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.

Should an elective contralateral neck dissection be performed in midline-reaching squamous cell carcinomas of the oral cavity and oropharynx?

OBJECTIVE: to compare the rate of occult contralateral neck metastases (OCNM) in oral and oropharyngeal squamous cell carcinomas (SCC) reaching or crossing the midline and to identify risk factors for OCNM. MATERIALS AND METHODS: we conducted a single-center retrospective study of oral and oropharyngeal SCC with contralateral cN0 neck. The cohort was divided into a midline-reaching (MR; approaching the midline from up to 10 mm) group and a midline-crossing (MC; exceeding the midline by up to 10 mm) group. Clinical N-status was assessed by a radiologist specializing in head and neck imaging. All patients underwent contralateral elective neck dissection (END). RESULTS: A total of 98 patients were included in this study, 59 in the MR group and 39 in the MC group. OCNM were present in 17.3% of patients, 20.3% in the MR group and 12.8% in the MC group (p = 0.336). In multivariable analysis, MR/MC status as well as distance from the midline (in mm) were not identified as risk factors for OCNM. Conversely, oropharyngeal primary and clinical N-status above N1 were significantly associated with a higher risk of OCNM, with odds ratios (OR) of 3.98 (95% CI = 1.08-14.60; p = 0.037) and 3.41 (95% CI = 1.07-10.85; p = 0.038) respectively. CONCLUSION: in patients with oral and oropharyngeal SCC extending close to or beyond the midline, tumor origin and clinical N-status should carry the most weight when dictating the indications for contralateral END, rather than the midline involvement in itself.

ESTIMation of the ABiLity of prophylactic central compartment neck dissection to modify outcomes in low-risk differentiated thyroid cancer: a prospective randomized trial.

BACKGROUND: Prophylactic central neck dissection in clinically low-risk cT1bT2N0 papillary thyroid carcinoma is controversial, due to a large number of conflicting retrospective studies, some showing an advantage in terms of locoregional recurrence, others showing no advantage. These previous studies all show high rates of excellent response. We aim to demonstrate the non-inferiority of thyroidectomy alone as compared to total thyroidectomy with prophylactic central neck dissection in conjunction with adjuvant RAI 30 mCi with rTSH stimulation in terms of excellent response at 1 year. TRIAL DESIGN AND METHODS: Prospective randomized open multicenter phase III trial including patients with 11-40-mm papillary thyroid carcinoma (Bethesda VI) or suspicious cytology (Bethesda V) confirmed malignant on intra-operative frozen section analysis, with no suspicious lymph nodes on a specialized preoperative ultrasound examination. Patients will be randomized 1:1 into two groups: the reference group total thyroidectomy with bilateral prophylactic central neck dissection, and the comparator group total thyroidectomy alone. All patients will receive an ablative dose of 30mCi of radioactive iodine (RAI) within 4 months of surgery. The primary outcome is to compare the rate of excellent response at 1 year after surgery between the groups, as defined by an unstimulated serum thyroglobulin (Tg) level ≤ 0.2 ng/mL with no anti-Tg antibodies, an normal neck ultrasound and no ectopic uptake on the post-RAI scintiscan. Non-inferiority will be demonstrated if the rate of patients with excellent response at 1 year after randomization does not differ by more than 5%. Setting the significance level at 0.025 (one-sided) and a power of 80% requires a sample size of 598 patients (299 per group). Secondary outcomes are to compare Tg levels at 8 +/- 2 postoperative weeks, before RAI ablation, the rate of excellent response at 3 and 5 years, the rate of other responses at 1, 3, and 5 years (biochemical incomplete, indeterminate, and structurally incomplete responses), complications, quality of life, and cost-utility. DISCUSSION (POTENTIAL IMPLICATIONS): If non-inferiority is demonstrated with this high-level evidence, prophylactic neck dissection will have been shown to not be necessary in clinically low-risk papillary thyroid carcinoma. TRIAL REGISTRATION: NCT03570021. June 26,2018.

Application of machine learning methods to guide patient management by predicting the risk of malignancy of Bethesda III-V thyroid nodules.

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

Circulating Exhausted PD-1+CD39+ Helper CD4 T Cells Are Tumor-Antigen-Specific and Predict Response to PD-1/PD-L1 Axis Blockade.

Tumor-infiltrating exhausted PD-1hiCD39+ tumor-antigen (Ag)-specific CD4 T cells contribute to the response to immune checkpoint blockade (ICB), but their circulating counterparts, which could represent accessible biomarkers, have not been assessed. Here, we analyzed circulating PD-1+CD39+ CD4 T cells and show that this population was present at higher proportions in cancer patients than in healthy individuals and was enriched in activated HLA-DR+ and ICOS+ and proliferating KI67+ cells, indicative of their involvement in ongoing immune responses. Among memory CD4 T cells, this population contained the lowest proportions of cells producing effector cytokines, suggesting they were exhausted. In patients with HPV-induced malignancies, the PD-1+CD39+ population contained high proportions of HPV Ag-specific T cells. In patients treated by ICB for HPV-induced tumors, the proportion of circulating PD-1+CD39+ CD4 T cells was predictive of the clinical response. Our results identify CD39 expression as a surrogate marker of circulating helper tumor-Ag-specific CD4 T cells.

The impact of physician's characteristics on decision-making inhead and neck oncology: Results of a national survey.

OBJECTIVES: The aim of this study was to identify the socio-professional and behavioral factors influencing decision-making between surgical and non-surgical treatment in Upper AeroDigestive Tract (UADT) oncology among surgeons and oncologists. MATERIALS AND METHODS: We conducted a nationwide online survey among surgeons and medical or radiation oncologists treating head and neck cancer patients in France. The questionnaire collected physicians' demographics, type of practice, individual behavioral characteristics (attitudes toward risk and uncertainty) and data on decision-making via clinical case scenarios. RESULTS: In total, 197 questionnaires were usable. Clinical case scenarios were grouped into three categories according to the prognostic and functional impact of the choice between surgical or non-surgical treatment. For clinical case scenarios where evidence-based medicine considered surgery as the best option, surgeons were significantly more likely to offer surgery in multivariable analysis. When surgery and non-surgical treatment were equivalent, multivariable analysis showed that the tendency to offer surgery increased with the physician's age, and decreased as the number of patients treated per year increased. When non-surgical treatment was the best option because of very high surgical morbidity, multivariable analysis showed a higher propensity to opt for surgery for the age group 40 - 59 versus 25 - 39, and a lower likelihood of choosing surgery among oncologists. CONCLUSION: This study sheds light on the physicians' socio-professional and behavioral factors influencing decision-making in UADT oncology. These mechanisms, poorly studied and probably underestimated, partly explain the variability of the decisions taken when confronted with clinical situations that are subject to debate. CLINICALTRIALS: gov ID: NCT03663985.

Adjuvant brachytherapy for oral squamous cell carcinomas: a single-center experience comparing low-dose and pulsed-dose-rate techniques.

OBJECTIVE: This study aims to assess the outcomes of adjuvant interstitial brachytherapy (BT) to the tumor bed for oral cavity squamous cell carcinoma (SCC), and to compare the oncological outcomes and toxicity profile of low-dose-rate (LDR) and pulsed-dose-rate (PDR) BT. DESIGN: This retrospective single-center study included all patients who underwent postoperative LDR- or PDR-BT to the tumor bed as the sole adjuvant treatment for an oral tongue or floor of the mouth SCC between January 2000 and December 2020. RESULTS: A total of 79 patients were eligible for this study. The cohort was divided into an LDR group (n = 38) and a PDR group (n = 41). The median time interval between surgery and brachytherapy was 55 days. Median delivered total dose was 55 Gy and median hospital stay was 5 days. Five patients (8.3%) experienced grade 3-4 early toxicity, 2 in the LDR group and 3 in the PDR group. Late toxicities were present in 28 patients (44.4%) and were dominated by grade 1-2 residual pain and dysesthesia, without a statistical difference between the groups. After a median follow-up of 65.1 months, 5­year local control (LC), disease-free survival (DFS), and overall survival (OS) for the whole cohort were 76.3% (95% CI = 63.4-85.1), 61.6% (95% CI = 49.0-72.0), and 71.4% (95% CI = 58.6-80.8), respectively. CONCLUSION: Adjuvant BT after excision of oral cavity SCC provides satisfactory oncological outcomes along with good tolerance. In our study, PDR-BT showed similar oncological and functional results to LDR-BT in this indication.

The external pudendal artery free flap in women: Anatomical study of a novel flap for buccopharyngeal reconstruction.

BACKGROUND: Because of the widespread and high reliability of free flaps in head and neck reconstruction, the challenge today is to reduce donor site morbidity. The external pudendal artery (EPA) free flap has been described in men and provides a minimal functional and cosmetic impact. This study aimed to assess the feasibility of the EPA free flap in women for buccopharyngeal reconstruction. METHODS: A dissection of the inguinal region was performed bilaterally on fresh female cadavers. The anatomy of the EPA and its angiosome were described, along with the design of the EPA free flap. A computed tomography angiographic study of the flap perfusion was performed. RESULTS: Fourteen cadavers were dissected. The EPA was constant. Its diameter ranged from 1.12 to 2.96 mm (median 2.0 mm). The mean area of its angiosome was 167.3 ± 38.5 cm2. An axial fasciocutaneous flap was designed with a horizontal skin paddle measuring on average 9.2 × 6 cm and a pedicle length of 8.4 ± 1.9 cm. The mean flap thickness was 11.7 ± 6.8 mm and depended on individual factors. A primary closure was achieved in all cases with a scar hidden in the underwear. CONCLUSIONS: This anatomical study demonstrates that the EPA seems constant despite variations in its origin pattern. Its diameter and angiosome allow the design of an EPA free flap in women. A clinical study should confirm that this flap is suitable for the repair of buccopharyngeal defects and could be added to the armamentarium of the head and neck reconstructive surgeon.

Exploratory window-of-opportunity trial to investigate the tumor pharmacokinetics/pharmacodynamics of the IAP antagonist Debio 1143 in patients with head and neck cancer.

Inhibitor of apoptosis proteins (IAPs) regulate apoptosis and modulate NF-κB signaling thereby driving expression of genes involved in immune/inflammatory responses. The orally available IAP antagonist Debio 1143 has potential to enhance tumor response to chemoradiotherapy and/or immunotherapy. Patients with pre-operative squamous cell carcinomas of the head and neck (SCCHN) received: Debio 1143 monotherapy (200 mg/day [D]1-15 +/- 2); Debio 1143 (200 mg/day D1-15 +/- 2) plus cisplatin (40 mg/m2 D 1 and 8); cisplatin alone (40 mg/m2 D 1 and 8; EudraCT: 2014-004655-31). Pharmacokinetic/pharmacodynamic effects were assessed in plasma and resected tumors. Primary end point; effect of Debio 1143 on cellular IAP-1 (cIAP-1). Levels of cIAP-1/-2, X-linked inhibitor of apoptosis protein (XIAP), tumor infiltrating lymphocytes (TILs), including CD8+ T cells, programmed cell death protein 1 (PD-1), PD-ligand 1 (PD-L1), and gene expression were also analyzed. Twenty-three of 26 patients completed treatment. In the Debio 1143 monotherapy cohort (n = 13), mean tumor concentrations of Debio 1143 were 18-fold (maximum 55.2-fold) greater than in plasma, exceeding the half-maximal inhibitory concentration for cIAPs and XIAP by 100 to 1000-fold, with significant engagement/degradation of cIAP-1 (p < 0.05). Overall, levels of CD8+ TILs, PD-1, and PD-L1 positive immune cells increased significantly (p < 0.05) following Debio 1143 treatment. Changes were observed in the expression of genes related to NF-κB signaling. Treatments were well-tolerated. Debio 1143 penetrated SCCHN tumors, engaged cIAP-1, and induced immune inflammatory changes in the tumor microenvironment. Based on the mode of action demonstrated here and in previous studies, these data support future combinations of Debio 1143 with immune-checkpoint agents.

Distinct Outcomes of Oropharyngeal Squamous Cell Carcinoma Patients after Distant Failure According to p16 Status: Implication in Therapeutic Options.

INTRODUCTION: Recent modifications in the epidemiology of oropharyngeal squamous cell carcinoma (OSCC) have led to the increase of Human papillomavirus (HPV) related metastatic head and neck cancer patients with high life expectancy even at advanced stage, low comorbidity and still restricted systemic therapy opportunities. In the recent era of ablative therapies' development, oligometastatic HPV OSCC patients are indubitably good candidates for intensified treatment. However, data related to outcomes after optimised management of metastatic sites are dramatically missing. MATERIALS AND PATIENTS: In our cohort of 186 unselected consecutive OSCC patients treated with curative intent at our institution between 2009 and 2013, we analysed the incidence, treatment and outcomes of distant metastatic (DM) failure according to p16 status. RESULTS: After a median follow-up of 4.2 years (95% CI: 3.8-4.4) from primary diagnosis of OSCC, 21/95 p16- patients (22.1%) vs. 8/91 (8.8%) p16+ patients presented DM failure with a median interval of 11 (range 0-46) and 28 months (range 0-71), respectively (p = 0.10). Overall survival (OS) after DM failure was significantly higher in p16+ patients with a two-year OS rate of 75% and 15% for p16+ and p16-, respectively (p = 0.002). In eight HPV-related metastatic patients, three underwent ablative lung metastasis treatment and are still complete responders four to five years later. CONCLUSION: This study highlights distinct outcomes of metastatic HPV-related OSCC patients emphasised by three long-term complete responders after lung ablative treatment. In patients with high life expectancy and limited tumour burden, the question of ablative treatment such as metastasectomy or stereotactic ablative radiotherapy (SBRT) should be addressed.

Risk Factors for Pharyngocutaneous Fistula After Total Pharyngolaryngectomy.

PURPOSE: To evaluate the risk factors of pharyngocutaneous fistula after total pharyngolaryngectomy (TPL) in order to reduce their incidence and propose a perioperative rehabilitation protocol. MATERIALS AND METHODS: This was a multicenter retrospective study based on 456 patients operated for squamous cell carcinoma by total laryngectomy or TPL. Sociodemographic, medical, surgical, carcinologic, and biological risk factors were studied. Reactive C protein was evaluated on post-op day 5. Patients were divided into a learning population and a validation population with patients who underwent surgery between 2006 and 2013 and between 2014 and 2016, respectively. A risk score of occurrence of salivary fistula was developed from the learning population data and then applied on the validation population (temporal validation). OBJECTIVE: To use a preoperative risk score in order to modify practices and reduce the incidence of pharyngocutaneous fistula. RESULTS: Four hundred fifty-six patients were included, 328 in the learning population and 128 in the validation population. The combination of active smoking over 20 pack-years, a history of cervical radiotherapy, mucosal closure in separate stitches instead of running sutures, and the placement of a pedicle flap instead of a free flap led to a maximum risk of post-op pharyngocutaneous fistula after TPL. The risk score was discriminant with an area under the receiver operating characteristic curve of 0.66 (95% confidence interval [CI] = 0.59-0.73) and 0.70 (95% CI = 0.60-0.81) for the learning population and the validation population, respectively. CONCLUSION: A preoperative risk score could be used to reduce the rate of pharyngocutaneous fistula after TPL by removing 1 or more of the 4 identified risk factors.

Equivalence Randomized Trial to Compare Treatment on the Basis of Sentinel Node Biopsy Versus Neck Node Dissection in Operable T1-T2N0 Oral and Oropharyngeal Cancer.

PURPOSE: Sentinel node (SN) biopsy is accurate in operable oral and oropharyngeal cT1-T2N0 cancer (OC), but, to our knowledge, the oncologic equivalence of SN biopsy and neck lymph node dissection (ND; standard treatment) has never been evaluated. METHODS: In this phase III multicenter trial, 307 patients with OC were randomly assigned to (1) the ND arm or (2) the SN arm (experimental arm: biopsy alone if negative, or followed by ND if positive, during primary tumor surgery). The primary outcome was neck node recurrence-free survival (RFS) at 2 years. Secondary outcomes were 5-year neck node RFS, 2- and 5-year disease-specific survival (DSS), and overall survival (OS). Other outcomes were hospital stay length, neck and shoulder morbidity, and number of physiotherapy prescriptions during the 2 years after surgery. RESULTS: Data on 279 patients (139 ND and 140 SN) could be analyzed. Neck node RFS was 89.6% (95% CI, 0.83% to 0.94%) at 2 years in the ND arm and 90.7% (95% CI, 0.84% to 0.95%) in the SN arm, confirming the equivalence with P < .01. The 5-year RFS and the 2- and 5-year DSS and OS were not significantly different between arms. The median hospital stay length was 8 days in the ND arm and 7 days in the SN arm (P < .01). The functional outcomes were significantly worse in the ND arm until 6 months after surgery. CONCLUSION: This study demonstrated the oncologic equivalence of the SN and ND approaches, with lower morbidity in the SN arm during the first 6 months after surgery, thus establishing SN as the standard of care in OC.

Dual Relief of T-lymphocyte Proliferation and Effector Function Underlies Response to PD-1 Blockade in Epithelial Malignancies.

Although understanding of T-cell exhaustion is widely based on mouse models, its analysis in patients with cancer could provide clues indicating tumor sensitivity to immune checkpoint blockade (ICB). Data suggest a role for costimulatory pathways, particularly CD28, in exhausted T-cell responsiveness to PD-1/PD-L1 blockade. Here, we used single-cell transcriptomic, phenotypic, and functional approaches to dissect the relation between CD8+ T-cell exhaustion, CD28 costimulation, and tumor specificity in head and neck, cervical, and ovarian cancers. We found that memory tumor-specific CD8+ T cells, but not bystander cells, sequentially express immune checkpoints once they infiltrate tumors, leading, in situ, to a functionally exhausted population. Exhausted T cells were nonetheless endowed with effector and tumor residency potential but exhibited loss of the costimulatory receptor CD28 in comparison with their circulating memory counterparts. Accordingly, PD-1 inhibition improved proliferation of circulating tumor-specific CD8+ T cells and reversed functional exhaustion of specific T cells at tumor sites. In agreement with their tumor specificity, high infiltration of tumors by exhausted cells was predictive of response to therapy and survival in ICB-treated patients with head and neck cancer. Our results showed that PD-1 blockade-mediated proliferation/reinvigoration of circulating memory T cells and local reversion of exhaustion occur concurrently to control tumors.

The super thin external pudendal artery (STEPA) free flap for oropharyngeal reconstruction - A case report.

The radial forearm flap is one of the most used micro-anastomotic flaps in cervicofacial reconstruction in a carcinological context. This flap is an ideal in terms of reliability and fineness; it has, however, some disadvantages in terms of the functional and aesthetic complications of its donor site. In alternative to a radial forearm free flap, we report the use of the free super thin external pudendal artery flap (STEPA flap) for an oropharyngeal reconstruction. The aim was to decrease the donor site morbidity. A 71-years-old man with a T2N0M0 oropharyngeal squamous cell carcinoma has undergone surgical treatment. A left STEPA free flap was performed to reconstruct a defect about 8 × 6 cm2 . This flap was designed as a half-scrotal free flap sized 9 × 7 cm2 and was inset after tunneling of the pedicle at the floor of the mouth. A surgical revision was needed on the 15th day postoperative for disunion. There was no skin flap failure. After 12 month of follow-up, no complication was observed at the donor site and no erectile dysfunction was recorded. Its characteristics in terms of fineness, flexibility, ease of conformation, and pedicle length are similar to those of the radial forearm flap with less aesthetic and functional sequelae of the donor site. The STEPA flap may be a promising free flap in oropharyngeal or oral cavity reconstruction.

Cutaneous Squamous Cell Carcinoma Tumour Size is Associated with Sentinel Lymph Node Metastasis in a Cohort of 69 Patients.

Ten to fifty percent of high-risk cutaneous squamous cell carcinoma may potentially metastasize. However, the concept of sentinel lymph node biopsy remains controversial for cutaneous squamous cell carcinoma. The aim of this study was to identify prognostic factors associated with sentinel lymph node positivity. A bicentric retrospective analysis was conducted between January 2006 and January 2018. All patients undergoing sentinel lymph node biopsy for high-risk cutaneous squamous cell carcinoma were included, based on the criteria of the prognostic classification of the French Society of Dermatology. Seventy-four patients were included. Five (6.8%) procedures failed. Of the 69 patients assessed, the positive sentinel lymph node biopsy rate was 11.6% (n = 8) with a false negative rate of 5.7% (n = 4). The positivity of sentinel lymph node biopsy was associated with tumour size (p = 0.0194). Sentinel lymph node biopsy is an effective staging procedure for clinically N0 high-risk cutaneous squamous cell carcinoma, with an acceptable morbidity. To date, 2 risk factors of sentinel lymph node positivity have been identified with statistical significance: tumour size and poor tumour differentiation.

Prevalence and characteristics of HPV-driven oropharyngeal cancer in France.

BACKGROUND: France has one of the highest incidence of head and neck cancers in Europe. Despite this, the epidemiological impact of high-risk human papilloma virus (HR-HPV) remains poorly investigated. METHODS: We prospective assessed the proportion of oropharyngeal cancers due to HR-HPV in 15 hospitals throughout France. HPV-status was determined by p16-immunohistochemistry, and by detection of HPV-DNA using in situ hybridization. Cancers were classified as HPV-driven if both p16-immunohistochemistry and HPV-DNA assays were positive. Demographical and clinical features were recorded. RESULTS: 291 patients with palatine-tonsil or tongue-base cancers were recruited from March-2011 to July-2012. Of these, 43.1% of samples were p16-positive and 37.7% were positive for both p16 and HPV-DNA. Prognosis was significantly better in patients with HPV-driven cancers, with smoking negatively impacting patients' oncological outcomes. CONCLUSION: In France, more than a third of tonsillar and tongue base cancers are HPV-driven. More research concerning the evolution of HPV-driven cancers over time is needed.

Definitive radiochemotherapy or initial surgery for oropharyngeal cancer : To what extent can p16 expression be used in the decision process?

BACKGROUND: The decision between definitive radio(chemo)therapy (RCT) or a surgical strategy, i. e. surgery ± adjuvant radio(chemo)therapy for optimal treatment of oropharyngeal cancer is highly debated. Human papillomavirus(HPV)-related tumours are a distinct entity associated with p16 overexpression. While this represents a major prognostic factor, its predictive significance remains unknown. RESULTS: Among 183 consecutive unselected patients treated between 2009 and 2013 with a state-of-the-art surgical procedure ± adjuvant radio(chemo)therapy or definitive RCT including intensity-modulated radiotherapy, 3­year disease-free survival (DFS) was 74 vs. 57%, respectively (p = 0.007). When focusing on p16+ patients (49%), there was no significant difference in tumour control rate between surgery ± radio(chemo)therapy and the definitive RCT group (3-year DFS 83 vs. 82%, respectively; p = 0.48). However, delayed severe dysphagia was significantly lower in favour of definitive RCT: 35 vs. 4%, respectively; p = 0.0002. CONCLUSION: Our results highlight distinct outcomes after definitive RCT or initial surgical treatment according to p16 status, which should thus be considered during the decision process.

Multicenter prospective micro-costing study evaluating mandibular free-flap reconstruction.

Free-flap mandibular reconstruction is a highly specialized procedure associated with severe complications necessitating re-interventions and re-hospitalizations. This surgery is expensive in terms of health workers' time, equipment, medical devices and drugs. Our main objective was to assess the direct hospital cost generated by osseocutaneous free-flap surgery in a multicentric prospective micro-costing study. Direct medical costs evaluated from a hospital perspective were assessed using a micro-costing method from the first consultation with the surgeon until the patient returns home, thus confirming the success or failure of the free-flap procedure. The mean total cost for free-flap intervention was 34,009€ (5151-119,604€), the most expensive item being the duration of hospital bed occupation, representing 30-90% of the total cost. In the event of complications, the mean cost increased by 77.3%, due primarily to hospitalization in ICU and the conventional unit. This surgery is effective and provides good results but remains highly complex and costly.

Intensity-modulated radiotherapy for laryngeal and hypopharyngeal cancer: minimization of late dysphagia without jeopardizing tumor control.

PURPOSE: The purpose of this work was to retrospectively determine the value of intensity-modulated radiotherapy (IMRT) in patients with laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC), on outcome and treatment-related toxicity compared to 3-dimensional conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: A total of 175 consecutive patients were treated between 2007 and 2012 at our institution with curative intent RT and were included in this study: 90 were treated with 3D-CRT and 85 with IMRT. Oncologic outcomes were estimated using Kaplan-Meier statistics; acute and late toxicities were scored according to the Common Toxicity Criteria for Adverse Events scale v 3.0. RESULTS: Median follow-up was 35 months (range 32-42 months; 95% confidence interval 95%). Two-year disease-free survival did not vary, regardless of the technique used (69% for 3D-CRT vs. 72%; for IMRT, p = 0.16). Variables evaluated as severe late toxicities were all statistically lower with IMRT compared with 3D-CRT: xerostomia (0 vs. 12%; p < 0.0001), dysphagia (4 vs. 26 %; p < 0.0001), and feeding-tube dependency (1 vs 13%; p = 0.0044). The rates of overall grade ≥ 3 late toxicities for the IMRT and 3D-CRT groups were 4.1 vs. 41.4%, respectively (p < 0.0001). CONCLUSION: IMRT for laryngeal and hypopharyngeal cancer minimizes late dysphagia without jeopardizing tumor control and outcome.