Guidelines for practical use of MAL‐PDT in non‐melanoma skin cancer

Methyl aminolaevulinate photodynamic therapy is increasingly practiced in the treatment of actinic keratoses, Bowen’s disease and basal cell carcinomas. This method is particularly suitable for treating multiple lesions, field cancerization and lesions in areas where a good cosmetic outcome is of importance. Good treatment routines will contribute to a favourable result. The Norwegian photodynamic therapy (PDT) group consists of medical specialists with long and extensive PDT experience. With support in the literature, this group presents guidelines for the practical use of topical PDT in non‐melanoma skin cancer.     

Low‐irradiance red LED traffic lamps as light source in PDT for actinic keratoses

LED light sources for photodynamic therapy have become increasingly popular due to their narrow emission spectra that accurately match the absorption spectrum of porphyrins. Photodynamic therapy at low fluence rates has been shown to be as effective as high output irradiation for treatment of non‐melanoma skin cancers. Fifteen patients with multiple non‐hypertrophic actinic keratoses covering the scalp and the face were treated with aminolaevulinic acid photodynamic therapy using ordinary red LED traffic lamps as light source. All 15 patients improved clinically after one photodynamic therapy session. Only two patients required a second session to obtain satisfactory remission. Pain was minimal during these sessions. Red LED traffic lights constitute a simple alternative to far more complicated and expensive PDT light sources.     

Successful sequential treatment with itraconazole and ALA‐PDT for chromoblastomycosis because of Alternaria alternata

Alternaria alternata is a rare etiology of phaeohyphomycosis in immunocompromised patients, which has never been reported to cause chromoblastomycosis. As far as we know, this is the first chromoblastomycosis case successfully treated with a short course of systemic antifungals and subsequent 5‐aminolevulinic acid‐photodynamic therapy.     

Fractionated aminolevulinic acid–photodynamic therapy provides additional evidence for the use of PDT for non-melanoma skin cancer

Background Photodynamic therapy (PDT) is an accepted treatment for superficial basal cel carcinoma (sBCC) and Bowens disease. In Rotterdam, extensive preclinical research has lead to an optimized twofold illumination scheme for aminolevulinic acid–PDT (ALA‐PDT). Objective To provide additional evidence of ALA‐PDT for sBCC, Bowens disease (BD), nodular BCC (nBCC) and actinic keratosis (AK) using a 2‐fold illumination scheme after a single application of ALA. Methods Five hundred fifty‐two lesions (430 sBCC, 20 nBCC, 32 BD, 70 AK) were treated with ALA‐PDT using a twofold illumination scheme. ALA was applied topically for 4 h. Lesions were treated with two light fractions of 20 and 80 J/cm² separated by a 2‐h dark interval. Results After a minimum follow‐up of 12 months, in average follow‐up of 2 years, an overall complete response of 95% was seen for all lesions. For sBCC, the complete response at 2 years was 97% (for AK 98%, for BD 84% and for nBCC 80% after 2 years). A sub‐analysis of the results of lesions larger than 2 cm showed CR at 2 years of 89% for all lesions (n = 57). Cosmetic outcome was good to excellent in 95% of the treated lesions. Conclusion ALA‐PDT using a twofold illumination scheme of 20 plus 80 J/cm² separated by a 2‐h dark interval leads to high complete response rates at 2 years and can be regarded as an evidence‐based treatment modality for superficial growing non‐melanoma skin cancer and the (pre)malignant AK. The Rotterdam fractionated approach should be included in future guidelines.     

018 New source for evaluating PDT drugs in the laboratory

To test the hypothesis that UV could alter collagen susceptibility to interstitial collagenase, acid-extracted Skh-1 hairless mouse collagen samples were (un)irradiated with 0–140 J/cm² of radiation from bank of filtered FS lamp (UVB/UVA = 0.33, fluence rate = 0.81 mW/cm²). Subsequent to UV irradiation, collagen samples were coupled with fluorescein isothiocyanate (FITC) and assayed for its susceptibility to bacterial collagenase by monitoring the appearance of supernatant FITC fluorescence (a measure of lysed collagen) over time of incubation. As a reference. unirradiated commercial FITC – labeled collagen (Elastin Products) was similarly analyzed. Mouse collagen had a lower rate of cleavage than did the calf skin sample. Mouse collagen initial cleavage followed a quasi-linear time course over the first 5 h. Calf-skin collagen displayed a 'sigmoidal' time course, reminiscent of a cooperative mechanism. UV irradiation afforded no significant effect on the ability of collagenase to cleave mouse collagen, although a small effect could be discerned after 48 h (140 J/cm²). On the other hand, these samples exhibited significant chain degradation. cross-linking and loss of intrinsic collagen fluorescence on UV photolysis. It appears that the rate of cleavage depends on the superstructure of the collagen, and that the collagen fluorophores are not in proximity to the specific site of collagenase cleavage.
Supported in part by NIH/MBRS Grant #GM 08248 and RCMI Grant #RR 03034.     

PDT and BF‐200 ALA: The therapy option for the treatment of Poikiloderma of Civatte

Poikiloderma is a chronic skin condition affecting middle‐age men and women that comprises cutaneous atrophy, telangiectasias, and changes in the pigmentation of the skin usually of mottled appearance (both hyper‐ and hypopigmentation). There is no specific medical treatment for Poikiloderma of Civatte (PC), but the use of photoprotector/sunscreen + SPF 50 to avoid prolonged sun exposure is highly recommended in these patients. Some authors recommend the use of topical corticoids in early stages; however, the results have not been satisfactory. Multiple topical (retinoids, dimethyl sulfoxide, or calcineurin inhibitors), systemic (cyclophosphamide), and physical (dermabrasion, phototherapy, and fractional photothermolysis) treatments have been described with unequal and inconsistent responses or unsatisfactory. This report underlies the combination of BF‐200 ALA and photodynamic therapy (PDT) with positive results at the clinical level: significant improvement of pigmentary changes and telangiectasias after two PDT sessions.     

A new protocol using a light-emitting fabric for PDT of AK

Actinic keratoses (AKs) are areas of sun-damaged skin found mainly on sun-exposed parts of the body, particularly the backs of the hands and forearms, the face and ears, and the scalp in balding men. They are usually harmless although they can be unsightly or inconvenient, and there is a very small risk of some actinic keratoses progressing to a form of skin cancer called squamous cell carcinoma. There are several possible treatments, including photodynamic therapy (PDT), in which a special light activates a cream called a photosensitiser, which has been applied to the affected area of skin. This treatment kills the abnormal cells in the skin. The photosensitisers approved in Europe for PDT of AKs require either activation by red light three hours after application of the photosensitiser (referred to as C-PDT) or activation by daylight within 30 minutes following application of the photosensitiser (referred to as D-PDT). The major drawback of C-PDT is pain during treatment, whereas D-PDT is nearly pain-free due to the short time between photosensitiser application and daylight activation. Unfortunately, D-PDT requires favourable weather conditions. The authors of this study, who belong to the ONCO-THAI research unit based in France, therefore tested a way to activate the photosensitiser 30 minutes after application, by red light using a flexible, light-emitting, fabric-based device (hereinafter referred to as FLEXI-PDT). This study aimed to assess whether FLEXI-PDT is at least as effective as C-PDT in destroying AK. The authors were also interested in whether pain scores differ between FLEXI-PDT and C-PDT. For these purposes, 35 patients with AKs on the scalp were treated with FLEXI-PDT on one side of the scalp and with C-PDT on the other side. Patients rated their pain during FLEXI-PDT and during C-PDT separately. The response of each AK (complete or incomplete disappearance) was assessed by a dermatologist at three months after treatment. From the analyses of the data collected, the authors showed that FLEXI-PDT, which can be performed in all weather conditions, is at least as effective as and less painful than C-PDT in destroying AK.     

Efficacy of lasers and PDT for the treatment of acne vulgaris

Acne vulgaris can represent a therapeutic challenge in terms of managing ongoing symptoms and preventing scar formation. While the copious variations of available treatments address milder forms of the disease, until recently, therapies for resistant or moderate-to-severe forms were limited to systemic agents that were accompanied by potentially severe side-effects. With the addition of lasers, light sources, and aminolevulinic acid-photodynamic therapy (ALA-PDT) therapies, dermatologists may now have viable new alternatives for treating all grades of acne severity that circumvent the negative side-effects associated with many conventional options.     

Daylight PDT with MAL – current data and practical recommendations of an expert panel

Photodynamic Therapy (PDT) is one of the standard treatment modalities for actinic keratoses (AKs). Daylight PDT (DL‐PDT) with MAL cream is a rather recent development, which, instead of an artificial light source, uses daylight for the activation of the photosensitizer. The present review summarizes available data based on a selective literature search, highlights practical aspects, and reflects the authors’ expert knowledge in using DL‐PDT. With respect to efficacy, study data shows that DL‐PDT is noninferior to conventional PDT (cPDT). However, given that DL‐PDT is markedly less painful, it is significantly better tolerated than cPDT. In Europe, DL‐PDT can be performed from March to October, on sunny as well as on cloudy days. UV protection of untreated areas of the body should be observed. Outside temperature should not fall below 10°C. On hot days, patients should be advised to stay in the shade if necessary. Representing a useful addition to current therapeutic options, DL‐PDT with MAL cream is, among others, suitable for patients with field cancerization and/or those who have experienced severe pain associated with cPDT.     

Our PDT experience in the treatment of non-melanoma skin cancer over the last 7 years

BACKGROUND: Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) was first described by Kennedy et al. in 1990; currently, accumulated evidence shows that topical PDT is effective in the treatment of actinic keratoses, Bowen's disease and superficial basal cell carcinoma, being potentially advantageous where size, anatomical location or number of lesions limit the efficacy and/or the acceptability of conventional therapies. It involves the use of photosensitizing drugs and the administration of an appropriate light source to activate the sensitizing agent, which leads to the production of activated oxygen species for tissue destruction. The topically administered prodrug 5-ALA is converted within cells into the active photosensitizer protoporphyrin IX, via haem cycle, with preferential accumulation in tumour cells. METHODS: The authors describe their experience with topical PDT, using 20% 5-ALA and two different incoherent light sources, 'Waldman 1200 L' and 'VersaLight', in the treatment of non-melanoma skin cancer and precursor lesions. More than 100 patients were treated since 1997, with up to a 7-year follow-up period. RESULTS: Cases are illustrated and results are presented and discussed in the light of the relevant Literature. CONCLUSION: The study suggests that 5-ALA PDT is effective in the treatment of superficial skin cancer and premalignant lesions.