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.

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.

[Rare cancers of the head and neck on behalf of the REFCOR, part 2]. / Cancers rares de la tête et du cou sous l'égide du REFCOR, partie 2.

Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology as well as their anatomical location when arising from the paranasal sinuses, salivary glands and ear. The management of these heterogeneous rare diseases of complex treatment has considerably been structured over the last 15 years, in particular via the French ENT Cancer Expertise Network (REFCOR) and international networks and registries (EURACAN, etc.). Structuration also favors research with identification of new entities and setting up of specific therapeutic trials. A first article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the REFCOR concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. This second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.

[Rare cancers of the head and neck on behalf of the REFCOR, part 1]. / Cancers rares de la tête et du cou sous l'égide du REFCOR, partie 1.

Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology, which determines their local invasiveness, and their hematogenous/nodal spread. Their diagnosis can be difficult and often requires comprehensive immunohistochemistry and genomic techniques. Expert pathology review is recommended in the cases of undifferentiated tumors, sarcomas and at the slightest diagnostic doubt. These rare cancers can also be rare by their anatomical location when arising from the paranasal sinuses, salivary glands and ear. Their location requires knowledge of their specific extension routes, and may call for a specific surgical technique (skull base endoscopic sinus surgery, extended total parotidectomy, etc.) and adapted radiotherapy to spare healthy organs surrounding the tumor. This article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the French ENT Cancer Expertise Network (REFCOR) concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. A second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.

Multicenter study to assess surgical treatments of 452 sinonasal intestinal-type adenocarcinomas: A REFCOR study.

PURPOSE: The objective was to assess the local oncological outcomes of endoscopic versus external surgical treatment of sinonasal intestinal-type adenocarcinomas (ITAC) and the factors of recurrence. METHODS: a retrospective non-randomized case-control multicenter study was carried out, including 452 untreated sinonasal ITACs recruited from 10 tertiary referral centers. The tumors were re-classified according to the UICC 2017 (pT). Survival curves were obtained using the Kaplan-Meier method. Univariate analysis was done with the log-rank test. Multivariate analysis was performed with a Cox model adjusted for age, T stage, and radiotherapy. A binary logistic regression compared surgical complications and performed two supplementary analyses on positive margins. RESULTS: We compared 195 and 257 patients operated by the external and endoscopic approach, respectively. The mean follow-up was 59.2 ± 48.7 months. Post-operative margins were invaded in 30.6 versus 18.9% of patients, respectively (p = 0.007). The overall recurrence rate was 33.8 versus 24.6%, respectively (p = 0.034). There was a significant difference in favor of the endoscopic approach regarding local recurrence-free survival thanks to better surgical margins in univariate and multivariate analysis (Odd Ratio = 2.01 (1.2-3.36) p = 0.0087). The complication rate (Odds Ratio = 3.4 (1.79-6.32) p < 0.001) was significantly lower in the endoscopic group. The histological positivity of signet-ring cells shows a statistically significant difference in recurrence-free survival (p = 0.0028). CONCLUSION: the oncological control of ITAC is better through the endoscopic approach, with negative margins and the absence of signet-ring-cells, two independent factors of recurrence.

Impact of HPV status in T1-2 oropharyngeal squamous cell carcinoma with bulky N3 nodes: a multicenter GETTEC study.

PURPOSE: The purpose of our study was to investigate the impact of HPV status in oncologic outcomes in patients with T1-2 oropharyngeal SCC associated with bulky N3 nodes, and to determine progression prognosis factors aiming to define the best therapeutic strategies for these patients. METHODS: This multicenter retrospective study included patients with T1-2 oropharyngeal SCC with N3 nodes treated between 2010 and 2015 in 8 French comprehensive cancer centers. HPV status was determined with P16 hyperexpression in immunohistochemistry. HPV-positive patients were separated into 2 groups according to the associated smoking history (HPV + T +) or not (HPV + T-). We compared the oncological outcomes of patients according to HPV-status and smoking history. RESULTS: Of 67 patients with T1-2 N3 oropharyngeal SCC, 36 patients (53.7%) were HPV negative and 31 patients (46.3%) HPV positive. 2-year PFS was significantly better in HPV + T- group (p = 0.036). The risk of death or progression was significantly reduced in HPV + T- comparatively to HPV- (HR 0.25 95%CI [0.07; 0.89]). 2-year OS was significantly better in HPV + T- group than in the other two groups (p = 0.017). CONCLUSION: In patients with T1-2 oropharyngeal SCC associated with bulky N3 nodes, HPV positive patients without smoking history had better OS and PFS than HPV positive patients with smoking history and HPV negative patients. Thus, HPV status is a significant prognostic factor for survival but this benefit is altered when smoking history is associated. N3 HPV positive patients with smoking history have to be classified as high-risk.

Safety of use of the ENDOSWIR near-infrared optical imaging device on human tissues: prospective blind study.

Cancer surgery requires removing the tumor tissue in necessary and sufficient quantities. Spectral optical imaging in the short-wave infrared (900-1700 nm) could provide an intraoperative guidance to the surgeon based on the absorption of the tissues without contrast agent. Our objective was to ensure the safety of our ENDOSWIR device on human tissues. Histological analysis of fresh human tonsils exposed to the SWIR light or not was compared and showed no histological differences. This demonstrates the safety of using the SWIR device on human tissues and allows us to initiate a clinical study for the resection of tumors intraoperatively.

Ophthalmic complications of Lemierre syndrome.

PURPOSE: Lemierre syndrome is a life-threatening condition characterized by head/neck bacterial infection, local suppurative thrombophlebitis and septic embolic complications in a range of sites of distant organs. No prior study focused on the course and characteristics of ophthalmic complications of Lemierre syndrome. METHODS: We analysed data of 27 patients with ophthalmic complications from a large cohort of 712 cases with Lemierre syndrome reported globally between 2000 and 2017. We focused on initial manifestations, early (in-hospital) course and long-term ophthalmic deficits at the time of hospital discharge or during postdischarge follow-up. The study protocol was registered in the International Prospective Register of Systematic Reviews PROSPERO (CRD42016052572). RESULTS: Nine (33%) patients were women; the median age was 20 (Q1-Q3: 15-33) years. Fusobacterium spp. was involved in 56% of cases. The most prevalent initial manifestations were decreased vision (35%) and periocular oedema (38%), followed by impaired eye movements/nerve palsy (28%) and proptosis (28%). Venous involvement, notably cerebral vein thrombosis (70%) and ophthalmic vein thrombosis (55%), explained the symptomatology in most cases. Septic embolism (7%), orbital abscesses (2%) and carotid stenosis (14%) were also present. Ophthalmic sequelae were reported in 9 (33%) patients, often consisting of blindness or reduced visual acuity, and nerve paralysis/paresis. CONCLUSION: Ophthalmic complications represent a severe manifestation of Lemierre syndrome, often reflecting an underlying cerebral vein thrombosis. Visual acuity loss and long-term severe complications are frequent. We call for an interdisciplinary approach to the management of patients with Lemierre syndrome and the routine involvement of ophthalmologists.

Polarized Secretion of APRIL by the Tonsil Epithelium Upon Toll-Like Receptor Stimulation.

In mucosa such as tonsil, antibody-producing plasmocytes (PCs) lie in sub-epithelium space, which is thought to provide a suitable environment for their survival. A proliferation inducing ligand (APRIL) is one key survival factor for PCs present in this area. According to in situ staining, apical epithelial cells produced APRIL, and the secreted product had to migrate all through the stratified surface epithelium to reach basal cells. A similar process also occurred in the less-organized crypt epithelium. Tonsil epithelial cells captured secreted APRIL, thanks to their surface expression of the APRIL coreceptor, either syndecan-1 or -4 depending on their differentiation stage. In the most basal epithelial cells, secreted APRIL accumulated inside secretory lamp-1+ vesicles in a polarized manner, facing the sub-epithelium. The tonsil epithelium upregulated APRIL production by apical cells and secretion by basal cells upon Toll-like receptor stimulation. Furthermore, LPS-stimulated epithelial cells sustained in vitro PC survival in a secreted APRIL-dependent manner. Taken together, our study shows that the tonsil epithelium responds to pathogen sensing by a polarized secretion of APRIL in the sub-epithelial space, wherein PCs reside.

The microenvironment of DLBCL is characterized by noncanonical macrophages recruited by tumor-derived CCL5.

Tissue invasion by tumor cells induces a host inflammatory response that variably impacts tumorigenesis. This has been well documented for tumor-associated macrophages (TAMs) that could play a pro/M2- or an anti/M1-tumoral function. TAMs frequently infiltrate diffuse large B-cell lymphoma (DLBCL), an aggressive neoplasm arising from germinal center-experienced B cells. However, the pathway leading to the presence of TAMs in DLBCL remains unknown, and their impact is unclear. Here, we show that some DLBCL tumor cells expressed the chemokine CCL5, enabling the differential recruitment of blood monocytes through their expression of CCR1 and CCR5. CCL5 expression by DLBCL was not related to molecular subtypes, and healthy tonsillar B cells did not produce this chemokine, implying a posttransformation event. A single-cell analysis revealed that most DLBCL TAMs had a noncanonical gene signature with the concomitant expression of M1 and M2 genes. The presence of noncanonical TAMs may explain the lack of impact of macrophages on DLBCL development reported in some survival studies.

Failure of anterior skull base reconstruction for sinonasal carcinoma: consequence on the postoperative follow up. A multicentre evaluation of management.

BACKGROUND: Numerous techniques for closure of the anterior skull base in cancer patients have a high success rate but management of failure is poorly documented. OBJECTIVES: To standardize the post-operative follow-up after reconstruction surgery of the anterior skull base after removal for sinonasal carcinoma. MATERIALS AND METHODS: Retrospective review of failure of anterior skull base reconstruction between 2005 and 2018 in a multicenter setting. RESULTS: Twenty four patients were included. Reconstruction failure was detected by a cerebrospinal (CSF) leak in 79.2%, by an infectious complication without CSF leak (i.e. meningitis) in 12.5%, and in 8.3% by extensive pneumocephalus. Failure was observed during the first week after surgery in 75% of patients, in the second week in 21%, and in 4% after day 15. The delay in discovery of the failure was associated with multilayer reconstruction (p=.03). Failure was treated surgically in 54% of the patients and medically in 46%, with a similar success rate (85 vs. 100%). CONCLUSION AND SIGNIFICANCE: After carcinologic resection of the anterior skull base, monitoring should be systematic during the first postoperative week. Surgical management of failure is not always necessary.

History of tonsillectomy and risk of oropharyngeal cancer.

OBJECTIVE: To investigate whether palatine tonsillectomy in youth influences the risk of oropharyngeal cancers (OPC) by assessing the association between history of tonsillectomy and risk of tonsillar, base of tongue (BOT) cancer, and other head and neck cancers (HNC). MATERIALS AND METHODS: RACKAM was a case-case study comparing frequency of tonsillectomy history in individuals diagnosed with HNC from 2013 to 2018 in 15 centers across France. History of tonsillectomy was defined using combined assessment of patients' recollections and surgeons' visualizations of tonsil area. OPC subsite-specific odds ratios (OR) of tonsillectomy were calculated using multinomial logistic regression with non-oropharyngeal HNC as reference. RESULTS: 1045 patients were included in the study. Frequency of tonsillectomy was 19.5% in patients with tonsillar cancer (N = 85), 49.3% in BOT (N = 76), 33.8% in other oropharyngeal cancers (N = 202) and 38.0% in non-oropharyngeal HNC (N = 682). History of tonsillectomy was inversely associated with tonsillar cancer (adjusted OR 0.4; 95% CI 0.2-0.8), and positively associated with BOT cancer (adjusted OR 1.8; 95% CI 1.1-3.1), but was not associated with all OPC combined (adjusted OR 1.1; 95% CI 0.8-1.4). Sensitivity analyses considering only patients' or surgeons' assessments of tonsillectomy provided comparable results. CONCLUSION: We confirm the long-term protective effect of tonsillectomy performed in youth on future risk of tonsillar cancer, and our study is the second to report a concurrent increased risk of BOT cancer. Our data suggest that tonsillectomy in youth shifts the site of the first diagnosed oropharyngeal tumor and has a limited impact on overall risk of OPC.

[A thyroid-like low-grade nasopharyngeal papillary adenocarcinoma]. / Un cas rare d'adénocarcinome papillaire nasopharyngé thyroid-like de bas grade.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma is a rare histopathological entity. Patients usually complain of nasal obstruction and epistaxis. Diagnosis is confirmed on endonasal biopsy using immunohistochemical studies. Surgery is the treatment of choice and this pathology exhibits no metastasizes nor recurrence after treatment.

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.

Locoregional control, progression-free survival and morbidity rates in N3 head and neck cancer patients with low primary tumour burden: A 301-patient study.

OBJECTIVES: In patients with N3 head and neck squamous cell carcinoma (HNSCC), N3 disease is associated with high regional relapse and metastatic risks. Patients with resectable N3 disease have better prognosis although their metastatic risk may be similar as in patients with unresectable disease. Neoadjuvant chemotherapy has been associated with lower metastatic rates, but N3 patients may die of rapid locoregional progression. We assessed outcomes with the three modalities in patients with low primary burden to better assess the specific prognosis of N3 disease. METHODS: This retrospective multicentric study included T0-2 N3 HNSCC patients. Outcomes and morbidity in upfront neck dissection (uND) vs non-surgical groups were analysed and oncological outcomes and morbidity compared between patients undergoing chemoradiation or neoadjuvant chemotherapy in patients with initially unresectable N3 nodes. RESULTS: Of 301 patients, 142 (47%) underwent uND, 68 (23%) neoadjuvant chemotherapy and 91 (30%) chemoradiation. The 24- and 60-month incidence of locoregional relapse was 23.2% [18.3%; 28.4%] and 27.4% [21.8%; 33.3%]; it was lower in patients undergoing uND (P = .006). In patients with non-surgical treatments, success rates were 57.8% [49.4%; 66.3%] after chemoradiation and 38.1% [29.6%; 46.7%] after neoadjuvant chemotherapy (P = .001). Overall morbidity was more frequent in patients undergoing uND (68.8%) (P < .001). CONCLUSION: uND improved locoregional control but increased morbidity and showed no survival benefit. Success rates were better after chemoradiation versus neoadjuvant chemotherapy. Neoadjuvant chemotherapy did not reduce metastatic rates but non-responders to chemoradiation had poor PFS and survival rate, suggesting that predictive criteria are warranted.

Consensus on resectability in N3 head and neck squamous cell carcinomas: GETTEC recommendations.

BACKGROUND: Among patients with T0-2 N3 head and neck squamous cell carcinomas (HNSCC), those undergoing upfront neck dissection have better oncological outcomes. However, there is no consensual definition of disease resectability of N3 nodes, leading to major treatment attrition and interpretation biases between studies. We established a Delphi method-based consensus to define resectability and impact on decision-making for upfront neck dissection in N3 patients. METHODS: The Delphi method was designed as recommended by the French Haute Autorite de Sante among head and neck surgeons from university hospitals and cancer centers, using a 24-item questionnaire. Strong and relative agreements were subsequently established, and recommendations were written. The resulting recommendations were assessed by 30 independent surgeons. RESULTS: N3 nodes with intraparenchymal brain invasion, foramen invasion, skull base erosion, nodes requiring bilateral XIIth cranial nerve sacrifice, retropharyngeal N3 node or a node above the plan of soft palate are major contraindications to neck dissection. When neck dissection requires unilateral sacrifice of the IXth or Xth or XIIth cranial nerves or cervical nerve roots, upfront neck dissection may be performed, based on a case-by-case assessment of other patient and tumor estimates. CONCLUSION: Consensual contraindications to neck dissection in patients with T0-2 N3 HNSCC were defined among French head and neck surgeons as concerns skull base invasion, retropharyngeal nodes and bilateral XIIth cranial nerve sacrifice. This consensus should allow more reliable comparisons between surgical and non-surgical strategies in N3 patients.

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.