INTRODUCTION:Subcricoid-hemilaryngopharyngectomy (SCHLP) with a reconstruction using a fasciocutaneous free flap armed with cartilage graft (FFACG) aims to avoid permanent tracheostomy while still maintaining the laryngopharyngeal functions. The purpose of this study is to report the outcome of this surgical approach.MATERIALS AND METHODS:Retrospective study including 17 men operated between 2001 and 2019. Specific survival rate included death caused by cancer or SCHLP complications. Complications, functional and oncological outcomes were evaluated retrospectively.RESULTS:There were no locoregional recurrences. One patient died due to inhalation pneumonia 3 years after surgery. Tracheostomy was closed in 13 patients (76.5%). Mean decannulation time was at six [1-14] months after surgery.CONCLUSION:SCHPL with FFACG could avoid total pharyngolaryngectomy with good oncologic results. However, tracheotomy is extended and deglutition recovery is long with high risk of aspirations. These complications justify that such surgery should be realized only on selected patients by experienced surgical teams. Expertise of the surgical team is critical.

OBJECTIVES:Sentinel node procedure (SN) is a standard procedure that has shown its safety and effectiveness for T1/T2 cN0 oral squamous cell carcinoma (OSCC), with completion neck dissection (CND) for patients with positive SN. The aim of this study was to characterize the nodal involvement in a cohort of SN + OSCC. MATERIALS AND METHODS:Patients with T1/T2 cN0 OSCC with positive SN with CND were included in this single-center, prospective cohort study between 2000 and 2013. RESULTS:54/301 patients had at least one positive SN. In 43/54 (80 %) cases, only the SN(s) were invaded; with only one SN involved (SN+=1) in 36/54 (67 %) cases. No predictive factors of nodal involvement in the CND were found considering the followings: SN micro/macrometastases, primary tumor's depth of invasion (DOI), perineural spread, lymphovascular involvement, primary tumor location, T stage and extranodal extension. The SN micrometastatic involvement (n = 22) was significantly associated with only one SN + CND- (p = 0.017). In the group of patients with unique micrometastatic involvement in the SN (n = 20/54), there was a higher isolated nodal recurrence free time (p = 0.017). CONCLUSION:80% of T1/T2 cN0 OSCC with positive SN had no other lymph node metastases in the CND, questioning the potential benefits of this procedure. Predictive factors such as the size of the SN metastasis need to be tested to stratify the risk of positive non-SN lymph nodes leading to a personalized treatment, lowering the therapeutic morbidity while maintaining the oncologic safety.

Treatment of locoregional failures or second primary in HNSCC in previously irradiated areas is a challenge. Reirradiation is currently the only treatment which can improve disease-free survival (DFS) after salvage surgery (SS) even if it has no impact on the overall survival (OS) because of high toxicity, showing the need to investigate other adjuvant therapies (AT) such as immunotherapy. The objectives of this study were to evaluate the 2-year DFS and OS of patients (pts) treated with nivolumab (N) after SS, the toxicity of N in this population and to determine biomarkers of response. This multicentric non-randomized phase II add trial pts with recurrence or second primary of HNSCC in previously irradiated area, operated by SS with curative intent, more than 6 months after initial radiotherapy and of bad prognosis justifying an AT. Within 8 weeks of SS, 240 mg of adjuvant N was administrated every 2 weeks during the first 3 months, and then N 480 mg every 4 weeks was administrated for the next 3 months. The design was performed using a binomial test with a 2-year DFS < 40% as ineffective (α=10%, power=80%). Between February 2018 and March 2021, 57 patients were included and treated. Median age was 61 years, 80% male. Median number of cycles of N was 9 (from 3 to 10). The reasons for off treatment were: 60% treatment completion, 21% tumor progression, 12% toxicity, 7% Others. 2-year DFS was 46.6%, 90%CI[36.1-57.5%] for the main endpoint and 2-year OS was 67.3%, 95%CI[54.2-78.2%]. Median follow-up was 48.2 months (from 5.3 to 59.6). 17 adverse events (AEs) grade ≥3 were related to N (mainly pancreatic hepatobiliary disorders, colitis, myositis andmyocarditis) and occurred in 11 pts (19%). No drug-related death occurred. Biomarkers data (CPS, Immunoscore) will be presented. N as AT after SS is well tolerated. The 2-year DFS and OS compared favorably with those from historical data of reirradiation trials. In JANORL2 trial (Radiother Oncol 2018), 2-year DFS and OS were respectively 33.4%, 95%CI [22.1-47.0%] and 54.0%, 95%CI [40.6-66.8%]. These encouraging results warrant further investigations.

Introduction: The Pentoxifylline, Tocopherol and Clodronate protocol (PENTOCLO) showed promising results for jaw osteoradionecrosis (ORN) management. However, the clinical and radiological improvements are often delayed, leading to unwanted long-term treatment, with potential loss of opportunity for more radical surgical treatments. Our objective was to assess the diagnosis performance of F-18-FDG PET/CT to early predict ORN response to the PENTOCLO protocol. Materials and methods: All patients from our center who were treated with the PENTOCLO protocol and with a F-18-FDG PET/CT performed at diagnosis and three months after the end of antibiotherapy were retrospectively included. The PENTOCLO protocol was always combined with prior appropriate antibiotherapy for six weeks. The healing endpoint was divided into healing, stability or worsening, according to the combination of clinical and radiological assessments at the date of last follow-up. For each patient, the difference between the maximal standardized uptake value (delta SUVmax) of the ORN lesion at three months and baseline were computed. Diagnostic performance of F-18-FDG PET/CT was evaluated by sensitivity, specificity and the area under the receiver operating characteristic curve (ROC-AUC) of delta SUVmax. Results: 24 patients were included with an average follow-up of 29.3 months. The healing, stability and wors-ening rate were 25%, 62.5% and 12.5% respectively. The AUC for discriminating worsening vs stability or heal-ing was 0.92 (IC95 [0.81-1.00]). A delta SUVmax greater than or equal to 0 was predictive of a worsening with a sensitivity and specificity of 84 and 66% respectively. Conclusion: F-18-FDG PET/CT imaging could be useful for early prediction of PENTOCLO treatment resistance with appropriate antibiotherapy. (c) 2021 Elsevier Masson SAS. All rights reserved.

At the study hospital, the lip-split mandibulotomy (LSM) has progressively been replaced by a pull-through (PT) approach. This study compared the outcomes of the LSM and PT approaches in a series of 192 patients with T3-T4a oral tongue and floor of the mouth squamous cell carcinoma treated over the two last decades. No difference in margin status (P = 0.254), rate of early complications (local infections) (P = 0.867), haematoma/haemorrhage (P = 0.221), delayed wound healing (P = 0.438), re-operation (P = 0.083), or Clavien-Dindo classification (P= 0.5281) was found. The LSM approach was associated with a higher rate of late complications such as pseudarthrosis (14.5% vs 0.9%; OR 17.89, P = 0.0005) and trismus (35% vs 13.8%; OR 3.32, P = 0.025), and a trend towards a higher rate of fistulas (24.6% vs 13.1%; OR 2.16, P = 0.088). The quality of life of long-term survivors (median 132 months) was similar in the two groups, with a mean QLQC30 score of 59.7 (P = 0.099) and mean MDADI score of 57.4 (P = 0.213). The 5-year local control rate was 86.4% in the PT group and 86.2% in the LSM group (P = 0.878), while the 5-year overall survival rates were 50.0% and 48.3%, respectively (P = 0.68). In our experience, replacement of LSM by a PT approach in oral carcinoma was associated with decreased rates of late complications such as pseudarthrosis, fistula, and trismus, without any difference in oncological outcomes.

Background Parotid spread tumor may occasion wide defect with facial nerve sacrifice. We report our one time reconstruction experience of this defect using a thoracodorsal artery perforator and nerve flap (TAPN). Methods Eight patients underwent a radical parotidectomy with facial nerve sacrifice between February 2010 and June 2016. A single time reconstruction was performed using a thoracodorsal artery perforator and nerve flap, with skin or fat paddle. The thoracodorsal nerve vascularized was harvested and used to reconstruct the facial nerve from the trunk to four until six distal branches. Patients underwent physiotherapy for 3 months at least. Facial outcomes were assessed using House-Brackmann scale and eFACE application. Outcomes Mean follow-up was 30 months. No complication occurred on donor site. All patients recovered a complete soft eye closure. No Frey syndrome occurred. Conclusion TAPN is adapted to wide and complex parotid defects.

ObjectivesWe investigated the prognostic factor of N3 head and neck squamous cell carcinoma (HNSCC), including the role of upfront neck dissection (UFND) before radiotherapy (RT).MethodsWe retrospectively reviewed the charts of consecutive N3 HNSCC patients treated with curative intent RT.ResultsIn the study, 323 N3 HNSCC patients were included. Of those, 125 patients (39%) had UFND. Median follow‐up was 3.9 years (0–14.8 years). Overall survival (OS) at 5 years was 31.2%, and progression‐free survival (PFS) was 26%. In the multivariate analysis, OS was improved in PS 0, T1‐2 tumors, patients receiving concurrent chemotherapy, never or former smokers, and UFND. UFND was strongly associated with increased OS (45.7% vs. 21.2%, P < .001), and PFS (P < .001). Regardless of neck node size, UFND improved survival (P = .001 for ≤ 7 cm and P = .004 for > 7 cm).ConclusionUFND could improve treatment outcomes in N3 HNSCC, especially for non‐oropharyngeal cancer, regardless of neck node size.Level of Evidence2B Laryngoscope, 131:E844–E850, 2021

Les carcinomes nasosinusiens représentent trois pour cent des cancers ORL. Ils sont subdivisés en carcinomes épidermoïdes (50 %), adénocarcinomes (20 %, majoritairement de type intestinal ITAC), et plus rarement, carcinomes adénoïdes kystiques, neuroblastomes olfactifs (=esthésioneuroblastomes), carcinomes neuro-endocrines ou carcinomes nasosinusiens indifférenciés (SNUC). Les taux de survie à cinq ans sont, par ordre décroissant, 72 % pour les neuroblastomes, 63 % pour les adénocarcinomes, 50–60 % pour les neuro-endocrines à grandes cellules, 53 % pour les épidermoïdes, 25–50 % pour les adénoïdes kystiques, 35 % pour les neuro-endocrines à petites cellules et 35 % pour les SNUC et nouvelles entités. Le traitement est chirurgical ; les voies endoscopiques réduisent la morbidité à contrôle tumoral équivalent. La résection endoscopique, si fragmentée, doit être carcinologique. La radiothérapie adjuvante conformationnelle en modulation d’intensité (RCMI) est quasi systématique. Le risque ganglionnaire est faible dans les adénocarcinomes ethmoïdaux et carcinomes adénoïdes kystiques ; il est intermédiaire et peut justifier une radiothérapie prophylactique pour les cous N0 dans les SNUC, neuroblastomes, épidermoïdes et neuro-endocrines nasosinusiens. Pour les formes non résécables, le traitement est une RCMI ou protonthérapie. Elle peut être optimisée par hadronthérapie par ions carbones pour les carcinomes adénoïdes kystiques, ou par chimiothérapie pour tous les carcinomes, dans le cadre d’essais thérapeutiques ouverts en France. La chimiothérapie néoadjuvante est réservée aux formes rapidement évolutives ou à haut potentiel métastatique comme les carcinomes neuro-endocrines ou les SNUC. Compte tenu de leurs spécificités histologiques, moléculaires et de profils évolutifs différents, une expertise du réseau REFCOR, avec relecture REFCORpath, est susceptible de redresser des diagnostics, rectifier des traitements, avec un impact sur la survie.

Sinonasal carcinomas account for 3% of ENT cancers. They are subdivided into squamous cell carcinomas (50%), adenocarcinomas [20%, mostly of intestinal type (ITAC)], and more rarely, adenoid cystic carcinomas, olfactory neuroblastomas (=esthesioneuroblastomas), neuroendocrine carcinomas or undifferentiated sinonasal carcinomas (SNUC). The 5-year survival rates are, in descending order, 72% for neuroblastomas, 63% for adenocarcinomas, 50-60% for large-cell neuroendocrine carcinomas, 53% for squamous cell carcinomas, 25-50% for adenoid cystic, 35% for small-cell neuroendocrine carcinomas and 35% for SNUC and newly discovered histologies. Surgery is the main treatment; endoscopic approaches reduce the morbidity with equivalent tumour control. Intensity-modulated radiation therapy (IMRT) is almost systematic. Nodal involvement is rare in ethmoidal adenocarcinomas and adenoid cystic carcinomas; it is intermediate and may justify prophylactic radiotherapy for N0 necks in SNUC, neuroblastoma, squamous cell carcinomas and sinonasal neuroendocrine carcinomas. IMRT or proton therapy is the mainstay of treatment of unresectable disease. Radiotherapy optimization by carbon ion therapy for adenoid cystic carcinomas, or by chemotherapy for all carcinomas with IMRT or proton therapy, is investigated within clinical trials in France. Neoadjuvant chemotherapy is reserved for rapidly progressive disease or histologies with a high metastatic potential such as neuroendocrine carcinomas or SNUC. Given their histologic and molecular specificities and different relapse patterns, an expertise of the REFCOR network, with REFCORpath review, is likely to correct diagnoses, rectify treatments, with an impact on survival.

Among the 20,000 new cases of head and neck neoplasms in France each year, squamous cell carcinomas (HNSCC) represent about 90 % of the cases. Among these, variants of conventional squamous cell carcinomas represent between 5% and 10% of cases. Patient history and risk factors are often similar from those of conventional HSNCC. Variants may, however, be misdiagnosed, which can lead to therapeutic mismanagement due to confusion with sarcomas, glandular tumors or even benign tumors. Diagnostic workup needs to be more cautionary or to include additional exams not to omit their most aggressive component in the case of composite tumors or to under stage the tumor. Immunohistochemistry and specific molecular analyses may be required for proper diagnosis. Central pathological review may also be essential for some of these variants. In addition, some variants are radioresistant and, conversely, others are radiosensitive. An update of the REFCOR 2008 standards was carried out in the light of the international literature and the 2017 WHO/IARC classification for the seven main variants of HNSCC, verrucous, acantholytic (to be named adenoid carcinomas), basaloid, papillary, spindle cell (incorrectly named sarcomatoid), adenosquamous and lymphoepithelial carcinomas.

Parmi les 20 000 nouveaux cas de cancers ORL, tête et cou et des voies aérodigestives (VADS) en France, les carcinomes épidermoïdes des VADS représentent environ 90 % des cas. Parmi ceux-ci, les variants des carcinomes épidermoïdes dits conventionnels représentent entre 5 % et 10 % des cas. Un recensement précis est difficile car ils ne sont pas actuellement colligés de façon systématique. L’anamnèse et le terrain sont rarement différents de ceux des carcinomes épidermoïdes conventionnels. Ces variants des carcinomes épidermoïdes peuvent pourtant être sujets à des erreurs diagnostiques, voire à des erreurs thérapeutiques, du fait de confusions avec des sarcomes, des tumeurs glandulaires, voire des tumeurs bénignes. Certaines précautions d’analyse (par biopsies profondes par exemple) doivent être connues pour ne pas omettre leur composante la plus agressive en cas de tumeurs avec contingents variés. L’immunohistochimie et certaines analyses moléculaires spécialisées peuvent, de plus, aider au diagnostic. Une relecture diagnostique paraît indispensable pour certains de ces variants. Par ailleurs, certains variants sont radiorésistants et à l’inverse, d’autres radiosensibles. Dans les autres cas, des compléments d’analyses moléculaires peuvent redresser certaines erreurs diagnostiques et permettre des traitements adéquats. Une actualisation des référentiels REFCOR 2008 a été réalisée au vu de la littérature internationale et de la nouvelle classification OMS/IARC (Organisation mondiale de la santé/International agency for research on cancer) 2017 pour les sept principaux variants de carcinomes épidermoïdes des VADS, les carcinomes verruqueux, acantholytiques (ou adénoïdes), basaloïdes, papillaires, à cellules fusiformes (improprement nommés sarcomatoïdes, adénosquameux et lymphoépithéliaux). Les éléments diagnostiques et thérapeutiques différenciants y sont rapportés.

Introduction: Neoadjuvant chemotherapy (neo-CT) for osteosarcomas is the standard of care. Management of maxillo-facial osteosarcomas (MFOS) is challenging. In this rare disease, we collected a large cohort of patients with the aim to report the histological and radiological local response rates to neo-CT. Patients and Methods: All consecutive adult patients treated between 2001 and 2016 in two French sarcoma referral centers (Pitie-Salpetriere Hospital, APHP, RESAP France and Gustave Roussy Institute France), for a histologically proved MFOS were included. Clinical, histological and radiological data were independently reviewed. Tumor response to neo-CT was assessed clinically, radiologically with independent review using RECIST v1.1 criterion and pathologically (percentage of necrosis). Multivariate analysis was done for outcomes, tumor response and disease-free survival (DFS). Results: A total of 35 high grade MFOS were collected. The clinical tumor response was 4% (1/24 receiving neo-CT), the radiological response was 0% (0/18 with available data) and the pathological response was 5% (1/20 with available data). Three patients (12.5%) initially resectable became unresectable due to clinical and radiological progression during neo-CT. Tumor size and R0 (clear margins) surgical resections were significantly associated with DFS. Conclusion: MFOS is a rare disease. This large retrospective cohort of MFOS indicates the lack of benefit and potentially deleterious effects of neo-CT. We suggest privileging primary surgery in initially localized resectable MFOS. The benefit of adjuvant chemotherapy should be prospectively studied.

Background The treatment outcomes for N3 HNSCC treated with induction chemotherapy (ICT) followed by definitive radiation were reported to clarify the role of ICT and potential prognostic factors. Methods A retrospective study was conducted on 120 patients with N3 (>= 6 cm) HNSCC, who were treated with ICT as initial treatment. Survival outcomes and potential prognostic factors were reported. Results The response rate to ICT was 68.3%. There was a statistically significant difference between responders and non-responders in terms of 5-year OS (35.1% vs 13.3%, P < .001) and PFS (29.4% vs 7.4%, P < .001). Good response to ICT (P < .001) and upfront neck dissection (UFND) before radiotherapy (P = .016) were factors predicting for better OS. However, UFND before radiotherapy was not associated with improved outcomes among responders. Conclusions This study suggests that ICT could be one treatment option for N3 HNSCC. Among responders to ICT, UFND before radiotherapy could be avoided.

Introduction: Free tissue transfer is an integral part of modern head and neck surgery in the adult population, while its use is often avoided in children. This is based on presumed technical challenges and increased risks of complications including flap failure, smaller vessels prone to vasospasm, challenging post-operative management, and concerns regarding donor-site morbidity and negative effects on patient craniofacial growth. The current literature on microsurgical pediatric reconstruction is sparse and only few data is available regarding the survival of microvascular free flaps following head neck tumor extirpation. Methods: This retrospective study included 100 patients (43 females; 57 males) who had undergone microvascular reconstruction (mean age at surgery: 12,4 years; range: 1–18 years) following ablative head and neck surgery between 1999 and 2018. Results: A total of 100 patients underwent 120 microvascular free tissue transfers. In our pediatric cohort, 16 patients required a second or multiple free flap procedures. The three most commonly used flaps were latissimus dorsi (n=47; 39 %), fibula (n=27; 22 %) and dorsal scapular (n=20; 17 %) free flaps. The majority of cases (87%) had a malignant disease, predominately sarcomas (n=64) and epidermoid carcinomas (n=10), while benign tumors constituted 13 cases. Primary reconstruction sites were the infratemporal fossa (35%), mandible (27%) and maxilla (18 %). Immediate post-operative complications (within 30 days) occurred in 6% and were mostly related to local infection, partial flap necrosis and cervical hematoma, while the overall microvascular free flap success rate was 99% (1 flap failure out of 120). Conclusion: Free tissue transfer should be considered a gold-standard in pediatric patients requiring soft tissue or bony reconstruction following extensive ablative tumor surgery. Despite the fact that a significant proportion of our patients received preoperative chemotherapy or radiation which are known risk factors for flap failure, the overall success rate (99%) was still comparable or better to those observed in the adult population. Conditions such as atherosclerosis, diabetes, hypertension, smoking, and alcohol abuse that deteriorate blood vessel quality are rather uncommon in children and may therefore explain the good outcomes in our study. However, long-term sequelae, such as donor-site morbidity and craniofacial growth impairment must be anticipated as they may result in repetitive corrective procedures throughout adolescence.

Objectives/Hypothesis We studied the influence of the neutrophil-to-lymphocyte ratio (NLR) and anemia on the response to induction chemotherapy (IC) and survival outcomes in laryngeal cancer patients treated with a preservation protocol. Study Design Retrospective single-center case series. Methods We analyzed patients with T3 laryngeal cancer treated with IC using a preservation protocol. The NLR and hemoglobin levels were assessed before treatment and after IC. The response to chemotherapy was assessed using Response Evaluation Criteria in Solid Tumours 1.1 and World Heath Organization standards. The oncological endpoints were overall survival (OS) and disease-free survival (DFS). Results Sixty-eight patients were analyzed. The median NLR and hemoglobin levels before and after IC were 2.76 and 14.5 g/dL, and 2.01 and 11.6 g/dL, respectively. The NLR and anemia before treatment were not correlated, and they were not associated with the response to chemotherapy. However, an NLR > 5 and anemia before treatment were both associated with shorter OS and DFS. Notably, they were the only factors found to be significantly associated with survival outcomes. Conclusions In laryngeal cancer, patients treated with a preservation protocol, a high NLR ratio, and anemia before IC were associated with shorter survival, independently of the response to chemotherapy. Level of Evidence 4 Laryngoscope, 130:E144-E150, 2020

Immune checkpoint inhibitors are now standard-of-care treatments for metastatic cutaneous melanoma. However, for rare sub-groups, such as mucosal melanomas, few published data are available, and with no established therapeutic guidelines. Our objective was to assess the response to anti-CTLA4 and anti-PD1 immunotherapy in patients with mucosal melanomas. We performed a single-center, prospective cohort analysis of patients with non-surgical locally advanced and/or metastatic mucosal melanoma receiving anti-CTLA4 and/or anti-PD1 immunotherapy from 2010 to 2016. Forty-four patients were enrolled, including 18 (40.9%) with head and neck, 12 (27.3%) with vulvo-vaginal and 14 (31.8%) with ano-rectal primary tumours. Eleven (25%) patients had stage 3 disease, and 11 (25%) had distant metastases. The first-line immunotherapy was ipilimumab in 24 patients and pembrolizumab in 20. The objective response rate (ORR) was 8.2% (one complete response) for ipilimumab and 35% (four complete responses) for pembrolizumab. No significant difference was observed for primary tumour location. The median follow-up was 24 months (range 4–73). The median progression-free survival (PFS) in the first-line ipilimumab and pembrolizumab groups was 3 months [95% confidence interval (CI) 2.5–4.6] and 5 months (95% CI 2.6–33.1), respectively (p = 0.0147). In the patients with unresectable and/or metastatic mucosal melanoma, we found ORR and PFS rates comparable to those in patients with cutaneous melanoma, with no significant differences in the types of mucosal surfaces involved. Anti-PD1 therapy has a more favorable benefit-risk ratio than ipilimumab and should be used preferentially.