ReviewPrognostic significance of radiologically determined neck node volume in head and neck cancer: A systematic review
Introduction
Many clinical parameters such as TNM classification, gender, comorbidity, site, weight loss, neck level, primary tumor volume,1, 2, 3 tumor thickness4, 5, 6 and extracapsular spread (ECS)7, 8, 9 are known to have prognostic significance in head and neck cancer.
TNM staging10 takes into consideration the one-dimensional size and anatomical extent of the primary tumor, size and number of regional lymph nodes and the presence or absence of distant metastasis. TNM classification is still the most frequently used prognostication system for head and neck cancer, although it does not represent the real tumor load involved, due to the use of one-dimensional parameters and anatomical extensions. The use of the maximal diameter of regional lymph nodes and the number of involved nodes is not an accurate measure of the tumor load in the neck. To avoid similar limitations of primary tumor staging, several studies have been performed to evaluate the value of pretreatment CT imaging with volumetric analysis1, 2 as an addition to the T-classification. Studies of laryngeal and pharyngeal tumors have shown tumor volume to be an important predictor for tumor recurrence.3, 11 In laryngeal cancer, treated by radiotherapy, increasing tumor volumes were related to significantly higher chance of recurrence. This was also found for other head and neck cancers with cut-off values ranging from 3.5 to 30 cm3.2, 3, 12 In general, both overall survival and local regional tumor control deteriorates with an increase of the primary tumor volume.1, 2
Besides primary tumor volume, multiple prognostic features related to the regional lymph nodes were studied in literature. Woolgar showed in 20069 that metastatic status (nodal metastasis present versus absent), laterality of positive nodes, number of positive nodes, size of metastatic deposits, anatomical level of involvement, extracapsular spread, embolization of perinodal lymphatics and pN stage are of prognostic significance. In 1998, Grabenbauer et al.13 showed the only independent variable, in multivariate Cox regression model, predicting for survival, was nodal CT density (p = 0.0003).
Measurements of tumor volume can be determined on radiologic images in different ways. For a mathematical determination of tumor volume the cuboid formula (volume = a × b × c) or an ellipsoid formula (volume = 1/6 × π × a × b × c) can be used. In most studies, however, tumor contours are outlined on every slice, the surface area is determined and summated (i.e. the summation-of-areas techniques). Both Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are valuable tools for an accurate outlining of both primary tumor and regional lymph node status.
There is wide variety of tumor measuring systems in the literature. The cut-off value for local tumor response also shows large variation. Most studies concentrate on the prognostic significance of the primary tumor volume. This systematic review addresses the prognostic significance of neck node volume in head and neck cancer.
Section snippets
Search strategy and selection criteria
Articles reporting prognosis and survival in nodal tumor volumes were collected by systematically reviewing publications listed in the Pubmed and Embase databases. Articles retrieved from both databases describe patient series with at least total tumor volume (i.e. primary tumor volume and nodal volume together) or nodal volume and survival. These were limited to the English language and were published between January 1, 1990, and June 1, 2011. The first step in the search aimed to find all
Results
Table 1 shows an overview of all available literature for the prognostic value of nodal volumes.
Discussion
This review shows that the role of nodal volume for prognosis of head and neck cancer is not yet studied extensively. Many different outcomes were used, for example: 2, 3 and 5-year survival, 2-year distant metastases free survival, disease free survival and local (regional) control. All studies report a decreasing control of outcome with increase in volume. Unfortunately, every referenced report used a different method for measuring volumes. Moreover, nodal volumes as a separate entity are
Conclusion
To evaluate the effect of volumes on prognosis, many different outcomes were used, for example: 2, 3 and 5-year survival, 2-year distant metastases free survival, disease free survival and local (regional) control. Even few studies with positive correlation used different methods for the measurements, so that no real consensus can be reached. In most studies, increased nodal volume has a negative effect on survival. Therefore, firstly consensus should be accomplished on standardization of
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