A history of occupational noise exposure is associated with steep-slope audiograms and poorer self-reported hearing-aid outcomes.

OBJECTIVE: To investigate the effects of previous occupational noise exposure in older adults with hearing loss on (1) audiometric configuration and acoustic reflex (AR) thresholds and (2) self-reported hearing abilities and hearing aid (HA) effectiveness. DESIGN: A prospective observational study. STUDY SAMPLE: The study included 1176 adults (≥60 years) with bilateral sensorineural hearing loss. Pure-tone audiometry, AR thresholds, and responses to the abbreviated version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ12) and the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire were obtained, along with information about previous occupational noise exposure. RESULTS: Greater occupational noise exposure was associated with a higher prevalence of steeply sloping audiograms in men and women and a 0.32 (95% CI: -0.57; -0.06) scale points lower mean SSQ12 total score among noise-exposed men. AR thresholds did not show a significant relation to noise-exposure status, but hearing thresholds at a given frequency were related to elevated AR thresholds at the same frequency. CONCLUSIONS: A noise exposure history is linked to steeper audiograms in older adults with hearing loss as well as to poorer self-reported hearing abilities in noise-exposed men. More attention to older adults with previous noise exposure is warranted in hearing rehabilitation.

Diagnostic Accuracy of Up-Front PET/CT and MRI for Detecting Cervical Lymph Node Metastases in T1-T2 Oral Cavity Cancer-A Prospective Cohort Study.

The diagnostic accuracy of up-front 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for detecting cervical lymph node metastases in patients with T1-T2 oral squamous cell carcinoma is reported with large discrepancies across the literature. We investigated the sensitivity, specificity, positive and negative predictive value, and accuracy of up-front PET/CT for detecting cervical lymph node metastases in this patient group and compared the performance to magnetic resonance imaging (MRI). In this prospective cohort study, 76 patients with T1-T2 oral squamous cell carcinoma underwent an up-front PET/CT and MRI at the Odense University Hospital from September 2013 to February 2016. Sentinel node biopsy and elective neck dissection were used for histopathological verification of the imaging modalities. Up-front PET/CT was significantly more sensitive than neck MRI (74% vs. 27%, p = 0.0001), but less specific (60% vs. 88%, p = 0.001). The accuracy of PET/CT and neck MRI was comparable (66% vs. 63%, p = 0.85), the PPV was slightly in favor of neck MRI (56% vs. 62%, p = 0.73), the NPV was slightly in favor of PET/CT (77% vs. 63%, p = 0.16). Neither PET/CT nor neck MRI should stand alone for N-staging T1-T2 oral cavity cancer.

Missed cancer in the Danish head and neck cancer fast-track program: results from a tertiary cancer center.

BACKGROUND: The Danish head and neck cancer fast-track program is a national standardized pathway aiming to reduce waiting time and improve survival for patients suspected of cancer in the head and neck (HNC). Until now, the frequency of missed cancer in the fast-track program has not been addressed. A missed cancer leads to treatment delay and may cause disease progression and worsening of prognosis. The study objective was to estimate the frequency of patients with missed cancers in the Danish HNC fast-track program and to evaluate the accuracy of the program. MATERIALS AND METHODS: Patients who were rejected from the HNC fast-track program because cancer was not found between 1 July 2012 and 31 December 2018 at Odense University Hospital, Denmark were included and followed for three years. Patients were categorized into groups depending on the diagnostic evaluation. Group 1 included patients evaluated with standard clinical work-up without imaging and biopsy. Group 2 included patients evaluated with imaging and/or biopsy in addition to the standard clinical work-up. The local cancer database and electronic patient records were reviewed to determine if a missed cancer had occurred within the follow-up period. RESULTS: A total of 8345 HNC fast-track courses were initiated during the study period. 1499 were patients suspected of recurrent cancer and were excluded leaving 6846 patients to be assessed for eligibility. Of these, 3752 patients were rejected because cancer was not found. Ten patients were subsequently diagnosed with cancer within the follow-up period resulting in an overall frequency of 0.15%. For group 1 and 2, the frequency was 0.04% and 0.10%, respectively. The sensitivity of the fast-track program was 99.67% and the negative predictive value was 99.73%. CONCLUSION: The frequency of missed cancer in a tertiary HNC center following the Danish fast track program is low.

Impact of hearing aid technology level at first-fit on self-reported outcomes in patients with presbycusis: a randomized controlled trial.

To provide clinical guidance in hearing aid prescription for older adults with presbycusis, we investigated differences in self-reported hearing abilities and hearing aid effectiveness for premium or basic hearing aid users. Secondly, as an explorative analysis, we investigated if differences in gain prescription verified with real-ear measurements explain differences in self-reported outcomes. The study was designed as a randomized controlled trial in which the patients were blinded towards the purpose of the study. In total, 190 first-time hearing aid users (>60 years of age) with symmetric bilateral presbycusis were fitted with either a premium or basic hearing aid. The randomization was stratified on age, sex, and word recognition score. Two outcome questionnaires were distributed: the International Outcome Inventory for Hearing Aids (IOI-HA) and the short form of the Speech, Spatial, and Qualities of Hearing Scale (SSQ-12). In addition, insertion gains were calculated from real-ear measurements at first-fit for all fitted hearing aids. Premium hearing aid users reported 0.7 (95%CI: 0.2; 1.1) scale points higher total SSQ-12 score per item and 0.8 (95%CI: 0.2; 1.4) scale points higher speech score per item, as well as 0.6 (95%CI: 0.2; 1.1) scale points higher qualities score compared to basic-feature hearing aid users. No significant differences in reported hearing aid effectiveness were found using the IOI-HA. Differences in the prescribed gain at 1 and 2 kHz were observed between premium and basic hearing aids within each company. Premium-feature devices yielded slightly better self-reported hearing abilities than basic-feature devices, but a statistically significant difference was only found in three out of seven outcome variables, and the effect was small. The generalizability of the study is limited to community-dwelling older adults with presbycusis. Thus, further research is needed for understanding the potential effects of hearing aid technology for other populations. Hearing care providers should continue to insist on research to support the choice of more costly premium technologies when prescribing hearing aids for older adults with presbycusis. Clinical Trial Registration: https://register.clinicaltrials.gov/, identifier NCT04539847.

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.

Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 2A in Denmark 1930­2021: A Nationwide Population-Based Retrospective Study

Studies of primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 2A (MEN 2A) shows divergence in frequency, disease definition, reporting of clinical characteristics and traces of selection bias. This is a nationwide population-based retrospective study of PHPT in MEN 2A, suggesting a representative frequency, with complete reporting and a strict PHPT definition. The Danish MEN 2A cohort 1930-2021 was used. Of 204 MEN 2A cases, 16 had PHPT, resulting in a frequency of 8% (CI, 5-12). Age-related penetrance at 50 years was 8% (CI, 4-15). PHPT was seen in the American Thyroid Association moderate (ATA-MOD) and high (ATA-H) risk groups in 62% and 38% of carriers, respectively. Median age at PHPT diagnosis was 45 years (range, 21-79). A total of 75% were asymptomatic and 25% were symptomatic. Thirteen underwent parathyroid surgery, resulting in a cure of 69%, persistence in 8% and recurrence in 23%. In this first study with a clear PHPT definition and no selection bias, we found a lower frequency of PHPT and age-related penetrance, but a higher age at PHPT diagnosis than often cited. This might be affected by the Danish RET p.Cys611Tyr founder effect. Our study corroborates that PHPT in MEN 2A is often mild, asymptomatic and is associated with both ATA-MOD and ATA-H variants. Likelihood of cure is high, but recurrence is not infrequent and can occur decades after surgery.

Evaluation of Surgeon-Performed Ultrasonography With or Without Contrast Enhancement vs Scintigraphy in Patients With Primary Hyperparathyroidism.

Importance: Scintigraphy and ultrasonography are common imaging modalities for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism. When comparing the 2 modalities, the benefits of ultrasonography in terms of convenience, patient comfort, duration, cost, and lack of radiation should be taken into account. Objective: To investigate whether surgeon-performed ultrasonography, with or without contrast-enhanced ultrasonography (CEUS), is noninferior to scintigraphy for localizing pathological parathyroid glands in patients with primary hyperparathyroidism. Design, Setting, and Participants: Prospective, paired, noninferiority cohort study performed at a high-volume tertiary referral center for parathyroidectomy with blinded examiners and a 6-month follow-up. Participants were adults (age ≥18 years) referred for parathyroidectomy due to primary hyperparathyroidism. Of 207 eligible patients, 35 were excluded, leaving 172 enrolled in the study. Inclusion lasted from September 2019 until February 2021. Follow-up ended in December 2021. Exposures: 99mTechnetium-pertechnetate/99mtechnetium-sestamibi subtraction scintigraphy with 99mtechnetium-sestamibi single-photon emission computed tomography/computed tomography, followed by surgeon-performed ultrasonography and CEUS. Main Outcomes and Measures: The sensitivity of each imaging modality in localizing pathological parathyroid glands, calculated on a per-quadrant and a per-patient basis, respectively. The a priori noninferiority margin was a lower 95% confidence limit for the difference in sensitivity not falling below -10%. Results: Out of 172 participants, 139 (80.8%) were women, the median (range) age was 65 (24-87) years, and the median (IQR) follow-up was 200.5 (181-280.25) days. Quadrant sensitivity (95% CI) was 70.9% (63.2%-78.5%) for ultrasonography, 68.4% (60.4%-76.5%) for ultrasonography plus CEUS, and 67.0% (60.0%-74.0%) for scintigraphy. The sensitivity difference (95% CI) compared with scintigraphy was 3.9% (-4.1% to 11.8%) for ultrasonography and 1.5% (-6.4% to 9.3%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. Per-patient sensitivity was 81.4% (74.8%-86.9%) for ultrasonography and 79.1% (72.2%-84.9%) for both scintigraphy and ultrasonography plus CEUS. The sensitivity difference compared with scintigraphy was 2.3% (-6.8% to 11.4%) for ultrasonography and 0.0% (-9.1% to 9.1%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. Conclusions and Relevance: In this cohort study, conventional ultrasonography by an experienced parathyroid surgeon-sonographer was noninferior to scintigraphy and may constitute a valid first-line imaging modality in patients with primary hyperparathyroidism, even without the addition of CEUS. Further imaging should be reserved for cases that are equivocal or nonlocalizing on ultrasonography.

Normative Voice Range Profile of the Young Female Voice.

OBJECTIVES: Normative data are important in the clinical setting of Speech and Language Pathology. The purpose of this study was to develop a normative reference dataset of voice range profiles from young females. STUDY DESIGN: Descriptive study including a prospective collection of voice range profile data. METHODS: Voice range profile recordings from 39 females with healthy voices aged 18 to 28 years were conducted. Seven voice range profile variables were analyzed: minimum and maximum fundamental frequency and intensity, semitone and intensity ranges, and voice range profile area. Descriptive statistical methods were applied. RESULTS: An age-specific voice range profile normative dataset was established. The mean values and standard deviations were as follows: semitone range 34.7 ± 3.9 ST, minimum fundamental frequency 143.6 ± 21.7 hertz, maximum fundamental frequency 1063.5 ± 160 hertz, intensity range 65.6 ± 5.0 dB, minimum intensity 43.2 ± 2.5 dB SPL, maximum SPL 108.9 ± 5.1 dB SPL, and voice range profile area 1346 ± 222 cells. CONCLUSION: A normative dataset usable for optimization of future voice assessments has been established. It may especially benefit evaluation and treatment planning for younger females suffering from vocal fold nodules.

Inter- and Intrarater Reliability and Agreement Among Danish Head and Neck Pathologists Assessing Extranodal Extension in Lymph Node Metastases from Oropharyngeal Squamous Cell Carcinomas.

BACKGROUND: Extranodal extension (ENE) in lymph node metastases is one of the most important prognostic factors in head and neck squamous cell carcinomas. Studies have shown inconsistency among pathologists in the assessment of ENE. The aims of this study were: (1) to determine the interrater and intrarater reliability and agreement in the assessment of ENE among Danish pathologists and (2) to test if a standardized assessment method may increase interrater agreement. METHODS: Four Danish head and neck pathologists assessed ENE presence or absence in 120 histological slides from lymph nodes with oropharyngeal squamous cell carcinoma metastases (first round). Subsequently, guidelines were introduced to the pathologists and a new assessment was performed (second round). Finally, two of the pathologists assessed the slides to determine intrarater reliability and agreement (third round). RESULTS: Interrater kappa coefficients varied between 0.57 and 0.67 in the first round and between 0.59 and 0.72 in the second round. The intrarater agreement between round 2 and 3 was 0.88 for pathologist 1 and 0.92 for pathologist 2 with resulting kappa coefficients of 0.76 (95% CI 0.64-0.88) and 0.84 (95% CI 0.74-0.94), respectively. CONCLUSION: We found a moderate level of reliability and agreement among pathologists for ENE in lymph node metastases from oropharyngeal squamous cell carcinomas. The intrarater reliability and agreement was generally higher than interrater measures. Interrater agreement was slightly improved by standardized assessment.

Vocal Outcome After Cordectomy by Transoral CO2 Laser Microsurgery in Patients With Laryngeal Intraepithelial Neoplasia and Non-neoplastic Lesions.

OBJECTIVES: This study investigates vocal outcome after cordectomy by transoral CO2 laser microsurgery (TLM-cordectomy) in patients with laryngeal intra-epithelial neoplasia (LIN) or non-neoplastic lesions (NNL), for improved individual patient advice and potential adjustment of national treatment strategy by which patients suspected to have glottic LIN or T1a cancer are offered TLM-cordectomy, without prior biopsy. STUDY DESIGN: Prospective, longitudinal, quasi-experimental time series. METHODS: Consecutively included patients (n = 155) with LIN (n = 84) or NNL (n = 71) who underwent voice assessments before and after TLM-cordectomy. The multi-dimensional voice assessment protocol comprised voice and speech range profiles, aerodynamics, acoustic analysis, self-evaluated voice handicap, and perceptual auditory voice ratings. RESULTS: Median follow-up time was 195 (range 50-1121) days for patients with LIN and 193 (range 69-1294) days for patients with NNL. Statistically significant changes, LIN: in voice handicap index (VHI) and breathiness after TLM-cordectomy. Statistically significant changes, NNL: voice range profile (voice range area, intensity range, and frequency range) and VHI after TLM-cordectomy. All group-wise changes were to less disordered voices. Previous smokers had the largest decreases in VHI and breathiness. Patients with baseline VHI scores >65 had smaller increases in VHI, however 13-19% of the patients had increases in VHI above the clinically relevant threshold after TLM-cordectomy. CONCLUSION: Overall, TLM-cordectomy in patients with LIN and NNL improved vocal outcome and our study thus supports the current Danish treatment strategy and improves the basis for proper patient advice. Multi-dimensional voice assessment is suggested preoperatively and six-nine months postoperatively, with focus on individual vocal differences and voice demands.

The Impact of Post-Thyroidectomy Neck Stretching Exercises on Neck Discomfort, Pressure Symptoms, Voice and Quality of Life: A Randomized Controlled Trial.

BACKGROUND: Following surgery for benign nodular goiter, patients may experience neck and shoulder pain, neck pressure and tightness, choking sensation, altered voice function, and dysphagia leading to decreased short-term quality of life (QoL). This single-blinded randomized controlled trial investigated the effect of post-thyroidectomy rehabilitative neck stretching and movement exercises on these variables including QoL. METHODS: Patients undergoing thyroid lobectomy or total thyroidectomy were randomized to perform neck stretching and movement exercises three times daily in four weeks following surgery (intervention group) or conventional follow-up without exercises (control group). Outcome measures were scores in the following questionnaires: Disease-specific Thyroid-Related Patient-Reported Outcome (ThyPRO-39) involving symptoms of "sense of fullness in the neck," "pressure in the throat," and "discomfort swallowing" combined in the multi-item Goiter Symptom Scale, the Voice Handicap-Index-10 (VHI-10), neck and shoulder pain measurement by a numeric rating scale (NRS), and General measure of health (EQ-5D-5L). All scores were assessed prior to surgery and one, two, four weeks, and three months after surgery. Data were analyzed using a linear mixed model. RESULTS: Eighty-nine patients were included and randomized to the control (n = 45) or the intervention group (n = 44). At three months after surgery, both the control and the intervention group experienced large to moderate improvements in the Goiter symptom and Hyperthyroid symptom scale of the ThyPRO questionnaire (p < 0.004). No significant between-group differences were found in any of the other applied scales. CONCLUSIONS: This study confirms that patients experience profound improvements in QoL after surgery for benign nodular goiter. However, early post-thyroidectomy neck stretching and movement exercises did not result in further QoL improvement, reduction in pain or less impacted subjective voice function for patients primarily undergoing thyroid lobectomy. Trial Registration Number NCT04645056 ( https://clinicaltrials.gov ).

Diagnosis of possible nasopharyngeal malignancy in adults with isolated serous otitis media; a systematic review and proposal of a management algorithm.

PURPOSE: The objective of this study was (1) to systematically review the evidence of routine post-nasal space blind biopsies and/or imaging of adults with isolated serous otitis media (SOM) of unknown cause for detection nasopharyngeal malignancy (NPM), and (2) to design a clinical management algorithm for these patients. METHODS: A systematic search was conducted in the databases PubMed, Embase and Cochrane Library guided by the study question "Should adults with isolated SOM of unknown cause undergo routine biopsies of the post-nasal space and/or diagnostic imaging for detection of NPM?". All retrieved studies were reviewed and quantitatively analyzed. RESULTS: The systematic literature search identified 552 publications accessible for title-abstract screening. This yielded 23 studies for full text assessment, of which 6 were found eligible for inclusion. All six studies dealt with nasopharyngeal blind biopsies, whereas no studies on cross-sectional imaging were identified. The derived summarized results of the included studies showed that 5.5% (31/568) of patients with isolated SOM of unknown cause were diagnosed with NPM. Of these, 6.5% (2/31) had normal nasopharyngeal endoscopy (i.e., malignancy was discovered by blind biopsies). Finally, 0.35% (2/568) of patients with isolated SOM of unknown cause diagnosed with NPM had normal nasopharyngeal endoscopy findings (i.e., nasopharyngeal endoscopy ruled-out malignancy in 99.65% of patients). CONCLUSIONS: We found no evidence supporting routine use of blind biopsies or cross-sectional imaging in adults with isolated serous otitis media of unknown cause. We propose a pragmatic management algorithm for workup of adults with persistent secretory otitis media.

Nasal vestibule squamous cell carcinoma: a population-based cohort study from DAHANCA.

BACKGROUND: Cancer of the nasal vestibule is a rare type of malignancy dominated by squamous cell carcinoma (SCC), and with poor survival. The treatment is either radiotherapy, surgery or a combination of both. Previous studies have shown a 5-year disease-specific survival of 74% and overall survival (OS) of 50%.Our objective was to describe the consecutive cohort of patients diagnosed with SCC of the nasal vestibule in Denmark from 2008 until 2018 and evaluate prognostic factors and treatment outcome using locoregional failure (LRF), disease-specific mortality (DSM), and OS as endpoints. METHODS: All patients diagnosed with SCC of the nasal vestibule from 2008 until 2018 were identified in the nationwide clinical database, DAHANCA and were followed for LRF and death (DSM and OS) until March 2021. OS was analysed using Kaplan-Meier estimator, and cumulative incidence of LRF and DSM were analysed using the Aalen-Johansen estimator. Analysis of prognostic factors was performed using Cox proportional hazard models. RESULTS: A total of 162 patients were identified. The median age was 71 years and 54% were male. Disease stage at the time of diagnosis were stage I (70%), II (17%), III (2%) and IV (11%). Curatively intended treatment was performed in 146 patients (90%), of which treatment failure occurred in 42 patients (29%). Most failures occurred at the primary tumour site (64%). Cancer Patient Pathways recommended time to treatment was fulfilled in 71% of patients. The 5-year OS and DSM in patients treated with curative intent were 65% and 11%, respectively. Stage was a significant independent prognostic factor. No difference in LRF, DSM or OS were shown between the applied treatments. CONCLUSIONS: Stage is the main independent prognostic factor, and failure most commonly appear at the primary tumour site.

Multiple endocrine neoplasia type 2: A review.

Multiple endocrine neoplasias are rare hereditary syndromes some of them with malignant potential. Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome due to germline variants in the REarranged during Transfection (RET) proto-oncogene. There are two distinct clinical entities: MEN 2A and MEN 2B. MEN 2A is associated with medullary thyroid carcinoma (MTC), phaeochromocytoma, primary hyperparathyroidism, cutaneous lichen amyloidosis and Hirschprung's disease and MEN 2B with MTC, phaeochromocytoma, ganglioneuromatosis of the aerodigestive tract, musculoskeletal and ophthalmologic abnormalities. Germline RET variants causing MEN 2 result in gain-of-function; since the discovery of the genetic variants a thorough search for genotype-phenotype associations began in order to understand the high variability both between families and within family members. These studies have successfully led to improved risk classification of prognosis in relation to the genotype, thus improving the management of the patients by thorough genetic counseling. The present review summarizes the recent developments in the knowledge of these hereditary syndromes as well as the impact on clinical management, including genetic counseling, of both individual patients and families. It furthermore points to future directions of research for better clarification of timing of treatments of the various manifestations of the syndromes in order to improve survival and morbidity in these patients.

Health-Related Quality of Life, Dysphagia, Voice Problems, Depression, and Anxiety After Total Laryngectomy.

OBJECTIVES/HYPOTHESIS: The aims were to determine health-related quality of life (HRQoL), including voice problems, dysphagia, depression, and anxiety after total laryngectomy (TL), and investigate the associations between HRQoL and the late effects. STUDY DESIGN: Cross-sectional study. METHODS: 172 participants having received a TL 1.6 to 18.1 years ago for laryngeal/hypopharyngeal cancer filled in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Core and Head and Neck module (EORTC QLQ-C30, EORTC QLQ-H&N35), Voice-Related Quality of Life questionnaire (V-RQOL), M.D. Anderson Dysphagia Inventory (MDADI), and Hospital Anxiety and Depression Scale (HADS) questionnaires. RESULTS: Participants scored worse than normative reference populations on all scales/items of the EORTC questionnaires, except one, and almost half of the scales/items showed a clinically relevant difference. Moderate/severe dysphagia was present in 46%, moderate/severe voice problems in 57%, depression in 16%, and anxiety in 20%. Decreasing age, increasing numbers of comorbidities, increasing voice problems, increasing dysphagia, and increasing depression symptoms, were associated with a lowered EORTC QLQ-C30 summary score. CONCLUSION: A substantial proportion of participants experienced clinically significant late effects and increasing levels of these were associated with a lowered HRQoL. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:980-988, 2022.

Germline RET Leu56Met Variant Is Likely Not Causative of Multiple Endocrine Neoplasia Type 2.

Activating variants in the receptor tyrosine kinase REarranged during Transfection (RET) cause multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominantly inherited cancer-susceptibility syndrome. The variant c.166C>A, p.Leu56Met in RET was recently reported in two patients with medullary thyroid cancer (MTC). The presence of a pheochromocytoma in one of the patients, suggested a possible pathogenic role of the variant in MEN 2A. Here, we present clinical follow up of a Danish RET Leu56Met cohort. Patients were evaluated for signs of MEN 2 according to a set of predefined criteria. None of the seven patients in our cohort exhibited evidence of MEN 2. Furthermore, we found the Leu56Met variant in our in-house diagnostic cohort with an allele frequency of 0.59%, suggesting that it is a common variant in the population. Additionally, none of the patients who harbored the allele were listed in the Danish MTC and MEN 2 registries. In conclusion, our findings do not support a pathogenic role of the Leu56Met variant in MEN 2.