Optical Imaging for Preoperative Delineation of Nonmelanoma Skin Cancers

The purpose of the study is to evaluate the ability and efficacy of using a
polarization-enhanced reflectance and fluorescence imaging device, PERFIS, (see the Device
Brochure) for demarcation of nonmelanoma skin cancer margins prior to surgery. PERFIS is a
harmless and non-invasive device that has been used to image biological tissue both in vitro
and in vivo. In this study it will be used to image nonmelanoma skin cancer lesions prior to
surgery. The use of PERFIS will not affect patient care or treatment decisions in any way.
No extra tissue will be used for imaging.

Prior to imaging, the patient's lesion will be prepared, and cleansed per routine aseptic
technique. Based on visual inspection, the major and minor axes of the tumor will be marked
exactly at the apparent tumor margins, to ensure unbiased tumor excision. For marking, the
investigators will use a sterile blue marking pen that will not be visualized in the optical
polarization images at 440 nm. After marking, the length of the major and minor axes of the
tumor will be measured using a ruler. A photograph of the tumor (and ruler as a reference
scale) will be taken. After measuring and photographing, polarized reflectance optical
imaging using the PERFIS device will be performed.

Photographs of the PERFIS imaging device are presented in the Device Brochure. During
imaging, the tumor and surrounding skin will be illuminated by a continuous wave low
intensity monochromatic light from a non-coherent light source (Xe-arc lamp combined with
interference filters) at the wavelength of 440 nm, with a power density on the skin of
approximately 0.4 mW/cm2. This power density is well below standard safety thresholds. No
other wavelengths or power densities will be utilized in this study. The light illuminator
is controlled by a shutter which remains closed except during user-controlled image capture.
Imaging will be initiated once the PERFIS device is positioned on the surface of the
patient's skin. The shutter opens and closes automatically to facilitate imaging. This
process ensures light will be transmitted only to the surface of the skin, thus minimizing
the risk of potential accidental eye exposure. Imaging requires only a few minutes and is
entirely noninvasive.

After imaging, local anesthesia will be administered, using 1% lidocaine with epinephrine by
deep dermal infiltration. The lesion will be prepared and cleansed per routine aseptic
technique. Surgical excision of the tumor will be performed using standard Mohs technique. A
regular photograph of the wound bed (and ruler as reference) will be taken. No extra tissue
will be excised for research imaging purposes.

The excised tumor lesion will then undergo standard Mohs frozen histopathological
preparation with Hematoxylin and Eosin (H&E) staining. Dr. Neel will analyze the
histological slides and record presence and location of residual tumor cells. He will not
utilize the images generated by PERFIS for his clinical decision making. After confirming
that the excision margins are free of tumor cells by histological evaluation, standard
post-Mohs protocol will be performed.

This is the first in-human trial of PERFIS collagen imaging to assist in tumor detection.
Therefore, the investigators plan to acquire a set of qualitative training images that can
also be subjected to a quasi-quantitative analysis if the device yields potentially valuable
information for localizing tumor. Forty patients (i.e. 40 tumors) will be imaged
pre-operatively to assess collagen irregularity or distortion at the operative site. The
Mohs surgeon will then mark the boundaries of surgical site for excision and a white light
image of this pre-surgical marking will be captured.

There are two possible outcomes during histopathological analysis of the tumor sample
following the first excisional stage of Mohs surgery: either the tumor margins are "clear,"
meaning no tumor is present at the boundaries of the surgeon's pre-surgical marking, or the
tumor margins are "positive," meaning that all or some of the surgical margin still has
tumor present. Residual tumor can be localized topologically to the original tumor specimen
so it can removed during an additional stage of Mohs excision.

In the first case of "clear" tumor margins, the surgeon's pre-surgical estimate was
sufficient and the Mohs procedure is completed. In this situation, PERFIS images of the
pre-surgical site will be overlain upon the digital images of the surgeon's primary markings
to determine if collagen distortion was present outside of the surgeon's original markings.
The presence of collagen distortion beyond the surgeon's original marking would indicate
failure of PERFIS to provide utility in guiding pre-surgical marking, since PERFIS would
overestimate the extent of tumor spread at the margins. If collagen distortion lies within
the pre-surgical marking of the surgeon, this would indicate that PERFIS could be useful in
guiding pre-surgical marking.

In the second case of "positive" tumor margins, the PERFIS image will again be overlain upon
the digital image of the pre-surgical marking by the surgeon. If PERFIS detects collagen
distortion in the area of tumor positivity such that the surgeon's pre-surgical marking
would be altered to include more inconspicuous tumor, and hence reduce the need for
additional excision after histological analysis, then the PERFIS analysis will be graded as
successful. PERFIS would provide utility in guiding pre-surgical marking in this case.

There may be areas of the PERFIS image that show distortion in both "normal" margins and in
areas with histologically-proven tumor. In this case, PERFIS will be graded as a failure
since extra, normal skin would be sacrificed if the surgeon relied on PERFIS images for
pre-surgical marking and excision.

At the conclusion of the study, meaningfulness of the image results and their applicability
to clinical practice will be discussed, along with the limitations of this subjective
evaluation. With an image set of 40 cases the investigators will be able to present an
argument whether further research with this technology is promising and would be of benefit
to a surgeon for delineating pre-surgical margins prior to excision. A larger, more thorough
quantitative analysis will be postponed to the next phase of study and development.

Inclusion Criteria:

- Male or female subjects, aged 18 and older, of any race or skin type

- At least one biopsy-proven nonmelanoma skin cancer, scheduled to be treated by Mohs
micrographic surgery

Exclusion Criteria:

- Pregnant women

- Patients with tumors within 1 cm of the eye

- Patients with tumors larger than 2 cm in diameter