Study of Methyl Aminolaevulinate Photodynamic Therapy With and Without Er:YAG Laser in Bowen's Disease
Condition: Bowen's Disease
MeSH terms: Bowen's Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      Methyl aminolaevulinate photodynamic therapy (MAL-PDT) is an effective treatment for Bowen's
      disease (BD) of the lower extremities. Er:YAG ablative fractional laser (AFL) treatment
      removes the stratum corneum to increase MAL uptake and may improve efficacy. However, no
      studies have directly compared the efficacy of MAL-PDT with and without Er:YAG AFL in
      treating BD of the lower extremities in Asians.
    

Detailed description: 
      Bowen's disease (BD) is a form of intraepidermal (in situ) squamous cell carcinoma (SCC)
      originally described in 1912.1 It presents as a gradually enlarging, well-demarcated
      erythematous plaque with an irregular border and surface crusting or scaling.2 BD is the
      frequent precancerous skin lesion in Caucasians.3 In the UK, BD occurrence is most common
      among patients in their 70s and in women (70-85%), and the majority (60-85%) of cases involve
      lesions of the lower leg.4,5 BD is estimated to evolve into invasive SCC in 3-5% of cases;
      therefore, treatment is recommended.6 Current guidelines suggest that the available
      therapeutic options (including cryotherapy, curettage, excision, topical 5-fluorouracil, and
      topical imiquimod) are broadly similar in efficacy, with 12-month recurrence rates of
      approximately 5-10%.7 However, cryotherapy can be painful, making treatment of multiple
      lesions difficult, and healing can be slow.8 Additionally, topical treatment with
      5-fluorouracil or imiquimod is relatively slow and typically causes local irritation.9,10
      Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an attractive treatment
      option for BD with large or multiple patches, and poor healing sites can be treated with good
      efficacy, low recurrence rates, and good cosmetic outcomes.7 PDT requires light activation of
      a photosensitizer in the presence of oxygen, which generates reactive oxygen species leading
      to selective and highly localized destruction of abnormal cells.11,12 MAL is an efficient
      photosensitizer, with deep lesion penetration resulting from enhanced lipophilicity. Compared
      to 5-aminolevulinic acid, MAL also has a greater specificity for neoplastic cells.13-15
      Because histologic features of BD include full-thickness keratinocyte atypia with disordered
      maturation, it is typically treated twice within an interval of 1 week.16,17 So,
      complementary techniques are needed to enhance the penetration and accumulation of MAL in
      order to improve PDT efficacy and decrease treatment duration.

      Er:YAG ablative fractional laser therapy (AFL) can ablate the stratum corneum in a precisely
      tuned manner without producing significant thermal injury. This approach creates microscopic
      vertical holes in the ablated tissue, surrounded by thin layers of coagulated tissue.18,19
      Since the Er:YAG AFL resurfaces 5-20% of the skin at one time and does not injure the entire
      thickness of the epidermis, healing times are minimized.18,19 Recent studies have
      demonstrated that AFL facilitates delivery and uptake of topical MAL deep into the skin,
      enhancing porphyrin synthesis and photodynamic activation.20,21 The objectives of this study
      were to compare the efficacy, recurrence rate, cosmetic outcomes, and safety of MAL-PDT with
      and without the use of Er:YAG AFL in Asian BD patients with multiple lower extremity lesions.
    

Intervention name(s): Er:YAG AFL-PDT; MAL-PDT
Intervention type(s): Drug; Drug
Intervention description(s): Er:YAG AFL was performed with 550-600 µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. MAL cream was then applied under occlusion for 3 hrs and illuminated with a red light-emitting diode light at 37 J/cm2.; a 1-mm thick layer of MAL (16% Metvix® cream, PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, Saint Paul, MN, US) for 3 hours, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light. Each treatment area was then separately illuminated with red light-emitting diode (LED) lamps (Aktilite CL128; Galderma, Bruchsal, Germany) with peak emission at 632 nm and total light dose of 37 J cm-2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later.
Other intervention name(s): Er:YAG ablative fractional laser-assisted MAL-PDT; methyl aminolaevulinate-Photodynamic therapy
Intervention MeSH terms: Methyl 5-aminolevulinate
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Bowen's disease; Er:YAG; AFL-assisted; MAL-PDT