A DNA biomarker of oral cancer metastasis

描述（由申请人提供）：对于临床无明显颈部转移的早期口腔癌患者，确定转移风险对生存至关重要。病理和分子技术不能准确预测转移。即使是早期口腔癌，隐匿性颈部转移的发生率也大于20%。如果转移的风险为20%或更多，通常进行预防性颈部清扫。尽管手术有风险，但外科医生通常会选择预防性颈部清扫术，因为在癌症诊断时未能手术切除隐匿性（未被发现的）颈部转移会导致5年生存率降低50%。然而，与此手术相关的风险是令人生畏的：一个3-4小时的主要手术过程涉及关键的解剖结构和包括中风在内的发病率。尽管如此，对于大多数患者来说，这种手术是一种不必要的但实用的解决方案，以解决隐性转移的隐蔽性幽灵所带来的困境。我们的实验室最近发现了一种潜在的基因组生物标志物，可以识别低风险患者

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.