Long-term Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy for Treatment of Lower Extremity Bowen's Disease

Study Overview
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Brief Summary
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Er:YAG ablative fractional laser-assisted methyl aminolevulinate photodynamic therapy (AFL-PDT) has shown significantly higher efficacy and a lower recurrence rate at 12 months than methyl aminolevulinate photodynamic therapy (MAL-PDT) for treatment of Bowen's disease (BD). However, long-term follow up data are not available.

Detailed Description
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To compare the long-term efficacy and recurrence rates of AFL-PDT and standard MAL-PDT for the treatment of lower extremity BD.

Official Title
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Long-term Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy for Treatment of Lower Extremity Bowen's Disease: A Prospective, Randomized, Controlled Trial With 5-year Follow up

Conditions
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Bowen's Disease

Intervention / Treatment
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* Drug: lidocaine-prilocaine 5% cream application
* Device: 2940-nm Er:YAG AFL pretreatment
* Drug: methyl-aminolevulinate application
* Device: Illuminating using red light-emitting diode lamps


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: •Patients aged 18 years or more who diagnosed as bowen's disease Exclusion Criteria: pregnancy or lactation active systemic infectious disease other inflammatory, infectious, or neoplastic skin diseases in the treated area allergy to MAL,other topical photosensitizers, or excipients of the cream history of photosensitivity use of immunosuppressive or photosensitizing drugs participation in any other investigational study in the preceding 30 days history or indicators of poor compliance Histological findings of acantholysis, desmoplasia, perineural or lymphovascular invasion, and echographic features of regional lymph node metastasis were the disease-specific exclusion criteria

Ages Eligible for Study
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Minimum Age: 42 Years
Maximum Age: 89 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAL-PDT<br>Patients were randomly assigned to receive either AFL-PDT or MAL-PDT in a 1:1 ratio. As result, the patients were randomized to treatment with AFL-PDT or MAL-PDT | Drug: methyl-aminolevulinate application<br>* Immediately after the AFL, a 1-mm thick layer of methyl-aminolevulinate (16% Metvix® cream; PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of the surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm; 3M, Co., Saint Paul, MN, USA) for 3 h, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light.<br>Device: Illuminating using red light-emitting diode lamps<br>* Each treatment area was then separately illuminated using red light-emitting diode lamps (Aktilite CL128; Galderma S.A., Bruchsal, Germany) with peak emission at 632 nm and a total light dose of 37 J/cm2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later. During the illumination, patients were asked to evaluate pain intensity using an 11-point visual analog scale.<br>|
| Experimental: AFL-PDT<br>Patients were randomly assigned to receive either AFL-PDT or MAL-PDT in a 1:1 ratio. As result, the patients were randomized to treatment with AFL-PDT or MAL-PDT | Drug: lidocaine-prilocaine 5% cream application<br>* The lesions were then cleansed with saline gauze, and a lidocaine-prilocaine 5% cream (EMLA®; Astra Pharmaceuticals, LP, Westborough, MA, USA) was applied to the treatment area for 30 min under occlusion<br>Device: 2940-nm Er:YAG AFL pretreatment<br>* After the anesthetic cream was removed, AFL was performed using a 2940-nm Er:YAG AFL (Joule; Sciton, Inc., Palo Alto, CA, USA) with a 500 µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse<br>Drug: methyl-aminolevulinate application<br>* Immediately after the AFL, a 1-mm thick layer of methyl-aminolevulinate (16% Metvix® cream; PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of the surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm; 3M, Co., Saint Paul, MN, USA) for 3 h, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light.<br>Device: Illuminating using red light-emitting diode lamps<br>* Each treatment area was then separately illuminated using red light-emitting diode lamps (Aktilite CL128; Galderma S.A., Bruchsal, Germany) with peak emission at 632 nm and a total light dose of 37 J/cm2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later. During the illumination, patients were asked to evaluate pain intensity using an 11-point visual analog scale.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of short-term complete response (CR) rate between AFL-PDT and MAL-PDT | The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion) | Short-term CR rate was evaluated at 3 months | 
| Difference of long-term complete response (CR) rate between AFL-PDT and MAL-PDT | The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion) | Long-term CR rate was evaluated at 60 months | 
| Difference of long-term recurrence rate between AFL-PDT and MAL-PDT at 60 months | In all cases of complete response, the patients were reviewed at 60 months to check for recurrence. Post-therapy punch biopsies were performed when there was doubt concerning incomplete-response and clinical recurrence | Recurrent rate was evaluated at 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of the cosmetic outcome between AFL-PDT and MAL-PDT | The overall cosmetic outcome was assessed by each investigator for all lesions that achieved complete response at 60 months, and was graded using a 4-point scale: excellent (only slight occurrence of redness or change in pigmentation), good (moderate redness or change in pigmentation), 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 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ablative fractional laser, photodynamic therapy, protoporphyrin IX, methy-aminolevulinate