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PDT - Frequently Asked Questions
A. WHAT IS IT?
What is photodynamic therapy?
Topical photodynamic therapy (PDT) is a relatively new treatment method that has been mainly used for certain non-melanoma skin cancers, but is also under evaluation in other skin diseases. It involves the application of a light sensitising cream followed some hours later (usually 3-6 hours depending on which photosensitiser cream/lotion is used) by illumination of the area to be treated by light that can activate the now absorbed photosensitiser. Pure red light is often used as this maximizes the depth of action of current photosensitisers, but blue light is being used in certain countries for superficial conditions. Three components, photosensitiser, light, and adequately oxygenated tissue, need to be present for the photodynamic reaction to take place. Most current practice relates to the use of topical 5-aminolaevulinic acid, or its methyl ester, methyl aminolevulinate, as 'pro-drugs' which are converted into protoporphyrin IX, the active photosensitiser within cells.
Is PDT only used for skin disease?
PDT using a topical cream or lotion photosensitiser is largely confined to skin disease, although certain superficial pre-cancers and cancers of the genital tract and mouth can respond. PDT using systemic photosensitization and endoscopic light delivery has permitted the treatment of many hollow organ tumours, including those in the oesophagus, stomach, bronchus and bladder, curing early superficial disease and palliating late disease. Intra-operative PDT has demonstrated encouraging results in certain brain tumours and mesothelioma, but the further discussion of the status of systemic PDT out-with Dermatology is beyond the current scope of this website and will not be considered further.
What is Photodynamic diagnosis?
PDD is more correctly known as fluorescence diagnosis. Most photosensitizers, given appropriate excitation, can be made to fluoresce, so that their distribution can be studied. PpIX, the photosensitiser made from ALA, fluoresces, (unlike 5-ALA itself) permitting the detection of subclinical disease and tumour margins, offering the potential for controlled excision or confirmation that illumination field is adequate for subsequent PDT. Refinement of this technique is still required, but offers the opportunity of delineating tumours and detecting recurrences.
How can I find out more about PDT?
You can find out more about photodynamic therapy by reading the published guidelines on PDT (Morton CA, Brown SB, Collins C, et al. Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group. Br J Dermatol 2002, 146, 552-567) and by attending training courses on PDT (see meetings events section of website) and by contacting the PDT resource centre via enquiries@skinpdt.org.
B. WHAT IS PDT USED FOR?
What are the current licensed indications for PDT in Dermatology?
The current licensed indications for topical photodynamic therapy (at September 2003) are treatment of actinic keratoses and basal cell carcinomas (rodent ulcers). In the UK and several European countries, the only licensed photosensitiser for these applications is methyl aminolevulinate as Metvix (Galderma, UK). In the US, Levulan (DUSA, Wilmington, US), a lotion formulation of ALA, is licensed for actinic keratoses.
Which patients respond best to PDT?
Patients with non-hyperkeratotic, so called thin and moderate thickness, actinic keratoses respond well. Patients with thin, i.e. superficial basal cell carcinomas also respond well to PDT, whilst those with nodular tumours can respond as long as careful preparation of lesions and the treatment protocol is fully adhered to.
What conditions would you recommend PDT for?
Certainly for the license indications of non-hyperkeratotic non-pigmented actinic keratoses on the face and scalp and for superficial basal cell carcinomas topical photodynamic therapy is an excellent treatment. Metvix photodynamic therapy is licensed also for the treatment of nodular basal cell carcinomas but it is important that careful lesion preparation is undertaken and treatment is undertaken to protocol (see specific treatment protocol on this site). I also consider that topical PDT is an excellent treatment for Bowen’s disease. Topical PDT should also be considered for patients with very extensive actinic keratosis on acral sites where a reduction in lesions can be achieved. It may also have an option in Erythroplasia of Queyrat. There is some work underway now looking at the experience of localised cutaneous T-cell lymphoma patches and plaques treated with topical PDT but more research is required here.
What non-cancer indications are there for topical PDT?
There are currently no licensed non-NMSC indications, but PDT has also been studied in many other skin conditions, especially acne, psoriasis and viral warts. A comprehensive review of the current situation can be found in: Ibbotson SH. Topical 5-aminolaevulinic acid photodynamic therapy for the treatment of skin conditions other than non-melanoma skin cancer. Br J of Dermatol. 2002; 146 :178-88.
Which conditions should not be treated with topical PDT?
Certainly pigmented or hyperkeratotic actinic keratoses or pigmented basal cell carcinomas or morpheaform basal cell carcinomas should not be treated. I would not recommend PDT in patients of course who have porphyria and it would appear, although potentially effective, probably advisable not to use a light mediated treatment in patients with xeroderma pigmentosum. It should also not be used for malignant melanoma or as we currently perform PDT, for squamous cell carcinoma. Results have often been disappointing for treating cutaneous metastases and as a monotherapy for extramammary Paget’s. It is important to note however that this advice will modify as new studies with reasonable follow-up times become available.
C. WHAT IS REQUIRED FOR PDT?
What photosensitisers are available for use in topical PDT?
The only licensed photosensitisers are methyl aminolevulinate (Metvix) (Scandanavia, many European countries including UK, and Australia (US under application)) and one 5-aminolevulinic acid formulation, Levulan (US only). Other formulations of ALA (e.g. Porphin cream, Crawford Pharmaceuticals, UK) and some DIY preparations to be made in one's pharmacy, from powder, are available, but these, at latest update of this website were not fully-licensed products, available to purchasing units on a named patient basis only. Colleagues are advised to seek the advice of their pharmacists as to which product should be used in their area for their particular disease indication.
What light sources are available for PDT?
Several light sources have been used in clinical PDT studies for cutaneous applications, including lasers, xenon arc/discharge lamps, incandescent filament lamps and solid-state light-emitting diodes (LEDs). LEDs represent the latest breakthrough in technology, with lights now capable of emitting light of sufficient intensity to ensure a relatively short, but effective treatment. The most widely used LED lights in skin PDT are the Actilite 16 and 128 from Galderma, UK and Omnilux from Phototherapeutics Ltd, UK. Other purpose built PDT lamps include the Waldmann 1200L (Waldmann, Germany), and the Paterson xenon lamp from Phototherapeutics Ltd.
Where can I find out about the light sources that are available for use in photodynamic therapy?
Contact the manufacturers, ask about studies that have used their light sources, or contact our Resource Centre for the latest information at enquiries@skinpdt.org.
What eye protection is advised for PDT?
The non-laser light usually used in topical PDT is relatively safe, but staff and patients are advised to wear suitable filter spectacles to limit the transmission of the high intensity light, to avoid discomfort and the temporary disturbance of colour perception that can arise from intense exposure to a limited colour bandwidth. Light suppliers now usually provide such goggles and the specification for replacements.
Are biopsies always required before undertaking PDT?
Biopsies are a useful clinical tool but if the lesion presents clearly with the clinical picture of a non-melanoma skin cancer, photodynamic therapy can be carried out without a biopsy having been done. Biopsies are probably of greatest value for basal cell carcinomas, where tumour thickness probably affects response. However, lesions up to 2mm thick appear to respond well to PDT - experienced PDT practitioners can probably predict those tumours that will respond well to therapy, hence possible saving the need for biopsy.
What lesion preparation is required before undertaking topical PDT?
To prepare lesions for photodynamic therapy any surface crusting can be removed on day of treatment. This can be done using a scalpel or a curette or simply swabs soaked in some normal saline rubbed over the area. In Falkirk we tend to use the scalpel. At the consultation visit if PDT is planned, if the area is particularly hyperkeratotic with lots of scale present, the patient can be advised to use yellow soft paraffin of a mild anti-keratolytic e.g.2% salicylic acid in yellow soft paraffin to be applied to the lesion for 2 weeks prior to treatment.
Who should perform PDT in a clinical dermatology unit?
Doctors, nurses, or technicians who have received adequate training in carrying out photodynamic therapy and are deemed competent by their supervising consultant.
All practitioners of PDT are encouraged to attended a photodynamic therapy training course before commencing a PDT practice. Consult the meetings section of this site.
What dressings can I use once I have applied the topical photosensitiser?
A plastic film dressing e.g. Tegaderm or Opsite can be used to cover the cream on the lesion. A light occluding dressing such as Mepore is applied on top of the plastic film dressing.
How long does a patient require to stay in the department for treatment?
The cream application can take 5-15 minutes depending on the extent of preparation required. The patient can then leave until the appropriate time has elapsed (3-6 hours). Only a few sites, around the eye, mouth, groin, may make cream retention difficult and staying in the same place is probably preferable. On return the treatment may take between 15 and 45 minutes depending on the light source used and the size or number of lesions to be treated.
What advice can I give my patient after they have received PDT?
You can advise your patients to kept the treated area covered for 48 hours to discourage any further light activation and therefore any further reaction taking place.
You can also tell then to take a mild painkiller e.g. paracetamol if the area is painful after treatment.Tell the patient to shower or bathe as normal but not to rub the treated area vigorously, just to pat it dry gently and to reapply a dressing if the advised time period has not elapsed.
D. IS PDT SAFE AND WHAT SIDE EFFECTS CAN OCCUR?
Is PDT safe - using light on sun-light induced cancers?
Although a relatively new treatment to many of us in Dermatology, there is considerable experience of treating tumours in humans with PDT over 25 years with no confirmed association of treatment with the induction of cancer. A case report noted a melanoma arising on a scalp that had previously undergone many treatments with PDT. However, the reason for the PDT was extensive actinic damage, with previous skin tumours already excised, so it is likely to have been coincidental. Another case report indicated that a pre-cancerous lesion had probably been inadequately treated by PDT and 5-fluorouracil before a squamous cell cancer developed. PDT does remain a new modality and careful observation of possible long-term sequelae is required. In our opinion, it is much more likely that an invasive lesion might arise through inadequate treatment by PDT (hence need to ensure adequate training to optimize efficacy) or the initial incorrect diagnosis of a lesion as a pre-cancer.
Is it safe to repeat PDT to the same site? How often?
Photodynamic therapy appears safe to use for repeated treatments to the same site, if required. This is different to radiotherapy with a well-accepted upper limit of exposure. We aim to treat basal cell carcinomas(rodent ulcers) twice in a short time span e.g.1 week apart then the patient is reviewed at a 6-12 week interval. Actinic keratoses receive a treatment then the patient is re-treated at one week if receiving Metvix. Time for a second treatment is less clear if unlicensed ALA is used - either repeating at one week, or perhaps reviewing need for further treatment at 6 weeks.
If a patient has extensive actinic disease e.g. all limbs affected, the nurses in the PDT unit can see the patient at intervals negotiated with the patient e.g.every 2-3 weeks, to treat different areas, and review is organised with the consultant after the treatment course is completed.
I have heard that pain is a significant issue in PDT, what is your experience?
The patients receiving PDT often describe pain as a heat or more correctly a stinging or prickling sensation. 71% of patients that have undergone trials with topical Metvix PDT experience some form of discomfort but this is almost always mild to moderate and local anaesthesia or discontinuation of treatment is very rarely required. Having audited our experience that historically has been with ALA-PDT, with all patients offered local anaesthesia, 20% took up the offer. It is important to note however that as a regional unit we frequently are undertaking treatments involving large areas e.g. vertex to frontal scalp or ulcerated lesions and with such large size and likelihood of discomfort we can usually predict when local anaesthesia will be required.
How can I reduce discomfort experienced in my patients during PDT?
We would recommend treating solitary lesions or small fields to gain initial experience of PDT. Covering large areas of skin with a topical photosensitiser and using a large area light source some hours later is likely to contribute to a greater PDT reaction, as subclinical disease will also be treated. Individual operators will find procedures that work best in their practice for reducing discomfort. The use of a topical anaesthetic such as Ametop or Emla has been associated with some benefit. Some units will consider pre-medication whilst others find that a nurse explaining the treatment and being present throughout treatment has a significant effect in allaying their anxieties. The provision of a local anaesthetic remains an option and whilst it may prove unnecessary to avoid Adrenaline containing preparations, it would appear reasonable that plain Lidocaine preparations are used in case there could be an effect on the oxygen availability to lesions for the PDT process.
What other side-effects can occur following PDT?
Immediately following illumination, erythema and oedema are common, with erosion, crust formation and healing over 2-6 weeks. Ulceration following PDT is very rare. No generalised photosensitivity has been reported following topical PDT in non-melanoma skin cancer. A good cosmetic outcome following ALA-PDT is widely reported, regardless of lesion or site, and a clinically obvious scar is rarely observed. Hyper- or hypo- pigmentation can occasionally be seen in treated areas and usually resolves within six months. Permanent hair loss has been observed following ALA-PDT of hirsute sites, but is much less than that which had followed radiotherapy.
E. WHY IS IT A GOOD TREATMENT?
What are the key advantages of PDT over standard treatment in skin cancer?
PDT with a topical photosensitiser offers a relatively selective non-invasive therapy that offers particular advantages over standard therapies for large and multiple lesions and lesions in sites where standard therapies are limited e.g. Bowen’s disease of the lower leg. PDT rarely causes ulceration compared with standard therapies, e.g. cryotherapy. Superior cosmetic outcome following PDT has been consistently observed in both ALA and Metvix studies.
F. HOW TO GET THE BEST RESULTS WITH PDT?
PDT sounds simple - why is training required?
Despite the relative simplicity of the technique, accurate dosimetry in PDT is complicated by multiple variables in drug formulation, delivery and duration of application, in addition to light-specific parameters. Experience over 10 years now has led us to be suspicious that poor response rates in otherwise appropriate skin conditions may well be due to poor technique.
I have found my response rates with PDT in actinic keratoses and basal cell carcinomas to be poor - any ideas?
We encounter the following problems when visiting new centres:
1. Inappropriate lesion/patient selection - thick hyperkeratotic actinic keratoses will not respond well. Neither will thick nodular basal cell carcinomas - only nodular BCC amenable to easy central debulking curettage can be expected to show a good response to topical PDT. A poor response should also raise doubt over the original diagnosis - especially if no pre-treatment biopsy was performed.
2. Inadequate preparation - we consider that thick adherent crust impedes response. It is fair to say that some units perform minimal preparation, noting crust lifts after cream application, but crust removal is usually easy and makes sense. Failure to prepare nodular basal cell carcinomas by de-bulking curettage is also likely to result in poor response.
3. Ensuring adequate photosensitiser cream application for at least the minimum application time. This can be difficult in some body sites, e.g. on edge of lips, where one suspects that cream is 'washed away' or where a large area is to be covered and areas are missed.
4. Inadequate coverage of cream during application interval - light exposure prior to switching on the treatment lamp could reduce efficacy by photo-bleaching the photosensitiser whilst it is superficial or at a time where insufficient photosensitiser is in lesional tissue resulting in failure to lethally damage that cell.
5. Light dose - usually too little - patients movement - excursion of the chest wall during breathing, head movements during speech or dozing off! All these activities can mean that the light does not hit the target for the full time intended. Supervision of patients is therefore encouraged as well as care in initial light placement.
6. Failure to follow full protocol - repeating treatment at one week - especially for BCC, likely to result in disappointment. If tumours are treated by ALA rather that Metvix, there remains no single correct protocol. It is unclear whether repeating treatment in everyone at one week is necessary, with assessment of the need for further treatment at 6 weeks a reasonable strategy (data to confirm which is preferable is awaited).
How can staff receive training in photodynamic therapy?
We would recommend staff proposing to undertake PDT attend a clinical course that provides for demonstration of treatment in patients as well as detailed discussion of methodology, indications, and adverse events and how to manage them. Details of forthcoming training events will be posted on this web-site (meetings section) and that of the European Society of Photodynamic Therapy (www.euro-pdt.com).
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