A Randomized Half-side Comparative Trial of Fractional Laser-assisted Daylight Photodynamic Therapy Versus Daylight Photodynamic Therapy in Organ Transplant Recipients With Multiple Actinic Keratoses of the Scalp or Forehead

Protocol for the study:

"A randomized half-side comparative trial of fractional laser-assisted daylight photodynamic therapy versus daylight photodynamic therapy in organ transplant recipients with multiple actinic keratoses of the scalp or forehead"

Organ transplant recipients (OTR) have an increased risk of non-melanoma skin cancer, in particular squamous cell carcinoma (SCC), often developing in areas of field cancerization, areas with multiple precancerous actinic keratoses. The risk of developing SCC in OTR is 65-100-fold the normal population (Jensen 1999, Lindeløf 2000), and this cancer often runs a more aggressive course with metastasis reported to occur in 5-8% of cases (Berg 2002). The treatment options in field cancerization are limited. In Norway, the registered treatment alternatives are the topical immune response modifier imiquimod and photodynamic treatment. Neither of these treatments has shown long term beneficial effects.

Photodynamic treatment (PDT) is a treatment that selectively targets abnormal cells, through radical oxygen species (ROS) generated by photosensitizers activated by visible light. Activation by light can be performed with lamps (LED lamps) or by daylight. Daylight-PDT is shown to be less painful than PDT performed with lamps (Wiegell 2008). The photosensitizer is applied directly on the skin surface after careful removal of hyperkeratosis. PDT is shown to be effective in treating epithelial dysplasia in the immunocompetent population, with clearance rates of 71-100% for facial and scalp keratosis, and 44-73% on acral sites (Morton 2002). The lesser effectiveness on extremities is possibly due to more hyperkeratosis on extremities with less absorption of the cream. PDT is shown to be less effective in the transplant population compared to the non-immunosuppressed (Dragieva 2004, Morton 2008). The reason is most likely multifactorial, but the thickness of the hyperkeratotic layer is regarded as an important factor.

In animal models as well as in humans, it has been shown by fluorescence measurements that ablative fractional laser treatment facilitates delivery of the photosensitizing cream deeply into the skin (Haedersdal 2010, Togsverd-Bo 2012). The laser ablates columns of skin, facilitating penetration and thereby increasing the absorption of the drug to deeper layers.