Head and neck ultrasound training improves the diagnostic performance of otolaryngology residents.

Objective: Surgeon-performed head and neck ultrasound (US) is increasingly used among otolaryngologists in office-based and surgical settings. However, it is unknown how formal US training affects otolaryngology residents' diagnostic workup of patients with cervical pathology. This study examined how a formal US course for residents affected their outpatient clinic US performance and diagnostic accuracy. Methods: We conducted a randomized cross-over trial, where 13 otolaryngology residents participated in a 6-h formal US course. Participants were randomized to perform head and neck US on four patient cases before and after completing the course. Eight patients with and without neck pathology were invited to participate as test cases. The ultrasound examinations were video recorded and anonymized before two consultants rated the US performance using the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale. Otolaryngology residents wrote an ultrasound report with a diagnosis based on their US examination, which was used to calculate the specificity and sensitivity. Results: We found a statistically significant difference in the OSAUS score before compared to after the hands-on training (p = .035). The diagnostic accuracy also increased from 62% before the course to 75% after the course (p = .02). Specificity increased from 54% prior to the course to 62% following the course, and sensitivity increased from 64% prior to the course to 79% following the course. The intraclass correlation coefficient with "absolute agreement" was 0.63. Conclusion: This study demonstrates that short, formal ultrasound training can improve otolaryngology residents' ultrasound skills and diagnostic accuracy in an outpatient clinic setting. Lay summary: This study looks at the change of otolaryngology residents' diagnostic workup of patients after they take a formal ultrasound course and shows that they get better at using ultrasound and make more accurate diagnoses if they take a formal course. Level of Evidence: Level 2.

Diagnostic accuracy of combined optical- and radio-guided SNB for neck staging of oral squamous cell carcinoma lesions in the anterior oral cavity.

PURPOSE: The purpose was to investigate the diagnostic performance of bimodal optical and radio-guided sentinel node biopsy (SNB) for oral squamous cell carcinoma (OSCC) sub-sites in the anterior oral cavity. METHODS: Prospective study of 50 consecutive patients with cN0 OSCC scheduled for SNB was injected with the tracer complex Tc99m:ICG:Nacocoll. A near-infrared camera was applied for optical SN detection. Endpoints were modality for intraoperative SN detection and false omission rate at follow-up. RESULTS: In all patients, a SN could be detected. In 12/50 (24%) of cases, the SPECT/CT showed no focus in level 1, but intraoperatively a SN in level 1 was optically detected. In 22/50 cases (44%), an additional SN was identified only due to the optical imaging. At follow-up, the false omission rate was 0%. CONCLUSION: Optical imaging appears to be an effective tool to allow real-time SN identification comprising level 1 unaffected by possible interference of radiation site from the injection.

Epidemiology, outcomes, and prognostic factors in submandibular gland carcinomas: a national DAHANCA study.

PURPOSE: The aim of this study is to present incidence, histological subtypes, survival rates, and prognostic factors based on a national cohort of patients with salivary gland carcinoma. METHODS: All Danish patients with submandibular gland carcinoma diagnosed from 1990 to 2015 (n = 206) were included and analyzed following histological re-evaluation. Data were collected by the Danish Head and Neck Cancer Group (DAHANCA). Overall, disease-specific and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression. RESULTS: The study population consisted of 109 (53%) men and 97 (47%) women, median age 62 years (range 11-102). Adenoid cystic carcinoma was the most frequent subtype (50%). Tumour classification T1/T2 (75%) and N0 (78%) was most frequent. The mean crude incidence was 0.17/100,000/year. Most patients (n = 194, 94%) were treated with primary surgery, and 130 (67%) received postoperative radiotherapy. The 5- and 10-year survival rates were for overall survival 64% and 41%, disease-specific survival 74% and 61%, and recurrence-free survival 70% and 56%, respectively. Survival rates were higher for adenoid cystic carcinoma compared to other subtypes, but the difference was not significant in multivariate analysis. Recurrence occurred in 69 patients, and 37 (53.6%) of them had recurrence in a distant site. Advanced T-classification and regional lymph-node metastases had significant negative impact on survival rates. CONCLUSION: The incidence of submandibular gland carcinoma in Denmark was 0.17/100,000/year and stable during the time period. The most frequent subtype was adenoid cystic carcinoma. Half of the recurrences presented in a distant site, and multivariate analysis confirmed that advanced stage was independent negative prognostic factor for recurrence and survival.

Dysphagia and QoL 3 Years After Treatment of Oropharyngeal Cancer With TORS or Radiotherapy.

OBJECTIVE(S): To investigate dysphagia and quality of life (QoL) outcomes 3 years after treatment of oropharyngeal cancer with either primary trans oral robotic surgery (TORS) or radiotherapy (RT). METHODS: A prospective cohort study conducted at the Copenhagen University Hospital. Endpoints were objective swallowing function, examined using fiberoptic endoscopic evaluation of swallowing (FEES) and video fluoroscopy (VF). QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30), Head & Neck Module (EORTC QLQ-HN35), and MD Anderson Dysphagia Inventory (MDADI). A comparison was made between 1-, and 3-year results. RESULTS: Forty-four patients were included prior to treatment, 31 treated with TORS and 13 with RT. One-year results for this cohort have previously been published (https://doi.org/10.1080/00016489.2020.1836395). Significant improvement on FEES in retention at the piriform sinus was noted in both groups. Patients treated with TORS had improved safety scores as well as dynamic imaging grade of swallowing toxicity (DIGEST) and efficiency scores, whereas patients treated with RT only had improvements in the latter two. Improvement in QoL scores was only noted for patients treated with TORS in composite MDADI scores. CONCLUSION: We found significant improvements in objective swallowing function from one to 3 years after treatment, particularly in patients treated with TORS. However, these improvements were not reflected as clinically meaningful improvements in QoL. LEVEL OF EVIDENCE: 3, cohort follow-up study Laryngoscope, 133:1893-1898, 2023.

[Transoral robotic surgery for the head and neck].

Transoral robotic surgery (TORS) has been utilized in the head and neck field for more than a decade. It is a minimally invasive technique which ensures flexible instrumentation and 3D visualization of the oropharynx. This has led to a paradigm shift in the treatment of early-stage oropharyngeal cancer and in the diagnostic management of unknown primary of the head and neck. Over time, the indications for TORS have broadened. This review discusses the development, current indications, and future perspectives of TORS within head and neck surgery.

Expression patterns of uPAR, TF and EGFR and their potential as targets for molecular imaging in oropharyngeal squamous cell carcinoma.

The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant cancer­specific biomarkers. The application of three membrane­bound receptors, namely urokinase­type plasminogen activator receptor (uPAR), tissue factor (TF) and EGFR have been previously explored for targeted imaging and therapeutic strategies in a broad range of solid cancers. The present study aimed to investigate the expression patterns of uPAR, EGFR and TF by immunohistochemistry (IHC) to evaluate their potential for targeted imaging and prognostic value in OPSCC. In a retrospective cohort of 93 patients with primary OPSCC, who were balanced into the 45 human papillomavirus (HPV)­positive and 48 HPV­negative groups, the IHC­determined expression profiles of uPAR, TF and EGFR in large biopsy or tumor resection specimens were analyzed. Using the follow­up data, overall survival (OS) and recurrence­free survival were measured. Specifically, associations between survival outcome, biomarker expression and clinicopathological factors were examined using Cox proportional hazards model and log­rank test following Kaplan­Meier statistics. After comparing the expression pattern of biomarkers within the tumor compartment with that in the adjacent normal tissues, uPAR and TF exhibited a highly tumor­specific expression pattern, whereas EGFR showed a homogeneous expression within the tumor compartment as well as a consistent expression in the normal mucosal epithelium and salivary gland tissues. The positive expression rate of uPAR, TF and EGFR in the tumors was 98.9, 76.3 and 98.9%, respectively. No statistically significant association between biomarker expression and survival outcome could be detected. Higher uPAR expression levels had a trend towards reduced OS according to results from univariate analysis (P=0.07; hazard ratio=2.01; 95% CI=0.92­4.37). Taken together, these results suggest that uPAR, TF and EGFR may be suitable targets for molecular imaging and therapy in OPSCC. In particular, uPAR may be an attractive target owing to their high positive expression rates in tumors and a highly tumor­specific expression pattern.

Human papillomavirus testing in metastatic squamous cell carcinoma of the neck with unknown primary using PCR on fine-needle aspiration smears: a prospective clinical study.

PURPOSE: Squamous cell carcinoma metastasis of the head and neck with unknown primary tumor (CUP) comprises a diagnostic challenge. Human papillomavirus (HPV) testing on cytologic specimens is gaining increasing focus as this may facilitate an early diagnosis of HPV-induced oropharyngeal carcinoma. This study aimed to prospectively assess PCR-based HPV-DNA testing on FNA smears in a clinical setting. METHODS: Patients referred to a tertiary Head and Neck Cancer Center with suspected CUP were included from November 2016 to November 2018. Scraped cell material from FNA smears was analyzed for HPV-DNA with PCR using general primers (GP5 + /GP6 +) and correlated with the origin and histology of the primary tumor (oropharynx vs. outside oropharynx or benign tumor). The turn-around time reflecting the workflow for HPV-DNA testing by PCR was also calculated. RESULTS: A total of 93 patients were enrolled in the study. The sensitivity and specificity were 86.7% [95% CI 75.4-94.1%] and 92.0% [95% CI 74.0-99.0%], and the positive and negative predictive values were 96.3% [95% CI 87.3-99.0%] and 74.2% [95% CI 59.9-84.7%], respectively. The turn-around time for HPV testing was a mean four calendar days. CONCLUSION: HPV-DNA testing on FNA smears can be performed within a reasonable timeframe and can guide for the detection of an HPV-positive oropharyngeal primary tumor in the clinical setting for patients presenting with CUP of the head and neck.

Long-term survival outcomes after primary transoral robotic surgery (TORS) with concurrent neck dissection for early-stage oropharyngeal squamous cell carcinoma.

BACKGROUND: In 2013, transoral robotic surgery (TORS) was implemented as a protocolled treatment alternative to the traditional radiotherapy (RT) in Denmark for oropharyngeal squamous cell carcinoma (OPSCC). In 2017, we published our first prospective feasibility study, showing that TORS with concurrent neck dissection successfully achieved negative margins in 29 out of 30 patients (97%) with early-stage OPSCC. AIMS/OBJECTIVES: This follow-up study aims to evaluate the five-year overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS). METHODS: Retrospective follow-up study including 30 patients treated with TORS for early-stage OPSCC (T1-T2, N0-N1, M0, UICC 7th edition) from September 2014 to January 2016 at a single head and neck cancer centre in Denmark. The five-year OS, DSS and RFS, including a detailed analysis of the recurrences, were addressed. RESULTS: The five-year OS, DSS and RFS was 90%, 93% and 87%, respectively. Median follow-up was 54.5 months. Four patients developed a recurrence, with one regional, one distant metastatic (M) and two locoregional recurrences. The median time to recurrence was 24 months (range 3-42 months). CONCLUSIONS AND SIGNIFICANCE: This follow-up study demonstrates good five-year OS, DSS and RFS in a prospective cohort of patients undergoing TORS and neck dissection for early-stage OPSCC.

Manuscript title: the maxillary swing approach - the first Scandinavian experience.

BACKGROUND: The maxillary swing approach was introduced three decades ago in the head and neck field providing optimal surgical exposure for tumors in the nasopharyngeal and/or the retromaxillary space. OBJECTIVES: To report the clinical experience, patient surgical morbidity and survival outcomes following the introduction of the maxillary swing approach in Denmark. MATERIAL AND METHODS: A retrospective study including patients who underwent the maxillary swing approach from January 2012 - January 2020. Baseline and perioperative data, pathology, postoperative morbidity and survival outcomes were registered. RESULTS: Sixteen patients were included of which 15 had a malignant tumor with different histology, while one patient had a benign tumor. Most commonly reported short-term morbidity were trismus, cheek hypoesthesia, nasopalatal fistula, lacrimation and nasal stenosis (<3 months postoperatively) improving markedly at 12 months follow-up. For patients with malignant tumors, the 5-year overall survival and recurrence-free survival rates were 60% and 66.7%, respectively. CONCLUSIONS AND SIGNIFICANCE: The maxillary swing approach was safely implemented by a multidisciplinary team at a high-volume centralized head and neck cancer center in Denmark. The procedure may be considered for salvage surgery of recurrent nasopharyngeal carcinomas and selected malignant and benign tumors located in the nasopharynx and/or retromaxillary space inaccessible by other surgical modalities.

Transoral robotic surgery: a 4-year learning experience in a single Danish Cancer Centre.

Background: The main indication for transoral robotic surgery (TORS) has been the primary treatment of oropharyngeal squamous cell carcinoma (OPSCC). In the western world this is highly relevant due to the increasing incidence of human papillomavirus (HPV)-positive OPSCC. In Denmark, TORS was implemented in 2013 for use in the protocolled primary treatment of OPSCC.Aims/objectives: To perform a year-by-year comparative analysis of indications for TORS, hospitalization and complication rates to identify optimal future indications for TORS.Methods and materials: This is a retrospective single-centre case review from 2013-2017. Data were collected from patient files through electronic health care systems.Results: Since 2013, there has been a change of indications from performing benign and salvage surgery to mainly primary treatment of OPSCC and diagnostic use in patients with cancer of unknown primary (CUP). The overall complication rates have reduced considerably over time.Conclusions and significance: Lower complication rates may be explained by improved surgical experience, through better patient selection and changes in indications for TORS. Future applications of TORS will be in the management of CUP and as part of a Danish national randomized clinical trial aiming to compare long-term functional outcomes after treatment of early-stage OPSCC with TORS versus radiation treatment.

Second primary cancers in pediatric head and neck cancer survivors in Denmark during 1980-2014: A nationwide study.

INTRODUCTION: The survival among children with cancer has improved considerably the past decades. Consequently, more children are at risk of second primary cancers (SPC). This study aimed to investigate the incidence of SPC among pediatric head and neck cancer (HNC) patients. METHODS AND MATERIALS: Data on children aged 0-17 years registered with a HNC in the Danish Registry of Childhood Cancer and the Danish National Patient Registry during the period 1980-2014 was obtained. SPC was defined as registration with any second malignancy that was not simultaneous with the first primary cancer (FPC) or a relapse hereof. All information was validated through review of medical charts. Standardized incidence rates (SIR) were calculated using the average incidence of all cancers in the general population of Denmark during the study period as reference. RESULTS: Among 234 pediatric HNC patients, six patients (four females) were registered with a SPC (2.6%), corresponding to an overall SIR of 4.8. No patients were diagnosed with more than one SPC. The median age at FPC and SPC was 15.2 years (range 9-16 years) and 35.0 years (range 19-41 years). The most common tumor histology and location among the patients with SPC was nasopharyngeal lymphoepithelial carcinoma for FPC and basal cell carcinoma of the skin for SPC. CONCLUSION: During 1980-2014 we identified six cases of SPC among 234 pediatric head and neck cancer patients in Denmark, corresponding to an overall SIR of 4.8.

Near-infrared fluorescence imaging improves the nodal yield in neck dissection in oral cavity cancer - A randomized study.

INTRODUCTION: Lymph node yield (LNY) in neck dissection has been identified as a prognostic factor in oral cavity cancer. The purpose of this study was to investigate the impact of additional use of optical imaging on LNY in therapeutic ND in oral cancer. METHODS: Consecutive patients with oral squamous cell carcinoma with clinical neck metastasis planned for primary tumor resection were randomized to conventional neck dissection or near-infrared fluorescence (NIRF)-guided neck dissection, respectively. In the intervention group, patients were injected with ICG-Nanocoll prior to surgery. Intraoperatively, an optical hand-held camera system was used for lymph node identification. Also, NIRF imaging of the neck specimen was performed, and optical signals were pinned with needle markings to guide the pathological examination. The endpoint of the study was LNY per neck side in levels Ib-III. RESULTS: 31 patients were included with 18 neck sides in the control group and 18 neck sides in the intervention group for evaluation. During NIRF-guided ND, individual lymph nodes could be identified by a bright fluorescent signal and individual tumor-related drainage patterns could be observed in the neck. The LNY in the intervention group was significantly higher compared to the control group (p = 0.032) with a mean of 24 LN (range: 12-33 LN in levels Ib-III compared to 18 LN (range: 10-36 LN) in the control group, respectively. CONCLUSIONS: NIRF-guided ND significantly improved the nodal yield compared to the control group. Intraoperative real-time optical imaging enabled direct visualization of tumor-related drainage patterns within the neck lymphatics.

Survival and characteristics of pediatric salivary gland cancer: A systematic review and meta-analysis.

A systematic search of PubMed, EMBASE, and the Cochrane Library for studies from 2000 to 2017 including children aged 0-19 with salivary gland cancer was performed. In 19 studies, 749 children (median age of 14.2 years, female to male ratio of 1.4:1) were included; 72% had parotid tumors and 95% underwent surgery, of whom 65% had surgery alone and 24% with adjuvant radiotherapy. Low-grade and stage mucoepidermoid carcinoma were the most frequent cancer. The 5-year overall- and disease-free survival was 94% and 83%. Recurrence was observed in 20% at a median of 1.1 years from diagnosis.

[Transoral robotic surgery for head and neck cancer].

Oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV) is highly prevalent in the western part of the world. Patients with HPV-induced OPSCC are often younger and have a much better prognosis than patients with HPV-negative OPSCC. The newly introduced transoral robotic surgery offers the ability to perform en bloc tumour resection with good margin control. It may be an alternative to the traditional radiation therapy for early-stage OPSCC. A Danish randomised clinical trial is now aiming at comparing these two treatments with a focus on long-term functional outcomes.

MicroRNA-based classifiers for diagnosis of oral cavity squamous cell carcinoma in tissue and plasma.

BACKGROUND: MicroRNAs (miRNAs) hold promise as diagnostic cancer biomarkers. Here we aimed to define the miRNome in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM), and to identify and validate new diagnostic miRNAs and miRNA combinations in formalin-fixed paraffin-embedded (FFPE) tissue samples and plasma samples. METHODS: We performed next-generation miRNA sequencing in FFPE tissue samples of OSCC (n = 80) and NOM (n = 8). Our findings were validated by quantitative polymerase chain reaction (qPCR) analysis of OSCC (n = 195) and NOM (n = 103) FFPE tissue samples, and plasma samples from OSCC patients (n = 55) and healthy persons (n = 18). RESULTS: The OSCC miRNome included 567 miRNAs, 66 of which were differentially expressed between OSCC and NOM. Using qPCR data, we constructed receiver operating curves to classify patients as NOM or OSCC based on miRNA combinations. The area under the curve was of 0.92 from FFPE tissue (miR-204-5p, miR-370, miR-1307, miR-193b-3p, and miR-144-5p), and 1.0 from plasma samples (miR-30a-5p and miR-769-5p). Model calibration and discrimination were evaluated using 10-fold cross-validation. CONCLUSIONS: Analysis of the miRNome from many OSCC cases improves our knowledge of the importance of individual miRNAs and their predictive potential in OSCC. We successfully identified miRNA classifiers in FFPE OSCC tissue and plasma with a high discriminatory ability between OSCC and NOM. The proposed combination of miR-30a-5p and miR-769-5p in plasma from OSCC patients could serve as a minimal invasive biomarker for diagnosis and control of T-site recurrences.

Comparison of clinical, radiological and morphological features including the distribution of HPV E6/E7 oncogenes in resection specimens of oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) represents a distinct tumour entity in comparison to HPV-negative OPSCC. The clinical, radiological, morphological features and distribution of HPV E6/E7 mRNA were investigated in resected specimens of OPSCC. METHODS: We retrieved formalin-fixed, paraffin-embedded whole section slides from 24 p16/HPV-DNA positive and 18 p16/HPV-DNA negative primary tumours and 16 corresponding metastases in patients with early-stage OPSCC who underwent planned curative or diagnostic primary transoral robotic surgery. A detailed clinicoradiological and histopathological investigation of the tumours was performed along with detection of HPV E6/E7 mRNA by in situ hybridisation. RESULTS: HPV-driven OPSCC was characterised by non-keratinising morphology and was dominated by a cohesive invasion pattern at the leading edge of the tumour. Dysplastic zones of the squamous epithelium were strictly located in the tonsillar crypts in contrast to HPV-negative OPSCC which predominantly arised from the dysplastic surface epithelium. Thirteen HPV-driven OPSCC invaded through the tonsillar lymphoid compartment and into soft tissue, causing a stromal desmoplastic reaction. HPV mRNA was consistently but inhomogenously expressed in the entire tumour area and in the dysplastic squamous epithelium. There was no HPV expression in the adjacent normal epithelium and in the non-neoplastic tissues. CONCLUSIONS: This study enhances the current understanding of HPV-driven OPSCC. Only tumours that invade through the lymphoid compartment induce a stromal desmoplastic reaction. A consistent but inhomogenous expression of E6 and E7 mRNA was found in tumour and dysplastic areas, emphasizing that the E6/E7 oncogenes are the driving factors in HPV-driven OPSCC.

Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): tumor expression patterns and prognostic value in oral cancer.

BACKGROUND: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhibit enhanced expression in many types of cancers, and have been investigated as potential biomarkers for targeted strategies and prognostication. The aim of the study was to investigate the expression patterns of uPAR, TF and EGFR and their potential prognostic value in OSCC. METHODS: Immunohistochemical expression of uPAR, TF and EGFR in tumor resection specimens from 191 patients with primary OSCC was analyzed. Overall (OS) and disease-free survival (DFS) was calculated. Associations between biomarker expression, clinicopathological factors and patient survival was analyzed using the Cox proportional hazards model for univariate and multivariate analysis, log rank and Kaplan-Meier statistics. RESULTS: uPAR and TF exhibited a highly tumor-specific expression pattern while EGFR also showed expression in normal tissues outside the tumor compartment. The overall positive expression rate of uPAR, TF and EGFR was 95%, 58% and 98%, respectively. High uPAR expression across the entire cohort was negatively associated with OS (p = 0.031, HR = 1.595 (95%CI 1.044-2.439)) in univariate analysis. The 5-year OS for high and low uPAR expression was 39% and 56%, respectively. The expression of TF and EGFR was not associated with survival outcome. CONCLUSIONS: This study may suggest that uPAR and TF could potentially be attractive targets for molecular imaging and therapy in OSCC due to high positive expression rates and tumor-specific expression patterns. High uPAR expression was significantly associated with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer.

Increasing incidence and survival in oral cancer: a nationwide Danish study from 1980 to 2014.

BACKGROUND: Oral carcinomas (OCs) make up a significant proportion of head and neck carcinomas (HNCs) and are an important cause of morbidity and mortality globally. The purpose of this population-based study was to determine trends in incidence and survival in OC in the Danish population from 1980 to 2014. MATERIAL AND METHODS: This study covered all patients registered in the nationwide Danish cancer registry (DCR) in the period 1980-2014. Age-adjusted incidence rate (AAIR) per 100,000 and annual percentage change (APC) were evaluated. Also, 5-year overall survival (OS) was calculated with Cox regression analysis in relation to location, gender, age, and calendar year at diagnosis. RESULTS: Altogether, 8299 patients with oral cancer were identified, 5062 (61%) of whom were males and 3237 (39%) were females. The median age at diagnosis was 63 years. The AAIR of patients with OC increased from 1.9 per 100,000 in 1980 to 3.5 per 100,000 in 2014, and we observed a significant increase in 5-year OS of 12% points (a relative increase of 38%) from the period 1980-1984 to 2005-2009. Women were found to have a better prognosis than men. CONCLUSIONS: We found an unexpected increase in the age-standardized incidence of OC during the last 30 years in Denmark, and also an improvement in survival. The 5-year OS was significantly better in recent years even when we adjusted the analysis for relevant covariates.

Genetic Characterization of Adenoid Cystic Carcinoma of the Minor Salivary Glands: A Potential Familial Occurrence in First-Degree Relatives.

Adenoid cystic carcinoma (AdCC) is a malignant salivary gland tumor. To date, no cases of AdCC in first-degree relatives have been reported in the literature. We present a 50-year-old female (Case 1) and this patients' father (Case 2), both of whom were diagnosed with AdCC of the minor salivary glands. Histology of Case 1 demonstrated a tubulocribriform AdCC whereas Case 2 primarily was an AdCC of solid type. Both cases harbored the MYB-NFIB gene fusion as demonstrated by FISH and RNA-sequencing. After filtering and selection of putative deleterious variants, whole exome sequencing identified 18 germline variants in common between Case 1 and Case 2. However, none of the variants were associated with AdCC or other head and neck cancers. To our knowledge, we present the first potential case of familial AdCC. The presented genetic data may contribute to further investigations of the underlying genetic mechanisms for AdCC susceptibility.

Primary transoral robotic surgery with concurrent neck dissection for early stage oropharyngeal squamous cell carcinoma implemented at a Danish head and neck cancer center: a phase II trial on feasibility and tumour margin status.

There is an increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the western world due to human papillomavirus (HPV). According to the Danish Head and Neck Cancer Group guidelines, the current recommended treatment of patients with OPSCC in Denmark is primary radiation therapy (RT) with or without concomitant chemotherapy. This is the first study in Scandinavia from a head and neck cancer centre that aims to demonstrate the feasibility of performing primary transoral robotic surgery (TORS) and concurrent neck dissection for patients with early stage OPSCC. Between September 2014 and January 2016, 30 consecutive patients with clinical T1-T2, N0-N1 OPSCC underwent primary TORS and concurrent neck dissection. The patients were offered postoperative adjuvant therapy according to pathological risk parameters: pT >2, T-site margin <2 mm, pN >1 or extracapsular extension (ECE). Concomitant chemotherapy was offered to patients with the presence of ECE or involved margins. Twenty-nine patients had negative margins on T-site after primary resection. Only one patient had a close margin of 1 mm. Unilateral neck dissection was performed in 21 patients while nine patients underwent bilateral neck dissection. Due to an upstaging following surgery, 13 patients were referred to adjuvant therapy. Four of these patients received RT and two patients received concomitant chemo-radiation (CCR) therapy. Seven patients declined the recommended adjuvant therapy one of whom later developed an N-site recurrence and received salvage surgery with postoperative RT. In summary, 43% of the patients were referred to adjuvant therapy following primary surgery which was mainly due to N-site stage migration and ECE. Primary TORS and concurrent neck dissection is a safe and feasible procedure that may be an alternative to primary RT and CCR in a selected group of patients with early stage OPSCC.