http://repub.eur.nl/res/aut/23297/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/32661/ 2012-06-22T00:00:00Z Head and neck cancer accounts for almost 5% of all malignant tumors in the Netherlands. The most up‐todate Dutch Cancer Registry (NCR) database from 2009 reported 2878 new patients with an invasive carcinoma of the lip, oral cavity, pharynx and larynx (general incidence 17:100.000). In this thesis we focus on head and neck squamous cell carcinoma (HNSCC). Head and neck squamous cell carcinomas originate from the mucosal lining of the upper aero‐digestive tract. Tobacco and alcohol are irritants to this mucosal lining and therefore form major risk factors for the genesis of malignant epithelial tumors. Other reported etiological factors are malnutrition, viral factors (Epstein Barr virus and Human Papilloma virus), genetic predispositions and occupational hazards. http://repub.eur.nl/res/pub/37218/ 2012-01-01T00:00:00Z Background. Electronic patient files generate an enormous amount of medical data. These data can be used for research, such as prognostic modeling. Automatization of statistical prognostication processes allows automatic updating of models when new data is gathered. The increase of power behind an automated prognostic model makes its predictive capability more reliable. Cox proportional hazard regression is most frequently used in prognostication. Automatization of a Cox model is possible, but we expect the updating process to be time-consuming. A possible solution lies in an alternative modeling technique called random survival forests (RSFs). RSF is easily automated and is known to handle the proportionality assumption coherently and automatically. Performance of RSF has not yet been tested on a large head and neck oncological dataset. This study investigates performance of head and neck overall survival of RSF models. Performances are compared to a Cox model as the "gold standard." RSF might be an interesting alternative modeling approach for automatization when performances are similar. Methods. RSF models were created in R (Cox also in SPSS). Four RSF splitting rules were used: log-rank, conservation of events, log-rank score, and log-rank approximation. Models were based on historical data of 1371 patients with primary head-and-neck cancer, diagnosed between 1981 and 1998. Models contain 8 covariates: tumor site, T classification, N classification, M classification, age, sex, prior malignancies, and comorbidity. Model performances were determined by Harrell's concordance error rate, in which 33% of the original data served as a validation sample. Results. RSF and Cox models delivered similar error rates. The Cox model performed slightly better (error rate, 0.2826). The log-rank splitting approach gave the best RSF performance (error rate, 0.2873). In accord with Cox and RSF models, high T classification, high N classification, and severe comorbidity are very important covariates in the model, whereas sex, mild comorbidity, and a supraglottic larynx tumor are less important. A discrepancy arose regarding the importance of M1 classification (see Discussion). Conclusion. Both approaches delivered similar error rates. The Cox model gives a clinically understandable output on covariate impact, whereas RSF becomes more of a "black box." RSF complements the Cox model by giving more insight and confidence toward relative importance of model covariates. RSF can be recommended as the approach of choice in automating survival analyses. http://repub.eur.nl/res/pub/34293/ 2011-09-01T00:00:00Z Background: Basic patient and tumor characteristics impact overall survival of head and neck squamous cell carcinoma patients. Severe malnutrition, defined as weight loss > 10% in 6 months preceding primary tumor diagnosis, impacts overall survival as well. Little attention has been paid to the interaction between severe malnutrition and other relevant prognostic covariables. This study investigates the impact of malnutrition on short-term mortality and overall survival, together with the covariables age, tumor site, gender, TNM-classification, comorbidity and prior tumors. Methods: 383 consecutive primary HNSCC patients, diagnosed and treated between 1995 and 1999 were followed until January 2010. Impact of covariables on short-term mortality and overall survival was studied univariately with Kaplan-Meier curves and the log-rank test. Cox-regression and binary logistic regression were used for multivariate analyses. Results: 28 (7.3%) patients were severely malnourished. All covariables, except gender and prior tumors had significant impact on overall survival. The relative risk of severe malnutrition was 1.8 and is comparable to the impact of a T2 tumor, a N1 neck or moderate comorbidity. A univariate relationship between severe malnutrition and short-term mortality was established. Conclusions: Severe malnutrition has an independent impact on overall survival of primary HNSCC patients. There is a clear distinction between patients with and without severe malnutrition from moment of diagnosis until 10 years after. This emphasizes the importance of identification and optimal treatment of malnutrition before, during and after cancer treatment. http://repub.eur.nl/res/pub/22042/ 2010-11-01T00:00:00Z Background. Patients with head and neck squamous cell carcinoma (HNSCC) usually have a history of tobacco and alcohol abuse. These 2 intoxications not only are main oncologic risk factors but also show a strong causal relationship with certain comorbid conditions. Examples are coronary artery disease, stroke, renal dysfunction, and heart failure, which are all proven major risk factors for an adverse postoperative outcome after stressful noncardiac surgery. Preoperative identification of these conditions could lead to preventive measures in patients with HNSCC that undergo extensive surgery. Preventing morbidity and mortality is of medical and economical importance. Methods. All comorbidity of 135 consecutive patients with HNSCC that underwent extensive oncologic and reconstructive surgery as the first form of treatment between 2001 and 2007 was investigated. Based on these data, a Lee Cardiac Risk Index (LCRI) Score and an overall Adult Comorbidity Evaluation (ACE-27) severity score were calculated. The predictive value of these scores and the American Society of Anesthesiologists' (ASA) classification toward major cardiovascular complication development were investigated. Major cardiovascular complications were defined as: cardiac death, nonfatal myocardial infarction, heart failure, and cardiac arrhythmias. The impact of these complications on duration of hospitalization, medical costs, and short-term mortality (defined as death within 6 months after primary tumor diagnosis) were investigated as well. The cardioprotective effect of preoperatively prescribed beta blockers and statins are discussed. Results. Twenty-two patients developed 23 major cardiovascular complications (16.3%). In univariate and multivariate analyses, a higher LCRI score was associated with an increased risk for major cardiovascular complications, as was an age >70 years (all values of p <.01). The area under the receiver operating characteristics (ROC) curve (AUC) for the multivariate model was 0.84, indicating a good prognostic value. In univariate and multivariate analysis, a higher ACE-27 score was associated with an increased risk for major cardiovascular complications, as was as age >70 years (all values of p <.01). The AUC for this model was 0.84, indicating a performance similar to that of the LCRI score model. No statistically significant results were found for the ASA scores (p =.38). Preoperative beta-blocker use showed a significant cardioprotective function in univariate analysis, whereas statins did not. The mean duration of hospitalization was prolonged by 7 days in patients with a major cardiovascular complication. In economic terms, this means a cost increase of at least 3500 euros. None of the patients died during admission because of a major cardiovascular complication. The short-term mortality rate was 11.1%, but no specific cardiovascular cause of death was reported in these patients. Conclusions. Prevention of major complication occurrence after extensive HNSCC surgery is of medical and economic importance. Our results show that the ACE-27 and the LCRI are suitable instruments for preoperative major cardiovascular complication risk assessment. Addition of the variable age >70 years shows an improvement in predictive value of both instruments. Because of its simplicity we advise the implementation of the LCRI into preoperative HNSCC screening protocols. We advise the exploration of low-dose long-acting beta blockers as a preventive treatment strategy. http://repub.eur.nl/res/pub/20602/ 2010-09-01T00:00:00Z Univariate analyses on malignant salivary gland tumors report a strong relation of histological subtypes and prognosis. However, multivariate analyses with sufficient patients and reflecting the broad spectrum of putative prognostic factors are rare. In order to study the prognostic value of cytology and histology in salivary carcinoma we performed multivariate analyses on 666 newly diagnosed patients. In multivariate analyses sex, tumor size, N- and M-staging, localization, comorbidity, skin involvement and pain were independent predictors of survival. Histology was an independent prognostic factor, mainly because acinic cell carcinoma acted differently from the other histological subtypes. However, a simple prognostic model without cytology and/or histology has similar predictive power compared to more elaborate models. The added prognostic value of cytology and/or histology factors in salivary carcinoma is limited, largely due to the combined prognostic value of other prognostic factors such as tumor size, N- and M-classification and comorbidity. http://repub.eur.nl/res/pub/28260/ 2010-06-01T00:00:00Z Background. In 2001, we presented a Cox regression model that is able to predict survival of the newly diagnosed patient with head and neck squamous cell carcinoma (HNSCC). This model is based on the TNM classification and other important clinical variables such as age at diagnosis, sex, primary tumor site, and prior malignancies. We aim to improve this model by including comorbidity as an extra prognostic variable. Accurate prediction of the prognosis of the newly diagnosed patient with head and neck cancer can assist the physician in patient counseling, clinical decision-making, and quality maintenance. Methods. All patients with HNSCC of the oral cavity, pharynx, and larynx diagnosed in the Leiden University Medical Centre between 1981 and 1998 were included. From these 1371 patients, data on primary tumor site, age at diagnosis, sex, TNM classification, and prior malignancies were already available. Comorbidity data were collected retrospectively according to the ACE27 manual. The prognostic value of each variable on overall survival was studied univariately by Kaplan-Meier curves and the log-rank test. The Cox regression model was used to investigate the impact of these variables on overall survival simultaneously. Furthermore, univariate analyses were performed to investigate the impact of comorbidity severity on short-term mortality and to investigate the impact of organ-specific-comorbidity on short-term mortality. Results. Comorbidity was present in 36.4% of our patients. Mild decompensation was seen in 17.4%, moderate decompensation in 13.5%, and severe decompensation in 5.5%. Most frequently observed ailments were cardiovascular, respiratory, and gastrointestinal. In univariate analyses, all prognostic variables, including comorbidity, contributed significantly to overall survival. Their contribution (except sex) remained significant in the multivariate Cox model. Internal validation of this model showed a concordance index of 0.73, indicating a good predictive value. Short-term mortality was seen in 5.7% of our patients. Cardiovascular comorbidity, respiratory comorbidity, gastrointestinal comorbidity, and diabetes showed a significant relationship with short-term mortality. Conclusions. Comorbidity impacts overall survival of the newly diagnosed patient with HNSCC. There is a clear distinction between the impact of the 4 ACE27 severity grades. The impact of an ACE27 grade 3 is comparable to the impact of a T4 tumor or an N2 neck. Comorbidity impacts short-term mortality as well. Especially cardiovascular comorbidity, respiratory comorbidity, gastrointestinal comorbidity, and diabetes show a strong relationship. http://repub.eur.nl/res/pub/19565/ 2010-01-01T00:00:00Z This article describes a 81-year-old man with a possible malignant nodular swelling in the left neck and an ulcerative lesion on the scalp. Both were surgically removed for further histological diagnosis. Post operatively a non-healing wound of both scalp and the left neck persisted for a long time. The eventual diagnosis was pyoderma gangrenosum, a rare, idiopathic and ulcerative skin disease, which can clinically be mistaken for a malignancy. Early recognition of this ailment allows for an adequate conservative therapy and can avoid surgical therapy. http://repub.eur.nl/res/pub/24492/ 2009-03-01T00:00:00Z This paper describes a novel method for the removal of a needle aspirated into the basal part of the right bronchial tree of a 14-year-old girl, where due to the distal location, earlier attempts at extraction had been unsuccessful. With careful advanced planning creative modelling, and the assistance of our medical engineer, a modified method was developed that allowed successful extraction in cooperation with the pulmonary physician, thereby obviating the need for a possible thoracotomy and lobectomy. Crown Copyright http://repub.eur.nl/res/pub/29321/ 2008-04-01T00:00:00Z Background: The OM-6 survey is a validated and multinationally accepted instrument to measure the treatment effect of otitis media in children. Routine use of the OM-6 in a busy general practice is not always possible and can lead to incomplete returned surveys. A simplified method is favoured when the aim is a continuous process of complete treatment-outcome-data collection. This study tests if a VAS can quantify how much a child suffers from chronic otitis media and how much this changes due to surgical treatment. The change in overall OM-6 scores due to surgical treatment, functions as the gold reference standard. Furthermore, this study tests if the VAS is faster to use than the OM-6 and if it leads to an improvement in complete data collection. Methods: Prospective cohort follow-up study of 175 consecutive children with chronic otitis media in a paediatric otolaryngology practice in a metropolitan area. Data collected included patient's age, gender, clinical presentation, type of surgical procedure performed, overall OM-6 score and VAS score (at initial presentation and at follow-up), time needed to complete an OM-6 survey and VAS separately and number of incorrect OM-6 surveys and VAS questions returned. Results: The VAS scores and overall OM-6 scores show a good, positive correlation at baseline (Spearman's ρ = 0.71). This correlation improves at follow-up, one and 6 months after intervention (ρ = 0.73 and ρ = 0.80, respectively). The change in VAS scores and overall OM-6 scores, interpreted as change due to surgical intervention, show a good positive correlation at follow-up (ρ = 0.70 and ρ = 0.77, respectively). The VAS is almost three times faster than the OM-6 (28 s versus 81 s). More than 13% of OM-6 surveys were returned incomplete. All VAS questions were returned correct. Conclusions: The VAS can be used as a simplified method for routine surgical treatment effect analysis in children with chronic otitis media.