New Treatment Option for Thick AKs Emerges

PRAGUE – Intensified photodynamic therapy assisted by ablative fractional laser resurfacing is a new and more effective way to treat thick actinic keratoses, according to Dr. Merete Haedersdal.

At 3 months’ follow-up, cure rates were significantly better with fractional CO₂ laser-assisted photodynamic therapy (PDT) than with standard PDT in a randomized trial, she reported at the annual congress of the European Academy of Dermatology and Venereology.

"As a side benefit, the combined therapy gives a nice decrease in photoaging. There is photorejuvenation of the skin," noted Dr. Haedersdal of the University of Copenhagen.

Stand-alone PDT gets good results in thinner AKs, Bowen’s lesions, and basal cell carcinomas, both superficial and nodular. But effectiveness drops off considerably for thicker lesions.

That’s why Dr. Haedersdal and her Copenhagen colleagues, together with researchers at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, where she has been a visiting scientist, are developing intensified PDT.

Basically, the dermatologists are using the fractional CO₂ laser at 10,600 nm to drill tiny vertical channels surrounded by areas of unexposed skin. These channels facilitate uptake of the photosensitizing agent, rendering PDT more effective at greater depths. The enhanced uptake of photosensitizer is not merely a hypothesis; it has been documented via a marked increase in fluorescence intensity during illumination, she explained.

Dr. Haedersdal reported on 15 patients with a total of 212 AKs on severely photodamaged skin of the scalp and face. Two symmetrical randomly selected areas were chosen on each patient to receive one fractional CO₂ laser-assisted PDT treatment and one standard PDT treatment. First, however, both treatment areas underwent curettage. Then one site was treated with the UltraPulse laser using the DeepFx handpiece set to 10 mJ per pulse and a single pulse density of 5%. The photosensitizing agent, methyl aminolevulinate cream, was then applied under occlusion for 3 hours at both sites. This was followed by illumination using a red light–emitting diode at 37 J/cm².

At 3 months’ follow-up, the complete response rate of thicker grade II-III AKs was 88% with intensified PDT, compared with 59% with conventional PDT. For thinner grade I lesions, the complete response rates were 100% and 79%, respectively.

Only 3 new lesions arose at the intensified PDT-treated sites within 3 months, compared with 11 new lesions in areas that received standard PDT.

"So there might – in terms of avoiding future treatment procedures – be a benefit in combining the photothermal efficacy of the laser with the photochemical response from the PDT procedure," Dr. Haedersdal noted.

Pain scores were significantly higher during illumination in the intensified PDT areas, with a mean of 6.5 on a 1-10 scale compared with 5.4 on skin sites that got standard PDT. Erythema and crusting were also more intense at intensified PDT sites, and long-term pigmentary changes were more frequent at these sites as well.

"We have to be aware that the clinical reactions that we see from this new procedure are more intense than with conventional PDT. So for now we have to take care that we’re not using it for really large treatment areas because then the patients will have really intense phototoxic reactions," the dermatologist cautioned.

She and her coinvestigators are conducting an ongoing clinical trial combining mild daylight PDT and intensified PDT in organ transplant recipients, who are highly prone to the development of numerous skin cancers.

In pig models, the investigators are able to get the photosensitizing agent to a depth of 1.8 mm with the help of the fractional CO₂ laser. This makes intensified PDT an attractive proposition for the treatment of basal cell carcinomas. Indeed, Dr. Haedersdal and her coinvestigators are now in the middle of a clinical trial of fractional CO₂ laser-assisted PDT in patients with difficult-to-treat basal cell carcinomas.

"It seems very promising so far. We don’t have an evidence base yet, but I believe in it," she said.

The dermatologist reported serving on the advisory boards of Lumenis and Galderma, which are providing financial support for the development of intensified PDT.

PRAGUE – Intensified photodynamic therapy assisted by ablative fractional laser resurfacing is a new and more effective way to treat thick actinic keratoses, according to Dr. Merete Haedersdal.

At 3 months’ follow-up, cure rates were significantly better with fractional CO₂ laser-assisted photodynamic therapy (PDT) than with standard PDT in a randomized trial, she reported at the annual congress of the European Academy of Dermatology and Venereology.

"As a side benefit, the combined therapy gives a nice decrease in photoaging. There is photorejuvenation of the skin," noted Dr. Haedersdal of the University of Copenhagen.

Stand-alone PDT gets good results in thinner AKs, Bowen’s lesions, and basal cell carcinomas, both superficial and nodular. But effectiveness drops off considerably for thicker lesions.

That’s why Dr. Haedersdal and her Copenhagen colleagues, together with researchers at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, where she has been a visiting scientist, are developing intensified PDT.

Basically, the dermatologists are using the fractional CO₂ laser at 10,600 nm to drill tiny vertical channels surrounded by areas of unexposed skin. These channels facilitate uptake of the photosensitizing agent, rendering PDT more effective at greater depths. The enhanced uptake of photosensitizer is not merely a hypothesis; it has been documented via a marked increase in fluorescence intensity during illumination, she explained.

Dr. Haedersdal reported on 15 patients with a total of 212 AKs on severely photodamaged skin of the scalp and face. Two symmetrical randomly selected areas were chosen on each patient to receive one fractional CO₂ laser-assisted PDT treatment and one standard PDT treatment. First, however, both treatment areas underwent curettage. Then one site was treated with the UltraPulse laser using the DeepFx handpiece set to 10 mJ per pulse and a single pulse density of 5%. The photosensitizing agent, methyl aminolevulinate cream, was then applied under occlusion for 3 hours at both sites. This was followed by illumination using a red light–emitting diode at 37 J/cm².

At 3 months’ follow-up, the complete response rate of thicker grade II-III AKs was 88% with intensified PDT, compared with 59% with conventional PDT. For thinner grade I lesions, the complete response rates were 100% and 79%, respectively.

Only 3 new lesions arose at the intensified PDT-treated sites within 3 months, compared with 11 new lesions in areas that received standard PDT.

"So there might – in terms of avoiding future treatment procedures – be a benefit in combining the photothermal efficacy of the laser with the photochemical response from the PDT procedure," Dr. Haedersdal noted.

Pain scores were significantly higher during illumination in the intensified PDT areas, with a mean of 6.5 on a 1-10 scale compared with 5.4 on skin sites that got standard PDT. Erythema and crusting were also more intense at intensified PDT sites, and long-term pigmentary changes were more frequent at these sites as well.

"We have to be aware that the clinical reactions that we see from this new procedure are more intense than with conventional PDT. So for now we have to take care that we’re not using it for really large treatment areas because then the patients will have really intense phototoxic reactions," the dermatologist cautioned.

She and her coinvestigators are conducting an ongoing clinical trial combining mild daylight PDT and intensified PDT in organ transplant recipients, who are highly prone to the development of numerous skin cancers.

In pig models, the investigators are able to get the photosensitizing agent to a depth of 1.8 mm with the help of the fractional CO₂ laser. This makes intensified PDT an attractive proposition for the treatment of basal cell carcinomas. Indeed, Dr. Haedersdal and her coinvestigators are now in the middle of a clinical trial of fractional CO₂ laser-assisted PDT in patients with difficult-to-treat basal cell carcinomas.

"It seems very promising so far. We don’t have an evidence base yet, but I believe in it," she said.

The dermatologist reported serving on the advisory boards of Lumenis and Galderma, which are providing financial support for the development of intensified PDT.

PRAGUE – Intensified photodynamic therapy assisted by ablative fractional laser resurfacing is a new and more effective way to treat thick actinic keratoses, according to Dr. Merete Haedersdal.

At 3 months’ follow-up, cure rates were significantly better with fractional CO₂ laser-assisted photodynamic therapy (PDT) than with standard PDT in a randomized trial, she reported at the annual congress of the European Academy of Dermatology and Venereology.

"As a side benefit, the combined therapy gives a nice decrease in photoaging. There is photorejuvenation of the skin," noted Dr. Haedersdal of the University of Copenhagen.

Stand-alone PDT gets good results in thinner AKs, Bowen’s lesions, and basal cell carcinomas, both superficial and nodular. But effectiveness drops off considerably for thicker lesions.

That’s why Dr. Haedersdal and her Copenhagen colleagues, together with researchers at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, where she has been a visiting scientist, are developing intensified PDT.

Basically, the dermatologists are using the fractional CO₂ laser at 10,600 nm to drill tiny vertical channels surrounded by areas of unexposed skin. These channels facilitate uptake of the photosensitizing agent, rendering PDT more effective at greater depths. The enhanced uptake of photosensitizer is not merely a hypothesis; it has been documented via a marked increase in fluorescence intensity during illumination, she explained.

Dr. Haedersdal reported on 15 patients with a total of 212 AKs on severely photodamaged skin of the scalp and face. Two symmetrical randomly selected areas were chosen on each patient to receive one fractional CO₂ laser-assisted PDT treatment and one standard PDT treatment. First, however, both treatment areas underwent curettage. Then one site was treated with the UltraPulse laser using the DeepFx handpiece set to 10 mJ per pulse and a single pulse density of 5%. The photosensitizing agent, methyl aminolevulinate cream, was then applied under occlusion for 3 hours at both sites. This was followed by illumination using a red light–emitting diode at 37 J/cm².

At 3 months’ follow-up, the complete response rate of thicker grade II-III AKs was 88% with intensified PDT, compared with 59% with conventional PDT. For thinner grade I lesions, the complete response rates were 100% and 79%, respectively.

Only 3 new lesions arose at the intensified PDT-treated sites within 3 months, compared with 11 new lesions in areas that received standard PDT.

"So there might – in terms of avoiding future treatment procedures – be a benefit in combining the photothermal efficacy of the laser with the photochemical response from the PDT procedure," Dr. Haedersdal noted.

Pain scores were significantly higher during illumination in the intensified PDT areas, with a mean of 6.5 on a 1-10 scale compared with 5.4 on skin sites that got standard PDT. Erythema and crusting were also more intense at intensified PDT sites, and long-term pigmentary changes were more frequent at these sites as well.

"We have to be aware that the clinical reactions that we see from this new procedure are more intense than with conventional PDT. So for now we have to take care that we’re not using it for really large treatment areas because then the patients will have really intense phototoxic reactions," the dermatologist cautioned.

She and her coinvestigators are conducting an ongoing clinical trial combining mild daylight PDT and intensified PDT in organ transplant recipients, who are highly prone to the development of numerous skin cancers.

In pig models, the investigators are able to get the photosensitizing agent to a depth of 1.8 mm with the help of the fractional CO₂ laser. This makes intensified PDT an attractive proposition for the treatment of basal cell carcinomas. Indeed, Dr. Haedersdal and her coinvestigators are now in the middle of a clinical trial of fractional CO₂ laser-assisted PDT in patients with difficult-to-treat basal cell carcinomas.

"It seems very promising so far. We don’t have an evidence base yet, but I believe in it," she said.

The dermatologist reported serving on the advisory boards of Lumenis and Galderma, which are providing financial support for the development of intensified PDT.