Margin guidance for oral cancer resection using light scattering spectroscopy

描述(申请人提供)：口腔癌是全球第八大最常见的癌症，2011年在美国的发病率为39,400。每年确诊的病例中，有一半以上会导致致命后果。手术切除仍然是治疗口腔癌的主要方法，但手术切除后局部和区域复发仍然是最常见的问题，导致前3年的复发率为60%-80%。肿瘤切除不充分是这种局部复发的常见原因。这可能是因为目前评估手术切缘的方法不足，以及“卫星”恶性细胞(“跳跃性病变”)出现在远离原发癌灶的部位，这是“野生性癌化”现象的结果。目前确定安全手术切缘的方法是高度可变的，远远不能令人满意。外科医生通常依靠自己的判断或在白光下的视觉来确定手术切缘。阴性切缘的确认通常是基于随机选择的冰冻切片活检样本，而大部分手术切缘没有进行检查。此外，冰冻切片分析可能会耗时、昂贵，而且假阴性率很高。因此，迫切需要一种更准确和更灵敏的辅助冰冻切片分析来在术中检测安全的手术切缘。光学技术可以用来区分原位的良性和恶性组织病变。弹性散射光谱(ESS)是一种点光谱测量技术，可以检测良、恶性组织之间的亚细胞形态差异，如核级别、核浆比、线粒体大小和密度的变化。ESS提供了实时、客观和快速的组织形态评估的优势。我们之前使用反射和荧光光谱进行的研究表明，当应用基于解剖学的算法时，光谱测量可以区分良性和发育不良/恶性病变。这项拟议的研究将探索将该技术扩展到口腔癌外科的新临床应用的可行性。我们将使用它来术前勾勒肿瘤边缘和术中指导手术切除。我们的假设是，与单独使用传统方法相比，ESS测量可以极大地提高外科医生确定和评估口腔癌切除手术切缘的准确性，从而显著降低局部复发率。我们将在40名接受口腔癌手术的患者中验证我们的假设。我们的目标是确定这种光学入路是否能够(1)在手术前提供准确的切缘轮廓；(2)指导和改进手术中的肿瘤切除。这将是第一次在口腔癌手术中使用这种光谱方法的同类研究。我们的期望是，它将显著提高口腔癌手术切除的准确性，并降低复发率。这种光学引导手术如果成功，将为外科医生提供一个理想的边缘评估工具，并将显著改善口腔癌患者的预后。

DESCRIPTION (provided by applicant): Oral cavity cancer is the eighth most common cancer globally with an incidence of 39,400 in the United States in 2011. Over half of the cases diagnosed annually result in a lethal outcome. Surgical resection remains a primary modality for treatment of oral cancers but local and regional recurrence remains the most common problem after surgical resection, resulting in a 60-80% recurrence rate in the first 3 years. Inadequate tumor excision is a common cause for such local recurrence. This could be explained by the current inadequacy of methods for assessing surgical margins and by the presence of "satellite" malignant cells ("skip lesions") in sites away from the primary cancerous lesion, which occur as a result of the "field cancerization" phenomenon. Current methods for determining a safe surgical margin are highly variable and far from satisfactory. Surgeons often depend on their own judgment or visualization under white light to determine surgical margins. Confirmation of negative margins is often is based on randomly selected samples for frozen-section biopsies, leaving much of the surgical margin unexamined. Moreover, frozen-section analysis can be time consuming, expensive, and have a high false-negative rate. A more accurate and sensitive adjunct to frozen section analysis for the intraoperative detection of safe surgical margins is therefore greatly needed. Optical technologies can be used to distinguish in situ benign from malignant tissue lesions. Elastic Scattering Spectroscopy (ESS) is a point spectroscopic measuring technique that can detect sub-cellular morphological differences between benign and malignant tissue, such as changes in nuclear grade, nuclear to cytoplasm ratio, mitochondrial size and density. ESS provides the advantage of real-time, objective and quick assessment of tissue morphology. Our previous studies using reflectance and fluorescence spectroscopy have shown that spectral measurements can distinguish between benign and dysplastic/malignant lesions when anatomy-based algorithms are applied. This proposed study will explore the feasibility of extending this technique for a new clinical application for oral cancer surgery. We will use it for pre-operative outlining of tumor margin and intra-operative guidance of the surgica excision. Our hypothesis is that ESS measurements can greatly improve surgeons' accuracy in determining and assessing surgical margins in excision of oral cancers compared to traditional approaches alone, thereby significantly reducing local recurrence rates. We will validate our hypothesis in 40 patients undergoing surgery for oral cancer. Our goal is to determine if this optical approach will be able to (1) provide an accurate margin outline before surgery; and (2) guide and improve tumor excision during surgery. This will be the first study of its kind to use this spectroscopic approach for surgery in oral cancers. Our expectation is that it will significantly improve accuracy in surgical resection of oral cancers and reduce recurrence rates. This optical-guided surgery, if successful, will provide surgeons with an ideal tool for margin assessment and will significantly improve prognosis for patients with oral cancer.