A DNA biomarker of oral cancer metastasis

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DESCRIPTION (provided by applicant): For patients with early-stage oral cancer who do not have clinically evident neck metastasis, determination of risk for metastasis is critical for survival. Pathologic and molecular techniques do not accurately predict metastasis. Even for early-stage oral cancers, the rate of occult neck metastasis is greater than 20%. Typically a prophylactic neck dissection is performed if the risk for metastasis is 20% or more. Surgeons usually opt for a prophylactic neck dissection despite the risks of the procedure because failure to surgically resect occult (undetected) neck metastasis at the time of cancer diagnosis results in a 50% reduction in 5 year survival. However, risks associated with this procedure are daunting: a 3-4 hour major surgical procedure involving critical anatomic structures and morbidity including stroke. Nonetheless, for most patients this procedure is an unneeded but pragmatic solution to the dilemma posed by the looming specter of occult metastasis. Our laboratories recently discovered a potential genomic biomarker that identifies patients at low risk of metastasis. The biomarker is binary and identifies patients at low risk of metastasis if they lack the genomic DNA copy number alterations +3q, -8p, +8q and +20. Tumors in these low risk patients are of the so-called non- 3q8pq20 subtype, whereas tumors harboring one or more of these aberrations are of the 3q8pq20 subtype and associated with a substantial risk of metastasis. The 3q8pq20 status is a promising biomarker with a sensitivity of 96% and a false negative rate of 7%. The primary goal of this prospective biomarker clinical evaluation study is to determine the accuracy of non-3q8pq20 status in identifying a low risk of metastasis in patients with N0 tumors. Secondary goals are to: (a) assess the impact of the biomarker in the presence of single covariates. We will evaluate whether our biomarker is more or less effective in the presence of potentially important clinical factors: patient age, gender, tobacco and alcohol history, oral SCC site, tumor thickness, clinical and pathologic features, (b) compare the 3q8pq20 biomarker to other currently used predictors of occult metastasis, and (c) assess whether the biomarker is accurate at predicting other key clinical outcome. The Aim of this R34 application is to: a) design and develop the clinical protocol, b) prepare the Essential Documents/Regulatory Binder, c) develop an outline for the data management protocol to meet the "Best Practice Recommendations" detailed in the NIDCR Data Management Considerations document (the web- based database will be developed during the U01 once appropriate funds are available), d) establish a Data Safety and Monitoring plan, e) train and calibrate the research team for standardization of protocol procedures, data collection and data entry, and f) establish the committee structure for the study, which will include an Executive Committee and an Independent Oversight Committee. These documents, participant calibration, and the established committees will be the deliverables for the R34.