The ABC of Photodynamic Therapy

1
The ABC of Photodynamic Therapy

• An overview of topical PDT

2
Photodynamic Therapy

• What is it?
• What are the skin applications of PDT?
• How to perform PDT - patient selection, lesion
  preparation
• Adverse event profile
• The future of PDT in Dermatology

3
Photodynamic Therapy (PDT)

• Photosensitiser (retained in tumour)
• Visible light - wavelength to activate
  phosensitiser
• ?
• Singlet oxygen
• ?
• Tumour cell death
• (necrosisapoptosis)

4
The History of Photodynamic Therapy

• 1903 - Jesionek/Tappeiner - eosin dye light in
  skin cancer
• 1942 - Auler/Banzer - tumour-localizing
  properties of porphyrins
• 1960 - Lipson - localisation of haematoporphyrin
  derivative (HpD) in neoplastic tissue
• 1978 - Dougherty - HpD-PDT in cutaneous tumours
• 1990 - Kennedy - Topical ALA-PDT in skin tumours

5
Topical PDT - Photosensitisers (2005, UK)

• 1. 5-ALA - only one formulation, Levulan (DUSA,
  USA) is approved - for non-hyperkeratotic actinic
  keratoses on the face/scalp by the FDA. Several
  other formulations are available for off-label
  use (e.g. Porphin, Crawfords, UK)
• 2. Methyl aminolevulinate (MAL) Metvix (Galderma,
  Paris)
• Esterified derivative, increased
  lipophilicity - 3hr application, improved
  selectivity described.
• Approved in UK for Thin/non-hyperkeratotic
  and non-pigmented AK face/scalp where other
  therapies are considered less appropriate and for
  superficial and nodular BCC unsuitable for other
  therapies

6
Patient Selection - a personal view

• Bowens disease (SCC-in situ) - a first-line
  option
• Large /- multiple AK/Bowens/BCC
• (Morton et al, Arch Dermatol, 2001 137
  319-24)
• AKs on acral sites (PDT5-FU)
• (Kurwa et al, JAAD, 1999, 41, 414-8)

7
Topical PDT - U.K. Guidelines 2002 C.A. Morton
et al, British Photobiology Group, BJD 2002,
146, 552-567

• A 1 AK (non-hyperkeratotic, face/scalp)
• A 1 Squamous cell ca. in situ
• A 1 Superficial BCC (lt2mm)
• C 11iii Nod. BCC (unless adjunctive Rx
  /fractionation)
• A There is good evidence to support the use of
  the procedure.
• C There is poor evidence...
• I Evidence obtained from at least one randomised
  control trial.
• IIiii Evidence - multiple time series /- the
  intervention or dramatic results...
• MAL-PDT studies support A1 rating for all above
  indications

8
MAL-PDT the evidence

• MAL (Metvix) is currently the only licensed
  topical photosensitiser in the UK
• Several multi-centre studies support efficacy in
  non-hyperkeratotic actinic keratoses and in BCC
• M. Szeimies,et al. Photodynamic therapy using
  topical methyl-5-aminolevulinate compared with
  cryotherapy for actinic keratosis A prospective,
  randomized study. JAAD 2002 47258-62.
• Foley P, et al. A comparison of photodynamic
  therapy using Metvix with cryotherapy in actinic
  keratosis. JEADV, 2001 15 (Suppl 2) 223.
• Pariser DM, et al. Photodynamic therapy with
  topical methyl aminolevulinate for actinic
  keratoses results of a prospective randomized
  multicenter trial. JAAD. 2003 48227-232.
• Basset-Sequin N, et al. Photodynamic therapy
  using Metvix is as efficacious as cryotherapy in
  BCC, with better cosmetic results. JEADV, 2001
  15 (Suppl 2) 226
• Rhodes LE, et al. Photodynamic therapy using
  topical methyl aminolevulinate vs surgery for
  nodular basal cell carcinoma. Arch Dermatol 2004
  140 17-23

9
MAL- PDT Efficacy in NMSC

• AK equivalent/superior to cryotherapy
• sBCC equivalent to cryotherapy
• nBCC equivalent to surgery
• SCC in-situ equivalent to cryotherapy and 5-FU
• (Morton C, et al. A placebo controlled
  European study comparing MAL-PDT with
  cryotherapy and 5-fluorouracil in patients with
  Bowens disease. JEADV 2004 18 Suppl
  2 415)
• Superiority in cosmetic outcome and patient
  preference

10
Lesion preparation for Metvix PDT

• AK and sBCC
• Remove scale and crusts and roughen the surface -
  several options gauze soaked in saline ? forceps
  OR gentle use of a curette OR edge of a scalpel
  blade.
• Nodular BCC
• Remove overlying epidermal keratin, then gently
  remove exposed tumour material without attempting
  to excise beyond tumour margins (debulking
  curettage - no anaesthesia required)

11
Metvix application

• MAL cream (1 mm thick) applied to lesion and 510
  mm of surrounding skin
• Treated area covered with occlusive dressing
• After 3 hours, dressing removed and area cleaned
  with saline

12
Optimal light delivery
- Longer wavelengths penetrate deeper - light
utilising the 635nm peak of protoporphyrin IX
absorption thus favoured for UK indications of
BCC as well as AK, treated by Metvix. - blue
light source licensed in US for Levulan treatment
of actinic keratoses - Blu-U (DUSA, USA) - red
light sources are probably most versatile for
current indications, but limited comparison
literature. blue light effective in
short-follow-up studies in AK
13
Aktilite

• LED lamps, 634/-3nm
• pre-set irradiance
• Dose 37J/cm2 equivalent to 75J/cm2 broadband
  source
• from original studies
• Irradiance 50mW/cm2 at 50mm from lesion
• Other LED (e.g. Omnilux, PTL, UK) available.
  Several other alternative light sources
  available, but require careful consideration of
  dosimetry conversion.

14
Fluorescence Diagnosis

• Utilisation of potential for the accumulation of
  fluorescent porphyrins within tumour cells (esp.
  PPIX) to assist determination of tumour
  outlines, recurrences, sub-clinical disease

15
Side-effects and their management - 1

• Pain/discomfort, often described as burning,
  stinging or prickling restricted to treatment
  area is common
• Onset in the early part of light exposure,
  peaking within minutes, then leveling out
• Most patients tolerate topical PDT without pain
  relief
• Face and scalp and large and/or ulcerated lesions
  may be more likely to be painful
• Option to reduce pain topical/injected local
  anaesthetic, pre-med., cooling fans or spraying
  water

16
Side-effects and their management - 2

• Immediately following illumination, erythema and
  oedema are common, with crust formation and
  healing over 2-6 weeks
• No generalised photosensitivity
• Hyper- or hypo- pigmentation occasionally seen
• Hair loss observed for thicker tumours in
  scalp/pubis, but much less than radiotherapy
• 25 years of porphyrin PDT indicates no confirmed
  carcinogenic risk of topical PDT

17
Topical PDT - Published Reports 2005

• Acne/sebaceous naevus
• Actinic cheilitis/leukoplakia
• Cutaneous leishmaniasis
• Cutaneous sarcoid
• Epidermodysplasia verruciformis
• Hailey-Hailey disease
• Lichen planus
• Lichen sclerosis
• Port wine stains
• Psoriasis
• Warts, Condyloma acuminata
• Scleroderma

• Actinic keratoses
• Bowens disease
• Basal cell carcinoma
• Naevoid BCC
• CTCL
• Erythroplasia of Queyrat

18
Topical PDT - Re-shaping Practice?

• Proven efficacy of PDT in AK BCC (Bowens)
• Clinical applications especially for
• large and/or multiple lesions
• lesions situated in difficult-to-treat sites
• Current therapies all have limitations
• Cosmetic advantages of PDT
• Future indications will extend the role of PDT

19
Advantages of Topical PDT

• Relatively selective treatment
• Non-invasive
• Multiple lesions may be treated simultaneously
• Safe
• Supervised outpatient procedure
• Repeated treatments possible
• Minimal or no scarring, good/excellent cosmesis

20
Topical PDT - Conclusion

• Effective PDT depends on appropriate patient
  selection, lesion preparation, cream application
  and correct light dose delivery
• Side-effects are comparable to conventional
  therapies and can be effectively controlled
• Superior cosmesis over standard therapies
• The reward - efficacy, good cosmesis and a
  satisfied patient