Two Photon Fluorescence Microscopy for Basal Cell Carcinoma

Overseen By Michael Giacomelli, Ph.D.

Age: Any Age

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: 1

Duration: 1 day

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to detect any remaining basal cell carcinoma, a common type of skin cancer, during standard skin surgery. The trial employs a special imaging technique called two-photon fluorescence microscopy to closely examine the edges of the removed tissue. This ensures the effective removal of all cancerous cells. Candidates may qualify if they are being treated for basal cell carcinoma without undergoing Mohs surgery and can understand the consent form. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance cancer detection methods.

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

The trial protocol does not specify if you need to stop your current medications.

What prior data suggests that Two Photon Fluorescence Microscopy is safe for detecting residual basal cell carcinoma?

Research has shown that two-photon fluorescence microscopy can reveal details in tissue using special light. Researchers are studying this technique to determine if it can help doctors identify skin cancer cells during surgery. However, specific information about its safety in detecting basal cell carcinoma in humans is not yet available.

The trial is labeled as "Not Applicable" in terms of phases, indicating a focus on testing the technology itself rather than a new drug or treatment. This also means direct safety information from human trials is not yet available. When a study is in its early stages or not assigned a specific phase, the technology is still being tested for practical use.

Prospective participants might find it helpful to discuss any risks or experiences from other studies using similar technology with the study organizers. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Two Photon Fluorescence Microscopy (TPFM) for basal cell carcinoma because it offers a novel way to examine surgical margins during tumor removal. Unlike traditional methods that rely on visual assessment or post-surgery histology, TPFM uses advanced imaging to precisely determine the distance from the tumor to the nearest inked margin in real-time. This technique could enhance surgical accuracy, potentially reducing the need for additional surgeries and improving patient outcomes.

What evidence suggests that Two Photon Fluorescence Microscopy is effective for detecting basal cell carcinoma?

Research has shown that two-photon fluorescence microscopy (TPFM) effectively detects basal cell carcinoma, a common type of skin cancer. One study demonstrated that TPFM accurately identified all cancerous cells without error, detecting every cancer cell and not misidentifying healthy cells as cancerous. In this trial, TPFM will image surgical margins of excised tissue to determine the distance from the tumor to the nearest inked margin. This detailed imaging method allows doctors to see deep into the skin, making it easier to spot any remaining cancer cells during surgery. This real-time check can enhance the success of skin cancer treatments by ensuring the removal of all cancerous tissue. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael Giacomelli

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

This trial is for individuals with basal cell carcinoma, a type of skin cancer. It's designed to see if a special imaging technique can help during surgery to remove the cancer.

Inclusion Criteria

Able to read and understand consent form

I am being treated for basal cell carcinoma without Mohs surgery.

Exclusion Criteria

N/A

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Excised tissue will be imaged with TPFM to determine the distance from tumor to nearest inked margin

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Two Photon Fluorescence Microscopy

Trial Overview The study is testing two photon fluorescence microscopy imaging. This technology is used during surgery to check if all the cancer has been removed.

How Is the Trial Designed?

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

Excised tissue will be imaged with TPFM to determine the distance from tumor to nearest inked margin.

Two Photon Fluorescence Microscopy 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 basal cell carcinoma
• Residual tumor detection during surgical excision

Approved in European Union as Two Photon Fluorescence Microscopy for:

• Diagnostic tool for nonmelanoma skin cancers
• Point-of-care diagnosis

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]

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]

In a study of 579 treatment-naive patients with various types of glaucoma, preservative-free tafluprost 0.0015% significantly reduced intraocular pressure (IOP) from a baseline of 23.6 mmHg to 16.8 mmHg after 3 months, demonstrating its efficacy in managing glaucoma.

The treatment was well tolerated, with 97.9% of patients continuing therapy after 3 months, indicating a favorable safety profile for this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preservative-free tafluprost in the treatment of naive patients with glaucoma and ocular hypertension. Lanzl, I., Hamacher, T., Rosbach, K., et al.[2021]

In a study involving 382 patients with 430 basal cell carcinoma (BCC) lesions, autofluorescence and fluorescence imaging were effective in distinguishing between different types of skin lesions and assessing the extent of neoplastic infiltration.

The research led to the development of diagnostic algorithms based on fluorescence intensity profiles, which could enhance the accuracy of diagnosing BCC and potentially guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can fluorescence and autofluorescence imaging be useful in diagnosis of basal cell cancer? Proposition of algorithms. Kwiatek, S., Kawczyk-Krupka, A., Mańka, E., et al.[2021]

Multiphoton microscopy (MPM) can effectively differentiate collagen changes in basal cell carcinoma (BCC) subtypes compared to normal skin and benign lesions, potentially reducing the need for invasive biopsies.

The study found that collagen surrounding BCC nests is more aligned than in normal skin, and that the orientation of collagen varies with BCC aggressiveness, suggesting that MPM could aid in both diagnosing and prognosticating BCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative collagen analysis using second harmonic generation images for the detection of basal cell carcinoma with ex vivo multiphoton microscopy. Sendín-Martín, M., Posner, J., Harris, U., et al.[2023]

Timolol maleate showed a small but significant dose-related reduction in intraocular pressure (IOP) in normotensive rabbits, even affecting the untreated fellow eye, indicating its potential systemic effect.

The combination of timolol and trifluormethazolamide (TFM) resulted in a greater reduction in IOP compared to TFM alone, although the increase in efficacy was modest, suggesting that while combined treatments can enhance hypotensive effects, they may not produce a synergistic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of separate and combined topical treatment with timolol maleate and trifluormethazolamide on the intraocular pressure in normal rabbits. Bar-Ilan, A.[2019]

This study found that using two-photon excitation to image endogenously formed protoporphyrin IX (PpIX) does not enhance tumor contrast in superficial basal cell carcinomas, as the PpIX signal is overwhelmed by the tissue's autofluorescent background.

To improve imaging of PpIX in clinical settings, the study suggests using a wavelength that induces one-photon anti-Stokes fluorescence, which could help overcome the limitations of autofluorescence in multiphoton microscopy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Stokes fluorescence from endogenously formed protoporphyrin IX--implications for clinical multiphoton diagnostics. Kantere, D., Guldbrand, S., Paoli, J., et al.[2023]

Ex vivo fluorescence confocal microscopy (FCM) effectively images nonpigmented nail tumours in real-time, allowing for immediate assessment during surgery, which can potentially shorten treatment time.

The study found excellent correlation between FCM imaging and conventional histopathology for malignant tumours, suggesting that FCM could help in making quick decisions about surgical margins during procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative diagnosis of nonpigmented nail tumours with ex vivo fluorescence confocal microscopy: 10 cases. Debarbieux, S., Gaspar, R., Depaepe, L., et al.[2015]

A multidimensional non-linear laser imaging technique was successfully used to visualize and differentiate basal cell carcinoma (BCC) from healthy skin samples, revealing distinct morphological and biochemical differences.

The use of aminolevulinic acid as a contrast agent improved the detection of tumor borders, supporting the potential for non-invasive imaging methods in diagnosing BCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidimensional non-linear laser imaging of Basal Cell Carcinoma. Cicchi, R., Massi, D., Sestini, S., et al.[2019]

In a study of 10 ex vivo skin samples, researchers found that basal cell carcinoma (BCC) exhibited significantly lower signals of nicotinamide adenine dinucleotide hydride (NADH) and collagen compared to healthy skin, indicating altered cellular and structural properties in BCC.

Advanced imaging techniques, such as two-photon excitation fluorescence and second harmonic generation, showed promise for improving the identification of BCC tumor borders, which could enhance surgical outcomes by providing better visualization of tumor margins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Analysis on Ex Vivo Nonlinear Microscopy Images of Basal Cell Carcinoma Samples in Comparison to Healthy Skin. Kiss, N., Haluszka, D., Lőrincz, K., et al.[2021]

In a study of 30 glaucoma patients with superficial punctate keratitis (SPK), switching to BAK-optimized tafluprost significantly improved the ocular surface condition, as indicated by a decrease in the superficial punctate keratitis score from 3.4 to 1.8 after 12 weeks (P<0.0001).

The treatment also effectively maintained intraocular pressure control, with a significant reduction from 15.6 mm Hg to 14.4 mm Hg (P<0.01), while improving tear film breakup time from 6.3 to 8.0 seconds (P<0.01).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Benzalkonium Chloride-optimized Tafluprost in Japanese Glaucoma Patients With Existing Superficial Punctate Keratitis. Suzuki, K., Teranishi, S., Sagara, T., et al.[2022]

In a study of 32 patients with primary open-angle glaucoma or ocular hypertension, the fixed combination of timolol maleate and latanoprost (TLFC) given once daily in the evening significantly reduced intraocular pressure (IOP) more than the twice-daily treatment of brimonidine and timolol, with a mean IOP decrease from 20.9 mmHg to 17.9 mmHg (p = 0.02).

Both treatment regimens had similar side effects, indicating that TLFC is not only more effective in lowering IOP but also maintains a comparable safety profile to the brimonidine and timolol combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of timolol maleate/latanoprost fixed combination versus timolol maleate and brimonidine given twice daily. Stewart, WC., Stewart, JA., Day, D., et al.[2019]

Tafluprost 0.0015% and latanoprost 0.005% both effectively lowered intraocular pressure (IOP) in patients with glaucoma, achieving maximum reduction by Day 7 and maintaining effects until Day 42, with similar overall efficacy.

Both treatments were well tolerated, with comparable rates of adverse events; however, tafluprost had a higher incidence of severe ocular adverse events (16% in the tafluprost group).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study on the duration and stability of the intraocular pressure-lowering effect and tolerability of Tafluprost compared with latanoprost. Traverso, CE., Ropo, A., Papadia, M., et al.[2018]

Citations

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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. 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.

3. ovid.com ovid.com/journals/jaderm/pdf/10.1001/jamadermatol.2022.3510~future-potential-of-2-photon-fluorescence-microscopy-in-mohs

Future Potential of 2-Photon Fluorescence Microscopy in Mohs ... the use of a 2-photon fluorescence microscopy (TPFM) sys- tem to diagnose basal cell carcinoma with perfect accuracy. (100% sensitivity and specificity), and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11501964/

and time-resolved two-photon microscopy - PMC Multidimensional quantitative characterization of basal cell carcinoma by spectral- and time-resolved two-photon microscopy

5. opg.optica.org opg.optica.org/vjbo/fulltext.cfm?uri=oe-15-16-10135

Multidimensional non-linear laser imaging of Basal Cell ... Two-photon excitation (TPE) fluorescence microscopy is a high-resolution laser imaging technique enabling deep optical tissue imaging [1,2].

6. withpower.com withpower.com/trial/two-photon-fluorescence-microscopy-for-basal-cell-carcinoma-9ac26

Two Photon Fluorescence Microscopy for Basal Cell ... The provided research does not contain any safety data related to Two Photon Fluorescence Microscopy or its variants for Basal Cell Carcinoma.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4607557/

In Vivo Multiphoton Microscopy of Basal Cell Carcinoma Multiphoton microscopy selectively visualizes the cellular and extracellular matrix based on 2-photon excited fluorescence (TPEF) from NADH, FAD, melanin ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0022202X15338690

Multiphoton Laser Scanning Microscopy on Non- ... This study describes the morphologic features of human non-melanoma skin cancer obtained using multiphoton laser scanning microscopy (MPLSM) on freshly ...

9. researchgate.net researchgate.net/publication/377357836_Multidimensional_quantitative_characterization_of_basal_cell_carcinoma_by_spectral-_and_time-resolved_two-photon_microscopy

Multidimensional quantitative characterization of basal cell ... This study combined spectral- and time-resolved two-photon microscopy with a spectral phasor to extract rich biochemical information describing ...

10. mdpi.com mdpi.com/2079-9284/12/3/111

Two-Photon Microscopy for the Investigation of ... Two infrared photons (800 nm each) are absorbed simultaneously by a fluorophore, promoting it from the ground state (S0) to an excited electronic state (Sn). A ...