A on treated areas, according to the results of a small, randomized trial.
Dr. Jeffrey Wargo
“Previous research suggests a new model to explain why older patients obtain nonmelanoma skin cancer in areas of ongoing sun exposure,” presenting author Jeffrey Wargo, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. “Insulinlike growth factor-1 produced by dermal fibroblasts dictates how overlying skin keratinocytes respond to UVB radiation. The skin of a patient aged in their 20s produces normal levels of healthy fibroblasts, normal levels of insulinlike growth factor 1, and appropriate UVB response via activation of nucleotide excision, repair, and DNA damage checkpoint-signaling systems.”
Older patients, meanwhile, have an increase in senescent fibroblasts, decreased insulinlike growth factor-1 (IGF-1), and an inappropriate UVB response to DNA damage, continued Dr. Wargo, a dermatologist at the Ohio State University Wexner Medical Center in Columbus. Previous studies conducted by his mentor, Jeffrey B. Travers, MD, PhD, a dermatologist and pharmacologist at Wright State University, Dayton, showed that fractionated laser resurfacing (FLR) restores UVB response in older patients’ skin by resulting in new fibroblasts and increased levels of IGF 2 years post wounding.
To determine if FLR of aged skin can prevent the development of actinic keratosis (AK) and nonmelanoma skin cancer, Dr. Travers and Dr. Wargo recruited 48 patients at the Dayton VA Medical Center who were 60 years or older and had at least five AKs on each arm that were 3 mm or smaller, with nothing concerning for skin cancer at the screening visit.
Randomization of which arm was treated was based on an odd or even Social Security Number. That arm was treated with the 2,790 nm Erbium:YSSG ablative laser at 120 J/m2 with one pass at 24% coverage from the elbow to hand dorsally. Previously published data reported outcomes for 30 of these patients at 3 and 6 months following treatment. Subsequent to that report, 18 additional subjects have been recruited to the study and follow-up has been extended. Of the 48 patients, 47 were male and their average age was 74, with a range between 61 and 87 years.
At 3 months following FLR, the ratio of AKs on the treated vs. untreated arms was reduced by fourfold, with a P value less than .00001, Dr. Wargo reported. “Throughout the current 30-month follow-up period, this ratio has been maintained,” he said. “In fact, none of the ratios determined at 3, 6, 12, 18, 24, or 30 months post FLR are significantly different. Hence, as described in our first report on this work, these data indicate FLR is an effective treatment for existing AKs. However, our model predicts that FLR treatment will also prevent the occurrence of new AK lesions.”
Among 19 of the study participants who have been followed out to 30 months, untreated arms continued to accumulate increasing number of AKs. In contrast, AKs on treated arms are decreasing with time, indicating the lack of newly initiated lesions.
“A second analysis of the data posits that, if FLR were only removing existing lesions, one would predict the number of AKs that were present at 3 months on both the untreated and FLR-treated [arms] would accumulate at the same rate subsequent to 3 months point in time,” Dr. Wargo said.
He pointed out that 12 patients were removed from the study: two at 12 months, one at 18 months, eight at 24 months, and one at 30 months, as they were found to have 20 or more AKs on their untreated arm and required treatment.
Over the entire study period, “consistent with the notion that FLR was preventing new actinic neoplasia, we noted a dramatic difference in numbers of nonmelanoma skin cancer diagnosed in the untreated areas (22) versus FLR treated areas (2),” Dr. Wargo said. The majority of nonmelanoma skin cancers diagnosed were SCC (17) and 5 basal cell carcinomas on the untreated arms, whereas the 2 diagnosed on the treated arm were SCC. “These studies indicate that a dermal-wounding strategy involving FLR, which upregulates dermal IGF-1 levels, not only treats AKs but prevents nonmelanoma skin cancer,” he said.
The study was funded by the National Institutes of Health. Dr. Travers is the principal investigator. Dr. Wargo reported having no financial disclosures.