Technical Aspects of Superficial PDT Treatments

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Technical Aspects of Superficial PDT Treatments

• Ron Allison, M.D.
• Professor and Chair
• Department of Radiation Oncology
• Brody School of Medicine
• Greenville, N.C.

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PDT is simple. Drug Light Reaction
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Photosensitizer

• Optimal Characteristics
• Reliable
• Non toxic
• Transparent
• Commercially available

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Light Sources

• Optimal Characteristics
• Reliable
• Flexible
• Cost Effective
• Commercially available

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Photodynamic Reaction

• Based on cytotoxic and vasculotoxic singlet O0
• Local reaction
• Regional reaction
• Systemic reaction

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Photosensitizing Agents (PS)

• Transfer and translate light energy
• Each PS has its own characteristics
• Not interchangeable

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Photofrin (Axcan)

• Porphyrin
• Multiple ??activation
• 630 nM for 1 cm depth
• Non-toxic

• Non-mutogenic
• Large pt. base
• Low singlet O2 production
• ( Tx time 10-20 min)
• Stays in system 4-8 weeks

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ALA ( DUSA)

• Porphyrin
• Pro drug
• Alters heme synthesis allowing accumulation of
  protoporphrin
• Topical, systemic formulations
• Blue light system (412 nM)
• Red light system (630 nM)
• Low singlet O2 production
• Topical Application- several hours phosensitivity

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FOSCAN

• 650 nM
• High singlet O2 production
• Tx time in seconds
• Dark light activated
• 2 wks sunlight sensitivity

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VERTIPORFIN

• Porphyrin
• 650 nM
• High singlet O2 production
• Tx time in minutes
• 2 days sunlight sensitivity

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PS

• Topical vs IV introduction
• Topical Local Sensitivity
• Systemic Systemic Sensitivity

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Topical Application of PS

• Good control of where PS is (?)
• Application to multiple lesions might be
  confusing
• Depth of PS penetration is the depth you can
  treat

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Systemic Application of PS

• Goes to all lesions
• Goes to non-detected lesions (inc. flexibility)
• Depth of Treatment Depth of Light

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Cutaneous Lesions- Choosing Sensitizers/Tx Mode

• Intravenous goes to
• All lesions via single rapid injection
• Superficial, in-situ and deep lesions in a
  therapeutic concentration
• Lesions you might not have recognized at the
  beginning of therapy
• Normal tissues so it will increase normal tissue
  sensitivity (however, you dont expect these pts
  to go outside naked)

• Topical
• Need to ID each lesion
• Question as to depth of possible treatment
• Pts with numerous lesions take a lot of time to
  put sensitizer on

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When Treating Cutaneous Lesions, System to

• ID lesions
• ID lesions treated
• Ensure each lesion is treated optimally
• Stay awake if this is an 8 hr therapy

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Illumination

• Specific wavelength for each PS
• White light with filters
• Blue fluorescent light
• Laser
• LED
• Broad spectrum light activates the sensitizer
  too! (sun)
• Light energy Joules

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Fiberoptics

• Brings light to the region
• Homogeneous output
• Flexibility
• Fits in scopes and needles
• Diffuser-multidirection
• Microlens- flashlight

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Optimal Treatment

• Many variables
• Working PS
• Working light source
• Appropriate drug dose, light dose, DLI
• DLI
• ALA- 4-6 hrs
• Photofrin- 2 days
• Foscan- 4 days

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PDT Art and Science

• Variable drug dose, light dose, illumination
  interval
• Rapid illumination after drug injection vascular
• Delay illumination tumor
• Select variables based on clinical situations

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PDT Art and Science
Can you exploit drug and light to control this
reaction? Low Drug Dose High Drug
Dose High Light Fluence Low Light
Fluence Concept of Photobleaching
Equivalent PDR
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Photobleaching

• Drug is selectively retained in tumors
• Drug is in lower concentration in normal tissue
• Use as little drug as possible
• Most in tumor
• Minimal amount in normal tissue
• When illumination occurs kills tumors but
  subthreshold amount of drug in normal tissue

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High Drug Concentration
Light
Normal Tissue Tumor
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
Drug
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Low Drug Concentration
Light
Normal Tissue Tumor
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Drug
0 0
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Technical Considerations

• Drug
• Photobleaching via low concentration
• Delay illumination- Tx tumor
• Early illumination- vasculature
• Illumination
• High vs Low light dose
• Homogeneous light field
• Overlap vs non-overlap
• System to demarcate treatment
• PD reaction
• Steroids, swelling

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l
l
5 cm
5 cm
Uneven illumination Uneven PDT
Even illumination Even PDT
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Cutaneous Caveats

• Swelling after treatment -Airway, eyes, lips,
  tongue (Medrol dose pack)
• Multiple lesions- Want a system to ensure each is
  treated.
• Crevices cause shadows- Dose inhomogeneity
  (nasal-labial fold)

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Technical Considerations Summary

• Before drug light reaction
• Appropriate PS for clinical situation
• Appropriate light sources available
• Appropriate fiberoptics
• Patient positioning
• Fiberoptic positioning
• System to demarcate Tx field
• System to demarcate Tx complete
• Pleasant environment
• Pain control
• Sunlight precautions
• Goggles please
• Emergency phone numbers

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Cutaneous Treatment

• AK
• Squamous cell
• Basal cell
• Lymphoma
• Kaposis sarcoma
• Metastatic lesions

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AK

• FDA approved Dosa Bluelight System
• Topical ALA cream
• Blue fluorescent lights
• gt 80 CR
• Stinging on TX

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Squamous Cell

• Photofrin
• gt 90 CR
• Excellent cosmesis

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Basal Cell

• Photofrin
• gt 90 CR
• Excellent cosmesis

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Kaposis Sarcoma

• Purlytin, Photophrin
• gt80 CR
• Excellent cosmesis

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Metastatic Lesions