Photodynamic Therapy (PDT)mpsevents.be/global/Caraibes/rapports/pdf/Roseeuw_PDT.pdf ·...
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Photodynamic Therapy (PDT) Basics and clinical applications D. Roseeuw, S. T’kint Department of Dermatology UZBrussel - VUB
Transcript of Photodynamic Therapy (PDT)mpsevents.be/global/Caraibes/rapports/pdf/Roseeuw_PDT.pdf ·...
Photodynamic Therapy (PDT) Basics and clinical applications
D. Roseeuw, S. T’kint Department of Dermatology UZBrussel - VUB
GOAL of PDT : selective destruction of targeted abnormal cells
Light
Photo-sensitiser
O2
O2
O2
O2 O2
It requires the presence of 3 components to form Reactive Oxygen Species
ROS
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Upon activation of photosensitiser with the light of specific spectra it transmits the energy to the oxygen
Light
Photosensitiserenergetic ground state
Localisation-dependent cellular damage
(i.e. plasma membrane,lysosomes, mitochondria)
Type-II-reaction
CytotoxicityModulationof cellularfunction
Photosensitiserexcited state
O•
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Photodynamic therapy requires the presence of 3 components to form Reactive Oxygen Species
O2
O2 O2
O2 O2
PHOTO -SENSITISER
LIGHT
ROS
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N H 2
O
O
O H 5-Aminolevulinate (ALA)
N H 2
O
O
O
C H 3 Methyl aminolevulinate (MAL)
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Photo-sensitiser
Protoporphyrin IX Ferrochetalase Haem
Intermediates
Porphobilinogen deaminase
Porphobilinogen ALA
MAL
Metabolic pathway
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Metvix specificity
Application of Metvix® leads to formation of porphyrins specifically at the lesion site.
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Metvix penetration
Metvix leads to formation of porphyrins at full lesion depth (here 1.2 mm) without affecting underlying tissue.
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Electromagnetic spectrum
Infrared UV
220 280 300 320 340 400 nm
UV C UV B2 UV B1 UV A2 UV A1
Microwaves X-ray
400 nm 700 nm
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Wavelength and skin penetration
Stratum corneum Epidermis Dermis Subcutis
nm
Porphyrin absorption spectrum
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Light sources
Conventional light sources
• Incandescent lamps • High pressure/low
pressure arc lamps (Light Emission Device) LED LEDL
Lasers
• Diode lasers • Pulsed dye lasers
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PDT 12 08/06/16
LED lamps
l LED lamps: red light of 635 nm for deep penetration
l Compact
l No calibration needed
l Easy to operate, to position and to store
l Mobile
l Built-in fan (cooler)
l Total illumination time: long
1. Lesion preparation Curette to remove
loose scales and crust
Avoid distressing
surrounding skin
Treatment procedure
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2. MAL application Apply Metvix about 1 mm thick Including 5 – 10 mm normal surrounding skin Cover with occlusive dressing Leave for 3 hours
Treatment procedure
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Treatment procedure
3. Illumination Wash off Metvix cream with saline Illuminate with red light (630 nm) Distance = 5-8 cm
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Treatment procedure
Standard AZ-VUB AK treatment BCC treatment
1 session 2 sessions, one week apart
2 sessions,1 week apart 2 sessions, 1-2 weeks apart
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PDT and Pain
• Common problem, variable, unpredictable and limiting factor.
• AK > Bowen > BCC • Head > trunk > extremities • Large > small lesions • Men > women • Pale complex phototype I > phototype IV • Inflammatory reaction > pain patients • Scoring: Visual analogue scale : VAS
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0 10
PDT and Pain Pathophysiology: not well known
• Pain in -40% - 60% • Photoreaction causes pain throught free nn fibers in epidermis
direct pain through photoreaction • 2 types (depolarisation)
indirect pain through inflammation (prostaglandins – bradykinine)
• ALA > MAL in normal skin
in AK (1 studie)
{
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PDT and Pain Management
1) Cooling - raises pain threshold -> ↓ skin temp to 20°C -> 30% pain reduction - 50% do not react on cooling - cooling fans – spray water – cold air
2)
Oral analgetics Time to be efficient
Paracetamol Melarnizol – Na (metanizol) Tramadol Benzodiazepine
35 min 60 min 90 min
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PDT and Pain Management
3) Block anesthesia (xylocaine type) ! Genital: spinal block hand? 4) Tumescent anesthesia 5) Infiltration: 0,5% (Xylocaine + adr.) 6) EMLA and tetracaine gel: of no help
{
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Clinical experience
Actinic keratosis
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Aims of clinical programme
• Document safety and efficacy of MAL in treatment of AK
• Compare with most common therapies – Efficacy and safety – Cosmetic outcome – Patient satisfaction
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Placebo-controlled vs cryotherapy:
Used as indicated in non-hyperkeratotic AKs on face and scalp MAL PDT when repeated after one
week is more effective than cryotherapy % lesions with complete response at 3 months
0
20
40
60
80
100
120
Overall Thin lesions Moderatelesions
Lesions on face Lesions onscalp
% c
om
ple
te r
esp
on
se
MAL Cryotherapy Placebo
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(Freeman M. et al; J Dermatol Treat 2003;14:258-62)
N=204 pts ’ 89
88
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AK: Clinical result
* Pariser DM et al; J Am Acad Dermatol 2003; 48(2): 227-232
Actinic keratosis before treatment*
Actinic keratosis after Metvix-PDT (two treatment cycles) treatment*, after 3 months
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MAL-PDT in Actinic Keratosis
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Cosmetic Outcome (Investigator) in AK
Percent Australia:
Fractionated PDT and single freeze-thaw cryotherapy
2 6 14
43
83
51
0 20 40 60 80
100
Metvix Cryotherapy Fair Good Excellent
* Pariser DM et al; J Am Acad Dermatol 2003; 48(2): 227-232
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Patient preference: actinic keratosis
Pooled data, Phase III studies: Patients prefer MAL PDT to previously received treatments
0
20
40
60
80
0
20
40
60
80
0
20
40
60
80
PDT vs cryotherapy N=102
PDT vs 5-FU N=21
PDT vs surgery N=37
PDT best Cryotherapy best 5-FU best Surgery best
* Pariser DM et al; J Am Acad Dermatol 2003; 48(2): 227-232 08/06/16 PDT 28
PDT
Indications + contraindications Indications • Thin/non-hyperkeratotic
and non-pigmented AKs on face and scalp
• sBCC and/or nBCC unsuitable for other therapies
• Hypersensitivity to MAL or any of the excipients
• Morpheaform BCC • Porphyria
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PDT
• Diagnostic tool • Rejuvenation • Acne • Rosacea • Infections:
- mycoses - MRSA
Other indications
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Photodynamic diagnosis: PDD
Development of special devices with high selectivity for tumor tissue (NMSC)
• Fluorescence guided biopsy • Detection clinical invasion • Tumor margin • Control of efficacy of treatment
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Extramammary Paget’s Disease (EMPD)
• Rare intraepithelial neoplasm arising in apocrine glandbearing skin
• In situ vs. invasive disease Primary cutaneous
• 2 Types Secondary: underlying neoplasm internal malignancy
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Standard treatment in situ EMPD
• Surgery with intraoperative margin control Wide Local Excision (WLE) Mohs Micrographic Surgery (MMS)
high recurrence rate
(31-61 %) & significant morbidity & discomfort
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Case report
• Woman of years old • In situ peri-anal EMPD • No associated malignancies • History of Crohn’s disease
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Case report • Pre-and peri-operative margin delineation with
MAL+ woodlight
→ 99,8 % sensitivity; 98 % specificity in vulvary EMPD
Obstet. Gynaecol. 1991: 77-156-9, Misas JE et al
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Case report
• Surgical WLE with VY-plasty : no complete removal ! • Treatment with PDT: Topical MAL under occlusion 4 hrs and visible red
light (200 J/cm²) at 2 week interval sessions
Post-surgical MAL Fluorescence Imaging
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Clinical Aspect after 3 MAL – PDT sessions
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Case report: results
Case report: results
• Complete clinical & histological response rate after 4 sessions
• Adverse events: pain VAS 4
• Cosmetic outcome: no scarring
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Conclusions: role of PDD and PDT for in situ EMPD
• PDD or FD is effective in detecting in situ neoplastic skin. • Tumor fluorescence mapping is a useful method for border
delineation and can be used to control disease clearance in the upperlayers of the skin.
• Multimodal approach with MMS & adjuvant PDT treatment
to improve the cure rate with minimal tissue destruction
• More research has to be done to optimize treatment variability's and to evaluate the long term follow-up
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PDT and Infection
Mycoses: Porphyrins metabolized by dermatophytes to protoporphyrin IX
fungicide effect at lower dosis than needed on keratinocytes
no genotoxic or mutagenic activity
no resistance till now Tested on CA and T. Rubrum
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Conclusion : • effective • not first line treatment
PDT and Side- effects (N = 3000)
• erythema 90% (1-2 weeks) + burning or itching + swelling • Scaling 80% treatment: emollients • crusting 26% • pustulation 2% sterile – damage to follicular wall treatment: - 2 weeks humid dressing
- benzoyl peroxide - anxiety • erosions 0,5% - healing time 6 weeks with wound dressings - irritation and anger • hyper/hypopigmentation: 2% • infection bacterial or viral (herpes) < 0,5%
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Summary • Effective in both sBCC and AK • Selective accumulation in lesions : can be used for delineation of lesions and other epidermal diseases (infections) • Non-invasive • Minimal scarring • Fast healing • Excellent cosmetic outcome • High patient satisfaction • Minimal side effects, except pain! 08/06/16 PDT 42
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THANK YOU
