Clinical Practice

By Louise Gagnon – Correspondent, The Chronicle

PDT effective for the treatment of AKs

PDT has a preventive impact on skin cancer and likely treats the sub-clinical damage that is not visible, says Dr. Lisa Kellett

Some Canadian clinicians are adopting daylight photodynamic therapy (PDT) to manage actinic keratoses (AKs) in their patients, seeing it as an alternative to conventional PDT, in months of the year where patients can be exposed to sufficient sunlight.

Dr. Lyne Giroux, assistant professor of medicine at the Northern Ontario School of Medicine in Sudbury, Ont., explains that a significant reduction in pain experienced by patients is what prompted her to turn to daylight PDT over conventional PDT, noting that she observes equivalent efficacy in outcomes in managing AKs, precursors to squamous cell carcinoma. The pain associated with conventional PDT is related to the concentration of protoporphyrin IX.

One benefit that Dr. Giroux sees with the application of methyl aminolevulinate cream and the use of PDT is an overall improvement in the appearance of the skin, according to Dr. Giroux.

“People like the cosmetic outcome with [the system],” Dr. Giroux said in an interview with The Chronicle of Skin & Allergy. “They like the way their skin looks and feels. They find it rejuvenating, and it also addresses the inflammatory aspect of rosacea.”

Some patients are uncertain about the appropriate application of self-administered topical therapies like ingenol mebutate and imiquimod, so PDT, both daylight and conventional, provide them with increased assurance of appropriate therapeutic application, according to Dr. Giroux. “They are concerned about the correct application of [ingenol mebutate] or [imiquimod],” says Dr. Giroux.

The other benefit of PDT is that it does not create a challenge of adherence to therapy the way topical agents do, explains Dr. Lisa Kellett, a dermatologist and medical director at DLK on Avenue in Toronto. “I find PDT very effective,” says Dr. Kellett. “We apply it to patients, put them under the light, and there is no issue of compliance.”

Dr. Kellett adds that PDT has a preventive impact on skin cancer and likely is treating the sub-clinical damage that is not visible. Indeed, that theory of field cancerization targeting subclinical “sleeping” cells and patches has been postulated, and data have shown a delay in the appearance of non-melanoma skin cancers, like AKs, with the use of PDT, researchers reported in the journal Current Problems in Dermatology (2015; 46:115–121), and with the use of ingenol mebutate and imiquimod.

One important consideration with daylight PDT is that patients need to apply a sunscreen that is not a physical blocker.

When Canadian clinicians have chosen conventional PDT, opting for methyl aminolevulinate cream over aminolevulinic acid because the former makes conventional PDT less painful and thus more tolerable (Annals of Dermatology June 2014; 26(3):321–331), they have made this decision despite the results of a meta-analysis published last year. That study concluded that conventional PDT, with 5-aminolevulinic acid applied as gel and involving the use of narrow-band lights, was the most effective treatment for complete clearance of mild AKs appearing on the face and scalp (PLoS One June 3 2014; 9(6):e96829).

Climate can limit the year-long application of PDT in Canada, notes

Dr. Mark Lupin, a dermatologist in Victoria and clinical instructor in the Department of Dermatology and Skin Science in the Faculty of Medicine at the University of British Columbia.

“The limitation of daylight PDT is the weather,” says Dr. Lupin. “We are using a more metered dose of light with the office-based treatment. The results are not as consistent with daylight PDT, but the patients are much more satisfied with daylight PDT because it is easier to tolerate than conventional PDT. Daylight-activated PDT can still be uncomfortable, but nowhere near what office-based treatment is.”

Patients will need at least two treatments, and may not return for a second treatment if they find the initial treatment too painful, says Dr. Lupin. Like other clinicians, Dr. Lupin ensures that patients apply a sunscreen that is broad spectrum and has an SPF of 30.

Another advantage of the methyl aminolevlulinate cream over aminolevulinic acid is that the former can treat superficial basal cell carcinomas, notes Dr. Lupin.

Still other dermatologists, like Dr. Ian Landells, clinical chief of the Division of Dermatology for Eastern Health, medical director (dermatology) at Nexus Clinical Research in St. John’s, N.L., and clinical associate professor in the Faculty of Medicine at Memorial University in St. John’s, prefer to avoid daylight PDT as an AK management option because of concerns regarding potentially excessive ultraviolet exposure. “There is a lack of control over the UV dose,” says Dr. Landells.

Instead, Dr. Landells uses topical therapies like ingenol mebutate and imiquimod and has found an innovative approach, although off-label, to elicit a response with imiquimod therapy in patients who show no response to imiquimod related to toll-like receptor 7.

“Some patients do not get a reaction from imiquimod,” explains Dr. Landells. “Adding tazarotene produces a reaction in patients who have had no reaction with imiquimod.”

Ongoing dosing studies will provide greater insight on optimal use of topical therapies such as ingenol mebutate, points out Dr. Melinda Gooderham, a dermatologist and medical director of Skin Centre for Dermatology in Peterborough, Ont. “Studies are looking at multiple concentrations to find out what can be full-face treatment,” says Dr. Gooderham in an interview with the Chronicle of Skin & Allergy.

Currently, the indication for ingenol mebutate is that one tube of the therapy should be applied to sun-damaged skin areas no larger than 5 cm by 5 cm, with the lower concentration indicated for the face and scalp and the stronger concentration applied to the trunk and extremities.

Clinicians still turn to more traditional therapies like 5-fluorouracil and cryotherapy, and need to evaluate whether the patient requires spot treatments or field treatments, points out Toronto dermatologist Dr. Benjamin Barankin, co-founder of the Toronto Dermatology Centre. Treatments that act as spot treatments are not an appropriate therapy if patients have multiple or recurring AKs, says Dr. Barankin.

And when lesions are “stubborn,” even appearing subsequent to exposure to field therapies, clinicians should consider biopsy and excision of lesions, advises Dr. Barankin. “The lesions warrant re-assessment if they persist [after field therapy],” he says.

Another innovation in AK management is the use of fractional laser. A recent study found the use of ablative fractional laser-assisted PDT, with a three-hour incubation time, produced greater efficacy than other modalities of PDT. Moreover, the recurrence rate with fractionated laser and a three-hour incubation period was significantly decreased, according to investigators who published their findings online on Feb. 1, 2015 in the Journal of the European Academy of Dermatology and Venereology (doi:10.1111/jdv.12953).

“There is general improvement in the quality of the skin [with the use of fractionated laser],” says Dr. Lupin, who uses fractionated laser to treat AKs in combination with other therapies. “There is less downtime [with the use of fractional laser] compared to topical creams. The use of fractionated laser does not create crusting the way that cryotherapy or topical treatments do.”

As with other dermatologic conditions, clinicians should consider the patients’ views regarding the presence of AKs and any emotional distress they may experience linked to concerns about cancer or concerns about engaging in outdoor activities and further exposure to ultraviolet light once they have been successfully treated, says Dr. Lupin.

Some patient populations, such as organ transplant recipients, are at increased risk of developing AKs. The lesions progress more rapidly in these patients and traditional therapies are more likely to prove ineffective in organ transplant recipients. Because of these factors, where possible, AK treatment should be initiated prior to organ transplantation.

Metvix^® (methyl aminolevulinate cream ingenol mebutate and imiquimod, so PDT, both daylight and conventional, provide them with increased assurance of appropriate therapeutic application, according to Dr. Giroux. “They are concerned about the correct application of Picato^® or Zyclara tazarotene