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 m-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.

Public Health Relevance

Reflectance confocal microscopy (RCM) is an optical imaging technology that noninvasively detects melanoma and non-melanoma skin cancers on patients. RCM imaging is helping guide diagnosis and surgery, and reducing the need for biopsy. Our proposal for RCM imaging-guided laser ablation may offer a less invasive approach, instead of traditional surgery, for treatment of certain types of non-melanoma skin cancers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB020029-03
Application #
9280970
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Krosnick, Steven
Project Start
2015-09-11
Project End
2019-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
3
Fiscal Year
2017
Total Cost
$550,785
Indirect Cost
$237,661
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
Research Institutes
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
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Iftimia, Nicusor; Yélamos, Oriol; Chen, Chih-Shan J et al. (2017) Handheld optical coherence tomography-reflectance confocal microscopy probe for detection of basal cell carcinoma and delineation of margins. J Biomed Opt 22:76006
Yélamos, Oriol; Hibler, Brian P; Cordova, Miguel et al. (2017) Handheld Reflectance Confocal Microscopy for the Detection of Recurrent Extramammary Paget Disease. JAMA Dermatol 153:689-693
Kose, Kivanc; Gou, Mengran; Yélamos, Oriol et al. (2017) Automated video-mosaicking approach for confocal microscopic imaging in vivo: an approach to address challenges in imaging living tissue and extend field of view. Sci Rep 7:10759
Sierra, Heidy; Yélamos, Oriol; Cordova, Miguel et al. (2017) Reflectance confocal microscopy-guided laser ablation of basal cell carcinomas: initial clinical experience. J Biomed Opt 22:1-13
Abeytunge, Sanjee; Larson, Bjorg; Peterson, Gary et al. (2017) Evaluation of breast tissue with confocal strip-mosaicking microscopy: a test approach emulating pathology-like examination. J Biomed Opt 22:34002
Yélamos, Oriol; Cordova, Miguel; Blank, Nina et al. (2017) Correlation of Handheld Reflectance Confocal Microscopy With Radial Video Mosaicing for Margin Mapping of Lentigo Maligna and Lentigo Maligna Melanoma. JAMA Dermatol 153:1278-1284
Sierra, Heidy; Damanpour, Shadi; Hibler, Brian et al. (2016) Confocal imaging of carbon dioxide laser-ablated basal cell carcinomas: An ex-vivo study on the uptake of contrast agent and ablation parameters. Lasers Surg Med 48:133-9
Hibler, B P; Sierra, H; Cordova, M et al. (2016) Carbon dioxide laser ablation of basal cell carcinoma with visual guidance by reflectance confocal microscopy: a proof-of-principle pilot study. Br J Dermatol 174:1359-64