Elsevier

Photodiagnosis and Photodynamic Therapy

Volume 6, Issues 3–4, September–December 2009, Pages 207-213
Photodiagnosis and Photodynamic Therapy

Long-term follow-up of topical 5-aminolaevulinic acid photodynamic therapy diode laser single session for non-melanoma skin cancer

https://doi.org/10.1016/j.pdpdt.2009.09.001Get rights and content

Summary

Photodynamic therapy (PDT) is based on the association of a light source and light sensitive agents in order to cause the selective death of tumor cells. To evaluate topical 5-aminolaevulinic acid (5-ALA) and diode laser photodynamic single session therapy single session for non-melanoma skin cancer (NMSC), a long-term follow-up was performed. Nineteen Bowen's disease (BD) and 15 basal cell carcinoma (BCC) lesions were submitted to 6-h topical and occlusive 20% 5-ALA plus DMSO and EDTA, and later were exposed to 630 nm diode laser, 100 or 300 J cm−2 dose. At 3 months tumor-free rate was 91.2% (31/34) whereas at 60 months, 57.7% (15/26), slightly higher in BCC (63.6%; 7/11). The relation between the reduction of the clinical response and the increase of tumor dimension observed at 18 months was lost at 60 months. The sBCC recurrence was earlier compared to the nBCC one. ALA-PDT offered important advantages: it is minimally invasive, an option for patients under risk of surgical complications; clinical feasibility; treatment of multiple lesions in only one session or lesions in poor healing sites and superior esthetical results. However, the recurrence rate increase after ALA-PDT diode laser single session can be observed at long-term follow-up, and the repetitive sessions, an additional advantage of the method, is strongly recommended. The clinical response and recurrence time seem to be related to the laser light dose and NMSC types/sub-types, thickness and dimension, which must be considered for the choice of the ALA-PDT.

Introduction

Photodynamic therapy (PDT) is an alternative, minimally invasive treatment that involves the activation of photosensitizer, a light source and the generation of cytotoxic species of oxygen and free radicals to cause the selective destruction of target tissues. The photodynamic reaction exemplifies the non-thermical effects of the interaction between the visible non-ionizing light of appropriate wavelength and the topical or systemic photosensitizer with therapeutic potential to eliminate tumor cells [1], [2], [3], [4]. Systemic photosensitizers, such as hematoporphyrin derivative and its purified successor, approved and most frequently used in clinical experiments for cancer treatment with PDT, lead to transient generalized skin photosensitivity for at least 4 weeks, and limits its wide clinical use [2].

Facing this difficulty in the 90 s, Kennedy et al. [5] presented an alternative method using topic 5-aminolaevulinic acid (5-ALA) that has restricted the phototoxicity at the application site. As a metabolic precursor of endogenous porphyrins in heme biosynthesis, the absorption of 5-ALA induces the production and accumulation of protoporphyrin IX (PpIX), a fluorescent substance that is as effective as a light sensitive agent.

Clinical research about ALA-PDT has reported high rates of clinical responses, but they are varied in superficial skin cancers and contrasting in nodular tumors [3], [4], [6], [7], [8]. Methodological differences related to: incubation time, treatment protocols, number of sessions, sources and doses of light, and follow-up time may have influenced the variability of clinical response rate. Despite those difficulties, exploring the advantages and overcoming the limitations of the method are desirable in order to propose the inclusion of ALA-PDT as an accessible oncological therapy in health services.

Considering that, the clinical response of the short- and long-term follow-up with topical 5-aminolaevulinic acid (5-ALA) and high diode doses single session PDT for treatment of superficial non-melanoma skin cancer (NMSC) were carried out in the open prospective study at the university hospital integrated to the public health system in São Paulo, Brazil.

Section snippets

Patients and tumor characteristics

Twenty NMSC patients showing difficulties, impediment, high risk or rejection of surgical procedure—all aware and in agreement to the protocol of the study approved by the Ethics Institution Committee, were included in the study. They were recruited consecutively over the period of February 2002 to March 2003. Criteria of exclusion were: clinical and/or histopathological presence of tumor infiltration in other planes and tissues; regional and distant metastatic disease; light sensitive

Spectrofluorometry essay

The spectrofluorometry of PpIX in the tumor area with 5-ALA, compared to the normal skin without 5-ALA, is exemplified in Fig. 1. In the fluorescence intensity graphics, the values of the 5-ALA areas were between 1.04 × 107 and 1.36 × 109, average 3.49 × 108 ± 3.12 × 108 counts s−1. There were not differences among the distinct type tumors, nBCC, sBCC and BD.

ALA adverse effects

In 6 h of 5-ALA occlusive, there was not any report of irritation, local or systemic light sensitization reaction. During the exposure to the light

Discussion

The expressive incidence in the world population and the morbidity elapsing from NMSC accounts for new and accessible therapeutic proposals, particularly to implement in health services. Surgical procedure is a standard therapy modality; however alternatives methods and clinical response rates, its benefits, cost and limitations to NMSC treatment must be critically analyzed in this context.

The advances in the past 20 years present PDT as an interesting alternative for NMSC treatment and recent

Conclusions

PDT with topic 5-ALA met some expectations as a therapy for NMSC, showing significant advantages: it is a non-invasive and alternative therapy for patients with difficulties, impediments, high risk or refusal to surgery; clinic feasibility; possibility of treatment for multiple lesions in only one session or lesions in poor healing sites and superior esthetic results. However, the recurrence rate increase after ALA-PDT diode laser single session can be observed in a long-term follow-up, and the

Acknowledgements

Supported by Brazilian agency FAPESP (The State of São Paulo Research Foundation).

Preliminary and partial data contained in this paper were published in the original article in Portuguese language [26].

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