Christian Grønhøj

Association between Hashimoto’s Thyroiditis and Thyroid Cancer in 64,628 Patients

Background The incidence of thyroid cancer (TC) is increasing although explanatory causes are lacking. A link between cancer and inflammation is well documented but unclear for autoimmune thyroid diseases and TC. We aimed to systematically review the association between Hashimoto’s thyroiditis (HT) and papillary, follicular, medullary, anaplastic thyroid carcinoma, and thyroid lymphoma (TL). Methods PubMed, OVID Medline, Google Scholar, and the Cochrane Library were searched from 1955 to 2016. The inclusion criteria were age >18 years, ≥20 cases of HT or TC. We collectively examined the incidence of HT in TC and of TC in HT. Results We identified 36 studies (64,628 subjects) published between 1955 and 2016 from 13 countries. We found a relative risk (RR) of HT among papillary thyroid cancer (PTC) of 2.36 [95% confidence intervals (CIs) 1.55–3.29, p < 0.001], an RR of PTC among HT of 1.40 (95% CI 1.07–1.85, p = 0.016), and an RR of TL among HT of 9.74 (95% CI 3.93–24.13, p < 0.001). Conclusion We report an association between HT and PTC and between HT and TL. No association was found between HT and follicular, medullary, or anaplastic thyroid cancer.

First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial

BackgroundSalivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia.MethodsThis is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention.DiscussionThe trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials.Trial registrationEudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015.ClinicalTrials.gov, Identifier: NCT02513238. First received on 2 July 2015.The trial is prospectively registered.

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

Abstract 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.

Increasing incidence and survival of head and neck cancers in Denmark: a nation-wide study from 1980 to 2014

Abstract Background: The purpose of the study was to determine trends in age-adjusted incidence rates (AAIR) and survival probability in head and neck cancers (HNCs) in the Danish population from 1980 to 2014. Material and methods: All patients registered with HNC in the nationwide Danish Cancer Registry from 1980 to 2014 were included. We evaluated the AAIR per 100,000 and the average annual percent change (AAPC). The relative survival probability at 5 years was calculated in relation to gender, anatomical location and histology, and we constructed age-period-cohort models of incidence. Results: About 34,606 patients were included (64.7% men). The AAIR increased from 9.1 per 100,000 in 1980 to 17.4 per 100,000 in 2014 with an AAPC of 2.1%. The greatest incidence increase was observed in oropharyngeal cancer (AAPC: 5.4%) followed by hypopharyngeal cancer (AAPC: 4.2%). Adenocarcinomas had the highest AAPC (5.0%) followed by squamous cell carcinomas (AAPC: 2.0%). The AAPC was significantly higher in women (2.4%) compared with men (1.6%). For all HNC patients, the relative survival at 5 years rose significantly from 49.0% in 1980–1984 to 62.4% in 2010–2014. Women had a significantly higher survival than men with a relative survival of 61.7% compared to 50.0% in men. Laryngeal cancer had the best survival probability of cancers in the upper aerodigestive tract with hypopharyngeal cancer having the poorest survival. Conclusion: This nation-wide study showed a significant rise in incidence of HNC for men and women along with a significant increase in relative survival. Oropharyngeal cancer had the highest increase in incidence followed by hypopharyngeal cancer which showed the poorest survival of HNCs.

Incidence of head and neck cancer in children: A Danish nationwide study from 1978 to 2014

Pediatric head and neck malignancies are rare and only a few descriptive epidemiological studies have been published. Using unique nationwide registries, we report age‐specific incidence rates of head and neck cancer (HNC) among children during four decades.

Cause-specific mortality in HPV+ and HPV− oropharyngeal cancer patients: insights from a population-based cohort

Identifying the causes of death in head and neck cancer patients can optimize follow‐up and therapeutic strategies, but studies in oropharyngeal squamous cell carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause‐specific mortality in a population‐based cohort of patients with OPSCC. Patients who had been diagnosed with OPSCC (n = 1541) between 2000 and 2014 in eastern Denmark were included in the study. Causes of death were collected through medical files and the Danish National Cause of Death registry. Deaths were grouped as (1) primary oropharyngeal cancer, (2) secondary malignancies, (3) cardiovascular and pulmonary disease, or (4) other/unspecified. The cumulative incidence of death and specific causes of death were determined using risk analysis. At follow‐up, 723 (47.5%) patients had died. The median time to and cause of death were determined: oropharyngeal cancer (n = 432; 1.00 year), secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16 status was the strongest predictor of improved survival across all causes of death. The only cause of death to decrease in incidence over the 2 years after treatment was death from OPSCC. HPV/p16 positivity was an independent factor for improved survival across all causes of death in patients with OPSCC. In addition, both HPV‐positive and HPV‐negative OPSCC patients faced high 5‐ and 10‐year mortality rates. Implementing secondary screening and prevention strategies for late toxicity and mortality are major goals in managing the treatment of these patients.

Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)

BackgroundThe proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries.MethodsConsecutive OPSCC patients treated in Denmark, 2000–2014 formed the development cohort. The validation cohorts were from Sweden, Germany, and the United Kingdom. We developed nomograms by applying a backward-selection procedure for selection of variables, and assessed model performance.ResultsIn the development cohort, 1313 patients, and in the validation cohorts, 344 German, 503 Swedish and 463 British patients were included. For the OS nomogram, age, gender, combined HPV-DNA and p16 status, smoking, T-, N-, and M-status and UICC-8 staging were selected, and for the PFS nomogram the same variables except UICC-8 staging. The nomograms performed well in discrimination and calibration.ConclusionsOur nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org.

Indications, risk of lower airway infection, and complications to pediatric tracheotomy: report from a tertiary referral center

Abstract Background: Although pediatric tracheotomy is potentially life-saving, the procedure is associated with high risk of complications, and indications have changed the last decade. We report indications, complications, and lower airway infections (LAIs) to pediatric tracheotomy performed at a tertiary referral center. Methods: We identified all children (<18 years) who underwent tracheotomy at our institution during 2008–2015. A review of hospital records was performed to extract data on indication of the procedure, complications, and information on pre- and postoperative LAI. Results: At a median age of 8 years (range: 4 months to 17 years), a total of 69 tracheotomies were performed. Neuromuscular disease (n = 21) was the most common cause for tracheotomy. The postoperative complication rate was 22%; early complications (<30 days) occurred in four patients, and nine patients encountered late complications such as wound granulation and tracheocutaneous fistula. Children without LAI prior to tracheotomy were at increased risk of LAI from the initial 30-days following surgery (OR: 2.91, 95% CI: 1.17–7.21; p = .02). Fifty-three percent (10/19) of all LAIs following tracheotomy were caused by Staphylococcus aureus (p < .01). Conclusions: Pediatric tracheotomy was associated with considerable rates of minor early and late complications and high risk of short-term LAI. The main cause leading to tracheotomy was neuromuscular disease.

Incidence and survival of oropharyngeal cancer in Denmark: a nation-wide, population-based study from 1980 to 2014

Abstract Background: Oropharyngeal carcinomas (OPCs) constitute a significant and increasing proportion of head and neck carcinomas and are an important global cause of morbidity and mortality. The purpose of this study was to determine trends in incidence and survival in OPC in the Danish population from 1980 to 2014. Methods: This study included all patients registered in the nationwide Danish Cancer Registry over the period 1980–2014. The age-adjusted incidence rates (AAIR) per 100,000, annual percentage change (APC) and average annual percent change (AAPC) were evaluated. Five-year relative survival (RS) was calculated with Cox regression analyses in relation to gender, anatomical location and histology. Results: A total of 6555 patients (69% male) were included, with a median age at diagnosis of 60 years. The AAIR of patients with OPC increased from 0.815 per 100,000 in 1980 to 4.51 per 100,000 in 2014 with an AAPC of 5.3. The 5-year RS increased significantly from 33.1% over the period 1980–1984 to 58.5% (25.4% points) over the period 2010–2014. With no significant difference stratified for gender. Tumors located at the palatine tonsils (n = 3333) and salivary gland OPC (n = 90) had significantly better survival compared with other sub-locations and histology subtypes. In the APC model the birth cohort effect rate ratio increased until 1925 and then decreased until 1935 from which point it increased in the last cohorts. Conclusions: In this population-based study, we observed a significant increase in the incidence of OPCs and in the RS for OPC. We also identified a profound birth cohort effect on the incidence.

Pattern of and survival following loco-regional and distant recurrence in patients with HPV+ and HPV− oropharyngeal squamous cell carcinoma: A population-based study

OBJECTIVES The incidence of human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (OPSCC) is increasing. Currently, data is sparse on the pattern and timing of recurrence. This long-term study concerning both HPV- and p16-status aimed to report predictive factors, pattern, timing of loco-regional recurrence (LRR) and distant recurrence (DR), and survival following recurrence in patients diagnosed with OPSCC. MATERIAL AND METHODS We included patients diagnosed with OPSCC from 2000 to 2014 in Eastern Denmark, who were treated with curative intent. Tumors were defined as HPV-positive when they were both HPV-DNA and p16-positive. Time-to-failure and -death were estimated by the Kaplan-Meier method. Cox proportional hazards models were used to evaluate predictors of failure. RESULTS The cohort consisted of 1244 consecutive patients with OPSCC of which 288 patients (23%) experienced recurrence. Of these patients, the majority (n = 197/1244; 16%) experienced LRR and the remaining (n = 91/1244; 7%) DR. Significantly more HPV-negative patients experienced recurrence (n = 170/486; 35%) compared to HPV-positive patient (n = 112/726; 15%). DR occurred for both groups predominantly to the lung (n = 63/91; 69.2%) followed by the liver and bone. Factors influencing risk of LRR included gender, T-classification, and HPV-status. The same variables influenced risk of DR in addition to the UICC-8 classification, N-classification, pack years of smoking, and performance status. HPV-status was the strongest risk factor for LRR and DR. CONCLUSION LRR and DR occur significantly less often in HPV-positive patients compared with HPV-negative patients. HPV-status is an independent and strong predictor of recurrence. DR most commonly occurs to the lungs, irrespective of HPV-status.