Two Photon Microscopy for Skin Cancer

Overseen By Michael G Giacomelli, Ph.D

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Rochester

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: During Mohs surgery

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how effectively a new imaging method, called two-photon microscopy imaging, detects residual basal cell carcinoma (a common type of skin cancer) during Mohs surgery. The researchers seek to determine if this imaging technique matches the current method, frozen section histology, in verifying complete cancer removal. Candidates for this trial include those undergoing Mohs surgery for basal cell carcinoma at the study site who can read and understand the consent form. As an unphased trial, this study provides a unique opportunity to contribute to the advancement of imaging techniques in skin cancer surgery.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that two photon microscopy imaging is safe for detecting residual basal cell carcinoma?

Research has shown that using two-photon fluorescence microscopy on human skin is safe. In one study, over 70% of skin cells remained healthy even at the microscope's highest power, indicating that the cells stayed healthy and the microscope did not irritate the skin.

Additionally, other skin studies have used two-photon microscopy without reporting any serious side effects, suggesting it is generally well-tolerated. However, as with any medical procedure, individual differences should be considered, and consultation with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about two photon microscopy (TPFM) for skin cancer because it offers a non-invasive way to evaluate surgical margins during skin cancer removal. Unlike traditional methods that rely on physical tissue removal and histopathological examination, TPFM imaging allows doctors to visualize the cellular structure of the skin in real-time, potentially reducing the need for additional surgeries. This technique could lead to quicker, more accurate assessments, helping to ensure all cancerous cells are removed while preserving as much healthy tissue as possible.

What evidence suggests that two photon microscopy is effective for detecting skin cancer?

Research has shown that two-photon fluorescence microscopy (TPFM), a special imaging method, can help detect nonmelanoma skin cancers, such as basal cell carcinoma, during surgery. In this trial, participants will undergo TPFM imaging of surgical margins. Studies have found that TPFM provides real-time images, enabling doctors to see cancer cells as they operate, which helps ensure the removal of all cancerous tissue. Previous research suggests TPFM effectively spots cancer cells in skin samples. This imaging technique could revolutionize fast and accurate diagnosis during skin cancer surgeries. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael G Giacomelli, Ph.D

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

This trial is for individuals who can read and understand a consent form and are currently undergoing Mohs surgery for basal cell carcinoma (BCC) at the location where the study is being conducted.

Inclusion Criteria

I am receiving Mohs surgery for basal cell carcinoma at the study site.

Able to read and understand consent form

Exclusion Criteria

Not applicable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Mohs surgery with TPFM imaging of surgical margins followed by standard of care frozen section analysis

During Mohs surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Two photon microscopy imaging

Trial Overview The study is testing two photon fluorescence microscopy to see if it's as good as the standard frozen section histology in identifying cancerous tissue during Mohs surgery for BCC.

How Is the Trial Designed?

Group I: TPFM imaging of surgical margins Experimental Treatment 1 Intervention

Patients will be imaged with TPFM

Two photon microscopy imaging is already approved in United States, European Union for the following indications:

Approved in United States as Two-photon fluorescence microscopy for:

• Diagnostic tool for non-melanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma

Approved in European Union as Two-photon fluorescence microscopy for:

• Research and diagnostic tool for skin cancers, including basal cell carcinoma

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Rochester Dermatologic Surgery

Collaborator

Trials

2

Recruited

140+

Published Research Related to This Trial

Two-photon microscopy (TPM) techniques, including two-photon excitation fluorescence microscopy and second harmonic generation microscopy, are increasingly being used in cancer research to study human tissue pathology both ex vivo and in vivo.

These advanced imaging methods have the potential to significantly enhance the translation of cancer research into clinical practice, paving the way for minimally invasive diagnostic and therapeutic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-photon and second harmonic microscopy in clinical and translational cancer research. Perry, SW., Burke, RM., Brown, EB.[2021]

The study used multiphoton microscopy (MPM) and fluorescence lifetime imaging microscopy (FLIM) to analyze skin differences between 30 young individuals and 19 elderly patients, revealing significant morphological changes in the skin of older adults.

Elderly subjects exhibited smaller cell and nucleus sizes, decreased basal cell numbers, and increased fluorescence lifetimes, indicating age-related alterations in skin structure that could help clinicians differentiate between healthy and diseased skin states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative evaluation of healthy epidermis by means of multiphoton microscopy and fluorescence lifetime imaging microscopy. Benati, E., Bellini, V., Borsari, S., et al.[2018]

Multiphoton imaging of skin biopsies using specific irradiation regimes causes skin damage similar to that of everyday UV exposure, indicating a potential risk for skin health.

The study quantitatively assessed the effects of multiphoton irradiation compared to UV irradiation by measuring cyclobutane-pyrimidine dimers (CPDs), providing a basis for risk assessment in skin imaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the risk of skin damage due to femtosecond laser irradiation. Fischer, F., Volkmer, B., Puschmann, S., et al.[2014]

Two-photon fluorescence microscopy (TPFM) can provide rapid, point-of-care diagnoses of nonmelanoma skin cancers (NMSCs) within minutes, showing similar histological features to conventional histology based on a study of 29 biopsy specimens.

TPFM demonstrated high diagnostic performance with 100% sensitivity and specificity for basal cell carcinoma, and overall 93% sensitivity and 100% specificity for NMSC, indicating its potential as an effective alternative to traditional biopsy analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time Analysis of Skin Biopsy Specimens With 2-Photon Fluorescence Microscopy. Ching-Roa, VD., Huang, CZ., Ibrahim, SF., et al.[2023]

Two-photon fluorescence lifetime imaging (FLIM) is a non-invasive technique that has been successfully used in clinical studies to assess skin inflammation, skin cancer, and brain tumors, providing rapid and detailed insights into tissue health.

This advanced imaging method also has applications in cosmetic research and space medicine, allowing researchers to evaluate the effectiveness of anti-aging products and study skin changes in astronauts during long-term space missions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Clinical in vivo multiphoton FLIM tomography. König, K.[2021]

Two-photon laser scanning fluorescence microscopy (TPM) is effective for noninvasive imaging of human skin, allowing for three-dimensional visualization of both natural and introduced fluorescent markers, which is useful for studying drug delivery and skin diagnostics.

An image-analysis algorithm developed for TPM images can accurately identify cell nuclei in nonmelanoma skin cancer samples with a sensitivity of 82% and specificity of 78%, although it requires further refinement to detect multinucleated cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-photon laser-scanning fluorescence microscopy applied for studies of human skin. Ericson, MB., Simonsson, C., Guldbrand, S., et al.[2009]

Intravital two-photon microscopy is a cutting-edge imaging technology that allows researchers to observe live tissues in real-time with high resolution and minimal damage, making it superior to traditional methods like confocal microscopy.

This technique has significantly advanced our understanding of skin biology, including its immune responses and tumor development, by enabling detailed visualization of skin layers in both healthy and diseased states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Research Techniques Made Simple: Two-Photon Intravital Imaging of the Skin. Obeidy, P., Tong, PL., Weninger, W.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9453637/

Real-time Analysis of Skin Biopsy Specimens With 2-Photon ... The study results suggest that 2-photon fluorescence microscopy may facilitate real-time diagnosis of nonmelanoma skin cancers and other dermatologic ...

2. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/2795725

Real-time Analysis of Skin Biopsy Specimens With 2- ... The study results suggest that 2-photon fluorescence microscopy may facilitate real-time diagnosis of nonmelanoma skin cancers and other dermatologic ...

3. withpower.com withpower.com/trial/phase-carcinoma-basal-cell-5-2023-85459

Two Photon Microscopy for Skin Cancer · Info for Participants This trial aims to see if a special imaging technique called TPFM can help doctors find any remaining cancer cells during skin cancer surgery.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36069886/

Real-time Analysis of Skin Biopsy Specimens With 2-Photon ... Two-photon fluorescence microscopy (TPFM) has the potential for point-of-care diagnosis of NMSC and other dermatologic conditions, which could ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0092867424008304

Multiphoton fluorescence microscopy for in vivo imaging Multiphoton fluorescence microscopy (MPFM) has been a game-changer for optical imaging, particularly for studying biological tissues deep within living ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1011134425001332

Defining safe operational conditions for two-photon ... Results showed maintenance of cell viability (>70 %) across all laser intensities, with no indication of sensitization, as evidenced by low CD54 and CD86 ...

7. pubs.acs.org pubs.acs.org/doi/10.1021/cbmi.5c00066

From Optical to Molecular Imaging on Human Skin: A Review In dermatology, two-photon microscopy is particularly valuable for live-cell imaging, enabling the study of skin architecture, cellular ...

8. nature.com nature.com/articles/s41598-024-76908-7

Handheld multiphoton and pinhole-free reflectance ... Handheld multiphoton and pinhole-free reflectance confocal microscopy enables noninvasive, real-time cross-sectional imaging in skin. Kate L.