Peri-operative confocal imaging-guided laser ablation of basal cell carcinomas

基底细胞癌围术期共焦成像引导激光消融术

• 批准号: 9022187
• 负责人: MILIND RAJADHYAKSHA
• 金额: $ 53.1万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-11 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9022187
• 关键词: Ablation; Acetic Acids; Address; Adopted; Alternative Therapies; Am 80; Area; Australia; Basal cell carcinoma; Biopsy; Clinical; Clinical Pathology; Coagulation Process; Confocal Microscopy; Contrast Media; Cornea; Curettage procedure; Cutaneous Melanoma; Detection; Diagnosis; Europe; Evaluation; Excision; Face; Feedback; Freezing; Goals; Head and neck structure; Human; Image; Imaging technology; Imiquimod; Incidence; Label; Lasers; Length; Low-Level Laser Therapy; Malignant Neoplasms; Microscopy; Mohs Surgery; Morphology; Nuclear; Operative Surgical Procedures; Outcome; Pathology; Patients; Physiologic pulse; Predictive Value; Procedures; Process; Radio; Residual Tumors; Residual state; Resolution; Sensitivity and Specificity; Skin; Skin Cancer; Skin Carcinoma; Specificity; Specimen; Testing; Tissue Viability; Tissues; Treatment Cost; Validation; cancer diagnosis; cost; follow-up; image guided; improved; in vivo; minimally invasive; optical imaging; public health relevance; standard care; tumor; uptake; wound

 DESCRIPTION (provided by applicant): The goal of this project is to develop and test a peri-operative confocal imaging-guided approach for laser ablation of basal cell carcinomas (BCCs). BCCs are among the most common malignancies in the world, with an estimated 2.5 million new cases diagnosed every year in the USA and 700,000 in Europe and Australia. Mohs surgery, guided by frozen pathology, is the standard treatment. However, the procedure is labor- intensive and expensive, with treatment costs of about $2 billion every year in the USA. Consequently, less invasive and less expensive non-surgical alternative therapies are being increasingly adopted. Laser ablation is particularly effective for minimally invasive removal of superficial and early nodular types of BCCs (about 600,000 cases per year in the USA and 200,000 in Europe and Australia). Skin can be ablated in µm-thin layers in a controlled manner. However, tissue is vaporized such that there is none available for immediate pathological evaluation for the presence or clearance of tumor. (One may say that there's "plenty of tissue" remaining on the patient that can be taken for pathology, but this would defeat the very purpose of a less invasive approach.) The lack of pathological feedback results in variable efficacy and limited cure rate. A high-resolution nuclear-level optical imaging approach such confocal microscopy may detect the presence or clearance of residual BCCs directly on the patient, and provide immediate pathology-like feedback. However, ablation produces thermal coagulation and loss of viability in the remaining underlying tissue (wound), which may subsequently impede the uptake of a contrast agent for labeling nuclear morphology and imaging of residual tumor. Our hypothesis is that adequate tissue viability may be preserved by controlling the thermal coagulation with optimal choice of ablation parameters (pulse duration, fluence, number of pulses, wave- length). This may subsequently allow uptake of contrast agent and detection of residual BCC tumor in vivo. Such an imaging-guided approach may improve the efficacy and cure rate of ablation for superficial and early nodular BCCs. About 800,000 patients (worldwide) may benefit, per year, with a less invasive procedure. Preliminary studies on excised human skin specimens confirms our hypothesis. Testing on five BCCs in vivo demonstrates the potential for peri-operative imaging directly on patients to guide ablation. The specific aims are to (1) investigate depth of thermal coagulation and viability of tissue in the underlying wound versus two ablation parameters (fluence, number of pulses), and determine optimal parameters for preserving adequate viability; (2) determine the uptake of contrast agent (acetic acid) versus optimal ablation parameters in excised human skin specimens, with quantitative validation against pathology; (3) simulate implementation on patients in vivo, by testing feasibility for detecting clearance of BCCs on excised human skin specimens versus optimal ablation parameters, with quantitative validation against pathology; (4) test feasibility of peri-operative imaging- guided ablation on patients, with quantitative validation against pathology and clinical follow-up.

 描述(申请人提供)：该项目的目标是开发和测试一种围手术期共聚焦成像引导的方法，用于激光消融基底细胞癌(BCC)。基底细胞癌是世界上最常见的恶性肿瘤之一，据估计，美国每年有250万例新诊断病例，欧洲和澳大利亚有70万例。冷冻病理指导下的Mohs手术是标准的治疗方法。然而，这一过程是劳动密集型和昂贵的，在美国每年的治疗费用约为20亿美元。因此，侵入性更小、成本更低的非手术替代疗法正越来越多地被采用。激光消融对于微创切除浅表和早期结节类型的基底细胞癌特别有效(美国每年约有60万例，欧洲和澳大利亚每年约20万例)。皮肤可以在受控的方式下以微米薄层的方式被烧蚀。然而，组织被汽化，因此没有可用于立即进行病理评估的肿瘤的存在或清除。(有人可能会说，病人身上还有“大量组织”可以用来做病理检查，但这将违背较小侵入性手术的根本目的。)缺乏病理反馈导致疗效参差不齐，治愈率有限。一种高分辨率的核水平光学成像方法，如共聚焦显微镜，可以直接检测患者身上残留的基底细胞癌的存在或清除，并提供立即的病理样反馈。然而，消融会在剩余的底层组织(伤口)中产生热凝和活力丧失，这可能会阻碍对比剂的摄取，以标记核形态和残余肿瘤的成像。我们的假设是，通过选择最佳的消融参数(脉冲持续时间、剂量、脉冲数量、波长)来控制热凝，可以保持足够的组织活力。这可能随后允许摄取造影剂和检测体内残留的基底细胞癌肿瘤。这种影像引导的方法可以提高表浅和早期结节状基底细胞癌的消融疗效和治愈率。每年，全球约有80万名患者可能会受益于一种侵入性较小的手术。对切除的人类皮肤样本的初步研究证实了我们的假设。在体内对五个基底细胞癌的测试表明，围手术期直接在患者身上成像来指导消融是可能的。其具体目的是(1)调查基本伤口中组织的热凝深度和活性与两个消融参数(剂量、脉冲次数)的关系，并确定保持足够的存活率的最佳参数；(2)确定人体皮肤标本中对比剂(醋酸)的摄取与最佳消融参数的对比，并与病理进行定量验证；(3)通过检测人体皮肤标本上的BCC清除与最佳消融参数的可行性来模拟在体内实施，与最佳消融参数进行对照病理的定量验证；(4)验证围手术期影像引导消融的可行性，并与病理对照和临床随访进行定量验证。