Margin guidance for oral cancer resection using light scattering spectroscopy

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。每年诊断的病例中有一半以上会导致致命的后果。手术切除仍然是口腔癌治疗的主要方式，但局部和区域复发仍然是手术切除后最常见的问题，导致60-80%的复发率在前3年。不适当的肿瘤切除是这种局部复发的常见原因。这可能是由于目前评估手术切缘的方法不充分，以及在远离原发癌变的部位存在“卫星”恶性细胞（“跳跃病变”），这是“野区癌变”现象的结果。目前确定安全手术切缘的方法变化很大，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边缘。阴性切缘的确认通常是基于随机选择的冷冻切片活检样本，留下大部分手术切缘未经检查。此外，冷冻切片分析可能耗时，昂贵，并且有很高的假阴性率。因此，迫切需要一种更准确、更灵敏的冷冻切片分析辅助术中安全手术边缘的检测。光学技术可用于区分原位良性和恶性组织病变。弹性散射光谱（Elastic Scattering Spectroscopy， ESS）是一种点光谱测量技术，可以检测良性和恶性组织的亚细胞形态差异，如核级、核质比、线粒体大小和密度的变化。ESS具有实时、客观、快速评估组织形态的优点。我们之前使用反射光谱和荧光光谱的研究表明，当应用基于解剖的算法时，光谱测量可以区分良性和发育不良/恶性病变。本研究将探索将此技术扩展到口腔癌手术的新临床应用。我们将用它来进行术前肿瘤边缘的勾画和术中手术切除的指导。我们的假设是，与传统方法相比，ESS测量可以大大提高外科医生在确定和评估口腔癌切除手术边缘时的准确性，从而显著降低局部复发率。我们将在40例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方法是否能够(1)在手术前提供准确的边缘轮廓；(2)指导和提高手术中肿瘤的切除。这将是同类研究中首次将这种光谱方法用于口腔癌手术。我们期望它能显著提高口腔癌手术切除的准确性，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种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.