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（由申请人提供）：本项目的目标是开发和测试用于基底细胞癌（BCC）激光消融的围手术期共聚焦成像引导方法。BCC是世界上最常见的恶性肿瘤之一，估计美国每年诊断出250万例新病例，欧洲和澳大利亚为70万例。莫氏手术，由冷冻病理学指导，是标准的治疗。然而，该手术是劳动密集型的且昂贵的，在美国每年的治疗费用约为20亿美元。因此，越来越多地采用侵入性较低和较便宜的非手术替代疗法。激光消融对于浅表和早期结节型BCC的微创切除特别有效（美国每年约60万例，欧洲和澳大利亚每年约20万例）。可以以受控的方式在μ m薄层中消融皮肤。然而，组织被汽化，使得没有可用于立即病理学评价肿瘤的存在或清除。(One可能会说，有“大量的组织”留在病人身上，可以采取病理学，但这将击败一个微创方法的目的。病理反馈的缺乏导致疗效不一和治愈率有限。高分辨率的核水平的光学成像方法，如共聚焦显微镜可以检测残留BCC的存在或清除直接在病人身上，并提供即时的病理反馈。然而，消融在剩余的下层组织（伤口）中产生热凝固和活力丧失，这可能随后阻碍用于标记核形态和残留肿瘤成像的造影剂的摄取。我们的假设是，通过选择最佳消融参数（脉冲持续时间、能量密度、脉冲数、波长）控制热凝固，可以保留足够的组织活力。这随后可以允许摄取造影剂并检测体内残留的BCC肿瘤。这种成像引导的方法可以提高浅表和早期结节性基底细胞癌的消融疗效和治愈率。每年约有800，000名患者（全世界）可能受益于微创手术。对人类皮肤标本的初步研究证实了我们的假设。对五个BCC的体内测试证明了直接对患者进行围手术期成像以指导消融的潜力。具体目的是（1）研究热凝固深度和下层伤口中组织的活力与两种消融参数的关系（注量，脉冲数），并确定最佳参数，以保持足够的活力;（2）确定造影剂的摄取（乙酸）与切除的人类皮肤样本中的最佳消融参数的比较，并针对病理学进行定量验证;（3）通过测试相对于最佳消融参数检测切除的人类皮肤样本上的BCC的清除的可行性，模拟在体内对患者的实施;（4）测试对患者的围手术期成像引导消融的可行性，针对病理学和临床随访进行定量验证。