Sally H. Ibbotson

Topical photodynamic therapy (PDT) is effective in the treatment of certain non-melanoma skin cancers and is under evaluation in other dermatoses. Its development has been enhanced by a low rate of adverse events and good cosmesis. 5-Aminolaevulinic acid (ALA) is the main agent used, converted within cells into the photosensitizer protoporphyrin IX, with surface illumination then triggering the photodynamic reaction. Despite the relative simplicity of the technique, accurate dosimetry in PDT is complicated by multiple variables in drug formulation, delivery and duration of application, in addition to light-specific parameters. Several non-coherent and coherent light sources are effective in PDT. Optimal disease-specific irradiance, wavelength and total dose characteristics have yet to be established, and are compounded by difficulties comparing light sources. The carcinogenic risk of ALA-PDT appears to be low. Current evidence indicates topical PDT to be effective in actinic keratoses on the face and scalp, Bowen's disease and superficial basal cell carcinomas (BCCs). PDT may prove advantageous where size, site or number of lesions limits the efficacy and/or acceptability of conventional therapies. Topical ALA-PDT alone is a relatively poor option for both nodular BCCs and squamous cell carcinomas. Experience of the modality in other skin diseases remains limited; areas where there is potential benefit include viral warts, acne, psoriasis and cutaneous T-cell lymphoma. A recent British Photodermatology Group workshop considered published evidence on topical PDT in order to establish guidelines to promote the efficacy and safety of this increasingly practised treatment modality.

An increase in the use of light-based technology and medical devices has created a demand for informative and accessible data showing the depth that light penetrates into skin and how this varies with wavelength. These data would be particularly beneficial in many areas of medical research and would support the use and development of disease-targeted light-based therapies for specific skin diseases, based on increased understanding of wavelength-dependency of cutaneous penetration effects. We have used Monte Carlo radiative transport (MCRT) to simulate light propagation through a multi-layered skin model for the wavelength range of 200-1000 nm. We further adapted the simulation to compare the effect of direct and diffuse light sources, varying incident angles and stratum corneum thickness. The lateral spread of light in skin was also investigated. As anticipated, we found that the penetration depth of light into skin varies with wavelength in accordance with the optical properties of skin. Penetration depth of ultraviolet radiation was also increased when the stratum corneum was thinner. These observations enhance understanding of the wavelength-dependency and characteristics of light penetration of skin, which has potential for clinical impact regarding optimizing light-based diagnostic and therapeutic approaches for skin disease.

Summary These guidelines for use of narrowband (TL-01) ultraviolet B have been prepared for dermatologists by the British Photodermatology Group on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment of patients with a variety of dermatoses and photodermatoses, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of background photobiology.

OBJECTIVE: To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ. DESIGN: Randomized, placebo-controlled study, with follow-up at 3 and 12 months after last treatment. SETTING: Forty outpatient dermatology centers in 11 European countries. PATIENTS: Random sample of 225 patients with histologically confirmed squamous cell carcinoma in situ (lesion size, 6-40 mm) and no evidence of progression. INTERVENTIONS: Treatment with PDT with methyl aminolevulinate (160 mg/g; n = 96) or matching placebo cream (n = 17), cryotherapy (n = 82), or topical fluorouracil (5% cream; n = 30). Methyl aminolevulinate or placebo cream was applied for 3 hours before illumination with broadband red light (75 J/cm2, 570-670 nm). Treatment was repeated 1 week later. Cryotherapy was performed with liquid nitrogen spray. Fluorouracil was applied for 4 weeks. Lesions with a partial response at 3 months were re-treated. MAIN OUTCOME MEASURES: Clinically verified complete response of lesions; blinded and on-site assessment of cosmetic outcome (4-point rating scale). RESULTS: At 12 months, the estimated sustained lesion complete response rate with methyl aminolevulinate PDT was superior to that with cryotherapy (80% vs 67%; odds ratio, 1.77; 95% confidence interval, 1.01-3.12; P = .047), and better than that with fluorouracil (80% vs 69%; odds ratio, 1.64; 95% confidence interval, 0.78-3.45; P = .19). Cosmetic outcome at 3 months was good or excellent in 94% of patients treated with methyl aminolevulinate PDT vs 66% with cryotherapy and 76% with fluorouracil, and was maintained at 12 months. CONCLUSION: Methyl aminolevulinate PDT is an effective treatment option for squamous cell carcinoma in situ, with excellent cosmesis.

This multicentre, randomized study compared photodynamic therapy using topical methyl aminolaevulinate (MAL PDT), a non-invasive modality, with cryotherapy for treatment of superficial basal cell carcinoma. Sixty patients with 114 lesions were treated with MAL cream (160 mg/g) applied for 3 hours before illumination (570-670 nm, light dose 75 J/cm) (1 session), and 58 with 105 lesions received cryotherapy (2 freeze-thaw cycles). Patients with an incomplete response at 3 months received 2 further MAL PDT sessions (n = 20) or repeat cryotherapy (n = 16). 100 lesions treated with MAL PDT and 93 lesions treated with cryotherapy were in complete response at 3 months after the last treatment and evaluable for recurrence over 5 years. There was no difference in 5-year recurrence rates with either treatment (20% with cryotherapy vs. 22% with MAL PDT, p = 0.86). However, more patients had an excellent cosmetic outcome with MAL PDT (60% vs. 16% with cryotherapy, p = 0.00078). These results provide support for the use of MAL PDT as a non-invasive, selective treatment alternative for primary superficial basal cell carcinoma.