BOSTON – Fractional laser-assisted photodynamic therapy can effectively treat actinic keratoses in organ transplant recipients, but at a cost of more intense postoperative skin reactions than with laser therapy alone, based on data from a randomized clinical trial.
Intensified ablative fractional laser-assisted photodynamic therapy (AFXL-PDT) was significantly more effective at clearing actinic keratoses (AKs) and warty lesions on the dorsal aspect of the hands of organ transplant recipients than AFXL alone, reported Dr. Merete Haedersdal of the University of Copenhagen and a visiting scientist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston.
The treatment was painful, and 3 of 10 patients reported intense inflammation a week afterward, Dr. Haedersdal noted.
However, "this new treatment modality also works well for immunosuppressed patients, and I do think it works very well for immunosuppressed patients with multiple AKs," she said at the annual meeting of the American Society for Laser Medicine and Surgery.
Organ transplant recipients are at a 100-fold or greater risk for developing squamous cell carcinomas, which can arise from AKs, because of their chronic immunosuppressive treatment regimens. Cancers that develop in these patients tend to be quite aggressive, with a high rate of metastases and an attributable morality rate of 6%-8%, said Dr. Haedersdal.
"Therefore, there is a huge motivation to come up with intensified treatment regimens for these patients," she said.
PDT is a well-established therapy in transplant recipients, but it is less effective in these patients than in patients with intact immune responses. It is also less effective for thick lesions or lesions on the extremities.
Dr. Haedersdal and her colleagues previously demonstrated the efficacy of AFXL-PDT for treating AKs with a carbon dioxide laser in immunocompetent patients. In the current study, they compared the therapy with ablative fractional CO2 laser alone in 10 organ transplant recipients with a total of 680 AKs and 409 wartlike lesions on the dorsal hands, and a collective history of 21 previous squamous cell carcinomas.
In a randomized intrapatient trial, the participants first underwent targeted ablation of localized keratotic lesions, and then were randomly assigned to receive one field treatment with AFXL-PDT on one hand, and AFXL alone on the other.
For AFXL, energy was delivered with the laser set to 30 W, a 0.12-mm spot size, a 1.32- to 2.06-millisecond pulse duration, and 40-60 mJ with the target of 4.3%-5.2% coverage; settings were based on the severity of skin atrophy.
After laser exposure, lesions randomized to receive PDT were treated with methyl aminolevulinate applied under occlusion for 3 hours, and were then exposed to red diode light at 37 J/cm2.
‘Really impressive’ cure rate
The combined modality completely cleared 73% of all AKs, compared with 31% cleared by AFXL alone (P = .002), and 37% of all wartlike lesions, compared with 14% for AFXL (P = .02) at 4 months’ follow-up. The patients were clinically assessed by raters blinded to treatment type.
"Normally, when we deliver PDT for these patients, we have – from just a single treatment – cure rates on the acral lesions of about 30%-40%, so this was really impressive to get a complete cure rate for AKs at a level of 73%," Dr. Haedersdal said.
Overall, AKs treated with AFXL-PDT were rated as improved by a median of 83%, 15% as unchanged, and 3% as worsened, compared with AFXL-only rates of 52%, 47%, and 4%, respectively.
Thinner AKs responded better to treatment than thick lesions, with an odds ratio (OR) for grade 2 vs. grade 1 lesions of 0.34 (P = .001) and an OR for grade 3 vs. grade 1 of 0.21 (P = .001).
Safety data showed that AFXL treatment was generally not painful, with a mean visual analog scale (VAS) pain score of 1, and the PDT was more painful, with a mean VAS of 4.5 during LED illumination. Seven of 10 patients requested anesthesia during the procedure, Dr. Haedersdal noted.
In addition, at 1 week post treatment, 3 of 10 patients reported intense inflammation of the treated sites, 3 had pigment changes with AFXL-PDT, and 1 had a pigment change with AFXL alone.
The take-home message, Dr. Haedersdal said, is: "Do not deliver laser-assisted PDT to large areas; you have to deliver it to refined areas."
However, eight patients gave a favorable overall assessment to the combined treatments, and the remaining two rated the combined therapy and laser-only therapy as being equally effective.
The study was supported by a research grant to Dr. Haedersdal from Galderma. She also disclosed serving on a Galderma advisory board.