Introduction and objective:
Photodynamic therapy (PDT) is a therapeutic option for low-risk basal cell carcinoma (BCC). The aim of the study was to assess the efficacy of topical PDT in the treatment of superficial BCC (sBCC) using two different photosensitizers: aminolevulinic acid hydrochloride (ALA-HCl) in a gel formulation with a lipid nanoemulsion (ALA-HCl in gel) and ALA methyl ester hydrochloride (MAL-HCl) in a cream formulation (MAL-HCl in cream).

Material and methods:
21 patients were treated twice with a one week interval between treatments. The formulations were applied onto lesions: 10 patients were treated with MAL-HCl in cream, and 11 with ALA-HCl in gel. After three hours of incubation and removing the preparations, fluorescence was assessed. The skin areas were then irradiated with red light 630 ± 5 nm.

At the follow-up visit 12 weeks after the second treatment, complete clinical remission was found in 82% after ALA-HCl in gel and in 80% after MAL-HCl in cream. An excellent cosmetic result was found in 96% of patients after MALHCl in cream and in 100% after ALA-HCl in gel. Faster skin healing and less post-inflammatory hyperpigmentation during follow-up visits was observed after treatment with ALA-HCl in gel.

Both formulations – ALA-HCl in gel and MAL-HCl in cream – were highly effective photosensitisers for PDT. The advantage of ALA-HCl in a gel formulation with a lipid nanoemulsion was faster skin healing, resulting in better cosmetic results.

Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol. 2015;151:1081. doi:10.1001/jamadermatol.2015.1187.
Nagarajan P, Asgari MM, Green AC, Guhan SM, Arron ST, Proby CM, Rollison DE, Harwood CA, Toland AE. Keratinocyte Carcinomas: Current Concepts and Future Research Priorities. Clin Cancer Res. 2019;25:2379–2391. doi:10.1158/1078-0432.CCR-18-1122.
Szewczyk M, Pazdrowski J, Golusiński P, Dańczak-Pazdrowska A, Łuczewski Ł, Marszałek S, Majchrzak E, Golusiński W. Basal cell carcinoma in farmers: an occupation group at high risk. Int Arch Occup Environ Health. 2016;89:497–501.
Cameron MC, Lee E, Hibler BP, Barker CA, Mori S, Cordova M, Nehal KS, Rossi AM. Basal cell carcinoma: Epidemiology; pathophysiology; clinical and histological subtypes; and disease associations. J Am Acad Dermatol. 2019;2:303–317. doi:10.1016/j.jaad.2018.03.060.
Naik PP, Desai MB. Basal Cell Carcinoma: A Narrative Review on Contemporary Diagnosis and Management. Oncol Ther. 2022;2:317–335. doi:10.1007/s40487-022-00201-8.
Christenson LJ, Borrowman TA, Vachon CM, Tollefson MM, Otley CC, Weaver AL, Roenigk RK. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA 2005;294:681–90. doi:10.1001/jama.294.6.681.
Fania L, Didona D, Morese R, Campana I, Coco V, Di Pietro FR, Ricci F, Pallotta S, Candi E, Abeni D, Dellambra, E. Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches. Biomedicines 2020;8:449. doi:10.3390/biomedicines8110449.
Seidl-Philipp M, Frischhut N, Höllweger N, Schmuth M, Nguyen VA. Known and new facts on basal cell carcinoma. J Dtsch Dermatol Ges. 2021;19:1021–1041. doi:10.1111/ddg.14580.
Grachtchouk M, Pero J, Yang SH, Ermilov AN, Michael LE, Wang A, Wilbert D, Patel RM, Ferris J, Diener J, Allen M, Lim S, Syu LJ, Verhaegen M, Dlugosz AA. Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations. J Clin Invest. 2011;121:1768–1781. doi:10.1172/JCI46307.
Sánchez-Danés A, Hannezo E, Larsimont JC, Liagre M, Youssef KK, Simons BD, Blanpain C. Defining the clonal dynamics leading to mouse skin tumour initiation. Nature 2016;536:298–303. doi:10.1038/nature19069.
Hsu YC, Li L, Fuchs E. Emerging interactions between skin stem cells and their niches. Nat Med. 2014;20:847–856. doi:10.1038/nm.3643.
Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol. 1994;30:774–778. doi:10.1016/s0190-9622(08)81509-5.
NCCN. Basal Cell Skin Cancer (Version 1.2022). Available at: Accessed May 3, 2023.
Heath MS, Bar A. Basal Cell Carcinoma. Dermatol Clin. 2023;41:13–21. doi:10.1016/j.det.2022.07.005.
Naik PP, Desai MB, Basal Cell Carcinoma: A Narrative Review on Contemporary Diagnosis and Management. Oncol Ther. 2022;10:317–335. doi:10.1007/s40487-022-00201-8.
Niculet E, Craescu M, Rebegea L, Bobeica C, Nastase F, Lupasteanu G, Stan DJ, Chioncel V, Anghel L, Lungu M, Tatu AL. Basal cell carcinoma: Comprehensive clinical and histopathological aspects, novel imaging tools and therapeutic approaches (Review). Exp Ther Med. 2022;23:60. doi:10.3892/etm.2021.10982.
Ou-Yang Y, Zheng Y, Mills KE. Photodynamic therapy for skin carcinomas: A systematic review and meta-analysis. Front Med. (Lausanne) 2023;19(10):1089361. doi:10.3389/fmed.2023.1089361.
Schmitz L, Novak B, Hoeh AK, Luebbert H, Dirschka T. Epidermal penetration and protoporphyrin IX formation of two different 5-aminolevulinic acid formulations in ex vivo human skin. Photodiagnosis Photodyn Ther. 2016;14:40–46. doi:10.1016/j.pdpdt.2015.11.004.
Zeitouni NC, Bhatia N, Ceilley RI, Cohen JL, Del Rosso JQ, Moore AY, Munavalli G, Pariser DM, Schlesinger T, Siegel DM, Willey A, Goldman MP. Photodynamic Therapy with 5-aminolevulinic Acid 10% Gel and Red Light for the Treatment of Actinic Keratosis, Nonmelanoma Skin Cancers, and Acne: Current Evidence and Best Practices. J Clin Aesthet Dermatol. 2021;14:E53-E65.
Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: Basic principles and present clinical experience. J Photochem Photobiol B Biol. 1990;6:143–148.
Collier NJ, Rhodes LE. Photodynamic Therapy for Basal Cell Carcinoma: The Clinical Context for Future Research Priorities. Molecules 2020;25:5398. doi:10.3390/molecules25225398.
Kou J, Dou D, Yang L. Porphyrin photosensitizers in photodynamic therapy and its applications. Oncotarget. 2017;8:81591–81603. doi:10.18632/oncotarget.20189.
Adamek M, Kawczyk-Krupka A, Mostowy A, Czuba Z, Krol W, Kasperczyk S, Jakobisiak M, Golab J, Sieron A. Topical ALA-PDT modifies neutrophils’ chemiluminescence, lymphocytes’ interleukin-1beta secretion and serum level of transforming growth factor beta1 in patients with nonmelanoma skin malignancies. A clinical study. Photodiagnosis Photodyn Ther. 2005;2:65–72. doi:10.1016/S1572-1000(05)00004-9.
Stringasci MD, Salvio AG, Moriyama LT, Vollet-Filho JD, Fortunato TC, Bagnato VS, Kurachi C. Energy analysis of PDT using thermography during the treatment of basal cell carcinoma. Photodiagnosis Photodyn Ther. 2020;29:101586. doi:10.1016/j.pdpdt.2019.101586.
Arits AH, Mosterd K, Essers BA, Spoorenberg E, Sommer A, De Rooij MJ, van Pelt HP, Quaedvlieg PJ, Krekels GA, van Neer PA, Rijzewijk JJ, van Geest AJ, Steijlen PM, Nelemans PJ, Kelleners-Smeets NW. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial. Lancet Oncol. 2013;14:647–654. doi:10.1016/S1470-2045(13)70143-8.
Jansen MHE, Koekelkoren FHJ, Nelemans PJ, Arits AHMM, Roozeboom MH, Kelleners-Smeets NWJ, Mosterd K. Comparison of long-term cosmetic outcomes for different treatments of superficial basal cell carcinoma. J Am Acad Dermatol. 2018;79:961–964. doi:10.1016/j.jaad.2018.04.053.
Roozeboom MH, Nelemans PJ, Mosterd K, Steijlen PM, Arits AH, Kelleners-Smeets NW. Photodynamic therapy vs. topical imiquimod for treatment of superficial basal cell carcinoma: a subgroup analysis within a noninferiority randomized controlled trial. Br J Dermatol. 2015;172:739–745. doi:10.1111/bjd.13299.
Roozeboom MH, Arits AHMM, Mosterd K, Sommer A, Essers BAB, de Rooij MJM, Quaedvlieg PJF, Steijlen PM, Nelemans PJ, Kelleners-Smeets NWJ. Three-Year Follow-Up Results of Photodynamic Therapy vs. Imiquimod vs. Fluorouracil for Treatment of Superficial Basal Cell Carcinoma: A Single-Blind, Noninferiority, Randomized Controlled Trial. J Invest Dermatol. 2016;136:1568–1574. doi:10.1016/j.jid.2016.03.043.
Basset-Seguin N, Ibbotson SH, Emtestam L, Tarstedt M, Morton C, Maroti M, Calzavara-Pinton P, Varma S, Roelandts R, Wolf P. Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial. Eur J Dermatol. 2008;18:547–553. doi:10.1684/ejd.2008.0472.
Kessels JPHM, Kreukels H, Nelemans PJ, Roozeboom MH, van Pelt H, Mosterd K, de Haas ERM, Kelleners-Smeets NWJ. Treatment of superficial basal cell carcinoma by topical photodynamic therapy with fractionated 5-aminolaevulinic acid 20% vs. two-stage topical methyl aminolaevulinate: results of a randomized controlled trial. Br J Dermatol. 2018;178:1056–1063. doi:10.1111/bjd.15967.
Szeimies RM, Ibbotson S, Murrell DF, Rubel D, Frambach Y, de Berker D, Dummer R, Kerrouche N, Villemagne H, Excilight Study Group. A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8–20 mm), with a 12-month follow-up. J Eur Acad Dermatol Venereol. 2008;22:1302–1311. doi:10.1111/j.1468-3083.2008.02803.x.
Salmivuori M, Grönroos M, Tani T, Pölönen I, Räsänen J, Annala L, et al. Hexyl aminolevulinate, 5-aminolevulinic acid nanoemulsion and methyl aminolevulinate in photodynamic therapy of non-aggressive basal cell carcinomas: A non-sponsored, randomized, prospective and double-blinded trial. J Eur Acad Dermatol Venereol. 2020;34:2781–2788. doi:10.1111/jdv.16357.
Morton CA, Dominicus R, Radny P, Dirschka T, Hauschild A, Reinhold U, et al. A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy. Br J Dermatol. 2018;179:309–319. doi:10.1111/bjd.16441.
Alique-García S, Company-Quiroga J, Sánchez Campos A, Hernández Núñez A, Borbujo J. Treatment of superficial basal cell carcinoma with photodynamic therapy. Observational study in 22 patients with 5-aminolaevulinic acid and methyl aminolaevulinate. Photodiagnosis Photodyn Ther. 2019;26:190–192. doi:10.1016/j.pdpdt.2019.03.018.
Redondo P, Marquina M, Pretel M, Aguado L, Iglesias ME. Methyl-ALA-induced fluorescence in photodynamic diagnosis of basal cell carcinoma prior to Mohs micrographic surgery. Arch Dermatol. 2008;144:115–117. doi:10.1001/archdermatol.2007.3.
Sánchez-López E, Guerra M, Dias-Ferreira J, Lopez-Machado A, Ettcheto M, Cano A, et al. Current Applications of Nanoemulsions in Cancer Therapeutics. Nanomaterials 2019;9:821. doi:10.3390/nano9060821.
Benaouda S, Jones A, Martin GP, Brown MB. Localized Epidermal Drug Delivery Induced by Supramolecular Solvent Structuring. Mol Pharm. 2016;13:65–72. doi:10.1021/acs.molpharmaceut.5b00499.
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