Vascular Characteristics of Treatment-resistant and -responsive Actinic Keratosis Identified with Dynamic Optical Coherence Tomography
DOI:
https://doi.org/10.2340/actadv.v104.42190Keywords:
dynamic optical coherence tomography, daylight photodynamic therapy, actinic keratosis, skin microvasculature, angiography, OCTAVAAbstract
Treatment-resistant actinic keratosis (AK) is of concern in clinical practice, often requiring retreatment. Microvascular assessments might help differentiate treatment-resistant from treatment-responsive AKs, enabling targeted treatment. Using dynamic optical coherence tomography, AK vascularization was investigated following daylight photodynamic therapy, comparing treatment-resistant with cleared AKs. AKs on face/scalp were graded according to the Olsen Classification Scheme and scanned with dynamic optical coherence tomography pre-treatment, and 3- and 12-months post-treatment. Employing dynamic optical coherence tomography, total vessel length, mean vessel length, mean vessel diameter, vessel area density, and branchpoint density were quantified. Thirty-eight patients with 62 AKs were enrolled, including 37 AK I, 18 AK II, and 7 AK III. Treatment-resistant AKs displayed a trend toward intensified vascularization compared with cleared AK at baseline (AKs I, II), suggested by higher total vessel length (median 144.0, IQR 104.3–186.6) and vessel area density (median 27.7, IQR 18.4–34.2) than in cleared AK (median 120.9, IQR 86.9–143.0 and median 22.9, IQR 17.3–26.8). Additionally, vascularization in treatment-resistant AK I–II appeared disorganized, with trends toward shorter mean vessel length (median 151.0, IQR 138.5–167.5) and increased branchpoint density (median 3.2, IQR 2.3–3.8) compared with cleared AK (median 160.0, IQR 152.0–169.3 and median 2.6, IQR 2.2–3.0). These findings suggest that dynamic optical coherence tomography holds potential to identify treatment-resistant AKs.
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Kandolf L, Peris K, Malvehy J, Mosterd K, Heppt MV, Fargnoli MC, et al. European consensus-based interdisciplinary guideline for diagnosis, treatment and prevention of actinic keratoses, epithelial UV-induced dysplasia and field cancerization on behalf of European Association of Dermato-Oncology, European Dermatology Forum, European Academy of Dermatology and Venereology and Union of Medical Specialists (Union Européenne des Médecins Spécialistes). J Eur Acad Dermatol Venereol 2024; 38: 1024-1047.
https://doi.org/10.1111/jdv.19897 DOI: https://doi.org/10.1111/jdv.19897
George CD, Lee T, Hollestein LM, Asgari MM, Nijsten T. Global epidemiology of actinic keratosis in the general population: a systematic review and meta-analysis. Br J Dermatol 2024; 190: 465-476.
https://doi.org/10.1093/bjd/ljad371 DOI: https://doi.org/10.1093/bjd/ljad371
Werner RN, Sammain A, Erdmann R, Hartmann V, Stockfleth E, Nast A. The natural history of actinic keratosis: a systematic review. Br J Dermatol 2013; 169: 502-518.
https://doi.org/10.1111/bjd.12420 DOI: https://doi.org/10.1111/bjd.12420
de Berker D, McGregor J, Mohd Mustapa M, Exton L, Hughes B. British Association of Dermatologists' guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol 2017; 176: 20-43.
https://doi.org/10.1111/bjd.15107 DOI: https://doi.org/10.1111/bjd.15107
Morton C, Baharlou S, Basset-Seguin N, Calzavara-Pinton P, Dirschka T, Gilaberte Y, et al. Expert recommendations on facilitating personalized approaches to long-term management of actinic keratosis: the Personalizing Actinic Keratosis Treatment (PAKT) project. Acta Derm Venereol 2023; 103: adv6229.
https://doi.org/10.2340/actadv.v103.6229 DOI: https://doi.org/10.2340/actadv.v103.6229
Aggarwal I, Puyana C, Chandan N, Jetter N, Tsoukas M. Field cancerization therapies for the management of actinic keratosis: an updated review. Am J Clin Dermatol 2024; 25: 391-405.
https://doi.org/10.1007/s40257-023-00839-8 DOI: https://doi.org/10.1007/s40257-023-00839-8
Schmitz L, Brehmer A, Falkenberg C, Gambichler T, Heppt MV, Steeb T, et al. Actinic keratosis grading. Ital J Dermatol Venereol 2021; 156: 213-219.
https://doi.org/10.23736/S2784-8671.21.06892-9 DOI: https://doi.org/10.23736/S2784-8671.21.06892-9
Reynolds KA, Schlessinger DI, Vasic J, Iyengar S, Qaseem Y, Behshad R, et al. Core outcome set for actinic keratosis clinical trials. JAMA Dermatol 2020; 156: 326-333.
https://doi.org/10.1001/jamadermatol.2019.4212 DOI: https://doi.org/10.1001/jamadermatol.2019.4212
Steeb T, Wessely A, Petzold A, Schmitz L, Dirschka T, Berking C, et al. How to assess the efficacy of interventions for actinic keratosis? A review with a focus on long-term results. J Clin Med 2021; 10: 4736.
https://doi.org/10.3390/jcm10204736 DOI: https://doi.org/10.3390/jcm10204736
Steeb T, Wessely A, Petzold A, Brinker TJ, Schmitz L, Leiter U, et al. Evaluation of long-term clearance rates of interventions for actinic keratosis: a systematic review and network meta-analysis. JAMA Dermatol 2021; 157: 1066-1077.
https://doi.org/10.1001/jamadermatol.2021.2779 DOI: https://doi.org/10.1001/jamadermatol.2021.2779
Benati E, Longhitano S, Pampena R, Mirra M, Raucci M, Pellacani G, et al. Digital follow-up by means of dermatoscopy and reflectance confocal microscopy of actinic keratosis treated with Imiquimod 3.75% cream. J Eur Acad Dermatol Venereol JEADV 2020; 34: 1471-1477.
https://doi.org/10.1111/jdv.16143 DOI: https://doi.org/10.1111/jdv.16143
Curiel-Lewandrowski C, Myrdal CN, Saboda K, Hu C, Arzberger E, Pellacani G, et al. In vivo reflectance confocal microscopy as a response monitoring tool for actinic keratoses undergoing cryotherapy and photodynamic therapy. Cancers 2021; 13: 5488.
https://doi.org/10.3390/cancers13215488 DOI: https://doi.org/10.3390/cancers13215488
Ishioka P, Maia M, Rodrigues SB, Lellis RF, Hirata SH. In vivo confocal laser microscopy for monitoring of actinic keratosis treatment: a comparison with histopathologic assessment after treatment with topical 5% 5-fluorouracil. J Eur Acad Dermatol Venereol 2018; 32: 1155-1163.
https://doi.org/10.1111/jdv.14716 DOI: https://doi.org/10.1111/jdv.14716
Markowitz O, Wang K, Levine A, Schwartz M, Minhas S, Feldman E, et al. Noninvasive long-term monitoring of actinic keratosis and field cancerization following treatment with ingenol mebutate gel 0.015. J Clin Aesthetic Dermatol 2017; 10: 28-33.
Markowitz O, Schwartz M, Feldman E, Bieber A, Bienenfeld A, Nandanan N, et al. Defining field cancerization of the skin using noninvasive optical coherence tomography imaging to detect and monitor actinic keratosis in ingenol mebutate 0.015%-treated patients. J Clin Aesthetic Dermatol 2016; 9: 18-25.
Ulrich M, Themstrup L, de Carvalho N, Manfredi M, Grana C, Ciardo S, et al. Dynamic optical coherence tomography in dermatology. Dermatology 2016; 232: 298-311.
https://doi.org/10.1159/000444706 DOI: https://doi.org/10.1159/000444706
Untracht GR, Matos RS, Dikaios N, Bapir M, Durrani AK, Butsabong T, et al. OCTAVA: an open-source toolbox for quantitative analysis of optical coherence tomography angiography images. PloS One 2021; 16: e0261052.
https://doi.org/10.1371/journal.pone.0261052 DOI: https://doi.org/10.1371/journal.pone.0261052
Untracht GR, Dikaios N, Durrani AK, Bapir M, Sarunic MV, Sampson DD, et al. Pilot study of optical coherence tomography angiography-derived microvascular metrics in hands and feet of healthy and diabetic people. Sci Rep 2023; 13: 1122.
https://doi.org/10.1038/s41598-022-26871-y DOI: https://doi.org/10.1038/s41598-022-26871-y
Fredman G, Wiegell SR, Haedersdal M, Untracht GR. Vascular feature identification in actinic keratosis grades I-III using dynamic optical coherence tomography with automated, quantitative analysis. Arch Dermatol Res 2024; 316: 391.
https://doi.org/10.1007/s00403-024-03022-z DOI: https://doi.org/10.1007/s00403-024-03022-z
Fargnoli MC, Piccioni A, Neri L, Tambone S, Pellegrini C, Peris K. Conventional vs. daylight methyl aminolevulinate photodynamic therapy for actinic keratosis of the face and scalp: an intra-patient, prospective, comparison study in Italy. J Eur Acad Dermatol Venereol 2015; 29: 1926-1932.
https://doi.org/10.1111/jdv.13076 DOI: https://doi.org/10.1111/jdv.13076
Fargnoli MC, Piccioni A, Neri L, Tambone S, Pellegrini C, Peris K. Long-term efficacy and safety of daylight photodynamic therapy with methyl amninolevulinate for actinic keratosis of the face and scalp. Eur J Dermatol EJD 2017; 27: 89-91.
https://doi.org/10.1684/ejd.2016.2882 DOI: https://doi.org/10.1684/ejd.2016.2882
Wiegell SR, Fredman G, Andersen F, Bjerring P, Paasch U, Hædersdal M. Pre-treatment with topical 5-fluorouracil increases the efficacy of daylight photodynamic therapy for actinic keratoses: a randomized controlled trial. Photodiagnosis Photodyn Ther 2024; 46: 104069.
https://doi.org/10.1016/j.pdpdt.2024.104069 DOI: https://doi.org/10.1016/j.pdpdt.2024.104069
Olsen EA, Abernethy ML, Kulp-Shorten C, Callen JP, Glazer SD, Huntley A, et al. A double-blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck. J Am Acad Dermatol 1991; 24: 738-743.
https://doi.org/10.1016/0190-9622(91)70113-G DOI: https://doi.org/10.1016/0190-9622(91)70113-G
Untracht GR, Durkee MS, Zhao M, Kwok-Cheung Lam A, Sikorski BL, Sarunic MV, et al. Towards standardising retinal OCT angiography image analysis with open-source toolbox OCTAVA. Sci Rep 2024; 14: 5979.
https://doi.org/10.1038/s41598-024-53501-6 DOI: https://doi.org/10.1038/s41598-024-53501-6
Reif R, Qin J, An L, Zhi Z, Dziennis S, Wang R. Quantifying optical microangiography images obtained from a spectral domain optical coherence tomography system. Int J Biomed Imaging 2012; 2012: 509783.
https://doi.org/10.1155/2012/509783 DOI: https://doi.org/10.1155/2012/509783
Fredman G, Fuchs CSK, Wenande E, Philipsen PA, Untracht GR, Andersen F, et al. Dynamic optical coherence tomography unveils subclinical, vascular differences across actinic keratosis grades I-III. Exp Dermatol 2024; 33: e15153.
https://doi.org/10.1111/exd.15153 DOI: https://doi.org/10.1111/exd.15153
Eisen DB, Asgari MM, Bennett DD, Connolly SM, Dellavalle RP, Freeman EE, et al. Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol 2021; 85: e209-233.
https://doi.org/10.1016/j.jaad.2021.02.082 DOI: https://doi.org/10.1016/j.jaad.2021.02.082
Marks R, Rennie G, Selwood Thomas S. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1988; 331: 795-797.
https://doi.org/10.1016/S0140-6736(88)91658-3 DOI: https://doi.org/10.1016/S0140-6736(88)91658-3
Dirschka T, Ekanayake-Bohlig S, Dominicus R, Aschoff R, Herrera-Ceballos E, Botella-Estrada R, et al. A randomized, intraindividual, non-inferiority, Phase III study comparing daylight photodynamic therapy with BF-200 ALA gel and MAL cream for the treatment of actinic keratosis. J Eur Acad Dermatol Venereol 2019; 33: 288-297.
https://doi.org/10.1111/jdv.15185 DOI: https://doi.org/10.1111/jdv.15185
Jansen MHE, Kessels JPHM, Nelemans PJ, Kouloubis N, Arits AHMM, van Pelt HPA, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med 2019; 380: 935-946.
https://doi.org/10.1056/NEJMoa1811850 DOI: https://doi.org/10.1056/NEJMoa1811850
Falkenberg C, Dirschka T, Gilbert G, Stockfleth E, Homey B, Schmitz L. Basal proliferation and acantholysis may represent histological high-risk factors for progression into invasive squamous cell carcinoma: a comparison study in solid organ transplant recipients and matched immunocompetent patients. Cancers 2023; 15: 1765.
https://doi.org/10.3390/cancers15061765 DOI: https://doi.org/10.3390/cancers15061765
Szeimies RM, Ulrich C, Ferrándiz-Pulido C, Hofbauer GFL, Lear JT, Lebbé C, et al. The "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) project: an expert panel opinion. Dermatol Ther 2024; 14: 1739-1753.
https://doi.org/10.1007/s13555-024-01215-y DOI: https://doi.org/10.1007/s13555-024-01215-y
Ruini C, Hartmann D, Bastian M, Ruzicka T, French LE, Berking C, et al. Non-invasive monitoring of subclinical and clinical actinic keratosis of face and scalp under topical treatment with ingenol mebutate gel 150 mcg/g by means of reflectance confocal microscopy and optical coherence tomography: new perspectives and comparison of diagnostic techniques. J Biophotonics 2019; 12: e201800391.
https://doi.org/10.1002/jbio.201800391 DOI: https://doi.org/10.1002/jbio.201800391
Soare C, Cozma EC, Celarel AM, Rosca AM, Lupu M, Voiculescu VM. Digitally enhanced methods for the diagnosis and monitoring of treatment responses in actinic keratoses: a new avenue in personalized skin care. Cancers 2024; 16: 484.
https://doi.org/10.3390/cancers16030484 DOI: https://doi.org/10.3390/cancers16030484
Kaçar N, Sanli B, Zalaudek I, Yildiz N, Ergin S. Dermatoscopy for monitoring treatment of actinic keratosis with imiquimod. Clin Exp Dermatol 2012; 37: 567-569.
https://doi.org/10.1111/j.1365-2230.2011.04272.x DOI: https://doi.org/10.1111/j.1365-2230.2011.04272.x
Mazur E, Kwiatkowska D, Reich A. Reflectance confocal microscopy and dermoscopy of facial pigmented and non-pigmented actinic keratosis features before and after photodynamic therapy treatment. Cancers 2023; 15: 5598.
https://doi.org/10.3390/cancers15235598 DOI: https://doi.org/10.3390/cancers15235598
Lee JH, Won CY, Kim GM, Kim SY. Dermoscopic features of actinic keratosis and follow up with dermoscopy: a pilot study. J Dermatol 2014; 41: 487-493.
https://doi.org/10.1111/1346-8138.12282 DOI: https://doi.org/10.1111/1346-8138.12282
Wang T, Han Q, Hu W, Ren H. Efficacy evaluation and dermoscopy predictors of photodynamic therapy with different pretreatments in the treatment of actinic keratosis. J Dermatol Treat 2022; 33: 2853-2857.
https://doi.org/10.1080/09546634.2022.2089325 DOI: https://doi.org/10.1080/09546634.2022.2089325
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Copyright (c) 2024 Gabriella Fredman, Merete Haedersdal, Peter A. Philipsen, Flemming Andersen, Peter Bjerring, Stine R. Wiegell, Gavrielle Untracht
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