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1
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Zalewski A, Musiał W, Jankowska-Konsur A. Photodynamic Therapy in Primary Cutaneous Skin Lymphoma-Systematic Review. J Clin Med 2025; 14:2956. [PMID: 40363989 PMCID: PMC12073078 DOI: 10.3390/jcm14092956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2025] [Revised: 04/21/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
Background/Objectives: Primary cutaneous lymphomas (CLs) are a group of skin-limited lymphoproliferative disorders, including cutaneous T-cell (CTCLs) and B-cell lymphomas (CBCLs). Photodynamic therapy (PDT), a non-invasive, light-activated treatment, has gained attention as a skin-directed therapy for early-stage CLs due to its selectivity and favorable safety profile. This systematic review evaluates the current evidence on the clinical use of PDT in managing CLs. Methods: A systematic literature search was conducted in PubMed, Scopus, and Embase through 1 September 2024 following PRISMA guidelines. Search terms included "primary cutaneous skin lymphoma", "CTCL", "CBCL", "mycosis fungoides", "lymphomatoid papulosis", and "photodynamic therapy". After screening 1033 records, 30 studies were included. Data were extracted and categorized by lymphoma subtype and clinical outcomes. Results: Of the included studies, 23 focused on mycosis fungoides (MF), 5 on lymphomatoid papulosis (LyP), and 2 on CBCL. PDT demonstrated notable clinical efficacy in early-stage and localized disease, particularly MF, using methyl aminolevulinate (MAL) or 5-aminolevulinic acid (5-ALA) as photosensitizers. Adjunctive techniques like microneedling and laser-assisted delivery improved treatment outcomes. PDT was generally well tolerated, with mild, transient side effects; rare complications such as localized neuropathy were reported. Conclusions: PDT is a promising, non-invasive treatment for early-stage CLs, especially MF and indolent CBCL variants. While current evidence supports its safety and effectiveness, further comparative and prospective studies are needed to refine protocols, evaluate long-term efficacy, and compare different photosensitizers.
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Affiliation(s)
- Adam Zalewski
- Clinical Department of Oncodermatology, University Centre of General Dermatology and Oncodermatology, Wroclaw Medical University, Borowska 213, 50-556 Wrocław, Poland;
| | - Witold Musiał
- Department of Physical Chemistry and Biophysics, Wroclaw Medical University, Borowska 211A, 50-556 Wrocław, Poland;
| | - Alina Jankowska-Konsur
- Clinical Department of Oncodermatology, University Centre of General Dermatology and Oncodermatology, Wroclaw Medical University, Borowska 213, 50-556 Wrocław, Poland;
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2
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Quaglino P, Pimpinelli N, Zinzani PL, Paulli M, Pileri S, Berti E, Cerroni L, Guitart J, Kim YH, Rupoli S, Santucci M, Simontacchi G, Vermeer M, Hoppe R, Pro B, Swerdlow SH, Barosi G. Identifying and addressing unmet clinical needs in primary cutaneous B-cell lymphoma: A consensus-based paper from an ad-hoc international panel. Hematol Oncol 2024; 42:e3215. [PMID: 37649350 DOI: 10.1002/hon.3215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 08/08/2023] [Accepted: 08/08/2023] [Indexed: 09/01/2023]
Abstract
Primary cutaneous B-cell lymphomas (PCBCLs) are lymphoproliferative disorders that appear on the skin without evidence of extracutaneous manifestations at the time of diagnosis. There is a lack of evidence-based guidelines for their clinical management due to the availability of very few large scale studies and controlled clinical trials. Here we present and discuss a series of major unmet clinical needs (UCNs) in the management of PCBCLs by a panel of 16 experts involved in research and clinical practice of PCBCL. The Panel produced recommendations on the appropriateness of the clinical decisions concerning the identified clinical needs and proposed research for improving the knowledge needed to solve them. Recommendations and proposals were achieved by multiple-step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. Recommendations and proposals lay in the domain of classification uncertainties of PCBCL, optimization of diagnosis, optimization of prognosis, optimization of staging and critical issues on therapeutic strategies with particular focus on new treatments. These recommendations are intended for use not only by experts but above all by dermatologists and hematologists with limited experience in the field of PCBCLs as well as general practitioners.
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Affiliation(s)
- Pietro Quaglino
- Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, Italy
| | - Nicola Pimpinelli
- Department of Health Sciences, Section of Dermatology, University of Florence, Florence, Italy
| | - Pier Luigi Zinzani
- IRCCS Azienda Ospedaliero-Universitaria di Bologna. Istituto di Ematologia "Seràgnoli", Bologna, Italy
- Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale. Università di Bologna, Bologna, Italy
- Istituto di Ematologia "Seràgnoli", Azienda Ospedaliero-Universitaria di Bologna - IRCCS, Bologna, Italy
| | - Marco Paulli
- Pathology Section, Department of Molecular Medicine, University of Pavia and Fondazione I.R.C.C.S. Policlinico "S.Matteo", Pavia, Italy
| | - Stefano Pileri
- IEO - European Institute of Oncology IRCCS (Milan) & Bologna University School of Medicine, Milano, Italy
| | - Emilio Berti
- Dermatology Unit, La Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, Milan, Italy
| | - Lorenzo Cerroni
- Department of Dermatology, Research Unit Dermatopathology, Medical University of Graz, Graz, Austria
| | - Joan Guitart
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Youn H Kim
- Department of Dermatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Serena Rupoli
- Clinica di Ematologia, Ospedali Riuniti di Ancona, Ancona, Italy
| | - Marco Santucci
- Pathology Unit, Careggi University Hospital, Florence, Italy
- Department of Health Sciences, Section of Pathological Anatomy, University of Florence, Florence, Italy
| | - Gabriele Simontacchi
- Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Maarten Vermeer
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Richard Hoppe
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Barbara Pro
- Northwestern University, Chicago, Illinois, USA
| | - Steven H Swerdlow
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Giovanni Barosi
- Center for the Study of Myelofibrosis, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy
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3
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Liu WT, Wang HT, Yeh YH, Wong TW. An Update on Recent Advances of Photodynamic Therapy for Primary Cutaneous Lymphomas. Pharmaceutics 2023; 15:pharmaceutics15051328. [PMID: 37242570 DOI: 10.3390/pharmaceutics15051328] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 04/16/2023] [Accepted: 04/22/2023] [Indexed: 05/28/2023] Open
Abstract
Primary cutaneous lymphomas are rare non-Hodgkin lymphomas consisting of heterogeneous disease entities. Photodynamic therapy (PDT) utilizing photosensitizers irradiated with a specific wavelength of light in the presence of oxygen exerts promising anti-tumor effects on non-melanoma skin cancer, yet its application in primary cutaneous lymphomas remains less recognized. Despite many in vitro data showing PDT could effectively kill lymphoma cells, clinical evidence of PDT against primary cutaneous lymphomas is limited. Recently, a phase 3 "FLASH" randomized clinical trial demonstrated the efficacy of topical hypericin PDT for early-stage cutaneous T-cell lymphoma. An update on recent advances of photodynamic therapy in primary cutaneous lymphomas is provided.
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Affiliation(s)
- Wei-Ting Liu
- Department of Dermatology, Cancer Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
| | - Han-Tang Wang
- Department of Dermatology, Cancer Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
| | - Yi-Hsuan Yeh
- School of Medicine, National Cheng Kung University, Tainan 701, Taiwan
| | - Tak-Wah Wong
- Department of Dermatology, Cancer Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
- Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
- Center of Applied Nanomedicine, National Cheng Kung University, Tainan 701, Taiwan
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4
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Toulemonde E, Faiz S, Dubois R, Verhasselt-Crinquette M, Carpentier O, Abi Rached H, Mortier L. Photodynamic therapy for the treatment of primary cutaneous B-cell marginal zone lymphoma: A series of 4 patients. JAAD Case Rep 2023; 33:62-66. [PMID: 36860806 PMCID: PMC9969199 DOI: 10.1016/j.jdcr.2022.12.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Affiliation(s)
- Elise Toulemonde
- Department of Dermatology, Claude Huriez Hospital, Lille University Hospital, Lille, France,Correspondence to: Elise Toulemonde, BA, 2 Ave Oscar Lambret, 59000, Lille, France.
| | - Sarah Faiz
- Department of Dermatology, Claude Huriez Hospital, Lille University Hospital, Lille, France,Department of Dermatology, Hospital of Douai, Douai, France
| | - Romain Dubois
- Department of Anatomopathology, Biology and Pathology Center Pierre-Marie Degand, CHU Lille, Lille, France
| | | | - Olivier Carpentier
- Department of Dermatology, Claude Huriez Hospital, Lille University Hospital, Lille, France,Department of Dermatology, Hospital of Roubaix, Roubaix, France
| | - Henry Abi Rached
- Department of Dermatology, Claude Huriez Hospital, Lille University Hospital, Lille, France
| | - Laurent Mortier
- Department of Dermatology, Claude Huriez Hospital, CARADERM and University of Lille, U1189 Inserm, Lille, France
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5
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Photodynamic Therapy as an Effective Treatment for Cutaneous Lymphomas. Pharmaceutics 2022; 15:pharmaceutics15010047. [PMID: 36678676 PMCID: PMC9861941 DOI: 10.3390/pharmaceutics15010047] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/13/2022] [Accepted: 12/16/2022] [Indexed: 12/25/2022] Open
Abstract
Topical photodynamic therapy (PDT) is a non-invasive treatment modality frequently used in dermatology to treat superficial skin cancers but also some inflammatory or infectious dermatoses. PDT appears a more and more promising therapeutic option also for cutaneous lymphomas, either of T- or B-cell origin. It is a well-tolerated treatment and has excellent cosmetic outcomes, less side effects compared to other therapies (steroids, surgery, radiotherapy, and so on), no particular contraindications, and is easily repeatable in case of relapses. However, how PDT works in the treatment of cutaneous lymphoproliferative diseases is poorly understood and the literature data are still controversial. Further randomized, controlled clinical trials involving a greater number of patients and centers with a long follow-up are necessary to assess the efficacy of PDT and establish a unique standardized treatment protocol in relation to the lymphomatous disease and the type, thickness, and location of the lesions.
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6
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Lang CCV, Ramelyte E, Dummer R. Innovative Therapeutic Approaches in Primary Cutaneous B Cell Lymphoma. Front Oncol 2020; 10:1163. [PMID: 32850331 PMCID: PMC7426470 DOI: 10.3389/fonc.2020.01163] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 06/09/2020] [Indexed: 01/03/2023] Open
Abstract
Background: Primary cutaneous B-cell lymphomas (pCBCL) include an infrequent group of non-Hodgkin lymphomas that are limited to skin sites at the time of diagnosis. They comprise roughly 20–25% of all cutaneous lymphomas and are subdivided into primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large cell B cell lymphoma, leg type (PCDLCBCL, LT). The first two show a rather indolent course while PCDLCBCL, LT carries a worse prognosis. Intravascular large cell B-cell lymphoma is the most infrequent subtype, and its therapy is not covered in this review. Topical Therapy: For solitary, single-site PCMZL and PCFCL, several topical treatment options exist. They include, but are not limited to, excision, radiotherapy, and intralesional therapies, discussed in this review. However, in selected cases, even “watchful waiting” is reasonable. Systemic Therapy: Indolent types of pCBCL rarely require systemic treatment. However, in extended cases and more importantly DLCBCL, LT, systemic treatment is the first choice. Monoclonal anti-CD20-antibody rituximab is often used as monotherapy in PCMZL and PCFCL or combined with chemotherapy in PCDLBCL, LT. Newer options are monoclonal anti-CD40 antibody dacetuzumab, anti-PD-1 and anti-PD-L1 checkpoint inhibitors, and Bruton tyrosine kinase inhibitors. Conclusion: Indolent pCBCL are treated with a risk-adapted strategy using intralesional steroids, RT, and interferon-α as first-line treatments. Relapsing cases may profit from rituximab. In aggressive PCDLCBCL, LT, rituximab with polychemotherapy is recommended. Innovative therapies include intralesional oncolytic virotherapy, systemic monoclonal antibodies, and small molecules.
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Affiliation(s)
- Claudia C V Lang
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.,Medical Faculty, University of Zurich, Zurich, Switzerland
| | - Egle Ramelyte
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.,Medical Faculty, University of Zurich, Zurich, Switzerland
| | - Reinhard Dummer
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.,Medical Faculty, University of Zurich, Zurich, Switzerland
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7
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Chaabani M, Ben Lagha I, Ben Tanfous A, Koubaa W, Ben Brahim E, Fenniche S, Zaouak A, Hammami-Ghorbel H. Contribution of conventional photodynamic therapy in the treatment of primary cutaneous follicle center lymphoma. Int J Dermatol 2020; 59:e204-e206. [PMID: 32043563 DOI: 10.1111/ijd.14817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 01/14/2020] [Accepted: 01/20/2020] [Indexed: 11/30/2022]
Affiliation(s)
- Mariem Chaabani
- Dermatology Department, Research unit "Genodermatoses and cancers LR12SP03", Habib Thameur Hospital, Tunis, Tunisia
| | - Imène Ben Lagha
- Dermatology Department, Research unit "Genodermatoses and cancers LR12SP03", Habib Thameur Hospital, Tunis, Tunisia
| | - Azima Ben Tanfous
- Dermatology Department, Research unit "Genodermatoses and cancers LR12SP03", Habib Thameur Hospital, Tunis, Tunisia
| | - Wafa Koubaa
- Anatomopathology Department, Habib Thameur Hospital, Tunis, Tunisia
| | - Ehsen Ben Brahim
- Anatomopathology Department, Habib Thameur Hospital, Tunis, Tunisia
| | - Samy Fenniche
- Dermatology Department, Research unit "Genodermatoses and cancers LR12SP03", Habib Thameur Hospital, Tunis, Tunisia
| | - Anissa Zaouak
- Dermatology Department, Research unit "Genodermatoses and cancers LR12SP03", Habib Thameur Hospital, Tunis, Tunisia
| | - Houda Hammami-Ghorbel
- Dermatology Department, Research unit "Genodermatoses and cancers LR12SP03", Habib Thameur Hospital, Tunis, Tunisia
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8
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Fonda-Pascual P, Moreno-Arrones OM, Alegre-Sanchez A, Saceda-Corralo D, Buendia-Castaño D, Pindado-Ortega C, Fernandez-Gonzalez P, Velazquez-Kennedy K, Calvo-Sánchez MI, Harto-Castaño A, Perez-Garcia B, Bagazgoitia L, Vaño-Galvan S, Espada J, Jaen-Olasolo P. In situ production of ROS in the skin by photodynamic therapy as a powerful tool in clinical dermatology. Methods 2016; 109:190-202. [PMID: 27422482 DOI: 10.1016/j.ymeth.2016.07.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Revised: 07/10/2016] [Accepted: 07/11/2016] [Indexed: 11/17/2022] Open
Abstract
Photodynamic therapy (PDT) is a clinical modality of photochemotherapy based on the accumulation of a photosensitizer in target cells and subsequent irradiation of the tissue with light of adequate wavelength promoting reactive oxygen species (ROS) formation and cell death. PDT is used in several medical specialties as an organ-specific therapy for different entities. In this review we focus on the current dermatological procedure of PDT. In the most widely used PDT protocol in dermatology, ROS production occurs by accumulation of the endogenous photosensitizer protoporphyrin IX after treatment with the metabolic precursors 5-methylaminolevulinic acid (MAL) or 5-aminolevulinic acid (ALA). To date, current approved dermatological indications of PDT include actinic keratoses (AK), basal cell carcinoma (BCC) and in situ squamous cell carcinoma (SCC) also known as Bowen disease (BD). With regards to AKs, PDT can also treat the cancerization field carrying an oncogenic risk. In addition, an increasing number of pathologies, such as other skin cancers, infectious, inflammatory or pilosebaceous diseases are being considered as potentially treatable entities with PDT. Besides the known therapeutic properties of PDT, there is a modality used for skin rejuvenation and aesthetic purposes defined as photodynamic photorejuvenation. This technique enables the remodelling of collagen, which in turn prevents and treats photoaging stygmata. Finally we explore a new potential treatment field for PDT determined by the activation of follicular bulge stem cells caused by in situ ROS formation.
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Affiliation(s)
- Pablo Fonda-Pascual
- Servicio de Dermatología, Hospital Universitario Ramón y Cajal, Madrid, Spain; Grupo de Dermatología Experimental y Biología Cutánea, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Oscar M Moreno-Arrones
- Servicio de Dermatología, Hospital Universitario Ramón y Cajal, Madrid, Spain; Grupo de Dermatología Experimental y Biología Cutánea, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Adrian Alegre-Sanchez
- Servicio de Dermatología, Hospital Universitario Ramón y Cajal, Madrid, Spain; Grupo de Dermatología Experimental y Biología Cutánea, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - David Saceda-Corralo
- Servicio de Dermatología, Hospital Universitario Ramón y Cajal, Madrid, Spain; Grupo de Dermatología Experimental y Biología Cutánea, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | | | | | - Kyra Velazquez-Kennedy
- Grupo de Dermatología Experimental y Biología Cutánea, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - María I Calvo-Sánchez
- Grupo de Dermatología Experimental y Biología Cutánea, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | | | - Lorea Bagazgoitia
- Servicio de Dermatología, Hospital Universitario Ramón y Cajal, Madrid, Spain; Grupo de Dermatología Experimental y Biología Cutánea, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Sergio Vaño-Galvan
- Servicio de Dermatología, Hospital Universitario Ramón y Cajal, Madrid, Spain; Grupo de Dermatología Experimental y Biología Cutánea, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Jesus Espada
- Laboratorio de Bionanotecnolgía, Universidad Bernardo ÓHiggins, Santiago, Chile.
| | - Pedro Jaen-Olasolo
- Servicio de Dermatología, Hospital Universitario Ramón y Cajal, Madrid, Spain.
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9
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Wan MT, Lin JY. Current evidence and applications of photodynamic therapy in dermatology. Clin Cosmet Investig Dermatol 2014; 7:145-63. [PMID: 24899818 PMCID: PMC4038525 DOI: 10.2147/ccid.s35334] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
In photodynamic therapy (PDT) a photosensitizer – a molecule that is activated by light – is administered and exposed to a light source. This leads both to destruction of cells targeted by the particular type of photosensitizer, and immunomodulation. Given the ease with which photosensitizers and light can be delivered to the skin, it should come as no surprise that PDT is an increasingly utilized therapeutic in dermatology. PDT is used commonly to treat precancerous cells, sun-damaged skin, and acne. It has reportedly also been used to treat other conditions including inflammatory disorders and cutaneous infections. This review discusses the principles behind how PDT is used in dermatology, as well as evidence for current applications of PDT.
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Affiliation(s)
- Marilyn T Wan
- Melanoma Program, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Jennifer Y Lin
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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10
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Negosanti L, Pinto V, Sgarzani R, Negosanti F, Zannetti G, Cipriani R. Photodynamic therapy with topical aminolevulinic acid. World J Dermatol 2014; 3:6. [DOI: 10.5314/wjd.v3.i2.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Revised: 12/26/2013] [Accepted: 03/14/2014] [Indexed: 02/06/2023] Open
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11
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Calzavara-Pinton PG, Rossi MT, Sala R, The Italian Group for Photodynamic Therapy. A retrospective analysis of real-life practice of off-label photodynamic therapy using methyl aminolevulinate (MAL-PDT) in 20 Italian dermatology departments. Part 2: Oncologic and infectious indications. Photochem Photobiol Sci 2013; 12:158-65. [DOI: 10.1039/c2pp25125f] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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12
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Morton C, Szeimies RM, Sidoroff A, Braathen L. European guidelines for topical photodynamic therapy part 2: emerging indications - field cancerization, photorejuvenation and inflammatory/infective dermatoses. J Eur Acad Dermatol Venereol 2012. [DOI: 10.1111/jdv.12026] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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13
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Topical photodynamic therapy for idiopathic hirsutism and hypertrichosis. Plast Reconstr Surg 2012; 129:1012e-1014e. [PMID: 22634678 DOI: 10.1097/prs.0b013e31824f00cc] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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14
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Zhao B, He YY. Recent advances in the prevention and treatment of skin cancer using photodynamic therapy. Expert Rev Anticancer Ther 2010; 10:1797-809. [PMID: 21080805 PMCID: PMC3030451 DOI: 10.1586/era.10.154] [Citation(s) in RCA: 113] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Photodynamic therapy (PDT) is a noninvasive procedure that involves a photosensitizing drug and its subsequent activation by light to produce reactive oxygen species that specifically destroy target cells. Recently, PDT has been widely used in treating non-melanoma skin malignancies, the most common cancer in the USA, with superior cosmetic outcomes compared with conventional therapies. The topical 'photosensitizers' commonly used are 5-aminolevulinic acid (ALA) and its esterified derivative methyl 5-aminolevulinate, which are precursors of the endogenous photosensitizer protoporphyrin IX. After treatment with ALA or methyl 5-aminolevulinate, protoporphyrin IX preferentially accumulates in the lesion area of various skin diseases, which allows not only PDT treatment but also fluorescence diagnosis with ALA-induced porphyrins. Susceptible lesions include various forms of non-melanoma skin cancer such as actinic keratosis, basal cell carcinoma and squamous cell carcinoma. The most recent and promising developments in PDT include the discovery of new photosensitizers, the exploitation of new drug delivery systems and the combination of other modalities, which will all contribute to increasing PDT therapeutic efficacy and improving outcome. This article summarizes the main principles of PDT and its current clinical use in the management of non-melanoma skin cancers, as well as recent developments and possible future research directions.
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Affiliation(s)
- Baozhong Zhao
- Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA
| | - Yu-Ying He
- Section of Dermatology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
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15
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Steinbauer JM, Schreml S, Kohl EA, Karrer S, Landthaler M, Szeimies RM. Photodynamic therapy in dermatology. J Dtsch Dermatol Ges 2010; 8:454-64. [PMID: 20136674 DOI: 10.1111/j.1610-0387.2010.07343.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Photodynamic therapy (PDT) is a modern therapy modality, based upon the application of a photosensitizing agent like aminolevulinic acid, a physiological precursor of porphyrins, onto the tissue followed by illumination with light of the visible wavelength spectrum. During this oxygen-dependent reaction, reactive oxygen species (ROS) are generated that have immunomodulatory or cytotoxic effects. PDT shows excellent cosmetic results especially for its key indication in dermatology - the treatment of non-melanoma skin cancer. The associated pain and the low tissue penetration are the most frequent limiting factors of PDT. We review basic principles and recent developments in photosensitizers and light sources. Key oncological and non-oncological indications are presented as well.
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16
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Choudhary S, Nouri K, Elsaie ML. Photodynamic therapy in dermatology: a review. Lasers Med Sci 2009; 24:971-980. [PMID: 19653060 DOI: 10.1007/s10103-009-0716-x] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2009] [Accepted: 07/11/2009] [Indexed: 12/18/2022]
Abstract
Photodynamic therapy (PDT) is used for the prevention and treatment of non-melanoma skin cancer. Until recently, clinically approved indications have been restricted to actinic keratoses, nodular and superficial basal cell carcinoma, and, since 2006, Bowen disease. However, the range of indications has been expanding continuously. PDT is also used for the treatment of non-malignant conditions such as acne vulgaris and leishmaniasis, as well as for treating premature skin aging due to sun exposure. The production of reactive oxygen intermediates like singlet oxygen depends on the light dose applied as well as the concentration and localization of the photosensitizer in the diseased tissue. Either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving inflammatory skin conditions are induced. Treating superficial non-melanoma skin cancer, PDT has been shown to be highly efficient, despite the low level of invasiveness. The excellent cosmetic results after treatment are beneficial, too.
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Affiliation(s)
- Sonal Choudhary
- Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, FL, USA
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Machado AHA, Soares CP, Beltrame Junior M, Pacheco MTT, Da Silva NS. Cytotoxicity of octal-bromide zinc phthalocyanine after photodynamic therapy with different light sources. Photomed Laser Surg 2009; 26:455-9. [PMID: 18922089 DOI: 10.1089/pho.2007.2117] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVE The objective of this study was to investigate the cytotoxicity of octal-bromide zinc phthalocyanine (ZnPcBr8) at different concentrations (0.25, 0.5, and 1 microM) after irradiating HEp-2 cell cultures with two different light sources: a diode semiconductor laser (660 nm, 30 mW) or an LED (640 nm, 70 mW). In order to obtain comparative results, the irradiation parameters of both light sources were adjusted so that the amount of energy density delivered would be the same (4.5 J/cm2). BACKGROUND DATA Numerous photosensitizers and light sources used in the treatment of human disease have been studied. Based on these studies, a comparative evaluation of two light sources used in photodynamic therapy (PDT) with ZnPcBr8 was proposed. MATERIALS AND METHODS HEp-2 cells were incubated with ZnPcBr8 at different concentrations (0.25, 0.5, or 1 microM) for 1 h, irradiated with the diode semiconductor laser (660 nm at 30 mW for 300 sec; 4.5 J/cm2) or the LED laser (640 nm at 70 mW for 128 sec; 4.5 J/cm2), and then incubated in MEM medium for 1 or 24 h. The cells were analyzed using the MTT and trypan blue dye exclusion tests. RESULTS The results demonstrated that the concentration of 1 microM of ZnPcBr8 was the most effective after PDT administered by both light sources. According to the MTT results, HEp-2-cell viability decreased by 97.96% 1 h after, and by 99.87% 24 h after irradiation with the diode semiconductor laser, and decreased by 94.03% 1 h after, and by 99.21% 24 h after irradiation with the LED. The results obtained using the trypan blue dye exclusion test confirmed the photodynamic efficacy of ZnPcBr8 employed with both light sources. With regard to HEp-2-cell viability, the following results were observed: a decrease of 98.73% 1 h after, and of 99.49% 24 h after irradiation with the diode semiconductor laser; and a decrease of 98.76% 1 h after, and of 99.23% 24 h after irradiation with the LED. CONCLUSIONS According to our results with the irradiation parameters studied here, both the LED and diode semiconductor laser can be used for PDT in vitro, since both light sources had excellent photodynamic efficacy.
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Affiliation(s)
- Aline Helena Araujo Machado
- Laboratório de Biologia Celular and Tecidual, Instituto de Pesquisa and Desenvolvimento, University of Vale do Paraiba, São José dos Campos, São Paulo, Brazil.
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Abstract
Multicentre randomized controlled studies now demonstrate high efficacy of topical photodynamic therapy (PDT) for actinic keratoses, Bowen's disease (BD) and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC, while confirming the superiority of cosmetic outcome over standard therapies. Long-term follow-up studies are also now available, indicating that PDT has recurrence rates equivalent to other standard therapies in BD and superficial BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast, current evidence does not support the use of topical PDT for squamous cell carcinoma. PDT can reduce the number of new lesions developing in patients at high risk of skin cancer and may have a role as a preventive therapy. Case reports and small series attest to the potential of PDT in a wide range of inflammatory/infective dermatoses, although recent studies indicate insufficient evidence to support its use in psoriasis. There is an accumulating evidence base for the use of PDT in acne, while detailed study of an optimized protocol is still required. In addition to high-quality treatment site cosmesis, several studies observe improvements in aspects of photoageing. Management of treatment-related pain/discomfort is a challenge in a minority of patients, and the modality is otherwise well tolerated. Long-term studies provide reassurance over the safety of repeated use of PDT.
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Affiliation(s)
- C A Morton
- Department of Dermatology, Stirling Royal Infirmary, Stirling FK2 8AU, UK.
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European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood 2008; 112:1600-9. [PMID: 18567836 DOI: 10.1182/blood-2008-04-152850] [Citation(s) in RCA: 274] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Primary cutaneous B-cell lymphomas (CBCL) represent approximately 20% to 25% of all primary cutaneous lymphomas. With the advent of the World Health Organization-European Organization for Research and Treatment of Cancer (EORTC) Consensus Classification for Cutaneous Lymphomas in 2005, uniform terminology and classification for this rare group of neoplasms were introduced. However, staging procedures and treatment strategies still vary between different cutaneous lymphoma centers, which may be because consensus recommendations for the management of CBCL have never been published. Based on an extensive literature search and discussions within the EORTC Cutaneous Lymphoma Group and the International Society for Cutaneous Lymphomas, the present report aims to provide uniform recommendations for the management of the 3 main groups of CBCL. Because no systematic reviews or (randomized) controlled trials were available, these recommendations are mainly based on retrospective studies and small cohort studies. Despite these limitations, there was consensus among the members of the multidisciplinary expert panel that these recommendations reflect the state-of-the-art management as currently practiced in major cutaneous lymphoma centers. They may therefore contribute to uniform staging and treatment and form the basis for future clinical trials in patients with a CBCL.
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Buggiani G, Troiano M, Rossi R, Lotti T. Photodynamic therapy: Off-label and alternative use in dermatological practice. Photodiagnosis Photodyn Ther 2008; 5:134-8. [DOI: 10.1016/j.pdpdt.2008.03.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2008] [Revised: 03/18/2008] [Accepted: 03/21/2008] [Indexed: 10/22/2022]
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Klein A, Babilas P, Karrer S, Landthaler M, Szeimies RM. Photodynamic therapy in dermatology--an update 2008. J Dtsch Dermatol Ges 2008; 6:839-45, 839-46. [PMID: 18400022 DOI: 10.1111/j.1610-0387.2008.06697.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
SUMMARY Photodynamic therapy (PDT) is used for the prevention and treatment of non-melanoma skin cancer. Until recently, clinically approved indications have been restricted to actinic keratoses, nodular and superficial basal cell carcinoma, and--since 2006--Bowen disease. However, the range of indications has been expanding continuously. PDT is also used for the treatment of non-malignant conditions such as acne vulgaris and leishmaniasis, as well as for treating premature skin aging due to sun exposure. Here, PDT is used for the stimulation of immunomodulatory effects in contrast to the induction of necrosis and apoptosis as produced in the treatment of skin tumors. The porphyrin precursor 5-aminolevulinic acid (ALA) or its methyl ester (MAL, so far the only approved formulation in Europe) is applied topically as photosensitizer to exclude systemic reactions. Possible light sources include lasers as well as incoherent light sources; irradiation with incoherent light sources is cheaper and more appropriate for large treatment areas. The main advantages of PDT in comparison to other treatment modalities are its excellent cosmetic results and its high remission rates despite low invasiveness.This article provides up-to-date information about PDT with focus on recently published studies.
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Affiliation(s)
- Annette Klein
- Clinic and Polyclinic for Dermatology, University of Regensburg, Regensburg.
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Nikkels AF, Thirion L, Quatresooz P, Piérard GE. Photodynamic therapy for cutaneous verrucous carcinoma. J Am Acad Dermatol 2007; 57:516-9. [PMID: 17434646 DOI: 10.1016/j.jaad.2007.02.025] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2006] [Revised: 02/05/2007] [Accepted: 02/26/2007] [Indexed: 11/20/2022]
Abstract
Cutaneous verrucous carcinoma is a low-grade and well-differentiated variant of squamous cell carcinoma. This rare neoplasm follows a seemingly indolent progression and exhibits a low metastatic potential. Photodynamic therapy relies on the selective intratumoral cell accumulation and photoactivation of a photosensitizer, leading to the generation of phototoxic compounds responsible for necrosis and apoptosis of the target cells. An 82-year-old man presenting with a large long-standing verrucous carcinoma on the leg was treated successfully by 6 photodynamic therapy sessions administered at weekly intervals using methyl-aminolevulinate and 57-J/cm(2) irradiations at 634-nm wavelength. The use of methyl-aminolevulinate-photodynamic therapy for treating cutaneous verrucous carcinoma had not been reported so far. It may represent a convenient therapeutic alternative in this setting.
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Affiliation(s)
- Arjen F Nikkels
- Department of Dermatopathology, University Hospital of Liège, Belgium.
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Fernández-Guarino M, García-Morales I, Harto A, Montull C, Pérez-García B, Jaén P. Terapia fotodinámica: nuevas indicaciones. ACTAS DERMO-SIFILIOGRAFICAS 2007. [DOI: 10.1016/s0001-7310(07)70091-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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Fernández-Guarino M, García-Morales I, Harto A, Montull C, Pérez-García B, Jaén P. Photodynamic Therapy: New Indications. ACTA ACUST UNITED AC 2007. [DOI: 10.1016/s1578-2190(07)70471-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Abstract
Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective and noninvasive therapy for superficial basal cell carcinoma (BCC) and Bowen's disease. It also may have a role in the treatment of nodular BCC and other cutaneous malignancies, including localized cutaneous lymphomas. ALA-PDT offers multiple advantages over traditional treatments, including little to no scarring, excellent cosmetic results, and the ability to treat multiple lesions simultaneously. It is not an effective therapy for aggressive subtypes of BCC or for invasive squamous cell carcinoma. Finally, ALA-PDT may be a useful way to prevent new skin cancers in certain high-risk patients.
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Affiliation(s)
- Jonathan E Blume
- Department of Dermatology, State University of New York at Buffalo, Elm and Carlton Streets, Buffalo, NY 14263, USA
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