Natural history of salivary gland secretory carcinoma: A REFCOR study.

BACKGROUND AND OBJECTIVES: Salivary gland Secretory Carcinoma (SC), characterized by Skalova in 2010 is a rare tumor studied within the REFCOR (French Network of experts on Rare Head and Neck Cancers). We conducted a prospective multicentric cohort study of 108 SC cases in the REFCOR database up to July 2021, analyzing diagnostic, therapeutic, and survival data. METHODS: Data was collected prospectively from diagnosis to the last update. Each patient had two histological readings including one by a REFCORpath pathologist, and all cases underwent molecular testing to confirm diagnosis. Statistical analyses were performed using R software. RESULTS: MRI was not contributive to malignancy diagnosis. After 2 histological readings, 79 % of patients were diagnosed, with 21 % requiring molecular testing to confirm diagnosis. Surgical treatment typically involved tumor excision and lymph node dissection. The tumor exhibited low lymph node involvement, with 95 % of patients being cN0, and no nodal metastases post-dissection. Five-year overall survival and recurrence-free survival were 91.4 % {95 % CI (0.84-1)} and 89 % {95 % CI (0.81; 0.98)} respectively, indicating a favorable prognosis. CONCLUSIONS: SC is a rare and newly recognized tumor, with generally favorable outcomes. Our cohort, among the largest to date, provides valuable insights. Future research should refine treatment guidelines.

Impact of facial nerve resection in parotid cancer abutting the facial nerve without preoperative paralysis: A multicentric propensity score-based analysis.

OBJECTIVES: The management of the facial nerve (FN) is a major issue in parotid cancer, especially when there is no preoperative facial palsy and FN invasion is discovered intraoperatively. The aim of this study was to assess the impact of FN resection in patients with parotid cancer abutting the FN, without pretreatment facial palsy, using a propensity score matching. MATERIALS AND METHODS: Data from all patients treated between 2009 and 2020 for a primary parotid cancer abutting or invading the FN but without pretreatment facial palsy were extracted from the national multicentric REFCOR database. Three different definitions of tumors abutting the FN were used for sensitivity analyses, in a retrospective setting. Propensity score matching was used to assess the impact of FN resection on disease-free survival (DFS), overall survival (OS) and locoregional recurrence-free survival (LRRFS). RESULTS: A total of 163 patients with parotid cancer abutting or invading the FN without pretreatment facial palsy were included. Among them, 99 patients (61 %) underwent FN resection. After overlap weighting and multiple imputation, no benefit of FN resection over preservation was found in terms of OS (HR = 1.21, p = 0.6), DFS (HR = 0.88, p = 0.5) and LRRFS (HR = 0.99, p = 1). Sensitivity analyses revealed similar results, and no significant efficacy was found in the subgroup analyses. CONCLUSION: In this retrospective study with propensity score analysis, FN resection did not improve survival outcomes in patients without preoperative facial palsy treated surgically for a primary parotid cancer abutting the FN. In line with recent guidelines, the results of this study suggest that FN preservation should be considered whenever possible in this specific group of patients.

Therapeutic strategy for advanced stages salivary carcinomas of the tongue: A multicenter REFCOR study.

INTRODUCTION: Salivary carcinomas of the tongue represent a therapeutic challenge as their radical excision is particularly mutilating. We aimed to study the oncologic and functional outcomes of advanced stages salivary carcinomas of the tongue. MATERIALS AND METHODS: This retrospective multicentric study, based on the French national network on rare head and neck cancers (REFCOR), included all patients with a T3-T4 salivary carcinoma of the tongue, diagnosed between January 2009 and December 2018. RESULTS: In total, 47 patients were included, of which 44.7 % underwent surgery. Histologies were mostly adenoid cystic carcinomas (61.7 %), followed by other adenocarcinomas (27.7 %) and mucoepidermoid carcinomas (10.6 %). Median follow-up duration was 63.9 months. In multivariable analysis, surgery was significantly associated with better Recurrence-Free Survival (HR = 0.23, 95 %CI [0.09;0.55]) and Local/Regional Recurrence-Free Survival (HR = 0.31, 95 %CI [0.10;0.95]). The rate of distant metastasis at the end of follow-up was 61.9 % in the surgical group and 57.7 % in the non-surgical group. The Distant Metastasis Free Survival was 54.9 % [38.3;68.7], without statistical difference between both groups. There were similar rates of definitive gastrostomies but the rate of normal oral diet at the last follow-up seemed higher in the surgery group (38.1 % vs 15.4 %). CONCLUSION: Radical surgery in that population mainly aims to improve local/regional control, which may result in better long-term swallowing functions. About half of these tumors may be associated with occult distant metastasis at initial presentation. More studies are warranted to establish the role of postoperative RT and non-surgical treatment with concurrent CRT.

Malignant salivary gland tumors of the tongue: A multicenter REFCOR study.

Salivary carcinomas of minor salivary glands are very infrequent tumors. When located in the tongue, the therapeutic strategy may comprise upfront surgery, which may be debilitating, and/or (chemo-)radiotherapy. The aim of this study was to identify the prognostic factors of salivary carcinomas of the tongue in a population-based cohort. This retrospective multicentric study, based on the "Réseau d'Expertise Français sur les Cancers ORL Rares" (REFCOR), included all the patients with a salivary carcinoma of the tongue, diagnosed between January 2009 and December 2018. Dubious slides were reviewed by REFCOR expert pathologists to ensure diagnostic accuracy. Treatment was performed in accordance with national REFCOR recommendations. From 28 centers, 103 patients were included in this study. Median age at diagnosis was 63 years, and 60.2% were female. Tumors were adenoid cystic carcinomas (41.7%), mucoepidermoid carcinomas (30.1%), and other adenocarcinomas (28.2%). Primary treatment was surgical for 61.2% of them. Five-year overall survival (OS) and event-free survival (EFS) rates were 84.7% and 38.6%, respectively. In multivariable analysis, EFS was significantly worse in case of nonsurgical treatment, alcohol consumption, and glossotonsillar sulcus involvement. N-positive status was the only significant prognostic factor for OS in multivariable analysis. Salivary carcinomas of the tongue represent a heterogeneous group of rare tumors, with a high risk of recurrence. In this national cohort, surgery was associated with better EFS and N-status was the main independent prognostic factor for OS.

[French national standard for the treatment of squamous cell carcinoma of upper aero-digestive tract - General principles of treatment]. / Référentiel national de traitement des carcinomes épidermoïdes des voies aérodigestives supérieures ­ Principes généraux de traitement.

OBJECTIVES: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations. METHODOLOGY: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS). RESULTS: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey. CONCLUSION: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field.

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.

Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR).

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. METHODS: This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. RESULTS: A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. CONCLUSION: In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.

Influence of EGF and pro-NGF on EGFR/SORTILIN interaction and clinical impact in head and neck squamous cell carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC) remains a cancer with a poor prognosis, with a 5-year survival rate of less than 50%. Although epidermal growth factor receptor (EGFR) is almost always overexpressed, targeted anti-EGFR therapies have modest efficacy and are mainly used in palliative care. Growth factors such as Nerve Growth Factor (NGF) and its precursor proNGF have been shown in our laboratory to play a role in tumor growth and aggressiveness. Interestingly, an interaction between Sortilin, a proNGF receptor, and EGFR has been observed. This interaction appears to interfere with the pro-oncogenic signaling of EGF and modulate the membrane expression of EGFR. The aim of this study was to characterize this interaction biologically, to assess its impact on clinical prognosis and to analyze its role in the cellular trafficking of EGFR. Using immunohistochemical staining on tumor sections from patients treated at our university center and PLA (Proximity Ligation Assay) labeling, we showed that Sortilin expression is significantly associated with reduced 5-year survival. However, when Sortilin was associated with EGFR, this association was not found. Using the Cal-27 and Cal-33 cancer cell lines, we observed that proNGF reduces the effects of EGF on cell growth by inducing the internalization of its receptor. These results therefore suggest a regulatory role for Sortilin in the degradation or renewal of EGFR on the membrane. It would be interesting in future work to show the intracellular fate of EGFR and the role of (pro)neurotrophins in these mechanisms.

Surgical treatment outcomes of solitary fibrous tumors in the head and neck: A retrospective study.

The aim of this study was to better characterize head and neck solitary fibrous tumors (SFTs) and to evaluate surgical treatment. This retrospective study included patients who presented with head and neck SFTs. Clinical, radiological, and histological information and data regarding the treatments performed were collected. The risk of locoregional and distant metastases was calculated, and for orbital SFTs a specific classification was used. Overall, 34 patients were included. The majority of the SFTs were found in the oral cavity (n = 10), followed by the neck region (n = 8). The mean time to recurrence was 67.4 months. All patients underwent primary surgical resection. Recurrence was observed in five patients with a low risk of locoregional recurrence and distant metastasis. The treatment of choice is complete resection. Recurrence seems to be highly correlated with positive surgical margins. The safety margin should be increased when removing the lesion, and long-term follow-up should be performed.

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.

Management of oral feeding following total laryngectomy around the world: YO-IFOS international study.

BACKGROUND: To analyze worldwide practices regarding the initiation of oral feeding after total laryngectomy (TL). METHODS: Online survey. RESULTS: Among the 332 responses received, 278 from 59 countries were analyzed. Our results showed that 45.6% of respondents started water and 45.1% started liquid diet between postoperative days 7 and 10. Semi-solid feeds were initiated between days 10 and 14 for 44.9% of respondents and a free diet was allowed after day 15 for 60.8% of respondents. This timing was significantly delayed in cases of laryngo-pharyngectomy and after prior radiotherapy (p < 0.001). A greater proportion of respondents in Africa and Oceania allowed early oral feeding before day 6 as compared with the rest of the world (p < 0.001). CONCLUSION: Despite increasing number of publications, there is still a lack of evidence to support early oral feeding. The majority of respondents preferred to delay its initiation until at least 7 days after surgery.

Oral mucosal melanoma - A systematic review.

Oral mucosal melanoma (OMM) is the subject of few studies, resulting in a lack of understanding. The aim of this study is to review the current literature on OMM. The term searched was "oral mucosal melanoma" between 01/01/2000 and 03/15/2021 in the PubMed Database (MEDLINE). Patients presenting with OMM and treated in our center between January 2009 and January 2020 were included in a case series. Demographics, location, risk factors, genetic mutations, treatment performed, and overall survival (OS) rates were evaluated. The PubMed database search yielded a total of 513 results, thirty-eight articles were finally included, which amounted to 2230 cases of OMM. 13 patients were included in the case series. A male-to-female ratio of 1.28:1.00 was found with a mean age at first diagnosis of 58.2 years old. Hard palate (1060 cases) and then gingiva (794 cases) were the two main locations. No risk factors could be identified. OMM were staged III or IV at diagnosis. Mutations were described as such: KIT in 14.6% of cases, BRAF in 7%, and NRAS in 5.6%. Treatment protocols varied but radical surgery was the cornerstone treatment associated with adjuvant therapies. Immunotherapy has not been evaluated for OMM. OS rates were 43.4% at 3 years, 33.1% at 5 year and 15.4% at 10 years. OMM show distinct features from cutaneous melanoma (CM): typical locations, no identified risk factors, different mutations profile, worse prognosis with advanced stage at diagnosis. Targeted therapies are still underused compared to CM.

Budesonide transnasal pulsating nebulization after surgery in chronic rhinosinusitis with nasal polyps.

Intranasal corticosteroid drugs are widely used in chronic rhinosinusitis with nasal polyps (CRSwNP). In contrast to classical delivery with nasal pump sprays, pulsating aerosols can deliver significant doses into superior and posterior sinonasal spaces. A case-control study was designed to assess the efficacy of corticosteroid transnasal nebulization on short-term mucosal recovery and quality of life (QoL) following endoscopic sinus surgery in CRSwNP. Thirty patients were prospectively enrolled to receive either 1-month budesonide nasal pump spray or 1-month budesonide 100-Hz acoustic pulsating nebulization at the first postoperative visit (day 8). Patients were evaluated with Lund-Kennedy endoscopic score at day 8 (D8) and 1 month later (M1). CRS-related QoL questionnaires (SNOT22 and RhinoQOL) were fulfilled at M1. The Lund-Kennedy endoscopic scores compared between D8 and M1 were suggestively improved in the group treated with budesonide nebulization (mean difference between groups, - 18.28 units; 95%CI, - 31.29 to - 5.28 units, p = 0.014). QoL measurements were comparable at M1 between the groups of patients. No unexpected adverse event was described with both budesonide delivery protocols. In the early postoperative period, patients with CRswNP may benefit from pulsating nebulization. Large studies should be conducted to confirm the results. Safety profile related to systemic steroid absorption and bioavailability in chronic respiratory diseases also need to be addressed for further use.

Appropriateness for SARS-CoV-2 vaccination for otolaryngologist and head and neck surgeons in case of pregnancy, breastfeeding, or childbearing potential: Yo-IFOS and CEORL-HNS joint clinical consensus statement.

PURPOSE: SARS-CoV-2 vaccines are a key step in fighting the pandemic. Nevertheless, their rapid development did not allow for testing among specific population subgroups such as pregnant and breastfeeding women, or elaborating specific guidelines for healthcare personnel working in high infection risk specialties, such as otolaryngology (ORL). This clinical consensus statement (CCS) aims to offer guidance for SARS-CoV-2 vaccination to this high-risk population based on the best evidence available. METHODS: A multidisciplinary international panel of 33 specialists judged statements through a two-round modified Delphi method survey. Statements were designed to encompass the following topics: risk of SARS-Cov-2 infection and use of protective equipment in ORL; SARS-Cov-2 infection and vaccines and respective risks for the mother/child dyad; and counseling for SARS-CoV-2 vaccination in pregnant, breastfeeding, or fertile healthcare workers (PBFHW). All ORL PBFHW were considered as the target audience. RESULTS: Of the 13 statements, 7 reached consensus or strong consensus, 2 reached no consensus, and 2 reached near-consensus. According to the statements with strong consensus otorhinolaryngologists-head and neck surgeons who are pregnant, breastfeeding, or with childbearing potential should have the opportunity to receive SARS-Cov-2 vaccination. Moreover, personal protective equipment (PPE) should still be used even after the vaccination. CONCLUSION: Until prospective evaluations on these topics are available, ORL-HNS must be considered a high infection risk specialty. While the use of PPE remains pivotal, ORL PBFHW should be allowed access to SARS-CoV-2 vaccination provided they receive up-to-date information.

The efficacy of a personalised treatment depending on the characteristics of reflux at multichannel intraluminal impedance-pH monitoring in patients with acid, non-acid and mixed laryngopharyngeal reflux.

OBJECTIVE: To assess the evolution of symptoms and findings of laryngopharyngeal reflux (LPR) patients according to the type of reflux (acid, non-acid, mixed and gastro-oesophageal (GERD)). DESIGN: Prospective uncontrolled multicentre study. METHODS: One hundred and six patients with LPR have been recruited from 3 European Hospitals. According to the reflux characteristics at the impedance-pH monitoring (acid, non-acid, mixed, GERD), patients received a personalised treatment based on the association of diet, pantoprazole, alginate or magaldrate for 3 months. Reflux Symptom Score (RSS) was assessed at baseline, 6 and 12 weeks post-treatment. Reflux Sign Assessment (RSA) has been used to rate laryngeal and extra-laryngeal findings at baseline and 12 weeks post-treatment. Overall success rate and the evolution of symptoms and findings were evaluated according to the LPR types. RESULTS: One hundred and two LPR patients (42 acid, 33 non-acid, 27 mixed, including 49 with LPR and GERD) completed the study. RSS and RSA total scores significantly improved from baseline to post-treatment time in acid, mixed and non-acid groups. The presence of GERD in addition to LPR did not impact the clinical improvement. The 3-month success rates of treatment ranged from 62% to 64%, and there were no significant differences between groups. The success rate of patients with non-acid LPR was similar to those of patients with mixed and acid LPR. CONCLUSION: MII-pH is useful to specify the type of LPR and the related most adequate therapeutic regimen. Non-acid or mixed LPR similarly respond to treatment than acid LPR but require a treatment based on alginate or magaldrate covering the non-acid proximal reflux events.

Mucoepidermoid carcinoma of salivary glands: A French Network of Rare Head and Neck Tumors (REFCOR) prospective study of 292 cases.

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