Sinonasal mucosal melanoma in The Netherlands between 2001 and 2021: a clinical and epidemiological overview of 320 cases.

PURPOSE: Sinonasal mucosal melanoma (SNMM) is a rare malignancy, characterised by high (local) recurrence rates and poor survival. Comprehensive understanding of tumour etiology is currently lacking, which complicates adequate tumour treatment. Besides examining trends in incidence, this study aims to assess the association between clinical characteristics, treatment practices and patient outcomes, with the objective of establishing a baseline from which SNMM management can be enhanced. METHODS: All newly diagnosed SNMM cases in The Netherlands between 2001 and 2021 were included using data from The Netherlands Cancer Registry (NCR). RESULTS: A total of 320 patients were included. The annual incidence rate for the overall population was stable over the inclusion period with an annual percentage change (APC) of only - 0.01%. The 5-year overall survival (OS) and relative survival (RS) were 24.5 and 32.4%, respectively. Relative survival did not increase over time. The addition of adjuvant radiotherapy to surgery was not associated with a higher OS and RS compared to surgery alone. CONCLUSION: Sinonasal mucosal melanoma is a rare disease with stable incidence rates in the Netherlands between 2001 and 2021. There has been no improvement in survival over the course of the inclusion period. The study reaffirms that adjuvant radiotherapy does not seem to improve patient outcomes. Given the generally poor outcomes for SNMM patients, novel therapeutic options ought to be considered in order to improve care.

The outcome of treatment in differentiated thyroid cancer according to recommendations in current Dutch and American guidelines.

OBJECTIVE: Assessment of treatment outcome in current de-escalation for differentiated thyroid cancer (DTC) according to the 2015 Dutch thyroid cancer guidelines (NL-15) and American Thyroid Association guidelines (ATA-15). DESIGN: Retrospectively, the recommendations of the NL-15 and ATA-15 guidelines were evaluated to estimate potentially adequate, under- and overtreatment of DTC in patients treated in the University Medical Center Groningen between 2007 and 2017. PATIENTS: A total of 240 patients with a cT1-T3aN0-1aM0 DTC fulfilled the inclusion criteria. MEASUREMENTS: After actual treatment was given, patients were again categorized according to both guidelines into low, intermediate, or high-risk based on tumour status. Next, they were categorized into a congruent low-risk (n = 60), congruent high-risk (n = 73), or incongruent risk group (n = 107). Follow-up data were used to estimate the proportion of potentially adequate, under-, and overtreatment according to both guidelines. RESULTS: Comparing treatment recommended by NL-15 and ATA-15 showed significantly more over- and adequate treatment when following NL-15 recommendations, and more undertreatment following ATA-15 (all: p < .001). Subanalysis of the congruent low-risk group showed overtreatment in 64% when following NL-15 guidelines (p < .001). No treatment differences were found in the congruent high-risk group. Undertreatment was most often seen in the incongruent risk group when following ATA-15 (p < .001). CONCLUSIONS: Low-risk patients were treated too aggressively when following NL-15 recommendations, where the less aggressive ATA-15 approach seemed more adequate. Treatment of intermediate risk DTC patients varies greatly, with a relative higher rate of undertreatment according to the recommendations of the ATA-15, advocating further refining of the risk classification in this patient group.

The relation between hypoxia and proliferation biomarkers with radiosensitivity in locally advanced laryngeal cancer.

PURPOSE: Treatment decision-making in advanced-stage laryngeal squamous cell carcinoma (LSCC) is difficult due to the high recurrence rates and the desire to preserve laryngeal functions. New predictive markers for radiosensitivity are needed to facilitate treatment choices. In early stage glottic LSCC treated with primary radiotherapy, expression of hypoxia (HIF-1α and CA-IX) and proliferation (Ki-67) tumour markers showed prognostic value for local control. The objective of this study is to examine the prognostic value of tumour markers for hypoxia and proliferation on locoregional recurrent disease and disease-specific mortality in a well-defined cohort of patients with locally advanced LSCC treated with primary, curatively intended radiotherapy. METHODS: In pre-treatment biopsy tissues from a homogeneous cohort of 61 patients with advanced stage (T3-T4, M0) LSCC primarily treated with radiotherapy, expression of HIF-1α, CA-IX and Ki-67 was evaluated with immunohistochemistry. Demographic data (age and sex) and clinical data (T- and N-status) were retrospectively collected from the medical records. Cox regression analysis was performed to assess the relation between marker expression, demographic and clinical data, and locoregional recurrence and disease-specific mortality. RESULTS: Patients with high expression of HIF-1α developed significantly more often a locoregional recurrence (39%) compared to patients with a low expression (21%) (p = 0.002). The expression of CA-IX and Ki-67 showed no association with locoregional recurrent disease. HIF-1α, CA-IX and Ki-67 were not significantly related to disease-specific mortality. Clinical N-status was an independent predictor of recurrent disease (p < 0.001) and disease-specific mortality (p = 0.003). Age, sex and T-status were not related to locoregional recurrent disease or disease-specific mortality. CONCLUSION: HIF-1α overexpression and the presence of regional lymph node metastases at diagnosis were independent predictors of locoregional recurrent disease after primary treatment with curatively intended radiotherapy in patients with locally advanced LSCC.

Association of histological features with laryngeal squamous cell carcinoma recurrences: a population-based study of 1502 patients in the Netherlands.

BACKGROUND: Recurrences remain an important problem in laryngeal squamous cell carcinoma. Little has been described about histological characteristics of the primary laryngeal tumor that may be associated with recurrences. Identifying risk factors for recurrences might help in adapting treatment or follow-up. Using real-life population-based data, we aimed to identify histological features of the primary tumor associated with recurrences and overall survival. MATERIAL AND METHODS: Demographic, clinical and treatment information on all first primary invasive laryngeal tumors diagnosed in 2010-2014 (N = 3705) were extracted from the population-based nationwide Netherlands cancer registry (NCR) and linked to PALGA, the nationwide Dutch pathology registry, to obtain data on histological factors and recurrences. For a random 1502 patients histological information i.e., keratinization, perineural invasion (PNI+), vascular invasion (VI+), growth pattern, degree of differentiation, extracapsular spread (ECS+), cartilage- and bone invasion and extralaryngeal extension, was manually extracted from narrative pathology reports and analyzed for locoregional recurrence and overall survival using cox regression analysis. RESULTS: In total, 299 patients developed a locoregional recurrence and 555 patients died. Keratinization (HR = 0.96 (95%CI: 0.68-1.34) p = 0.79), two or three adverse characteristics (PNI+, VI+, non-cohesive growth) (HR = 1.38 (95% CI: 0.63-3.01) p = 0.42), and ECS+ (HR = 1.38 (95% CI: 0.48-4.02) p = 0.55) were not associated to recurrence. For death, also no significant association was found. CONCLUSION: In this population-based real-life dataset on laryngeal carcinoma in the Netherlands, histological factors were not associated with locoregional recurrences or overall survival, but future studies should investigate the role of these features in treatment decisions.

Age-related Differences in Tumour Characteristics and Prognostic Factors for Disease Progression in Cutaneous Squamous Cell Carcinoma of the Head and Neck.

Guidelines for cutaneous squamous cell carcinoma of the head and neck do not take the age of the patient into account, but instead assume equal tumour characteristics and prognostic factors for poor outcome in younger and elderly patients. The aim of this study was to compare tumour characteristics of younger (< 75 years) and elderly (≥ 75 years) patients and identify age-specific risk factors for progression of disease, comprising local recurrence, nodal metastasis and distant metastasis. Patient and tumour characteristics were compared using χ2 or Fisher's exact tests. Multivariable competing risk analyses were performed to compare risk factors for progression of disease, incorporating the risk of dying before developing progression of disease. A total of 672 patients with primary cutaneous squamous cell carcinoma of the head and neck were retrospectively included. Larger tumour diameter, worse differentiation grade and deeper invasion were observed in older patients. In elderly patients, but not in younger patients, tumour diameter ≥ 40 mm, moderate differentiation grade and an invasion depth ≥ 2 mm were independent risk factors for progression of disease.

The effect of treatment delay on quality of life and overall survival in head and neck cancer patients.

OBJECTIVE: Head and neck squamous cell carcinomas (HNSCC) are rapidly developing tumours, and substantial delay in treatment initiation is associated with decreased overall survival. The effect of delay on health-related quality of life (HRQOL) is unknown. The aim of this study was to assess the impact of delay on QOL and overall survival. METHODS: Patients with mucosal HNSCC were prospectively included. HRQOL and 2-year overall survival were analysed using linear mixed-model analyses and cox regression, respectively. Delay was defined as care pathway interval (CPI) of ≥30 days between first consultation and treatment initiation. RESULTS: Median CPI was 39 days for the 173 patients included. A trend towards higher HRQOL-scores (indicating better HRQOL) during 2-year follow-up for patients with delay in treatment initiation was visible in the adjusted models (HRQOL summary score-ß: 2.62, 95% CI: 0.57-4.67, p = 0.012). Factors associated with decreased overall survival were moderate comorbidities (HR: 5.10, 95% CI: 1.65-15.76, p = 0.005) and stage-IV tumours (HR: 12.37, 95% CI: 2.81-54.39, p = 0.001). Delay was not associated with worse overall survival. CONCLUSION: Timely treatment initiation is challenging, especially for patients with advanced tumours and initial radiotherapy treatment. Encountering delay in treatment initiation did not result in clinically relevant differences in HRQOL-scores or decreased overall survival during 2-year follow-up.

Determinants of delay in the head and neck oncology care pathway: The next step in value-based health care.

OBJECTIVE: Head and neck squamous cell carcinomas (HNSCC) are relatively fast-growing tumours, and delay of treatment is associated with tumour progression and adverse outcomes. The aim of this study is to identify determinants of delay in a head and neck oncology centre. METHODS: This cohort study with prospectively collected data investigated associations between patient (including geriatric assessment at first consultation), tumour and treatment characteristics and treatment delay. Two quality indicator intervals assessing value-based healthcare were studied: care pathway interval (CPI, interval between first visit in an HNOC and treatment initiation) and time-to-treatment initiation (TTI, interval between histopathological confirmation of HNSCC and treatment initiation), using regression analyses. RESULTS: Stage-IV tumours and initial radiotherapy were independent predictors of delay in CPI. Initial radiotherapy was associated with delay in TTI. Overall, 37% of the patients started treatment within 30 days after first consultation (67% in case of initial surgical treatment and 11.5% if treated with (chemo)radiation, p < 0.001). Geriatric assessment outcomes were not associated with delay. Indicators for delay in initial surgery patients were stage-IV tumours (CPI). CONCLUSION: The majority of HNSCC patients encounter delay in treatment initiation, specifically in patients with advanced-stage tumours or when radiotherapy is indicated.

Predictors for distant metastasis in head and neck cancer, with emphasis on age.

PURPOSE: Distant metastasis (DM) in patients with head and neck squamous cell carcinoma (HNSCC) is uncommon, but strongly deteriorates prognosis. Controversy exists regarding age as a predictor for the presence and development of DM. The aim of this study was to investigate age and other predictors for DM in HNSCC patients. METHODS: From 1413 patients diagnosed with a primary HNSCC between 1999 and 2010 in a tertiary referral centre, patient, disease and pathological characteristics were extracted from patient files. Uni- and multivariable Cox regression analyses were performed to identify risk factors for DM as primary outcome. RESULTS: DM occurred in 131 (9.3%) patients, of which 27 (1.9%) were diagnosed simultaneously with the primary tumour, 27 (1.9%) were diagnosed synchronous, and 77 (5.4%) were diagnosed metachronous. The most common site of DM was lung (51.1%), followed by bone (19.1%) and liver (11.5%). Multivariable analysis identified male gender (HR = 1.95, 95% CI 1.23-3.10) hypopharyngeal tumours (HR = 3.28, 95% CI 1.75-6.14), advanced T-stage (HR = 1.61, 95% CI 1.09-2.38), poor differentiation grade (HR = 2.49, 95% CI 1.07-5.78), regional lymph node metastasis (HR = 5.35, 95% CI 3.25-8.79) and extranodal extension of regional lymph nodes metastasis (HR = 3.06, 95% CI 1.39-6.72) as independent prognostic factors for the presence or development of DM. No relation with age was found. CONCLUSION: Age is not related to the presence or development of DM. This study emphasizes the importance of screening for DM, especially in males, patients with hypopharyngeal tumours, advanced T-stage, histopathological poor differentiation grade, regional lymph node metastasis and extranodal extension.

Surgical Complications and Referral Patterns in 567 Patients with Differentiated Thyroid Cancer in the Northern Region of the Netherlands: A Population-Based Study Towards Clinical Management Implementation.

BACKGROUND: In the Netherlands, differentiated thyroid cancer (DTC) is treated surgically in three different hospital types, including university, teaching, and non- teaching peripheral hospitals. This study evaluates postoperative complications and referral patterns in patients with DTC in the northern region of the Netherlands to gain an understanding on how to improve management implementation. METHODS: Data from 567 patients diagnosed between 1989 and 2009 were obtained from the Netherlands Cancer Registry and were supplemented with information from hospital digital information systems and patient records from 15 hospitals: 1 university, 3 teaching, and 11 peripheral hospitals. Surgically treated patients with a histologically proven DTC derived from the original pathology reports were included. RESULTS: Surgical treatment could be performed in a single procedure in 234 patients (41.3%), but several surgeries were needed in the remaining 333 patients (58.7%). Recurrent laryngeal nerve (RLN) palsy occurred after all types of thyroid surgical procedures, but mostly after initial (hemi)thyroidectomy and reoperations. RLN was temporary in 3.2% of the nerves at risk and persistent in 1.8%. Temporary hypocalcemia developed in 13.7% of patients, and persistent hypocalcemia occurred in 4.8%. Patients were mainly referred to the university hospital from a non-teaching (40.7%, 48/118) or teaching hospital (11.1%, 16/144); however, 80% of patients were not referred. CONCLUSIONS: The complication rate and number of multiple surgeries support the efforts in optimizing clinical management in thyroid cancer. Careful considerations prior to initial surgical treatment by early discussion in telemedicine-based regional tumor boards could possibly prevent reoperations and potentially diminish complications.

Is C-11 Methionine PET an alternative to 18-F FDG-PET for identifying recurrent laryngeal cancer after radiotherapy?

OBJECTIVE: 18F FDG-PET is superior to other imaging techniques in revealing residual laryngeal cancer after radiotherapy. Unfortunately, its specificity is low, due to FDG uptake in inflammation and in anaerobic conditions. PET imaging with the amino acid-based radiopharmaceutical C11-methionine (MET) should be less influenced by post-radiation conditions. The aim of this study was to investigate the potential of MET in diagnosing recurrent laryngeal cancer after radiotherapy as compared to 18F-FDG. METHODS: Forty-eight patients with a clinical suspicion of local residual disease at least 3 months after completion of radiotherapy or chemoradiotherapy for a T2-4 laryngeal carcinoma, along with an indication for direct laryngoscopy, were included. They received MET-PET and FDG-PET prior to the direct laryngoscopy. One senior nuclear medicine physician assessed both the FDG-PET and MET-PET images visually for the degree of abnormal uptake. The gold standard was a biopsy-proven recurrence 12 months after PET. The nuclear physician had no access to the medical charts and was blinded to the results of the other PET. Sensitivity, specificity and positive and negative predictive value were calculated. RESULTS: The sensitivity of FDG was 77.3% and the specificity 56.0% after the conservative reading, with these values equalling 54.5% and 76.0% for MET. The positive predictive value of FDG was 60.7% and the negative predictive value 73.7%. The PPV of MET was 66.7%, and the NPV was 65.5%. The McNemar test within diseased (sensitivity comparison) shows a p-value of 0.125, and the McNemar test within non-diseased (specificity comparison) shows a P-value of 0.180. CONCLUSION: MET-PET is not superior to FDG-PET in terms of identifying recurrent laryngeal cancer.

Variation in Integrated Head and Neck Cancer Care: Impact of Patient and Hospital Characteristics.

Background: Monitoring and effectively improving oncologic integrated care requires dashboard information based on quality registrations. The dashboard includes evidence-based quality indicators (QIs) that measure quality of care. This study aimed to assess the quality of current integrated head and neck cancer care with QIs, the variation between Dutch hospitals, and the influence of patient and hospital characteristics. Methods: Previously, 39 QIs were developed with input from medical specialists, allied health professionals, and patients' perspectives. QI scores were calculated with data from 1,667 curatively treated patients in 8 hospitals. QIs with a sample size of >400 patients were included to calculate reliable QI scores. We used multilevel analysis to explain the variation. Results: Current care varied from 29% for the QI about a case manager being present to discuss the treatment plan to 100% for the QI about the availability of a treatment plan. Variation between hospitals was small for the QI about patients discussed in multidisciplinary team meetings (adherence: 95%, range 88%-98%), but large for the QI about malnutrition screening (adherence: 50%, range 2%-100%). Higher QI scores were associated with lower performance status, advanced tumor stage, and tumor in the oral cavity or oropharynx at the patient level, and with more curatively treated patients (volume) at hospital level. Conclusions: Although the quality registration was only recently launched, it already visualizes hospital variation in current care. Four determinants were found to be influential: tumor stage, performance status, tumor site, and volume. More data are needed to assure stable results for use in quality improvement.

Trends in treatment, incidence and survival of hypopharynx cancer: a 20-year population-based study in the Netherlands.

Hypopharynx cancer has the worst prognosis of all head and neck squamous cell cancers. Since the 1990s, a treatment shift has appeared from a total laryngectomy towards organ preservation therapies. Large randomized trials evaluating treatment strategies for hypopharynx cancer, however, remain scarce, and frequently this malignancy is evaluated together with larynx cancer. Therefore, our aim was to determine trends in incidence, treatment and survival of hypopharynx cancer. We performed a population-based cohort study including all patients diagnosed with T1-T4 hypopharynx cancer between 1991 and 2010 in the Netherlands. Patients were recorded by the national cancer registry database and verified by a national pathology database. 2999 patients were identified. The incidence increased significantly with 4.1% per year until 1997 and decreased non-significantly afterwards. For women, the incidence increased with 1.7% per year during the entire study period. Total laryngectomy as primary treatment significantly decreased, whereas radiotherapy and chemoradiation increased. The 5-year overall survival significantly increased from 28% in 1991-2000 to 34% in 2001-2010. Overall survival for T3 was equal for total laryngectomy and (chemo)radiotherapy, but for T4-patients the survival was significantly better after primary total laryngectomy (± adjuvant radiotherapy). This large population-based study demonstrates a shift in treatment preference towards organ preservation therapies. The 5-year overall survival increased significantly in the second decade. The assumed equivalence of organ preservation and laryngectomy may require reconsideration for T4 disease.

Feedback preferences of patients, professionals and health insurers in integrated head and neck cancer care.

BACKGROUND: Audit and feedback on professional practice and health care outcomes are the most often used interventions to change behaviour of professionals and improve quality of health care. However, limited information is available regarding preferred feedback for patients, professionals and health insurers. OBJECTIVE: Investigate the (differences in) preferences of receiving feedback between stakeholders, using the Dutch Head and Neck Audit as an example. METHODS: A total of 37 patients, medical specialists, allied health professionals and health insurers were interviewed using semi-structured interviews. Questions focussed on: "Why," "On what aspects" and "How" do you prefer to receive feedback on professional practice and health care outcomes? RESULTS: All stakeholders mentioned that feedback can improve health care by creating awareness, enabling self-reflection and reflection on peers or colleagues, and by benchmarking to others. Patients prefer feedback on the actual professional practice that matches the health care received, whereas medical specialists and health insurers are interested mainly in health care outcomes. All stakeholders largely prefer a bar graph. Patients prefer a pie chart for patient-reported outcomes and experiences, while Kaplan-Meier survival curves are preferred by medical specialists. Feedback should be simple with firstly an overview, and 1-4 times a year sent by e-mail. Finally, patients and health professionals are cautious with regard to transparency of audit data. CONCLUSIONS: This exploratory study shows how feedback preferences differ between stakeholders. Therefore, tailored reports are recommended. Using this information, effects of audit and feedback can be improved by adapting the feedback format and contents to the preferences of stakeholders.

Trends in oral cavity cancer incidence, mortality, survival and treatment in the Netherlands.

Information on epidemiology is essential to evaluate care for the growing group of oral cancer patients. We investigated trends in incidence, mortality and relative survival rates for oral cavity cancer (OCC) and its subsites in the Netherlands from 1991 to 2010, and relate these to changes in stage and treatment. Patient (age, sex), tumour (subsite, stage) and treatment characteristics of patients diagnosed with OCC (ICD-O-3: C02-C06) in 1991-2010 were extracted from the Netherlands Cancer Registry. Incidence, mortality and 5-year relative survival rates over time are presented, as well as trends in type of treatment. The incidence of OCC increased with +1.2% (95%CI: +0.9%;+1.6%) per year: more strongly in women, stage I and IV disease, and in cancers of the tongue and gum. The mortality rate slightly rose (+0.8%, 95%CI: +0.3%;+1.3% per year), but differed by subsite. The 5-year relative survival improved from 57% in 1991-1995 to 62% in 2006-2010. The 5-year relative survival was better for women compared with men (64% and 55%, respectively), decreased with increasing stage, was the best for tongue cancer (63%) and the worst for cancer of the gum (56%) and floor of mouth cancer (55%). The relative excess risk of dying was higher for non-surgery-based treatments. Surgery was the main treatment option and the proportion of "surgery only" rose in stage I and III disease. The incidence and, to a lesser extent, mortality of OCC are increasing and therefore, even with slightly improving survival rates, OCC is an increasingly important health problem.

Free flap reconstruction for head and neck cancer can be safely performed in both young and elderly patients after careful patient selection.

Surgical treatment of head and neck cancer often results in complex defects requiring reconstruction with microvascular free tissue transfer. However, in elderly patients, curative treatment with radical surgery and free flap reconstruction is often withheld. The objective of this study is to assess the outcomes of free flap surgery in elderly patients, using a standard surgical complication classification system. A retrospective review was conducted of patients who underwent primary free flap reconstruction following major surgery for head and neck cancer between 1995 and 2010. Complications were assessed using the Clavien Dindo classification system, and grades III-V were classified as major complications. Comorbidity was classified according to the adult comorbidity evaluation index 27. A comparison was done between patients <70 and ≥70 years. Two hundred-two patients were included in this study. Multivariate analysis showed that only disease stage was a significant predictor of recipient site complications, and comorbidity was the only significant predictor of medical complications. Age was not a predictor of complications. There were no significant differences in disease specific or overall survival between young and elderly patients. Optimal patient selection for free flap surgery is essential. This requires thorough pre-operative assessment, including analysis of comorbidity in both young and elderly patients. Patients' biological age, and not chronological age, should be individually determined to assess feasibility of major surgery. Patients should not be denied surgery based on age alone.

Progress against laryngeal cancer in The Netherlands between 1989 and 2010.

Cancer of the larynx is a frequently occurring head and neck cancer in The Netherlands. The main risk factors are smoking and excessive alcohol consumption. The aim of our study was to evaluate the progress against laryngeal cancer by studying trends in incidence, mortality and survival in The Netherlands. All patients in The Netherlands Cancer Registry diagnosed with invasive primary squamous cell carcinoma of the larynx during the period 1989-2010 were included for analysis. Time trends in incidence, mortality, treatment and survival were described for the total group and stratified by sex and subsite: glottis, supraglottis and subglottis. The most frequently affected subsite for men was the glottis (69%) and for women the supraglottis (55%). Glottic cancer was diagnosed at lower stages than supraglottic cancer. Incidence and mortality rates decreased for males with -2.5 and -2.8% per year, respectively, but remained stable for women, except for an increasing mortality rate in older women (EAPC: +2.5%). Five-year relative survival rates were stable for glottic (85%) and supraglottic (50%) cancer, whereas patients with high-staged cancers more often received radiotherapy. Multivariable analysis showed lower relative excess risks of dying for women, younger patients (<75 years), glottic cancer, lower stage cancer and those undergoing surgery. Changes in incidence and mortality rates are in line with changing smoking habits in The Netherlands. Declining incidence with stable survival rates gives rise to hope and worry at the same time.

Relation between age, comorbidity, and complications in patients undergoing major surgery for head and neck cancer.

BACKGROUND: Multiple factors have been identified as predictors of complication after head and neck surgery. However, little is known about the exact role of different comorbid conditions in the development of postoperative complications. This question is especially interesting in the elderly population. The aim of this study was to investigate the association between comorbidity and types of postoperative complications with special attention to age differences. METHODS: A retrospective analysis was performed of 1,201 major surgical interventions for head and neck malignancies in a tertiary referral center between 1995 and 2010. The Adult Comorbidity Evaluation 27 (ACE-27) index was used to analyze severity (mild, moderate, and severe comorbidity) and type (12 different organ systems) of comorbidity. The Clavien-Dindo index was used to evaluate grade and type of complications after treatment. RESULTS: In univariate analysis gender, comorbidity, stage, mandibulectomy, total laryngectomy, neck dissection, and length of surgery significantly predicted grade of complication. In a multivariate analysis, complication was predicted by age, stage, length of surgery, and various comorbidities. After specification of the complications, age was only a predictor of medical complications; tumor stage was a significant factor in surgical complications. Length of surgery was the only significant variable in all types of complications. CONCLUSIONS: Specific comorbidities are associated with specific complications; however, age itself seems not to be a contraindication for major head and neck surgery. With careful preoperative assessment and risk analysis, physicians can better individualize treatment recommendations.

Chronic Stress Related to Cancer Incidence, including the Role of Metabolic Syndrome Components.

Epidemiological results on the link between chronic stress and cancer initiation have been inconsistent. This study examined the relation between chronic biological stress, indicated as hair cortisol (HairF) and hair cortisone (HairE), and cancer incidence, adjusting for metabolic syndrome (MetS) components. We analyzed HairF and HairE samples from 6341 participants from the population-based cohort Lifelines in 2014. A linkage with the Dutch Nationwide Pathology Databank (Palga) provided the cancer incidence from 2015 to 2021. The association between dichotomized HairF and log-transformed HairE (LogHairE) and cancer incidence was estimated using Cox regression. MetS components were evaluated as confounders or moderators. Of the 2776 participants with known HairF levels and no cancer history, 238 developed cancer. The HairF level did not predict cancer incidence (HR: 0.993, 95%CI: 0.740-1.333). No confounders or moderators were identified. Among the 4699 participants with known HairE levels and no cancer history, 408 developed cancer. There was no association between LogHairE and cancer incidence (HR: 1.113, 95%CI: 0.738-1.678). When including age as a confounder and gender as a moderator, LogHairE was statistically significantly associated with cancer incidence (HR: 6.403, 95%CI: 1.110-36.92). In a population-based cohort, chronic biological stress, measured by HairE, was associated with cancer incidence, after controlling for age and gender.