ISTANBUL – A novel form of photodynamic therapy achieved a much higher cure rate than did conventional PDT, based on a randomized controlled trial of organ transplant recipients with numerous actinic keratoses.
The novel approach combines pretreatment with ablative fractional laser resurfacing followed immediately by application of a photosensitizing agent and natural light exposure. In addition to its efficacy, the novel PDT approach was painless. Conventional PDT can be particularly painful for organ transplant recipients as they tend to have particularly thick and widespread lesions located at pain-sensitive sites including the underarms, dorsal hands, and face, Dr. Merete Haedersdal reported at the annual congress of the European Academy of Dermatology and Venereology.
"From a clinical point of view, we are struggling with these patients. ... Now we can individualize PDT. We already have a wonderful conventional PDT, but now we’re better off with these combined techniques, especially when we are going to treat larger areas as in this high-risk group of patients," said Dr. Haedersdal, professor of dermatology at the University of Copenhagen.
As a result of their long-term immunosuppressive therapy, organ transplant recipients have a 100-fold higher risk than the general population for squamous cell carcinoma. Further, their skin tumors grow aggressively; 6%-8% of organ transplant recipients die due to nonmelanoma skin cancers.
The novel PDT approach begins with ablative fractional laser resurfacing to create tiny holes in the skin, allowing increased uptake of the photosensitizer. Dr. Haedersdal and her coworkers used methyl aminolevulinate 16% cream, applied immediately after laser treatment. It takes 30 minutes to start the biochemical process of protoporphyrin-9 production, and the patient then goes outside for a full 2 hours of natural light exposure. This photoactivation period averaged 62,583 lux in the study. The patient then covers the treated area or stays inside for the rest of the day.
Dr. Haedersdal reported on 16 patients with a total of 542 actinic keratoses (AKs) on the scalp, chest, and extremities. The patients had received a donor organ a median of 14 years earlier. In each patient, four symmetrical skin areas within the same anatomic region were mapped out and randomized to receive a single treatment with either the novel laser-assisted daylight PDT, conventional PDT with a red light–emitting diode light source, PDT with daylight rather than the LED light source, or ablative fractional laser therapy alone.
The primary endpoint was the cure rate, or complete lesion response of all AKs at 3 months post treatment. The cure rate was 74% in the laser-assisted daylight PDT group compared with 50% with daylight PDT, 48% with conventional PDT, and 0 with laser-only treatment. When the analysis was restricted to the thicker, grade II and III AKs, the cure rate was 67% with the novel therapy, 50% with conventional PDT, 40% with daylight PDT, and 0 with laser-only treatment.
Median pain scores on a 0-10 visual analog scale were 0 for the areas treated with laser-assisted daylight PDT, laser only, and daylight PDT compared with 4.5 for the portion of skin targeted with conventional PDT. The key to pain-free PDT, according to Dr. Haedersdal, is to do the laser resurfacing at a very low fluence, allowing for continuous daylight photobleaching. The fractional laser therapy is delivered at a total of 5.6 mJ using 4.6 mJ per pulse, 1.15 W, a 50-microsecond pulse duration, 500 Hz, and 2.4% density using a 2,940-nm erbium laser. The laser holes are drilled into the epidermal layer, but not below the basement membrane.
Crusting and erythema developed in all PDT-treated patients but were slightly more intense in the areas treated with laser-assisted PDT. One patient in the laser-assisted PDT group had transient hypopigmentation.
Based on blinded assessments at 3 months, the laser-assisted daylight PDT areas displayed significantly greater skin smoothening and rejuvenation with less dyschromia than the other treatment zones. Cosmesis was rated "excellent" in the laser-treated zones of 10 out of 16 patients, a much higher rate than seen in the other treatment areas.
Dr. Haedersdal reported having received research grants from roughly half a dozen medical device and pharmaceutical companies.