Ann-Marie Wennberg

A randomized multicenter study to compare two treatment regimens of topical methyl aminolevulinate (Metvix®)-PDT in actinic keratosis of the face and scalp

Photodynamic therapy (PDT) with topical methyl aminolevulinate (MAL) administered in two treatment sessions separated by 1 week is an effective treatment for actinic keratoses. This open prospective study compared the efficacy and safety of MAL-PDT given as a single treatment with two treatments of MAL-PDT 1 week apart. Two hundred and eleven patients with 413 thin to moderately thick actinic keratoses were randomized to either a single treatment with PDT using topical MAL (regimen I; n=105) or two treatments 1 week apart (regimen II; n=106). Each treatment involved surface debridement, application of Metvix cream (160 mg/g) for 3 h, followed by illumination with red light using a light-emitting diode system (peak wavelength 634+/-3 nm, light dose 37 J/cm2). Thirty-seven lesions (19%) with a non-complete response 3 months after a single treatment were re-treated. All patients were followed up 3 months after the last treatment. A total of 400 lesions, 198 initially treated once and 202 treated twice, were evaluable. Complete response rate for thin lesions after a single treatment was 93% (95% CI=87-97%), which was similar to 89% (82-96%) after repeated treatment. Response rates were lower after single treatment of thicker lesions (70% (60-78%) vs 84% (77-91%)), but improved after repeated treatment (88% (82-94%)). The conclusion of this study is that single treatment with topical MAL-PDT is effective for thin actinic keratosis lesions; however, repeated treatment is recommended for thicker or non-responding lesions.

Pain caused by photodynamic therapy of skin cancer

Summary Pain resulting from photodynamic therapy (PDT) of skin cancer was investigated. The study included 69 lesions (60 patients) with different types of skin tumours or precursors. Protoporphyrin IX, which is produced by the topical application of δ‐aminolevulinic acid, was used as a photosensitizing agent. Twenty‐three of the lesions (19 patients) were examined with a fluorescence imaging system which demarcates the tumour area from the healthy skin and visualizes the contrast between the fluorescence from healthy skin and that from the tumour. EMLA® is used on all patients as part of our routine PDT protocol but despite this the major side‐effect of PDT is pain during treatment. There is a large variation in pain intensity experienced by the patients, as measured by a visual analogue scale (VAS). Patients with actinic keratoses experienced more pain than those with Bowens disease or basal cell carcinoma. The mean VAS score was higher when treating lesions located on the head than when treating lesions on the torso or the extremities. Also, treatment of large skin areas resulted in more pain than treatment of small areas, and men experienced more pain than women. The pain experienced by the patients did not correlate with treatment dose, Fitzpatrick skin type, age or fluorescence intensity.

Review of photodynamic therapy in actinic keratosis and basal cell carcinoma

The number of non-melanoma skin cancers is increasing worldwide, and so also the demand for effective treatment modalities. Topical photodynamic therapy (PDT) using aminolaevulinic acid or its methyl ester has recently become good treatment options for actinic keratosis and basal cell carcinoma; especielly when treating large areas and areas with field cancerization. The cure rates are usually good, and the cosmetic outcomes excellent. The only major side effect reported is the pain experienced by the patients during treatment. This review covers the fundamental aspects of topical PDT and its application for treatment of actinic keratosis and basal cell carcinoma. Both potentials and limitations will be reviewed, as well as some recent development within the field.

Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris : results of a randomized, controlled study

Background  There is a need for alternative treatments for moderate to severe acne vulgaris. Preliminary experience suggests that topical methyl aminolaevulinate photodynamic therapy (MAL‐PDT) may have potential.

Percutaneous absorption of the sunscreen benzophenone-3 after repeated whole-body applications, with and without ultraviolet irradiation

Background  Benzophenone‐3 (BZ‐3; 2‐hydroxy‐4‐methoxybenzophenone, oxybenzone) is commonly used to absorb ultraviolet (UV) radiation. BZ‐3 penetrates the skin and can be found in the urine. The amount varies between 0·4% and 2%. This seems to be the main metabolic pathway in rats.

Important factors for pain during photodynamic therapy for actinic keratosis

Photodynamic therapy (PDT) is an efficient treatment for actinic keratosis. A common problem, however, is pain. The aim of this study was to investigate pain during PDT for actinic keratosis. The possibility of using capsaicin cream for pain relief was also assessed. Pain was investigated during aminolaevulinic acid PDT in 91 patients. Size, redness, scaling and induration of the lesions were recorded. Maximum pain during treatment was registered, using a visual analogue scale (0-10). The pain-reducing efficacy of capsaicin was tested in a pilot study in six patients (10 lesions). These patients were pre-treated with capsaicin cream for one week before commencing PDT. Pain was found to be normally distributed around a mean value of visual analogue scale 4.6. Larger lesions gave more pain (p=0.001). The redness of the actinic lesions was found to be related to PDT-induced pain (p=0.01), the reduction of actinic area (p=0.007), and the cure rate (p=0.01). The redder the actinic area, the better the treatment outcome and the more pain experienced. Patients with the largest reduction in the actinic area experienced more pain (p=0.053). The most important factors for presence of pain seem to be the size and the redness of the lesion. No significant pain relief was experienced after pre-treatment with capsaicin.

Photodynamic therapy with methyl aminolevulinate for prevention of new skin lesions in transplant recipients: a randomized study.

Background. Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions. Repeated field photodynamic therapy using topical methyl aminolevulinate (MAL) may have potential as a preventive treatment. Methods. This open randomized, intrapatient, comparative, multicenter study included 81 transplant recipients with 889 lesions (90% actinic keratoses (AK)]. In each patient, the study treatment was initially administered to one 50 cm2 area on the face, scalp, neck, trunk, or extremities (n=476 lesions) twice (1 week apart), with additional single treatments at 3, 9, and 15 months. On each occasion, the area was debrided gently and MAL cream (160 mg/g) applied for 3 hr, before illumination with noncoherent red light (630 nm, 37 J/cm2). The control, 50 cm2 area (n=413 lesions) received lesion-specific treatment (83% cryotherapy) at baseline and 3, 9, and 15 months. Additionally, all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas. Results. At 3 months, MAL photodynamic therapy significantly reduced the occurrence of new lesions (65 vs. 103 lesions in the control area; P=0.01), mainly AK (46% reduction; 43 vs. 80; P=0.006). This effect was not significant at 27 months (253 vs. 312; P=0.06). Hypopigmentation, as assessed by the investigator, was less evident in the treatment than control areas (16% vs. 51% of patients; P<0.001) at 27 months. Conclusion. Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed.

Treatment of superficial basal cell carcinomas using topically applied delta-aminolaevulinic acid and a filtered xenon lamp

Objective To evaluate the treatment of superficial basal cell carcinomas (SBCC) using photodynamic therapy with topically applied delta-aminolaevulinic acid (ALA) and a filtered short arc xenon lamp as a light source.Method An oil-in-water emulsion containing 20% ALA was applied topically to the lesion sites which were then occluded for 3 h. Irradiation was performed in a single session of 10 min using 125 or 166 mW/cm2 in the wavelength range (620–670 nm, giving a radiation dose of 75 or 100 J/cm2, respectively. Urine samples obtained in connection with the treatment were examined for traces of porphobilinogen and porphyrin. The therapy outcome was determined by histological examination of punch biopsies or by clinical verification. A follow-up scheduled for 5 years was initiated.Patients A group of 37 patients with histologically verified SBCCs were included. A total of 190 SBCCs were treated. Also included were six patients with 10 nodular basal cell carcinomas and five patients with 18 Mb. Bowen. The urine samples from three patients showed traces of porphyrins.Results Of the 157 SBCCs followed-up for 6 months, 144 were cleared giving a clearance rate of 92%. Of the nodular basal cell carcinomas and Mb. Bowens, 2 of ten and 11 of 18 were cleared, respectively.Conclusion Photodynamic therapy is well suited to the treatment of SBCCs giving good cosmetic results regardless of lesion size. The filtered xenon lamp proved to be particularly suitable for photodynamic therapy.

Nerve blocks enable adequate pain relief during topical photodynamic therapy of field cancerization on the forehead and scalp.

Background  Topical photodynamic therapy (PDT) is an effective method when treating extensive areas of sun‐damaged skin with multiple actinic keratoses (AKs) (field cancerization) on areas such as the forehead and scalp, and offers excellent cosmetic outcome. The major side‐effect of PDT is the pain experienced during treatment.

Penile Intraepithelial Neoplasia: Results of Photodynamic Therapy

Failure of response to treatment or recurrent disease is often noted in patients with penile intraepithelial neoplasia. Photodynamic therapy has recently been added to the list of treatment modalities used for this diagnosis. Our primary objective was to study the results of photodynamic therapy in the treatment of penile intraepithelial neoplasia in men over the age of 40 years. Ten patients aged 42-82 years with histopathologically confirmed lesions were studied. Lesions initially responded to photo-dynamic therapy in 7 out of 10 patients. Four of these patients presented no recurrences during a mean follow-up of 35 months, and were completely cleared after 2-8 treatments (mean 4.5 treatments). Three patients presented recurrences after treatment. No patient developed invasive penile cancer (mean follow-up 46.5 months). Photodynamic therapy is an alternative in the treatment of penile intraepithelial neoplasia, although prospective randomized trials are required to provide therapeutic guidelines.