Impact of comorbidity on short-term mortality and overall survival of head and neck cancer patients

Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands.
Head & Neck (Impact Factor: 2.64). 11/2009; 32(6):728-36. DOI: 10.1002/hed.21245
Source: PubMed


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.
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.
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.
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.

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    • "A limitation of this study is that the results were based on a single cohort of 1282 Dutch patients, diagnosed at a single center [16]. We had to rely on bootstrap validation to estimate the performance of alternative modeling techniques. "
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    ABSTRACT: Background The use of alternative modeling techniques for predicting patient survival is complicated by the fact that some alternative techniques cannot readily deal with censoring, which is essential for analyzing survival data. In the current study, we aimed to demonstrate that pseudo values enable statistically appropriate analyses of survival outcomes when used in seven alternative modeling techniques. Methods In this case study, we analyzed survival of 1282 Dutch patients with newly diagnosed Head and Neck Squamous Cell Carcinoma (HNSCC) with conventional Kaplan-Meier and Cox regression analysis. We subsequently calculated pseudo values to reflect the individual survival patterns. We used these pseudo values to compare recursive partitioning (RPART), neural nets (NNET), logistic regression (LR) general linear models (GLM) and three variants of support vector machines (SVM) with respect to dichotomous 60-month survival, and continuous pseudo values at 60 months or estimated survival time. We used the area under the ROC curve (AUC) and the root of the mean squared error (RMSE) to compare the performance of these models using bootstrap validation. Results Of a total of 1282 patients, 986 patients died during a median follow-up of 66 months (60-month survival: 52% [95% CI: 50%−55%]). The LR model had the highest optimism corrected AUC (0.791) to predict 60-month survival, followed by the SVM model with a linear kernel (AUC 0.787). The GLM model had the smallest optimism corrected RMSE when continuous pseudo values were considered for 60-month survival or the estimated survival time followed by SVM models with a linear kernel. The estimated importance of predictors varied substantially by the specific aspect of survival studied and modeling technique used. Conclusions The use of pseudo values makes it readily possible to apply alternative modeling techniques to survival problems, to compare their performance and to search further for promising alternative modeling techniques to analyze survival time.
    PLoS ONE 06/2014; 9(6):e100234. DOI:10.1371/journal.pone.0100234 · 3.23 Impact Factor
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    • "The majority of patients with HNSCC are generally diagnosed at an advanced stage, and hence the survival of HNSCC patients is poor [19]. Treatment of HNSCC has evolved over the last two decades to incorporate modalities that have resulted in decreased patient morbidity but with limited success [20]. Therefore, molecular markers for use as prognostic indicators have been studied to improve prediction of the clinical outcome of HNSCC. "
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    ABSTRACT: Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein and plays an important role in mitochondrial ATP production and biogenesis. High expression levels of LETM1 have been correlated with numerous human malignancies. This study explored the clinicopathological significance of LETM1 expression as a prognostic determinant in head and neck squamous cell carcinoma (HNSCC). HNSCC samples from 176 patients were selected for immunohistochemical staining of LETM1 protein. Correlations between LETM1 overexpression and clinicopathological features of HNSCC were evaluated by Chi-squared tests and Fisher's exact tests, and relationships between prognostic factors and patient survival were analyzed using Cox proportional hazards models. Our results demonstrated that the strongly positive rate of LETM1 protein was 65.3% in HNSCC, which was significantly higher than in either adjacent nontumor tissue (25.0%) or normal squamous epithelia (6.7%). LETM1 overexpression correlated with poor differentiation, presence of lymph node metastasis, advanced stage, absence of chemoradiotherapy, and 5-year disease-free survival and overall survival rates in HNSCC. Further analysis showed that high LETM1 expression, advanced stage, and nonchemoradiotherapy were significant independent risk factors for mortality in HNSCC. In conclusion, LETM1 plays an important role in the progression of HNSCC and is an independent poor prognostic factor for HNSCC.
    02/2014; 2014(8):850316. DOI:10.1155/2014/850316
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    • "Disability resulting from co-morbid illness may influence patient perception of QOL; however, advanced co-morbidity is mainly associated with poorer survival [15,16]. Datema et al. reported that co-morbidity impacts overall survival and short-term mortality of the newly diagnosed patient with head and neck squamous cell cancer [17]. Therefore, co-morbidity seems to have a closer correlation with overall survival, rather than QOL. "
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    ABSTRACT: This study describes 2-year impact on quality of life (QOL) in relation to the anatomical discrepancy among T4a oral cancer patients after free flap reconstruction in Taiwan. Thirty-two patients who underwent tumor ablation with simultaneous microvascular free flap transfer at 2-year follow-up were recruited. They were divided into six subgroups, according to the resected area, consisting of: (1) buccal/retromolar trigone; (2) cheek; (3) commissure; (4) lip; (5) mandible; and (6) tongue. Functional disturbances and daily activity were analyzed using the Version-1 UW QOL Questionnaire with one more specific category: 'Drooling'. Kruskal-Wallis rank sums analysis was used to test differences in average QOL scores between these subgroups. Post-hoc analysis was applied to assess influence of dominant categories between subgroups. The category 'Pain' revealed the highest average score and reached significant statistical difference (P = 0.019) among all the categories, however, the category 'Employment' averaged the lowest score. Regarding 'Pain', there existed a statistical significance (P = 0.0032) between the commissure- and cheek-involved groups, which described the former showed poorer pain quality of life. The commissure-involved group had the lowest average score, which might imply the worst QOL in our study, especially for the categories 'Pain' and 'Drooling'. This present study of T4a patients was the first carried out in Taiwan implementing the QOL questionnaire, and its results may serve for future reference.
    World Journal of Surgical Oncology 07/2012; 10(1):145. DOI:10.1186/1477-7819-10-145 · 1.41 Impact Factor
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