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Jes Sloth Mathiesen,1,2 Jens Peter Kroustrup,3 Peter Vestergaard,3,4 Kirstine Stochholm,5,6 Per Løgstrup Poulsen,6 Åse Krogh Rasmussen,7 Ulla Feldt-Rasmussen,7 Sten Schytte,8 Stefano Christian Londero,8 Henrik Baymler Pedersen,9 Christoffer Holst Hahn,10 Jens Bentzen,11 Sören Möller,2,12 Mette Gaustadnes,13 Maria Rossing,14 Finn Cilius Nielsen,14 Kim Brixen,2 Anja Lisbeth Frederiksen,2,15 Christian Godballe1 On behalf of the Danish Thyroid Cancer Group (DATHYRCA) 1Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark; 2Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 4Steno Diabetes Center North Jutland, Aalborg, Denmark; 5Department of Internal Medicine and Endocrinology, Aarhus University Hospital, Aarhus, Denmark; 6Center for Rare Diseases, Aarhus University Hospital, Aarhus, Denmark; 7Department of Medical Endocrinology, Copenhagen University Hospital, Copenhagen, Denmark; 8Department of ORL Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark; 9Department of ORL Head & Neck Surgery, Aalborg University Hospital, Aalborg, Denmark; 10Department of ORL Head & Neck Surgery, Copenhagen University Hospital, Copenhagen, Denmark; 11Department of Oncology, Herlev Hospital, Herlev, Denmark; 12Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark; 13Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; 14Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark; 15Department of Clinical Genetics, Odense University Hospital, Odense, Denmark Background: The completeness of REarranged during Transfection (RET) testing in patients with medullary thyroid carcinoma (MTC) was recently reported as 60%. However, the completeness on a population level is unknown. Similarly, it is unknown if the first Danish guidelines from 2002, recommending RET testing in all MTC patients, improved completeness in Denmark. We conducted a nationwide retrospective cohort study aiming to evaluate the completeness of RET testing in the Danish MTC cohort. Additionally, we aimed to assess the completeness before and after publication of the first Danish guidelines and characterize MTC patients who had not been tested.Methods: The study included 200 patients identified from the nationwide Danish MTC cohort 1997–2013. To identify RET tested MTC patients before December 31, 2014, the MTC cohort was cross-checked with the nationwide Danish RET cohort 1994–2014. To characterize MTC patients who had not been RET tested, we reviewed their medical records and compared them with MTC patients who had been tested.Results: Completeness of RET testing in the overall MTC cohort was 87% (95% CI: 0.81–0.91; 173/200). In the adjusted MTC cohort, after excluding patients diagnosed with hereditary MTC by screening, completeness was 83% (95% CI: 0.76–0.88; 131/158). Completeness was 88% (95% CI: 0.75–0.95; 42/48) and 81% (95% CI: 0.72–0.88) (89/110) before and after publication of the first Danish guidelines, respectively. Patients not RET tested had a higher median age at diagnosis compared to those RET tested. Median time to death was shorter in those not tested relative to those tested.Conclusion: The completeness of RET testing in MTC patients in Denmark seems to be higher than reported in other cohorts. No improvement in completeness was detected after publication of the first Danish guidelines. In addition, data indicate that advanced age and low life expectancy at MTC diagnosis may serve as prognostic indicators to identify patients having a higher likelihood of missing the compulsory RET test. Keywords: RET testing, medullary thyroid carcinoma, Denmark

Jes Sloth Mathiesen,1,2 Jens Peter Kroustrup,3 Peter Vestergaard,3,4 Kirstine Stochholm,5,6 Per Løgstrup Poulsen,5 Åse Krogh Rasmussen,7 Ulla Feldt-Rasmussen,7 Sten Schytte,8 Henrik Baymler Pedersen,9 Christoffer Holst Hahn,10 Jens Bentzen,11 Sören Möller,2,12 Mette Gaustadnes,13 Maria Rossing,14 Finn Cilius Nielsen,14 Kim Brixen,2 Anja Lisbeth Frederiksen,2,15 Christian Godballe1 1Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark; 2Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 4Steno Diabetes Center North Jutland, Aalborg, Denmark; 5Department of Internal Medicine and Endocrinology, Aarhus University Hospital, DK-8000 Aarhus, Denmark; 6Center for Rare Diseases, Aarhus University Hospital, Aarhus N, Denmark; 7Department of Medical Endocrinology, Copenhagen University Hospital, Copenhagen, Denmark; 8Department of ORL Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark; 9Department of ORL Head and Neck Surgery, Aalborg University Hospital, Aalborg, Denmark; 10Department of ORL Head and Neck Surgery, Copenhagen University Hospital, Copenhagen, Denmark; 11Department of Oncology, Herlev Hospital, Herlev, Denmark; 12Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark; 13Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; 14Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark; 15Department of Clinical Genetics, Odense University Hospital, Odense, Denmark Background: The incidence and prevalence of multiple endocrine neoplasia 2A (MEN2A) have only been reported once in a nationwide setting. However, it is unclear whether the figures are representative of other populations, as the major component of the syndrome, hereditary medullary thyroid carcinoma (MTC), has been reported as rare in the same country. We conducted a nationwide retrospective cohort study of MEN2A in Denmark from 1901 to 2014, aiming to describe the incidence and prevalence. Methods: This study included 250 unique MEN2A patients born or resident in Denmark before December 31, 2014. Patients were identified through the Danish REarranged during Transfection (RET) cohort, linkage of MEN2A pedigrees, the Danish MTC cohort, a nationwide collaboration of MEN2 centers, cross-checking of other relevant cohorts, and a systematic literature search. Results: The incidence from 1971 to 2000 was 28 (95% CI: 21–37) per million live births per year. Incidence for the specific mutations or for the overall MEN2A group did not change significantly from 1901 to 2014 (P>0.05). Point prevalence at January 1, 2015, was 24 per million (95% CI: 20–28). Conclusion: The incidence and prevalence of MEN2A in Denmark seem higher than those reported in other countries. This is likely explained by the Danish C611Y founder effect. Also, our data indicate no significant change in MEN2A incidence during the last century. Keywords: multiple endocrine neoplasia 2A, incidence, prevalence, Denmark

Jens Overgaard,1 Aleksandar Jovanovic,1 Christian Godballe,2,3 Jesper Grau Eriksen3 1Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, 2Department of ORL – Head and Neck Surgery, 3Department of Oncology, Odense University Hospital, Odense, Denmark Aim of the database: The Danish Head and Neck Cancer database is a nationwide clinical quality database that contains prospective data collected since the early 1960s. The overall aim of this study was to describe the outcome of the national strategy for multidisciplinary treatment of head and neck cancer in Denmark and to create a basis for clinical trials. Study population: The study population consisted of all Danish patients referred for treatment of squamous cell carcinoma of the larynx, pharynx, oral cavity, or neck nodes from unknown primary or any histopathological type (except lymphoma) of cancer in the nasal sinuses, salivary glands, or thyroid gland (corresponding to the International Classification of Diseases, tenth revision, classifications C.01–C.11, C.30–C.32, C.73, and C.80). Main variables: The main variables used in the study were symptoms and the duration of the symptoms; etiological factors; pretreatment and diagnostic evaluation, including tumor–node–metastasis classification, imaging, histopathology, and laboratory tests; primary treatment with semidetailed information of radiotherapy, surgery, and medical treatment; follow-up registration of tumor status and side effects; registration of relapse and treatment thereof; and registration of death and cause of death. Main results: Data from >33,000 patients have been recorded during a period of >45 years. In this period, the outcome of treatment improved substantially, partly due to better treatment as a result of a series of continuous clinical trials and subsequent implementation in national guidelines. The database has furthermore been used to describe the effect of reduced waiting time, changed epidemiology, and influence of comorbidity and socioeconomic parameters. Conclusion: Half a century of registration of head and neck cancer treatment and outcome has created the basis for understanding and has substantially contributed to improve the treatment of head and neck cancer at both national and international levels. Keywords: head and neck cancer, squamous cell carcinoma, radiotherapy, national population cohort

Primarily to understand whether clinically relevant factors affect the International Outcome Inventory (IOI-HA) scores and to examine if IOI-HA scores improve when renewing the hearing aids (HA) for experienced users. Secondly, to estimate the overall HA effectiveness using the IOI-HA. A prospective observational study. In total, 1961 patients with hearing loss were included. All patients underwent a hearing examination, were fitted with HAs, and answered the IOI-HA. Factor analysis of IOI-HA separated the items into a Factor 1 (use of HA, perceived benefits, satisfaction, and quality of life) and Factor 2 (residual activity limitation, residual participation restriction and impact on others) score. Degree of hearing loss, word recognition score, motivation, HA usage time, tinnitus, asymmetry, and sex were significantly associated with total IOI-HA, Factor 1, or Factor 2 scores. The seven IOI-HA items increased on average by 0.4 (p < 0.001) when renewing HAs. The total median IOI-HA score at follow-up was 29 (7) for experienced (n = 460) and first-time users (n = 1189), respectively. Degree of hearing loss, word recognition score, motivation, tinnitus, asymmetry, and sex may be used to identify patients who require special attention to become successful HA users. [ABSTRACT FROM AUTHOR]

To identify clinical and histologic prognostic factors and to investigate whether immunohistochemical detection of p53 expression might contain prognostic information, a retrospective study of patient and tumor characteristics was performed in 225 cases of papillary and follicular thyroid carcinomas. The analyses were based on cause-specific and crude survival. In univariate analysis, age at diagnosis, tumor size, presence of distant metastases, histology (papillary contra follicular type), extrathyroidal invasion, necrosis in primary tumor, and p53 expression were significant prognostic indicators. For 211 patients (96%) all information was available and Cox's proportional hazard model was applied. The authors found that age, distant metastases, necrosis in primary tumor, extrathyroidal invasion, and p53 expression were significant prognostic factors. Analyses of cause-specific and crude survival gave similar results. The authors conclude that age at diagnosis, presence of distant metastases, necrosis in primary tumor, and extrathyroidal invasion are important prognostic factors, and that immunohistochemical detection of p53 protein in the primary tumor is a significant and independent prognostic indicator, which might be of value in the treatment planning in patients with papillary or follicular thyroid carcinomas. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the treatment outcome for sino-nasal carcinomas in Denmark from 1995-2004 and compare the results to the previous Danish survey covering 1982-1991. Design. Retrospective follow-up. Materials and methods. In the five Danish head and neck oncology centres, charts of all consecutive patients with sino-nasal carcinomas were reviewed and data extracted to a common database. Altogether 242 patients from the period 1995-2004 were identified. Of these 162 (67%) were male and 80 (33%) female. Histologies included squamous cell carcinoma (55%), adenocarcinoma (28.5%), adenoid-cystic carcinoma (5.0%), undifferentiated carcinoma (4.5%), transitiocellular carcinoma (1.7%), mucoepidermoid carcinoma (0.8%), neuroendocrine carcinoma (2.5%), small cell carcinomas (1.2%) and carcinomas not otherwise specified (0.8%). Treatments included radiotherapy alone 79 (33%), surgery alone 29 (12%), combined surgery and radiotherapy 96 (40%), palliative/no treatment 38 (16%). A total of 204 (86%) patients were treated with curative intent. Results. Of the 204 patients treated with curative intent, 94 (46%) relapsed. Most failures were in T-site (63, 30%). N-site failures were 10 (5%) and M-site failures six (3%). Failure occurring in T+N-site, T+M-site, N+M-site and T+N+M-site were seven (3%), two (1%), one (0.5%) and five (3%) respectively. The 5-year actuarial local, nodal and loco-regional control rates were 55±4%, 86±3%, 49±4%, respectively. The overall 5-year actuarial survival rate for the entire cohort was 47±3%, and the corresponding cancer-specific 5-year actuarial survival rate was 57±3%. Female gender, nasal cavity tumour, adenocarcinoma and low clinical stage were significant positive prognostic factors in univariate analysis. A Cox multivariate analysis showed that only tumour site and clinical stage were independent significant prognostic factors. Conclusion. The current series has confirmed stage and tumour site as independent prognostic factors. Compared to the previous Danish survey covering the period 1982-1991, the overall survival and cancer-specific survival rates have improved significantly. [ABSTRACT FROM AUTHOR]