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

基本信息

批准号：
9143766
负责人：
MILIND RAJADHYAKSHA
金额：
$ 53万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
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/9143766
关键词：
Ablation Acetic Acids Address Adopted Alternative Therapies 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 Health 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 microscopic imaging minimally invasive optical imaging standard care tumor uptake wound

项目摘要

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）：该项目的目标是开发和测试围手术期共聚焦成像引导的基底细胞癌（BCC）激光消融方法，BCC 是世界上最常见的恶性肿瘤之一。据估计，美国每年诊断出 250 万例新病例，欧洲和澳大利亚诊断出 70 万例，以冷冻病理学为指导的莫氏手术是标准治疗方法。激光消融是一种劳动密集型且昂贵的治疗方法，每年的治疗费用约为 20 亿美元，在美国，越来越多地采用侵入性较小且非手术较少的替代疗法，对于昂贵的浅表和早期结节类型的微创切除特别有效。 BCC（美国每年约 600,000 例，欧洲和澳大利亚约 200,000 例）可以通过可控方式将皮肤消融成微米薄层。组织被蒸发，因此无法立即对肿瘤的存在或清除进行病理评估（有人可能会说患者身上残留有“大量组织”可用于病理学，但这会达不到目的。）缺乏病理反馈会导致疗效参差不齐，治愈率有限。诸如共聚焦显微镜之类的高分辨率核级光学成像方法可以直接检测患者身上残留 BCC 的存在或清除，并提供治疗方法。即时然而，消融会在剩余的底层组织（伤口）中产生热凝固和活力丧失，这可能随后阻碍用于标记残留肿瘤的核形态和成像的造影剂的摄取。可以通过控制热凝固并选择消融参数（脉冲持续时间、能量密度、脉冲数、波长）来保留活力，这随后可以允许摄取造影剂并检测体内残留的BCC肿瘤。影像引导方法可以提高浅表和早期结节性 BCC 消融的疗效和治愈率，通过对切除的人体皮肤标本进行的初步研究，每年大约有 800,000 名患者可能受益。对五个体内 BCC 的研究证明了直接对患者进行围手术期成像以指导消融的潜力，具体目标是 (1) 研究热凝固深度和组织活力。基础伤口与两个消融参数（注量、脉冲数）的比较，并确定保持足够活力的最佳参数；（2）确定对比剂（乙酸）的摄取与切除的人体皮肤标本中的最佳消融参数，并进行定量验证对照病理学；(3) 通过测试在切除的人体皮肤标本上检测 BCC 清除率与定量最佳消融参数的可行性，模拟在患者体内的实施，并根据病理学进行验证；(4) 测试围手术期成像引导的可行性；对患者进行消融，并根据病理学和临床随访进行定量验证。