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.

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

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

Salivary duct carcinoma: Prospective multicenter study of 61 cases of the Réseau d'Expertise Français des Cancers ORL Rares.

BACKGROUND: The purposes of this study were to describe the characteristics of a prospective multicenter series of patients with salivary duct carcinoma and to investigate prognostic factors. METHODS: Patients included for salivary duct carcinoma between 2009 and 2016 in the Réseau d'Expertise Français des Cancers ORL Rares (REFCOR) database were selected. Immunohistochemical analyses were performed. RESULTS: Sixty-one patients were included in this study. The primary site was the parotid gland in 90% of the cases. Fifty-seven percent of the tumors were stage IV, 65% of patients had lymph node involvement, and 10% had metastases. Tumors showed androgen receptor (89%) and human epidermal growth factor receptor 2 (HER2)/neu (36%). Ninety-four percent of patients underwent surgery and 86% had postoperative radiotherapy. Six patients were treated with targeted therapies. The 3-year overall survival (OS) was 74% and the 3-year disease-free survival (DFS) was 44%. Tumor stages III to IV reduced DFS (hazard ratio [HR] 4.3; P = .04). The N2/3 class reduced distant metastasis-free survival (HR 7.3; P = .007). CONCLUSION: Salivary duct carcinoma prognosis is poor and is correlated with tumor stage and lymph node classification. Androgen receptor and HER2/neu should be tested as they offer the possibility of targeted therapies.

Does smoking alter the mutation profile of human papillomavirus-driven head and neck cancers?

BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) patients are characterised by a better prognosis than their HPV-negative counterparts. However, this significant survival advantage is not homogeneous and among HPV-positive patients those with a smoking history have a significantly increased risk of oncologic failure. The reason why tobacco consumption impacts negatively the prognosis is still elusive. Tobacco might induce additional genetic alterations leading to a more aggressive phenotype. The purpose of this study was to characterise the mutational profile of HPV-positive OPCs by smoking status. We hypothesise a higher frequency of mutations affecting smokers. METHODS: Targeted next-generation sequencing of 39 genes that are recurrently mutated in head and neck cancers (HNCs) caused by tobacco/alcohol consumption was performed in 62 HPV-driven OPC cases including smokers and non-smokers. RESULTS: The study population included 37 (60%) non-smokers and 25 (40%) smokers. Twenty (32%) patients had no mutation, 14 (23%) had 1 mutation and 28 (45%) had 2 or more mutations. The most commonly mutated genes regardless of tobacco consumption were PIK3CA (19%), MLL2 (19%), TP53 (8%), FAT 1 (15%), FBXW7 (16%), NOTCH1 (10%) and FGFR3 (10%). Mutation rate was not significantly different in smokers compared with non-smokers even when analyses focused on heavy smokers (>20 pack-years vs. <20 pack-years). Similarly, there was no significant difference in mutations patterns according to tobacco consumption. CONCLUSION: In HPV-positive patients, smoking does not increase the mutation rate of genes that are recurrently mutated in traditional HNC. Additional studies are warranted to further describe the molecular landscape of HPV-driven OPC according to tobacco consumption.

Value of radiofrequency ablation in the management of retropharyngeal lymphatic malformation.

Lymphatic malformations are benign malformations frequently occurring in the head and neck. Retropharyngeal location is rare, can be life threating and its management is particularly challenging. Over a three-year period, three patients presented with symptomatic (dyspnea and/or dysphagia) retropharyngeal lymphatic malformation. All were treated using a radiofrequency ablation of lymphatic malformation through a trans-oral approach. No major complications occurred following the surgery. During the follow-up, no recurrence was noted and all patients were asymptomatic. Radiofrequency ablation in the management of retropharyngeal lymphatic malformations is a simple technique with very good results and allows a fast recovery with minimum morbidity and a short hospital stay.

Use of bone anchoring device in electromagnetic computer-assisted navigation in lateral skull base surgery.

CONCLUSION: The use of the bone anchoring device associated with a fiducial marker, both fixed close to the operating field, improves the reproducibility and effectiveness of the computer-assisted navigation in lateral skull base surgery. OBJECTIVES: Computer-assisted navigation in lateral skull base surgery using the electromagnetic system Digipointeur(®) needs an external fiducial marker (titanium screw) close to the operating field to increase position accuracy (PA) to about 1 mm. Displacement of the emitter placed in the mouth (Buccostat(®)) induces a drift of the system, leading to at least 20% of unsuccessful procedures. The aim of this study was to evaluate the PA, stability, and reproducibility of computer-assisted navigation in lateral skull base surgery using a bone anchoring device to provide a fixed registration system near the operating field. METHODS: Forty patients undergoing a lateral skull base procedure with the Digipointeur(®) system performed with both the titanium screw and bone anchoring device were included in this prospective study. They were divided in two groups. In the first one (n = 9), the PA was measured before and after screw registration for five intratemporal landmarks, during a translabyrinthine approach. In the second group (n = 31), all lateral skull base procedures were included and the PA was evaluated visually by the surgeon on different landmarks of the approaches as well as the stability of the system. RESULTS: In the first group, the PA was 7.08 ± 0.59 mm and 0.77 ± 0.17 mm (mean ± SEM, p < 0.0001) before and after screw registration, respectively. In the second group, the PA was considered as accurate by the surgeon in all cases and no drift of the system was observed. Computer-assisted surgery was never abandoned due to increased stability of the bone-anchored emitter.