Optical coherence tomography-guided photodynamic therapy for skin cancer: Case study

doi:10.1016/j.pdpdt.2010.08.004

Photodiagnosis and Photodynamic Therapy

Volume 8, Issue 1, March 2011, Pages 49-52

https://doi.org/10.1016/j.pdpdt.2010.08.004 Get rights and content

Summary

Photodynamic therapy (PDT) has been identified as a successful therapy for skin cancer. This case study investigates the role of optical coherence tomography (OCT) in lesion (squamous cell carcinoma) mapping, assisting the surgeon to correctly deliver PDT and monitor the outcome. Optical coherence tomographic images were acquired pre-treatment to assess tumour extent and margins to enable guidance of the PDT. Tomographic images taken post-PDT up to 6 months revealed complete response to the treatment and no recurrence. OCT-guided PDT is one of the promising approaches to efficiently discriminate between tumor involved and noninvolved margins. It reduces the untoward healthy tissue necrosis and provides an encouraging monitoring of the healing process.

Introduction

Skin cancer, especially non-melanoma type, continues to be a major problem in the developed world with more than 100,000 new diagnoses per year. Non-melanoma skin cancer (NMSC) involves mainly squamous and basal cell carcinomas, SCC and BCC respectively. BCCs are mostly slow-growing local tumours with minimal invasion, while SCCs are fast-growing invading tumours and usually metastasise early to loco-regional lymph nodes [1].

There is currently no gold standard treatment modality; however surgery is advocated in many centres around the world. Radiotherapy is applied when positive margins are identified after surgical resection or even as a primary neoadjuvant modality. A few centres apply the Mohs micrographic surgery which can be costly (in set up, training and maintenance) and associated with some local morbidity. In this type of surgical resection the specialist surgeon/pathologist is required to provide an accurate assessment of the resected skin at every piecemeal resection [1]. The huge advantage of this technique is that it allows the surgical resection to be guided by the pathology reducing the extent of resection to achieve clear margins. Such a guided technique has distinct advantage over a ‘normal’ resection in terms of completeness of excision. Similarly radiotherapy which in some cases is used as the primary or only treatment modality may offer a ‘potential’ cure but at the cost of bystander tissue morbidity and ignorance of immediate treatment efficacy in terms of cancer cell death because of a lack of any histological information.

Photodynamic therapy (PDT) has been identified as a potential therapy for NMSC. PDT usually involves an interaction between a photosensitising drug, oxygen in the target tissue and the light delivered to that area. Photodynamic therapy using 5-ALA (for thin skin tumours) or mTHPC (for thicker ones) has been used successfully to eradicate SCCs and BCCS. In some studies, a complete response has been achieved with excellent cosmetic results and minimal scarring [1].

The treatment largely depends upon the operator in question and their experience in predicting the safe treatment margin [2]. Failure to achieve this may ultimately increase the probability of tumour recurrence. To avoid managing skin cancer empirically as is the current practice, an in vivo real time in situ imaging system seems necessary [3].

One of the most important clinical applications of optical coherence tomography (OCT) is the diagnosis of skin cancer [1], [2], [3]. However, it is role in mapping the tumour margin has yet to be explored. OCT is a laser assisted optical imaging technology (based on inferometry and akin to B mode ultrasonograpy except that it uses light) that allows a ‘virtual’ optical biopsy to be taken without the physical removal of tissue. In terms of margins comparison needs, OCT-guided PDT treatment provides a similar resolution to that guiding Mohs surgery but without the need to excise tissue. This reduces healthy bystander tissue damage and consequently reduces scarring. Since Mohs surgery is by necessity followed by surgical reconstruction.

This case study investigates the role of OCT in lesion mapping, assisting the surgeon to correctly deliver the treatment and in monitoring the healing after PDT for facial skin carcinoma [4], [5], [6]. To our knowledge, this case study reports the first application of OCT for in vivo imaging, mapping of non-melanoma skin cancer. Additionally, OCT may help clinicians to monitor the outcome after the treatment, improving their understanding of the technique and offering an indication of the possible result to the patients.

Section snippets

Case study

A 56-year-old Caucasian male was referred by his general practitioner to UCLH Head and Neck Unit in September 2009, for suspected basal cell carcinoma of the right infra-orbital region. The skin lesion began as a small slowly growing pinpoint boil which progressed to widespread skin breakdown, resulting in an ulcer of 2.2 cm × 2.6 cm. Physical examination revealed fixed ulcerated lesion with rigid irregular margins (Fig. 1). An incisional biopsy revealed a well differentiated squamous cell

Discussion

PDT is far from a simple technique of light activation of photoactive drugs. There are many variables which can be modified to achieve the best results with least complications [4], [5]. The dermatological applications of PDT have a long proven tract record of success; however it remains to be validated as a reliable modality in terms of the conservative management of lesions.

The main issue as clinicians we have with PDT (or for that matter any non excisional in situ treatment option) is the

References (6)

W. Jerjes et al.
In vitro examination of suspicious oral lesions using optical coherence tomography
Br J Oral Maxillofac Surg
(2010)
T. Gambichler et al.
In vivo optical coherence tomography of basal cell carcinoma
J Dermatol Sci
(2007)
C.S. Betz et al.
Optimization of treatment parameters for Foscan-PDT of basal cell carcinomas
Lasers Surg Med
(2008)

There are more references available in the full text version of this article.

Cited by (38)

In vivo optical coherence tomography in assessment of suspicious facial lesions: A prospective study
2021, Photodiagnosis and Photodynamic Therapy
Citation Excerpt :
The OCT scanner is a safe optical diagnostic technique. Because of the fast scanning mode and the low output power of the light source (in a range of a few milliwatts), the technique meets the safety standards for irradiation of tissue.[21] OCT have shown that there are qualitative differences in OCT image features of skin with varying degrees of pathology, and between normal and pathological skin.
Skin cancer continues to be the most common cancer in the Caucasian population. Over the past two decades, researchers around the world started assessing the possibility of diagnosing tissue pathologies by using optical systems. In this study, we aimed to use in vivo optical coherence tomography (OCT) technology to describe the morphologic features of normal and pathologic skin conditions.
In this study, 72 patients with suspected skin pre-cancer/cancer were recruited. The lesions were subjected to in vivo OCT scanning using compact size probe. The main scanned areas were the centre of the lesion, periphery of the lesion and control reading at least 2cm from the lesion periphery but within the same dermatomal distribution. Following assessment, each lesion was surgically excised. All acquired OCT images were correlated with the corresponding histopathology images to ensure an accurate diagnosis and appropriate co-localisation of abnormal lesion on both OCT image and pathology slide. This was achieved in every resected lesion.
Histopathological analysis revealed that of the 96 macroscopically suspicious scanned lesions 26 were actinic keratosis (AK), 51 were basal cell carcinoma (BCC) and 19 were cutaneous squamous cell carcinoma (SCC). Different layers of healthy skin can be distinguished with clear demarcation between the epidermis and papillary dermis. An increase in epidermal thickness was observed in OCT images in AK that appeared relatively hyperintense. Cutaneous SCC was characterized by hypoechoic signal free spaces within the dermis and damaged of dermal-epidermal junction. BCCs were visualized as hypoechoic structures but showed a mixed echogenicity. Solid nodular BCC appeared as single or multiple areas with no clear arrangement surrounding low-reflectivity lobular structures surrounded. Cystic structures were identifiable by signal-free areas adjacent to healthy skin. Sensitivity and specificity for in vivo OCT in diagnosing these lesions were impressive, based on this small sample size.
OCT have shown that there are qualitative differences in OCT image features of skin with varying degrees of pathology, and between normal and pathological skin. This study indicates that in vivo OCT shows a good promise as a useful optical diagnostic technique in diagnosing skin pathologies.
In vivo optical coherence tomography-guided photodynamic therapy for skin pre-cancer and cancer
2021, Photodiagnosis and Photodynamic Therapy
The primary aim of this prospective study is to demonstrate the technical feasibility of OCT to map real tumor margins and to monitor skin changes that occurred post- PDT. Moreover, to optimize PDT efficacy based on the relationship between measured OCT features and treatment outcome.
A series of 12 patients with overall 18 facial skin lesions were investigated by OCT before surface illumination by PDT to determine tumor free margins. Monitoring of the healing process was undertaken at 3, 6 and 12 months post-PDT. Parameters measured by the in vivo OCT during healing phase were the organization of skin layer and the degree skin fibroses for the active center and peripheral transit zone of the treated lesion. Clinical and aesthetics assessment was carried out at 12-month post-PDT.
Distinct microstructural differences between normal skin, pre-cancer, cancer, and the transition zone between the two tissues were observed on OCT images. In the subsequent healing phase, OCT demonstrate marked delineation and organization of skin layer at late stage of healing. Early features showing bizarre non-homogenous disorganized layering (scab) but afterwards, OCT was able to differentiate between different histological layers. One lesion demonstrated clinical healing by fibrosis (scar) without sign of recurrence. Another lesion demonstrated skin erythema. Only one lesion did not response to treatment despite margins clearance. The CR rate was 95% at the end of the study. The cosmetic effect was "excellent" in 89% of the patients.
This feasibility study lays the groundwork for using OCT as a real-time, noninvasive monitoring device for PDT in patients with skin cancer.
Emerging imaging technologies in dermatology: Part II: Applications and limitations
2019, Journal of the American Academy of Dermatology
Clinical examination is critical for the diagnosis and identification of response to treatment. It is fortunate that technologies are continuing to evolve, enabling augmentation of classical clinical examination with noninvasive imaging modalities. This article discusses emerging technologies with a focus on digital photographic imaging, confocal microscopy, optical coherence tomography, and high-frequency ultrasound, as well as several additional developing modalities. The most readily adopted technologies to date include total-body digital photography and dermoscopy, with some practitioners beginning to use confocal microscopy. In this article, applications and limitations are addressed. For a detailed discussion of the principles involved in these technologies, please refer to the first part of this review article.
Skin permeation, biocompatibility and antitumor effect of chloroaluminum phthalocyanine associated to oleic acid in lipid nanoparticles
2018, Photodiagnosis and Photodynamic Therapy
Citation Excerpt :
PDT may also be used to treat other dermatosis and non-melanoma skin cancers [5]. This therapy typically involves the interaction of a photosensitizer drug, oxygen and light irradiation at the treatment site [6]. Phthalocyanines are very efficient photosensitizers that preferentially accumulate in tumor tissues [7].
The objective of this study was to develop and characterize lipid nanoparticles (LNs) containing chloroaluminum phthalocyanine (ClAlPc) to reduce the aggregation of the drug and improve its skin penetration and its antitumor effect. LNs were prepared and characterized by using stearic acid (SA) as solid lipid and oleic acid (OA) as liquid lipid in different proportions. in vitro and in vivo skin penetration was evaluated using modified Franz diffusion cells and fluorescence microscopy, respectively. in vitro biocompatibility and Photodynamic Therapy (PDT) were performed using L929-fibroblasts cell line and A549 cancer cell line and melanoma BF16-F10, respectively. OA promoted the increase in the encapsulation efficiency and drug loading, reaching values of 95.8% and 4%, respectively. The formulation with 40% OA (NLC 40) showed a significantly higher (p < 0.01) amount of drug retained in the skin compared to other formulations. All formulations developed were considered biocompatible. PDT evidenced the antitumor efficacy of NLC 40 with reduced cell viability for approximately 10% of cancer cells, demonstrating that the presence of OA in the NLC seems to potentialize this antitumor effect. PDT in BF16-F10 melanoma using NLC 40 resulted in a reduction in mean cell viability of approximately 99%. According to the results obtained, the systems developed may be promising for the incorporation of ClAlPc in the treatment of skin cancer by photodynamic therapy.
Dynamic infrared imaging for skin cancer screening
2015, Infrared Physics and Technology
Citation Excerpt :
Since biopsies are intrusive and can be painful, different non-invasive techniques are being researched in order to minimize the number of excess biopsies performed [7,8]. Some of these techniques include multispectral (MS) imaging [9–11], digital dermatoscopy and videodermatoscopy (sequential digital dermatoscopy) [12,13], reflectance-mode confocal microscopy [14], ultrasound [15,16], laser Doppler perfusion imaging [17], and optical coherence tomography (OCT) [18,19], to name a few. Currently, there are two FDA-approved non-invasive imaging devices MelaFind™ and Vivosight Multi-Beam System™, which are based on MS imaging and OCT, respectively.
Dynamic thermal imaging (DTI) with infrared cameras is a non-invasive technique with the ability to detect the most common types of skin cancer. We discuss and propose a standardized analysis method for DTI of actual patient data, which achieves high levels of sensitivity and specificity by judiciously selecting pixels with the same initial temperature. This process compensates the intrinsic limitations of the cooling unit and is the key enabling tool in the DTI data analysis. We have extensively tested the methodology on human subjects using thermal infrared image sequences from a pilot study conducted jointly with the University of New Mexico Dermatology Clinic in Albuquerque, New Mexico (ClinicalTrials ID number NCT02154451). All individuals were adult subjects who were scheduled for biopsy or adult volunteers with clinically diagnosed benign condition. The sample size was 102 subjects for the present study. Statistically significant results were obtained that allowed us to distinguish between benign and malignant skin conditions. The sensitivity and specificity was 95% (with a 95% confidence interval of [87.8% 100.0%]) and 83% (with a 95% confidence interval of [73.4% 92.5%]), respectively, and with an area under the curve of 95%. Our results lead us to conclude that the DTI approach in conjunction with the judicious selection of pixels has the potential to provide a fast, accurate, non-contact, and non-invasive way to screen for common types of skin cancer. As such, it has the potential to significantly reduce the number of biopsies performed on suspicious lesions.
Optical diagnostic techniques for use in lesions of the head and neck: Review of the latest developments
2014, British Journal of Oral and Maxillofacial Surgery
Citation Excerpt :
It has been used to guide photodynamic therapy in a patient with BCC, and after clinical assessment, showed that the surgical margin was more extensive than had appeared to the naked eye. The patient was examined 3, 6, and 12 months after treatment and it showed the delineation and organisation of the skin layers together with changes consistent with healing.23 Tumour-specific intrinsic fluorescence arises from tumour-induced morphogenic and biochemical alterations which change the way tissues interact with light.
Optical biopsy systems are a potential adjunct to the histopathological assessment of tissue specimens; they are not invasive and can give an immediate result. We review the most common optical biopsy techniques used to detect lesions of the head and neck: elastic scattering spectroscopy, microendoscopy, narrow band imaging, fluorescence, and optical coherence tomography, and discuss their clinical use.

View all citing articles on Scopus

View full text

Case Report/Research LetterOptical coherence tomography-guided photodynamic therapy for skin cancer: Case study

Summary

Introduction

Section snippets

Case study

Discussion

Br J Oral Maxillofac Surg

J Dermatol Sci

Optimization of treatment parameters for Foscan-PDT of basal cell carcinomas

Lasers Surg Med

Case Report/Research Letter
Optical coherence tomography-guided photodynamic therapy for skin cancer: Case study