours (REFCOR).

BACKGROUND: Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database. METHODS: Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions. RESULTS: A total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis. CONCLUSION: Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies.

Carcinomas of the external auditory canal: Management and results: A multicenter REFCOR propensity score matching study.

OBJECTIVES: To analyse prognostic factors and survival outcomes of malignant tumors of the external auditory canal, to investigate the role of regional surgery, and adjuvant radiotherapy in early stages and to investigate the role of surgery in operable T4 stage. SETTING: A retrospective analysis was conducted on all patients prospectively included in the national database of the French Expertize Network for Rare ENT Cancers (REFCOR) from January 2000 to December 2016. PARTICIPANTS: 103 patients from 19 reference centers were included. A propensity score matching analysis was applied to enable comparisons between treatments. MAIN OUTCOMES AND MEASURES: Event-free survival, overall survival and factors of poor prognosis of the cohort were described. The interest of local and regional surgery and postoperative radiotherapy were evaluated. RESULTS: The factors of poor prognosis on event-free survival were immunosuppression (p = 0.002), Karnofsky status less than 90% (p = 0.02), body mass index less than 19 Kg / m2 (p = 0.0009), peripheric facial palsy (p = 0.0016), and positive margin (p = 0.0006). In early stages, locoregional surgery was associated with an increase in event-free survival (p = 0.003, HR = 0.21) versus local surgery alone, while postoperative radiotherapy was not associated with an increase in event-free survival (p = 0.86, HR = 0.91) or overall (p = 0.86, HR = 0.91). In locally advanced stages, locoregional surgery followed by radiotherapy was associated with an increase in event-free survival (p = 0.03, HR = 0.39) and overall (p = 0.02, HR = 0.34) versus chemoradiotherapy alone. CONCLUSION AND RELEVANCE: Regional surgery is recommended for early stages of cancers of the external auditory canal. In operable cases, locoregional surgery followed by radiotherapy is recommended.

Functional or radical surgical treatment of laryngeal chondrosarcoma, analysis of survival and prognostic factors: A REFCOR and NetSarc-ResOs multicenter study of 74 cases.

INTRODUCTION: Laryngeal chondrosarcoma (LCS) is a rare tumor of slow evolution whose treatment is poorly codified. For a long time, a radical treatment by total laryngectomy (TL) was proposed. More recent studies tend to propose a conservative surgical approach of the larynx. The objective of this study was to compare the overall survival (OS) of total laryngectomized patients (TL+) versus non-laryngectomized patients (TL-). The secondary objectives were to analyse the reoperation free survival (RFS), the total laryngectomy free survival (TLFS) and to identify the preoperative factors leading surgeons to propose TL. MATERIALS AND METHODS: A retrospective analysis of prospectively collected incident cases from the REFCOR and NetSarc-ResOs multicenter databases between March 1997 and June 2021 was conducted. A propensity score matching analysis was performed to compare the OS of TL+ and TL-patients. RESULTS: 74 patients were included. After propensity score, the 5-year OS of TL+ and TL-patients was comparable (100 %, p = 1). The 5-year RFS rate was 69.2 % (95 % CI [57.5-83.4]) and the 5-year TLFS was 61.7 % (95 % CI [50.4-75.5]). Cricoid involvement greater than 50 % (HR 3.58; IC 95 % [1.61-7.92] p < 0.001), an ASA score of 3 or 4 (HR 5.07; IC 95 % [1.64-15.67] p = 0.009) and involvement of several cartilages (HR 5.26; IC 95 % [1.17-23.6] p = 0.04) are prognostic factors for TL. Dyspnea caused by the tumour is a prognostic factor for reoperation (HR 2.59; IC 95 % [1.04-6.45] p = 0.03). CONCLUSION: These results demonstrate that conservative treatment should be considered as first-line treatment for laryngeal chondrosarcoma.

The microvillar protocadherin CDHR5 associates with EBP50 to promote brush border assembly.

Transporting epithelial cells of the gut and kidney interact with their luminal environment through a densely packed collection of apical microvilli known as a brush border (BB). Proper brush border assembly depends on the intermicrovillar adhesion complex (IMAC), a protocadherin-based adhesion complex found at the distal tips of microvilli that mediates adhesion between neighboring protrusions to promote their organized packing. Loss of the IMAC adhesion molecule Cadherin-related family member 5 (CDHR5) results in significant brush border defects, though the functional properties of this protocadherin have not been thoroughly explored. Here, we show that the cytoplasmic tail of CDHR5 contributes to its correct apical targeting and functional properties in an isoform-specific manner. Library screening identified the Ezrin-associated scaffolds EBP50 and E3KARP as cytoplasmic binding partners for CDHR5. Consistent with this, loss of EBP50 disrupted proper brush border assembly with cells exhibiting markedly reduced apical IMAC levels. Together, our results shed light on the apical targeting determinants of CDHR5 and further define the interactome of the IMAC involved in brush border assembly.

Diagnosis with confidence: deep learning for reliable classification of laryngeal dysplasia.

BACKGROUND: Diagnosis of head and neck (HN) squamous dysplasias and carcinomas is critical for patient care, cure, and follow-up. It can be challenging, especially for grading intraepithelial lesions. Despite recent simplification in the last WHO grading system, the inter- and intraobserver variability remains substantial, particularly for nonspecialized pathologists, exhibiting the need for new tools to support pathologists. METHODS: In this study we investigated the potential of deep learning to assist the pathologist with automatic and reliable classification of HN lesions following the 2022 WHO classification system. We created, for the first time, a large-scale database of histological samples (>2000 slides) intended for developing an automatic diagnostic tool. We developed and trained a weakly supervised model performing classification from whole-slide images (WSI). We evaluated our model on both internal and external test sets and we defined and validated a new confidence score to assess the predictions that can be used to identify difficult cases. RESULTS: Our model demonstrated high classification accuracy across all lesion types on both internal and external test sets (respectively average area under the curve [AUC]: 0.878 (95% confidence interval [CI]: [0.834-0.918]) and 0.886 (95% CI: [0.813-0.947])) and the confidence score allowed for accurate differentiation between reliable and uncertain predictions. CONCLUSION: Our results demonstrate that the model, associated with confidence measurements, can help in the difficult task of classifying HN squamous lesions by limiting variability and detecting ambiguous cases, taking us one step closer to a wider adoption of AI-based assistive tools.

Septal Nasopharyngeal "Kite Flap" for Long-Term Patency of Petrous Apex Cholesterol Granuloma.

Medial petrous apex cholesterol granuloma is a benign lesion which treatment is generally based on a trans-nasal marsupialization. When the artificial ostium is created, it is usually kept open with local flaps, like the septal nasopharyngeal "kite flap", a reliable local vascularized flap. Laryngoscope, 134:2111-2114, 2024.

Expression, Prognostic Value and Correlation with HPV Status of Hypoxia-Induced Markers in Sinonasal Squamous Cell Carcinoma.

(1) Background: In head and neck squamous cell carcinoma, tumor hypoxia has been associated with radio/chemoresistance and poor prognosis, whereas human papillomavirus (HPV)-positive status has a positive impact on treatment response and survival outcomes. The aim of this study was to evaluate the expression and the potential prognostic value of hypoxia-induced endogenous markers in patients treated for squamous cell carcinoma of the nasal cavity and paranasal sinuses (SNSCC), and their correlation with HPV status. (2) Methods: In this monocentric study, patients treated in a curative intent for a SNSCC were screened retrospectively. Protein expression of CA-IX, GLUT-1, VEGF, VEGF-R1, and HIF-1α was determined by immunohistochemical staining, scored, and then correlated with overall survival (OS) and locoregional recurrence free survival (LRRFS). HPV status was assessed and correlated with hypoxic markers. (3) Results: 40 patients were included. A strong expression of CA-IX, GLUT-1, VEGF, and VEGF-R1 was detected in 30%, 32.5%, 50%, and 37.5% of cases, respectively. HIF-1α was detected in 27.5% of cases. High CA-IX expression was associated in univariate analysis with poor OS (p = 0.035), but there was no significant association between GLUT-1, VEGF, VEGF-R1, and HIF-1α expression, and OS/LRRFS. There was no correlation found between HPV status and hypoxia-induced endogenous markers (all p > 0.05). (4) Conclusions: This study provides data on the expression of hypoxia-induced endogenous markers in patients treated for SNSCC and underlines the potential role of CA-IX as a prognostic biomarker for SNSCC.

Water soluble swallow for leak detection after total laryngectomy post radiotherapy.

AIM: Pharyngeal leak (PL) and pharyngocutaneous fistula (PCF) are serious complications following total laryngectomy and their incidence is higher in the salvage setting. The aim of this study is to describe the accuracy of water soluble swallow (WSS) to rule out salivary postoperative leak after salvage total laryngectomy (STL) to expedite start of oral intake. MATERIAL AND METHODS: Retrospective study including patients undergoing STL between 2008 and 2021 at Guy's Hospital. WSS was routinely performed within 15 days post operation. RESULTS: Sixty-six patients underwent STL. Nine developed clinically diagnosed PCF; one died before having WSS. Fifty-six patients underwent WSS post STL. WSS was performed within 15 days after STL when no postoperative complications occurred (76.8%). Among patients undergoing WSS with no clinical suspicion for fistula (56), PL was identified in 15 cases (26.8%). They were managed conservatively; PCF was avoided in 7(46.7%) cases. Three patients (7.3%) developed PCF after having started oral intake with a negative WSS. These three cases were further analysed, 2 cases where recorded at the beginning of the studied period when less experience was available possibly leading to incorrect results. Sensitivity and negative predictive value (NPV) for fistula prediction were 72.7% and 92.7%, respectively. CONCLUSION: Taking into account the high NPV of WSS, it is safe to start oral intake after negative WSS. Further studies to evaluate its accuracy earlier on after SLT are justified taking into account the results and the impact that delayed feeding has on patient's quality of life.

Survival outcomes, prognostic factors, and effect of adjuvant radiotherapy and prophylactic neck dissection in salivary acinic cell carcinoma: A prospective multicenter REFCOR study of 187 patients.

BACKGROUND: Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands. PATIENTS AND METHODS: Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS. RESULTS: A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3-T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16). CONCLUSIONS: These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3-T4 status and/or intermediate/high histological grade.

Invasive Fungal Rhinosinusitis Due to Co-infection with Mucormycosis and Exserohilum rostratum in a Patient with Acute Lymphoblastic Leukemia.

Invasive fungal infections remain an important cause of complication and morbidity in the management of acute leukemias. Here we report the case of a 27-year-old patient from French Polynesia who was diagnosed with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia. After induction chemotherapy, she developed rhinosinusitis with extensive bone lysis. The context and clinical presentation quickly made us suspect an invasive mucormycosis infection. However, a multidisciplinary investigation including mass spectrometry techniques also revealed the presence of Exserohilum rostratum, a pathogen member of the genus Exserohilum that is ubiquitous in tropical and subtropical regions but rarely implicated in invasive sinusitis. Antifungal treatment combined with an early surgical approach resulted in a favorable clinical response.

Beyond Surgical Treatment in Adenoid Cystic Carcinoma of the Head and Neck: A Literature Review.

Introduction: Adenoid cystic carcinoma (AdCC) is a rare tumour as it accounts for about 10% of all salivary gland neoplasms. It occurs in all age groups with a predominance of women, but no risk factors have been identified to date. Although AdCC behaves as a slow-growing tumour, it is characterized by multiple and late recurrences. Therefore, we aim to update the knowledge of the treatment options in advanced and recurrent cases. Materials and Methods: We performed a systematic literature review to provide a synthesis of the practical knowledge required for AdCC non-surgical management. Altogether, 99 out of the 1208 available publications were selected for analysis. Results: AdCC is described as a basaloid tumour consisting of epithelial and myoepithelial cells. Immunohistochemistry is useful for diagnosis (PS100, Vimentin, CD117, CKit, muscle actin, p63) and for prognosis (Ki67). Identified mutations could lead to therapeutic opportunities (MYB-NFIB, Notch 1). The work-up is mainly based on neck and chest CT scan and MRI, and PET-CT with 18-FDG or PSMA can be considered. Surgical treatment remains the gold standard in resectable cases. Post-operative intensity modulated radiotherapy is the standard of care, but hadron therapy may be used in specific situations. Based on the available literature, no standard chemotherapy regimen can be recommended. Conclusion: There is currently no consensus on the use of chemotherapy in AdCC, either concomitantly to RT in a postoperative setting or at a metastatic stage. Further, the available targeted therapies do not yet provide significant tumour response.

Diagnosis of mucormycosis using an intercalating dye-based quantitative PCR.

PCR-based methods applied to various body fluids emerged in recent years as a promising approach for the diagnosis of mucormycosis. In this study, we set up and assess the value of a qPCR to detect a wide variety of Mucorales species in a single tube. A pair of degenerated primers targeting the rDNA operon was used in a qPCR utilizing an intercalating fluorescent dye. Analytical assessment, using a wide variety of both Mucorales strains (8 genera, 11 species) and non-Mucorales strains (9 genera, 14 species), showed 100% sensitivity and specificity rates with a limit of detection at 3 rDNA copy/qPCR reaction. Subsequently, 364 clinical specimens from 166 at-risk patients were prospectively tested with the assay. All the seven patients classified as proven/probable mucormycosis using the EORTC-MSG criteria had a positive qPCR as well as a patient with a proven uncharacterized invasive mold infection. In addition, three out of seven patients with possible mold invasive infections had at least one positive qPCR test. Sensitivity was calculated between 73.33 and 100% and specificity between 98.10 and 100%. The qPCR method proposed showed excellent performances and would be an important adjunctive tool for the difficult diagnosis of mucormycosis diagnosis. LAY ABSTRACT: qPCR-based diagnosis is the most reliable approach for mucormycosis. We set up a pan-Mucorales qPCR able to detect in a single reaction not less than 11 different species. Both analytical and clinical performances support its use in the clinical setting.

Donor site sequelae and patient satisfaction after head and neck reconstruction with a radial forearm free flap.

PURPOSE: Radial forearm free flap (RFFF) being a workhorse flap in head and neck reconstruction, we investigated its donor site delayed consequences. METHODS: Multicentric case series evaluating 189 patients who underwent RFFF for carcinologic reasons at least 6 months before. Patients and surgeon's appreciation regarding the aesthetic and functional consequences of the flap harvest on their daily life were evaluated by questionnaires using likert scales. Medical data were collected from patients' charts retrospectively. RESULTS: Thirty percent of patients had at least one sequelae. Experiencing a graft necrosis did not worsen long-term results. Cosmetic satisfaction was significantly worst for women, according to patients' and surgeons' opinion. For 81% and 92% patients, respectively, the flap harvest had no impact on daily life nor sport practice. Ratio between the benefits of reconstruction and the sequelae at the donor site was judged "excellent" for 77% patients. CONCLUSIONS: Although objectively important, RFFF morbidity has little impact in head and neck cancer patient's life.

Localized Talaromyces marneffei infection presenting as a tonsillar mass mimicking malignancy.

Talaromyces marneffei is an opportunistic fungal infection seen in immunocompromised patients including those with HIV/AIDS. It is usually seen in patients who live in or are from tropical Asia. In HIV patients, oropharyngeal and laryngeal lesions are usually part of disseminated infection. We describe a case of 63-year-old Vietnamese male with history of HIV/AIDS who presented with localized T. marneffei tonsillar infection without disseminated disease. Imaging studies showed a right tonsillar mass with right cervical lymphadenopathy which was initially thought to be malignancy. The patient underwent biopsy of the mass and histology showed noncaseating granulomas on hematoxylin and eosin stain as well as yeast on Grocott methenamine silver stain. Fungal culture of the biopsy specimen grew suede-like grayish-white colonies with diffuse underlying deep red color pigment which was identified as Talaromyces marneffei. The patient was treated with intravenous liposomal amphotericin B and achieved resolution of symptoms and tonsillar mass. In HIV/AIDS patients who are either from endemic regions or with history of travel to endemic areas particularly Southeast Asia and China, T. marneffei infection should be considered in differential diagnoses of a tonsillar mass.

A prospective multicentre REFCOR study of 470 cases of head and neck Adenoid cystic carcinoma: epidemiology and prognostic factors.

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<16.5 (HR = 2.62), and lymph node invasion cN (HR = 2.08). CONCLUSION: Age, BMI and N stage are the three main clinical prognostic factors determining EFS identified in this prospective series of patients with ACC. Such findings open new research perspectives on the influence of these components on initial patient care.

Should a neck dissection be performed on patients with cN0 adenoid cystic carcinoma? A REFCOR propensity score matching study.

BACKGROUND: Patterns of nodal involvement in adenoid cystic carcinoma (ACC) of the head and neck have not been sufficiently assessed to guide a decision of prophylactic neck dissection (ND). The objective of this study is to analyse the influence of ND on event-free survival (EFS) for patients with cN0 ACC. PATIENTS AND METHODS: A multicentre prospective study was conducted between 2009 and 2018. Patients presenting cN0 non-metastatic ACC on any site, and who received surgery on the tumour, were included. EFS was the main judgement criterion. A comparative survival analysis between the groups that received a ND versus those that did not was performed, using a propensity score. Analyses were carried out using the R software. RESULTS: Between 2009 and 2018, 322 patients with cN0 ACC were included, out of which 58% were female. The average age was 53 years. Tumours were in minor salivary glands in 58% of cases, and 52% had T3/T4 stages. ND was performed on 46% of patients. Out of them, seven had histological lymph node invasion, out of which six had tumour infiltration in the mucosa of oral cavity. After propensity score, the median EFS for N0 patients with ND was 72 months (95% Confidence Interval (CI) [48-81]), compared to 73 months (95% CI [52-85]) for patients without ND (HR = 1.33; 95% CI [0.82-2.16]; p = 0.2). CONCLUSION: ND of cN0 patients does not provide any benefit on EFS, which suggests that its application on such patients is not necessary.

Effects of tobacco abuse on major chromosomal instability in human papilloma virus 16-positive oropharyngeal squamous cell carcinoma.

A substantial number of patients with oropharyngeal squamous cell carcinoma (OPSCC) have two oncogenic risk factors: Human papilloma virus (HPV) infection and tobacco use. These factors can be competitive or synergistic at the chromosomal and genomic levels, with strong prognostic and therapeutic implications. HPV16 has been shown in vitro to be a high­risk HPV that induces low rates of chromosomal copy number alterations. However, chromosomal instability can be increased by smoking. Evaluating chromosomal instability in HPV­positive patients according to their smoking status is therefore critical for assessing the prognosis and therapeutic impact. The aim of this study was to assess chromosomal instability in patients with HPV­positive OPSCC according to smoking status. Chromosomal instability was investigated with array­based comparative genomic hybridization (aCGH) in 50 patients with OPSCC. Differences in chromosomal alterations were examined according to the HPV and smoking status of the patients. HPV­positive tumors (24/26 were HPV16­positive) had fewer genomic aberrations (P=0.0082) and fewer breakpoints (P=0.048) than HPV­negative tumors. We confirmed the association between HPV­positive OPSCC and chromosomal losses at 11q. We verified the association between HPV­negative OPSCC and losses at 3p and 9p and gains at 7q and 11q13. In the patients with OPSCC who were HPV­positive, the total number of chromosomal aberrations per tumor was significantly higher in the group of patients who were smokers (P=0.003). However, the cytobands did not differ significantly according to the smoking status. On the whole, the data of this study may help to improve the stratification of HPV­positive OPSCC patients and must be supplemented by next­generation sequencing studies in order to describe the mutational and transcriptomic profiles of such patients according to smoking status.

Leukocytosis, prognosis biomarker in locally advanced head and neck cancer patients after chemoradiotherapy.

OBJECTIVE: To study the prognostic value of leukocyte increase in a retrospective cohort of locally advanced head and neck squamous cell carcinoma (HNSCC) patients receiving definitive concurrent cisplatin and radiation. MATERIALS AND METHODS: Clinical records of consecutive previously untreated locally advanced HNSCC patients treated in our Institution between March 2006 and October 2012 by concurrent cisplatin (100 mg/m2, every 3 weeks) and radiation (70 Gy in 7 weeks) were collected. The prognostic value of pretreatment leukocyte increase was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophils count exceeding 10 and 7.5 G/L, respectively. RESULTS: We identified 193 patients, all treated with concurrent cisplatin-based chemoradiotherapy. Respectively 24% and 20% patients displayed baseline leukocytosis or neutrophilia. Mean leukocyte count were significantly more elevated in current smokers, patients with performance status (PS) >0, T4 and less in HPV + tumor. The 5-year actuarial overall survival (OS) and progression-free survival (PFS) were 56% and 51% respectively. In univariate analysis, both leukocytosis and neutrophilia were strongly associated with worse OS and PFS (p < 0.001). In multivariate analysis, N classification, HPV/p16, smoking status and leukocytosis were associated with worse OS and PFS. Patients with <3 cycles of cisplatin had worse survival. CONCLUSION: In locally advanced HNSCC treated with concurrent cisplatin and radiation, baseline leukocytosis predicts OS and PFS. In addition with HPV status, this independent biomarker could help identifying patients with high risk of tumor relapse.