A Comparison of the Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy according to the Density of Ablative Laser Channel in the Treatment of Actinic Keratosis Yeo-Rye Cho, Jeong-Hwan Kim, Ho-Jin Kim, Jeong-Wan Seo, Ki-Ho Kim, Ki-Hoon Song Department of Dermatology, College of Medicine, Dong-A University, Busan, Korea U n i v e r s i t y L O G O
Disclosure No financial interest or affiliation concerning material discussed in this presentation.
Background Actinic keratosis Cutaneous neoplasm consisting of proliferations of abnormal epidermal keratinocytes that develop in response to prolonged exposure to ultraviolet. Photodynamic Therapy (PDT) A highly effective, non-invasive, and selective light therapy to treat AK.
Background Photodynamic Therapy in Hyperkeratotic Actinic Keratosis Stratum corneum (SC) is the major barrier against drug permeation, decreasing transdermal MAL uptake. Stratum corneum (SC) Pretreatment options Curettage Microdermabrasion Microneedling Non-Ablative Fractional Laser Ablative Fractional Laser Ablative Fractional Laser-pretreated Photodynamic Therapy Effective in enhancing the penetration and accumulation of photosensitizers Photochem Photobiol Sci. 2015 Oct;14(10):1765-80.
Background Photodynamic Therapy in Hyperkeratotic Actinic Keratosis Complete response rates between groups treated with MAL-PDT and FL-PDT 100.0% 80.0% 60.0% 40.0% 20.0% 0.0% Olsen grade I 100.0% 100.0% 79.3% 69.0% 12 weeks 48 weeks 100.0% 80.0% 60.0% 40.0% 20.0% 0.0% Olsen grade II 93.5% 84.8% 71.7% 56.7% 12 weeks 48 weeks 100.0% 80.0% 60.0% 40.0% 20.0% 0.0% Olsen grade III 69.4% 55.6% 32.5% 10.0% 12 weeks 48 weeks J Eur Acad Dermatol Venereol. 2014 Nov;28(11):1529-39
Background Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) : Effective for treating multiple facial actinic keratosis (AK). Ablative fractional laser (AFL) pretreatment : Highly potential to enhance the treatment response of PDT by creating microscopic ablation zones (MAZs). Stratum corneum Epidermis Dermis MAZ
Background MAZs depend on variables such as laser density, depth, and coagulation level. The clinical outcome of AFL-PDT with different laser density for the treatment of actinic keratosis is not yet compared. Lower density Higher density
Objective To evaluate whether the different laser channel densities of the pretreatment of AFL make different results in efficacy, protoporphyrin IX(PpIX) accumulation, side effects, and cosmetic outcomes in AFL-PDT for multiple facial AK. Ablative Fractional Laser 5.5%-AFL 11%-AFL 22%-AFL Photodynamic therapy Efficacy PpIX Accumulation Side effects Cosmetic outcomes
Materials & Methods Patients 47 Korean patients with 312 AK lesions who visited the Department of Dermatology, Dong-A University Hospital, from February 2017 to October 2017, were enrolled in this study. Korean patients 18 years of age Patients who had biopsy-confirmed AK lesions Inclusion criteria Lactating or pregnant women Allergy to any of the constituents of the MAL cream and lidocaine History of malignant melanoma Keloid formation Patients with systemic disease Exclusion criteria Patients with porphyria Any AK treatment of the area in the previous 4 weeks Tendency for melasma development Patients on immunosuppressive treatment Any conditions associated with a risk of poor protocol compliance
Materials & Methods Study protocol flowchart
Results Baseline characteristics of the patients Characteristics 5.5%-AFL-PDT 11%-AFL-PDT 22%-AFL-PDT P value Sex, n (%) 16 15 16 0.940 Male 6 (37.5%) 6 (40.0%) 7 (43.8%) Female 10 (62.5%) 9 (60.0%) 9 (56.3%) Age (years) 0.806 Mean ± SD 71.43 ± 9.95 72.40 ± 9.30 70.19 ± 8.85 Skin type, n (%) 0.940 III 6 (37.5%) 5 (33.3%) 5 (31.3%) IV 7 (43.8%) 7 (46.7%) 7 (43.8%) V 3 (18.8%) 3 (20.0%) 4 (25.0%) No. of lesions, n (%) 110 96 106 0.469 Grade I/thin + 29 (26.4%) 29 (30.2%) 32 (30.2%) Grade II/moderate + 47 (42.7%) 46 (47.9%) 42 (39.6%) Grade III/severe + 34 (30.9%) 21 (21.9%) 32 (30.2%)
Results Clinical Image of AFL 5.5%-AFL-PDT 11%-AFL-PDT 22%-AFL-PDT
Results Clinical Image of AFL-PDT (Olsen Grade III) A A A B B B 5.5%-AFL-PDT 11%-AFL-PDT 22%-AFL-PDT
A.U. (Arbitrary Units) Results PpIX Accumulation p =0.117 77.69 ± 3.62 78.34 ± 3.30 78.26 ± 4.53 5.5%-AFL-PDT 11%-AFL-PDT 22%-AFL-PDT
Results Complete response (CR) rates summarized at 3 months and 12 months 100.0% 80.0% * P=0.037 88.7% 84.4% 80.0% * P=0.003 81.1% 74.0% 60.0% 40.0% 60.9% 5.5% 11.0% 22.0% 20.0% 3 Months 12 Months
Results CR rates summarized at 3 months and 12 months by Olsen grade 100.0% 80.0% Olsen grade I 100.0% 96.9% 93.1% 93.1% 89.7% 79.3% 100.0% 80.0% Olsen grade II 88.1% 84.8% 78.6% 74.5% 71.7% 66.0% 100.0% 80.0% Olsen grade III 71.4% 81.3% P=0.043 * 68.8% 60.0% 60.0% 60.0% 55.9% 57.1% 40.0% 40.0% 40.0% 38.2% 20.0% 3 Months 12 Months 20.0% 3 Months 12 Months 20.0% 3 Months 12 Months 5.5% 11.0% 22.0%
Results Side effects Pain 5.5% 11% 22% P-value Pain (VAS) 5.02 ± 1.26 5.04 ± 1.34 5.13 ± 1.38 0.804 Frequency of local skin reactions Adverse Events 5.5% 11% 22% P-value n (%) 110 (100%) 96 (100%) 106 (100%) Burning sensation 81 (70.7%) 72 (75.0%) 79 (74.5%) 0.902 Pruritus 48 (43.6%) 44 (45.8%) 49 (46.2%) 0.294 Crust 84 (76.4%) 76 (79.2%) 85 (80.2%) 0.780 Edema 11 (10.0%) 11 (11.5%) 13 (12.3%) 0.565 Bullae 3 (2.7%) 4 (4.2%) 6 (5.7%) 0.560
Results Erythema and Hyperpigmentation Erythema Hyperpigmentation
Results Cosmetic outcomes 12 months after treatment Fair 5.5% Poor 2.7% 5.5% Fair 6.3% Poor 3.1% 11% Poor 2.8% Fair 5.7% 22% P=0.129 Good 33.6% Exellent Good 31.3% Exellent Good 34.9% Exellent 58.2% 59.3% 56.6%
Discussion
Discussion Laser channel density and drug delivery There is a minimum channel density to achieve maximum drug penetration but that increasing channel density beyond this point will not improve delivery. (6hrs after lidocaine apply) (24hrs after lidocaine apply) Bachhav Y et al. Journal of Controlled Release 146 (2010) 31 36
Discussion The porphyrins induced by MAL extended without significant decrease to a distance of 1.5mm from each laser hole. Laser channel density and drug delivery C.S. Haak et al. Lasers in Surgery and Medicine. 2010;42:113-122
Discussion Laser channel density and drug delivery AFL density of 5% seems to facilitate uptake of sufficient amounts of MAL to saturate the enzymatic pathway for PpIX formation and enable a homogeneous PpIX accumulation. C.S. Haak et al. J Photochem Photobiol B. 2016 Jun;159:42-8.
Discussion Gan SD et al. J Am Acad Dermatol. 2016 Feb;74(2):387-9 Debulking effect A single AFXL treatment was demonstrated to produce a modest temporary reduction in AKs and a trend toward decreased development of new lesions.
Discussion Pain Pain during illumination was strongly correlated to the amount of PpIX. Susanne Fabricius, et al. Photochem. Photobiol. Sci., 2013, 12, 117 Catharina M. Lerche et al. Photochem. Photobiol. Sci.,2015, 14, 875
Discussion Post-inflammatory hyperpigmentation Higher laser density Increase PIH Metelitsa AI, Alster TS. Dermatol Surg. 2010 Mar;36(3):299-306. Chan HH, Manstein D, Yu CS, et al. Lasers Surg Med 2007;39:381 5.
Conclusion AFL-PDT with higher laser channel density showed better CR rate with lesser recurrence, especially in AK with severe hyperkeratosis. When AFL-PDT is used to treat AK with severe hyperkeratosis, we recommend AFL with higher laser channel density.
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