|
Practical Pearls for Topical Photodynamic Therapy in NMSC
Optimal PDT response can be achieved through appropriate patientselection,appropriate lesion preparation and careful attention to dosimetry during treatment. Adverse events can be minimized/controlled to ensure PDT is tolerable.Suggestions towards achieving these goals are described below:
1. Consult published guidelines:
British Photodermatology Group (BPG) has published guidelines on the use of topical PDT in dermatology. (Morton CA, Brown SB, Collins S, et al. Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group. Br J Dermatol 2002;146:552–567). This group reviewed the available evidence for efficacy of PDT in NMSCs and concluded that there was good evidence (supported by at least one randomized controlled clinical trial) to support the use of PDT in non-hyperkeratotic actinic keratosis (AK) on the face and scalp, squamous cell carcinoma in situ (Bowen’s disease) and superficial basal cell carcinoma (sBCC, < 2mm in thickness). They also concluded that there was little data to support the use of PDT in nodular BCC (nBCC) and evidence against the use of PDT for the treatment of squamous cell carcinoma. Since these guidelines were developed, a number of PDT studies have been published using topical methyl aminolevulinate (MAL, Metvix® cream). These studies further support the use of PDT in AK and sBCC. Furthermore, they also support the use of PDT in nBCC provided that lesions are appropriately prepared and treatment is repeated 7 days after the first application.
2. Careful patient/lesion selection:
There is now good evidence to support the use of PDT in a range of NMSCs. These include large and multiple lesions of Bowen’s disease and sBCC, with patients with multiple actinic keratoses and nBCC also likely to benefit. PDT can promote clearance of non-hyperkeratotic AK on the face and scalp, but AK on acral sites can also benefit from PDT, PDT should also be considered as a first-line therapy for lesions at sites where concern over poor healing, e.g. lower legs in the elderly, or cosmesis, favour a therapy with consistent reports of good healing, virtually always without ulceration, and high quality of cosmetic outcome.
3. Consider licensed indications for Metvix® in Europe
Metvix® is licensed in Europe for PDT of sBCC and nBCC and thin or non-hyperkeratotic and non-pigmented AK on the face and scalp where other therapies are unsuitable. Treatment can be repeated on one occasion, one week after the initial treatment. Metvix® is not indicated for morpheaform BCC nor for patients with porphyria. Although not licensed for Bowen’s disease, there is increasing evidence of its efficacy in this disease area.
4. Lesion Preparation*
Skin preparation required before PDT will depend on the type of lesion and is undertaken in the clinic immediately prior to treatment. Local anaesthesia is not required during this preparation process.
Actinic keratosis
Before PDT, scales and crusts should be removed from the AK lesions. This can be achieved using gauze soaked in saline with or without the use of plastic forceps; by gentle curettage; or by gentle scraping with the edge of a scalpel blade.
BCC
When preparing BCC lesions, it is important to carefully remove the overlying epidermal keratin and scrape or debride the exposed tumour material. The exact procedure used to prepare the treatment area is often misunderstood. The intention should be to de-bulk the lesion by removing material from the central core of the tumour (leaving the margins), rather than perform full curettage of the entire lesion.
5. Application of the photosensitizer*
Once the lesion has been prepared, the photosensitizer is applied. The manufacturer recommends that Metvix® cream should be applied in an even 1 mm layer to the whole lesion and extending with a margin of 5–10 mm around the lesion onto the surrounding normal skin to ensure that the whole tumour is treated. The area is then covered with a light-occlusive dressing and the cream left in place for three hours. The dressing is then removed and the area cleaned with saline.
6. Optimal dosimetry*
As well as the dose of the sensitizer, the dose of light used in treatment is also an important factor in PDT. For optimal PDT effect, we wish to maximise light absorption by the photosensitiser with adequate tissue penetration of this activating light. Red light has been widely used and sources emitting narrow band red light, centred around the ‘red’ peak of absorption of protoporphyrin IX, the actual intra-cellular photosensitiser formed following application of MAL, are potentially the most efficient sources for topical Metvix® PDT in NMSC. Several lights have been developed to include absorption around 635nm, an absorption peak for PpIX, including the light emitting diode (LED) source, the Aktilite®, specifically designed for use with Metvix®. Using the compact mobile narrowband 634+/-3nm LED lamp, the Aktilite®, a dose of 37J/cm2 is equivalent to 75J/cm2 from the broadband sources used for most Metvix studies, permitting short treatment times. There is the additional advantage of a pre-set irradiance of 50mW/cm2 at 50mm from lesion, ensuring these sources are relatively easy to use in the routine clinic/office setting.
7. Minimise side effects of PDT
Discomfort is the most common side effect topical PDT. This effect takes the form of a burning, stinging, or prickling sensation restricted to the treatment area. This sensation typically starts early during the light exposure, peaking in intensity after a few minutes and subsequently levelling out during the remainder of treatment. Lesions on the face and scalp and large or ulcerated lesions are particularly associated with this effect of treatment. If required, topical or injected local anaesthetics, pre-medication, or cooling fans can provide relief from these effects, although most patients do not require any intervention.
8. Remember the principal method of action
PDT relies on the interaction of drug and light in tissue to produce reactive oxygen species to achieve a photodynamic reaction. Clinical delivery of PDT must ensure this attainment of drug and light if an effective outcome is to be expected.
9. Persuading the patient...
Topical PDT offers a relatively selective, non-invasive therapy, which can be performed on a supervised out-patient basis, ensuring compliance in the many elderly patients requiring treatment. This may offer benefits over topical therapies that require prolonged home application, with compliance issues especially for those medications known to irritate/inflame in order to promote their therapeutic effect. Topical PDT appears safe and multiple lesions can be treated simultaneously. Repeat treatments are safe, with no identified upper limit, with repetition of treatment 7 days after initial therapy appearing to improve efficacy. PDT presents few problematic side effects with several options for managing the common experience of stinging/burning discomfort during therapy. The side-effects are comparable to conventional therapies, but cosmesis and healing appear superior.
10. Treating more than can be seen?
Topical PDT offers an area rather than a lesional treatment, providing for the opportunity for additional treatment of subclinical disease within the field of illumination. Topical PDT may therefore offer an additional preventative option in treating patients with NMSC.
*MAL-PDT, i.e. using Metvix, has been discussed principally in this section as it is the only licensed topical photosensitizer in most European countries for the skin indications discussed. Preparation routine and dosimetry characteristics differ when considering Levulan or a ‘named-patient’ ALA preparation.
|
