Melanoma: Moseley H

Morton CA, Brown SB, Collins S, Ibbotson S, Jenkinson H, Kurwa H, Langmack K, McKenna K, Moseley H, Pearse AD, Stringer M, Taylor DK, Wong G, Rhodes LE. · Department of Dermatology, Falkirk Royal Infirmary, Falkirk FK1 5QE, U.K. · Br J Dermatol. · Pubmed #11966684 No free full text.

Abstract: 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.

Lesar A, Ferguson J, Moseley H. · Department of Photobiology, Ninewells Hospital, Dundee, UK. · Photodermatol Photoimmunol Photomed. · Pubmed #19614897 No free full text.

Abstract: BACKGROUND: Treatment of non-melanoma skin cancers (NMSC) with topical photodynamic therapy (PDT) is a treatment of choice for many clinicians. The two most commonly used PDT photosensitizer precursors are 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL). Current PDT treatment regimes advise longer (4-6 h) application times for ALA and shorter times (3 h) for MAL. AIMS: To establish the time course characteristics of protoporphyrin IX (PpIX) fluorescence following the application of ALA and MAL in normal skin. METHODS: A total of 17 healthy volunteers were recruited, and both ALA and MAL were applied to the inner forearm for varying times (1-6 h). PpIX fluorescence was detected using a non-invasive spectroscopy system. RESULTS AND CONCLUSION: PpIX fluorescence (following the application of either ALA or MAL) is dependent on duration of application. Following the application of ALA for 1-3 h peak fluorescence was noted at 7 h. Longer duration times (4-6 h) resulted in sustained fluorescence, which peaked at 24 h. MAL-induced fluorescence peaked at 7 h and was significantly decreased by 24 h for all application times. ALA induced fluorescence was shown to be significantly greater than MAL. The findings from this study have shown that potentially it would be more beneficial to apply ALA for shorter periods of time and MAL for longer than current practice.

Moseley H, Brancaleon L, Lesar AE, Ferguson J, Ibbotson SH. · The Photobiology Unit, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK. · Photodermatol Photoimmunol Photomed. · Pubmed #18353086 No free full text.

Abstract: BACKGROUND/PURPOSE: Photodynamic therapy (PDT) using aminolaevulinic acid (ALA) is widely used in the treatment of non-melanoma skin cancer. Surface preparation of the lesion is commonly performed before application of ALA but the extent of the preparation varies from centre to centre and there has been no study of its effects. The purpose of this study was to examine the effects of surface preparation on the local uptake of ALA by recording fluorescence from accumulated protoporphyrin IX (PPIX). METHODS: The study was performed on 16 lesions, either superficial basal cell carcinoma (BCC) or Bowen's disease (BD). Each half of the lesion was randomly assigned to (a) no surface preparation or (b) surface preparation (randomly allocated to gentle curettage or abrasion with a spatula). ALA was left for 4 h (BCC) or 6 h (BD). PPIX fluorescence was measured using an excitation wavelength of 405+/-5 nm and emission spectrum recorded using a photodiode array. Spectra were measured (a) before and (b) after surface preparation, (c) immediately before and (d) after laser irradiation at 630 nm. RESULTS: The ratio of fluorescence after incubation to that before incubation was 6.1+/-1.2 in the non-prepared section. This increased slightly but not significantly to 6.8 +/-1.8 in the prepared section (P<0.1). There was no significant difference between curettage and abrasion. There was also no significant difference in outcome after PDT. CONCLUSIONS: The clinical assessment agrees with the fluorescence data as no significant difference was seen between prepared and unprepared halves of the lesion 12 months after PDT. Overall our data seem to suggest that for most BCC and BD lesions, surface preparation did not increase ALA uptake.

Clark C, Dawe RS, Moseley H, Ferguson J, Ibbotson SH. · Photobiology Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland. · Photodermatol Photoimmunol Photomed. · Pubmed #15030596 No free full text.

Abstract: BACKGROUND: Topical photodynamic therapy (PDT) is increasingly used to treat superficial non-melanoma skin cancers. Knowledge of the characteristics of 5-aminolaevulinic acid (ALA)-induced phototoxicity will increase our understanding of PDT and may facilitate optimisation of treatment regimes. METHODS: We examined the characteristics of ALA-induced erythema in 10 healthy subjects and investigated the effect of light source and body site. RESULTS AND CONCLUSIONS: Maximal erythema occurred within 1-2 h of PDT and inter-individual variation in ALA-induced phototoxicity was seen. No detectable differences were seen in the phototoxicity on back or leg sites or between coherent and non-coherent light sources. These data provide further information to allow us to optimise topical PDT regimes.

Clark C, Bryden A, Dawe R, Moseley H, Ferguson J, Ibbotson SH. · Department of Dermatology, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK. · Photodermatol Photoimmunol Photomed. · Pubmed #12914598 No free full text.

Abstract: BACKGROUND: Topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) is increasingly used for superficial non-melanoma skin cancers and their precursors. METHODS: We report our 3-year experience of topical ALA-PDT, with a preliminary comparison of the effects of broadband and laser light sources. RESULTS: We performed 688 treatments on 483 lesions in 207 patients. Complete clearance was achieved in 222/239 lesions of Bowen's disease (BD), superficial basal cell carcinoma (sBCC) and actinic keratosis (AK) (93%) - 117/129 BD (91%), 84/87 sBCC (97%) and 21/23 AK (91%), with a median follow up of 48 weeks. Broadband and laser light sources were of similar efficacy. Recurrences have occurred in 10.3% BD, 4.8% sBCC and 4.8% AK. Adverse effects from PDT were uncommon but included pigmentary change (2%) and minor scarring (2%). How-ever, severe pain was experienced in 16-21% of treatments using the high-output broadband and laser sources, but in only 2% with the low-output xenon arc source. CONCLUSION: Topical ALA-PDT is effective for BD, sBCC and AK and has been an invaluable addition to our dermatology service. Efficacy is similar for broadband and laser light sources, although treatment at higher surface irradiance may be painful, and excellent cosmetic results can be achieved.