Efficacy of AFL-assisted PDT With Short Incubation Time in Actinic Keratosis

Study Overview
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Brief Summary
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Photodynamic therapy (PDT) using methyl aminolevulinate (MAL) is an effective first-line treatment for actinic keratosis (AK). Erbium: yttrium-aluminium-garnet (Er:YAG) ablative fractional laser-assisted MAL-PDT (AFL-PDT) has shown significant benefit for the treatment of AK. However, knowledge on the optimal photosensitizer incubation time for AFL-PDT is limited

Detailed Description
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Photodynamic therapy (PDT) is widely used in the treatment of superficial skin cancer. It has an excellent cosmetic outcome, and it could be considered the first-line therapy for Actinic keratosis (AK). In PDT incubation time is required so that the photosensitizer can be converted to PpIX. The recommended treatment regimen of PDT requires a relatively long incubation time with ALA (4 hours) and MAL (3 hours) before illumination. Theoretically, ablative fractional laser (AFL) pre-treatment may facilitate the penetration and distribution of topically applied drugs, since the ablated laser holes extend into the dermis, thereby possibly acting as channels for drug uptake. However, knowledge on the optimal photosensitizer incubation time for AFL-PDT is limited. The objectives of this study were to compare the efficacy, recurrence rate, cosmetic outcome, and safety between AFL-PDT with 2 and 3hours of incubation vs. conventional MAL-PDT in patients with facial and scalp AK.

Official Title
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Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy With Short Incubation Time for the Treatment of Facial and Scalp Actinic Keratosis: 12-month Follow-up Results of a Randomized, Prospective, Comparative Trial

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: 2h-AFL-PDT
* Drug: 3h-AFL-PDT
* Drug: 3hr-MAL-PDT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >18 years the presence of 2-10 facial AK lesions Exclusion Criteria: lactating or pregnant women patients with porphyria a known allergy to any of the constituents of the MAL cream and lidocaine patients with systemic disease history of malignant melanoma tendency for melasma development or keloid formation any AK treatment of the area in the previous 4 weeks any conditions associated with a risk of poor protocol compliance patients on immunosuppressive treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 87 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2h-AFL-PDT<br>All 440 AK lesions of the 93 patients were randomly assigned to treatment with MAL-PDT (3h-MAL-PDT) or AFL-PDT with 2 hours (2h-AFL-PDT) and 3 hours (3h-AFL-PDT) of incubation time, using restricted randomization, with a computer-generated program. | Drug: 2h-AFL-PDT<br>* AFL therapy was performed using a 2940-nm Er:YAG AFL (Joule; Sciton Inc., Palo Alto, CA, USA) at 300-550µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. In the 3h-MAL-PDT group, the above mentioned procedures were not performed. Immediately after AFL treatment, an approximately 1-mm thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, St. Paul, MN, USA). After incubation for 2 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface and total light dose of 37 J/cm-2<br>|
| Active Comparator: 3hr-AFL-PDT<br>All 440 AK lesions of the 93 patients were randomly assigned to treatment with MAL-PDT (3h-MAL-PDT) or AFL-PDT with 2 hours (2h-AFL-PDT) and 3 hours (3h-AFL-PDT) of incubation time, using restricted randomization, with a computer-generated program. | Drug: 3h-AFL-PDT<br>* AFL therapy was performed using a 2940-nm Er:YAG AFL (Joule; Sciton Inc., Palo Alto, CA, USA) at 300-550µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. In the 3h-MAL-PDT group, the above mentioned procedures were not performed. Immediately after AFL treatment, an approximately 1-mm thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, St. Paul, MN, USA). After incubation for 3 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface and total light dose of 37 J/cm-2<br>|
| Active Comparator: 3hr-MAL-PDT<br>All 440 AK lesions of the 93 patients were randomly assigned to treatment with MAL-PDT (3h-MAL-PDT) or AFL-PDT with 2 hours (2h-AFL-PDT) and 3 hours (3h-AFL-PDT) of incubation time, using restricted randomization, with a computer-generated program. | Drug: 3hr-MAL-PDT<br>* an approximately 1-mm thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, St. Paul, MN, USA). After incubation for 3 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface and total light dose of 37 J/cm-2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of the efficacy between 3h-AFL-PDT, 2hr-AFL-PDT and 3h-MAL-PDT | The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion) | Efficacy was evaluated at 3 months and 12 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of the cosmetic outcome between 3h-AFL-PDT, 2hr-AFL-PDT and 3h-MAL-PDT | It was graded as excellent (slight redness or pigmentation change), good (moderate redness or pigmentation change), fair (slight-to-moderate scarring, atrophy, or induration), or poor (extensive scarring, atrophy, or induration). | Cosmetic outcome was assessed by each investigator for all lesions that achieved a complete response at 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ablative fractional laser, Actinic keratosis, Efficacy, Photodynamic therapy, Short incubation time