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UBC Theses and Dissertations

Nodal disease burden of oral cancer in British Columbia and a novel approach for risk assessment Liu, Kelly Yi Ping


For patients of oral squamous cell carcinoma (OSCC), tumour spread to regional lymph nodes reduces survival by half. On the account of this widely demonstrated fact, prophylactic neck treatment has been advocated for clinically node negative (cN0) necks of which the risk of nodal disease is considerably high. However, there is a lack of sensitive and specific marker to determine such risk and benefits of prophylactic treatment await confirmation. The first part of this thesis presents a population-based retrospective review on OSCC in British Columbia. The incidence of regional failure (RF) in early-stage, cN0 patients was 28%, with median time of only 10 months after local excision. This group of patients needed to be identified and treated at earliest time possible. Tumour depth of invasion (DOI) was significantly associated with RF (P=0.01). However, it has low accuracy in predicting nodal disease with AUC of 63%. Moreover, assessment of performance for 4mm cut-off of DOI showed 55% sensitivity and 68% specificity. Furthermore, we demonstrated that using DOI as an indicator of neck treatment resulted in 25% under-treated occult metastasis and 55% over-treated necks. Thus, we concluded that, at least for BC population, conventional histological attributes of tumour cannot predict RF and we need a new marker for risk assessment. The second part presents a pilot study exploring a novel approach of risk assessment by utilizing Quantitative Tissue Pathology (QTP) on tumour nests. We were able to quantitate and evaluate 120 features describing nuclear phenotypes of tumour cell nuclei and tissue architectures of tumour nests. Compared to node-negative (N0) group, cell nuclei of the node positive (N+) group had higher fractions of heterochromatin regions. Also, the combination of two features, which describe chromatin condensation, from the outermost two layers of tumour nests had performance of AUC 94%, sensitivity of 100% and specificity of 75% in discriminating N0 and N+ group. QTP may be a potential proxy for predicting the metastatic risk of OSCC. Further investigation on potential biomarkers in risk assessment for nodal disease of early-stage OSCC patients is warranted to provide precision management to improve mortality and reduce morbidity.

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