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Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma

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ABSTRACT

It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method to evaluate the predictive value of tumor budding. We developed a semi-automated image-analysis algorithm, Digital Tumor Bud Count (DTBC), to evaluate tumor budding. The algorithm was tested in 222 consecutive patients with early-stage OSCC and major endpoints were overall (OS) and progression free survival (PFS). We subsequently constructed and cross-validated a binary logistic regression model and evaluated its clinical utility by decision curve analysis. A high DTBC was an independent predictor of both poor OS and PFS in a multivariate Cox regression model. The logistic regression model was able to identify patients with occult lymph node metastases with an area under the curve (AUC) of 0.83 (95% CI: 0.78–0.89, P <0.001) and a 10-fold cross-validated AUC of 0.79. Compared to other known histopathological risk factors, the DTBC had a higher diagnostic accuracy. The proposed, novel risk model could be used as a guide to identify patients who would benefit from an up-front neck dissection.

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The frequency and survival analyses of the digital tumor bud countA. Frequency of tumor buds in patients with OSCC. Note that the majority has between 0 and 1000 buds per section. B. Relationship between the size of tumor bud area (i.e. estimated number of cell per tumor island) and the relationship with overall survival per tertile increment. There is a significant linear relationship between the size of the tumor buds and prognostic importance; as the islands of the tumor buds increases its importance in predicting survival diminishes significantly. C. Relationship between the Digital Tumor Bud Count (DTBC) and overall survival. The DTBC has been divided into upper, middle and lower tertiles, and the comparison is significant (P < 0.01). D. Relationship between the DTBC, divided into tertiles, and progression-free survival, and the comparison is significant (P < 0.01). Notice that almost none of the patients with a DTBC in the lower tertile have a progression after 5 years; 95% are without progression. In C and D: the numbers of patients at risk are shown at the time of 0, 1, 3, and 5 years.
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Figure 2: The frequency and survival analyses of the digital tumor bud countA. Frequency of tumor buds in patients with OSCC. Note that the majority has between 0 and 1000 buds per section. B. Relationship between the size of tumor bud area (i.e. estimated number of cell per tumor island) and the relationship with overall survival per tertile increment. There is a significant linear relationship between the size of the tumor buds and prognostic importance; as the islands of the tumor buds increases its importance in predicting survival diminishes significantly. C. Relationship between the Digital Tumor Bud Count (DTBC) and overall survival. The DTBC has been divided into upper, middle and lower tertiles, and the comparison is significant (P < 0.01). D. Relationship between the DTBC, divided into tertiles, and progression-free survival, and the comparison is significant (P < 0.01). Notice that almost none of the patients with a DTBC in the lower tertile have a progression after 5 years; 95% are without progression. In C and D: the numbers of patients at risk are shown at the time of 0, 1, 3, and 5 years.

Mentions: Using digital image analysis, we obtained an objective measure of the degree of tumor dissociation, i.e. a tumor bud count (Figure 1). The total number of tumor buds per tumor section varied considerably from patient to patient (Figure 2A).


Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma
The frequency and survival analyses of the digital tumor bud countA. Frequency of tumor buds in patients with OSCC. Note that the majority has between 0 and 1000 buds per section. B. Relationship between the size of tumor bud area (i.e. estimated number of cell per tumor island) and the relationship with overall survival per tertile increment. There is a significant linear relationship between the size of the tumor buds and prognostic importance; as the islands of the tumor buds increases its importance in predicting survival diminishes significantly. C. Relationship between the Digital Tumor Bud Count (DTBC) and overall survival. The DTBC has been divided into upper, middle and lower tertiles, and the comparison is significant (P < 0.01). D. Relationship between the DTBC, divided into tertiles, and progression-free survival, and the comparison is significant (P < 0.01). Notice that almost none of the patients with a DTBC in the lower tertile have a progression after 5 years; 95% are without progression. In C and D: the numbers of patients at risk are shown at the time of 0, 1, 3, and 5 years.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392322&req=5

Figure 2: The frequency and survival analyses of the digital tumor bud countA. Frequency of tumor buds in patients with OSCC. Note that the majority has between 0 and 1000 buds per section. B. Relationship between the size of tumor bud area (i.e. estimated number of cell per tumor island) and the relationship with overall survival per tertile increment. There is a significant linear relationship between the size of the tumor buds and prognostic importance; as the islands of the tumor buds increases its importance in predicting survival diminishes significantly. C. Relationship between the Digital Tumor Bud Count (DTBC) and overall survival. The DTBC has been divided into upper, middle and lower tertiles, and the comparison is significant (P < 0.01). D. Relationship between the DTBC, divided into tertiles, and progression-free survival, and the comparison is significant (P < 0.01). Notice that almost none of the patients with a DTBC in the lower tertile have a progression after 5 years; 95% are without progression. In C and D: the numbers of patients at risk are shown at the time of 0, 1, 3, and 5 years.
Mentions: Using digital image analysis, we obtained an objective measure of the degree of tumor dissociation, i.e. a tumor bud count (Figure 1). The total number of tumor buds per tumor section varied considerably from patient to patient (Figure 2A).

View Article: PubMed Central - PubMed

ABSTRACT

It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method to evaluate the predictive value of tumor budding. We developed a semi-automated image-analysis algorithm, Digital Tumor Bud Count (DTBC), to evaluate tumor budding. The algorithm was tested in 222 consecutive patients with early-stage OSCC and major endpoints were overall (OS) and progression free survival (PFS). We subsequently constructed and cross-validated a binary logistic regression model and evaluated its clinical utility by decision curve analysis. A high DTBC was an independent predictor of both poor OS and PFS in a multivariate Cox regression model. The logistic regression model was able to identify patients with occult lymph node metastases with an area under the curve (AUC) of 0.83 (95% CI: 0.78&ndash;0.89, P &lt;0.001) and a 10-fold cross-validated AUC of 0.79. Compared to other known histopathological risk factors, the DTBC had a higher diagnostic accuracy. The proposed, novel risk model could be used as a guide to identify patients who would benefit from an up-front neck dissection.

No MeSH data available.


Related in: MedlinePlus