Photodynamic therapy

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Photodynamic therapy
4B Ri ???
Slide 001
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• A treatment requiring a single injection of drug
  followed after a certain time interval
  (drug-light interval) by single illumination.

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History of PDT
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History of PDT

• 1903- eosin topically to BCC prior to
  illumination (von Tappeiner and Jesionek)
• PDT the dynamic interaction among
• light, a photosensitizing agent, and oxygen
  ?resulting in tissue destruction
• 1975- hematoporphyrin derivative (HpD)
• 5-aminolevulinic acid (ALA)
• Methylester of ALA
• Meso-tera-hydroxy-phenyl-chlorin

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Mechanism of PDT
Singlet molecular oxygen
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Mechanism of PDT

• Kill tumor cells by
• Induction of apoptosis and necrosis
• Damages the vasculature and the surrounding
  healthy vessels
• ?induction of hypoxia and starvation
• Initiate an immune response against remaining
  tumor cells

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• Induction of apoptosis and necrosis
• Bcl-2 (mitochondria, endoplasmic reticulum,
  nuclear envelope) Ca2
• Not rely on p53? can target malignant cells which
  are resistant to R/T, C/T

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• Damages the vasculature and the surrounding
  healthy vessels
• ?induction of hypoxia and starvation
• NO inhibition, leukocyte adhesion, and thrombus
  formation,
• Platelet activation
• release of thromboxane

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• Tumor drug dose were relative high (?)
• Plasma concentration (vascular?)
• Complete shutdown of vessels
• ? long term cure
• Vasoconstriction decrease tumor response
• ?vascular integrity difference!!

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• Initiate an immune response against remaining
  tumor cells
• After initial damage, cellular fragments undergo
  phagocytosis by macrophages or dendritic cells
• Recognized by helper T lymphocytes

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Mechanism of PDT
Singlet molecular oxygen
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• Photosensitizer
• Light
• Oxygen

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Photosensitizers

• Preferential uptake in tumor
• Rapid clearance
• Strong absorption peak at light gt630nm (longer!)

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Light Application

• Conventional, broad-spectrum light sources
• Lasers
• LED
• Optical fiber technology
• Delivery, homogeneous light distribution
• Superficial / hollow organ
• Balloon-centering device

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Clinical Application

• Specific indication?
• Benefits/ disadvantages
• Simplicity and limited treatment time
• A Local treatment
• Limited light penetration,
• fiber-optic technique
• Minimal long-term fibrosis
• (spare subepithelial collagen, elastin)
• ?can be repeated in previously treated area

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• Bladder cancer
• Skin cancer
• Head and Neck cancer
• Esophageal cancer
• Barretts Esophagus
• Endobronchial cancer

• Cholangiocarcinoma
• Pituitary tumors
• debuling surgery
• Prostate cancer
• Pancreatic cancer

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In unresectable Esophageal and lung cancer

• Barretts esophagus
• Esophageal cancer?
• 50 have metastasis or unresectable
• Dysphagia, malnutrition and bleeding
• Lung cancer
• Endobronchial obstruction

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• Injected 24-72 hrs before treatment
• Tumor cells need time to selectively retain
• delivering light therapy
• (rigid tip)
• Follow-up endoscopy-bronchoscopy
• in 48 hrs

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Side effects

• Sunburns
• Perforation
• Stricture
• Candida esophagitis
• Symptomatic pleural effusions

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PDT in Esophageal Cancer

• Palliative for symptomatic late stage disease
• In patients with HGD and early cancer who are not
  candidate or minimally invasive esophagectomy

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PDT in Esophageal Cancer
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PDT in Esophageal CancerComplications
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PDT in Endobronchial tumors

• Significant morbidity, especially in the larger
  airways.
• Patients who are not surgical candidates
  (smoking, COPD, aging population)- could receive
  palliative or rarely curative treatment with
  minimally invasive bronchoscopic interventions.

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PDT in Endobronchial tumors

• Useful in palliation of late stage NSCLC.
• Improve symptoms cough,
• obstruction,
• Ventilation
• performance status 6-8 weeks after treatment

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PDT in Endobronchial tumors

• PDT prior to surgical resection pneumonectomy?
  Lobectomy
• Non-bronchogenic or metastasis tumor
• ? palliation of dyspnea and hemoptysis
• ? post-operative respiratory distress

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Future Perspectives

• A new technique / a good standard Tx?
• Costly to setup of a new PDT center
• No large randomized trials
• Standardized protocols
• Vasculature / tumor cells
• Selective delivery
• Combine therapy

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Reference

• Photodynamic Therapy in Oncology
• Martijn Triesscheijn,a Paul Baas,a,b Jan H. M.
  Schellens,a c Fiona A. Stewarta aDivision of
  Experimental Therapy (H6) and bDepartment of
  Medical Oncology, The Netherlands Cancer
  Institute/Antoni van Leeuwenhoek Hospital,
  Amsterdam, The Netherlands cFaculty of
  Pharmaceutical Sciences, Division of Drug
  Toxicology, Utrecht University, Utrecht, The
  Netherlands
• Role of Photodynamic Therapy in Unresectable
  Esophageal and Lung Cancer
• Mang Chen, MD, Arjun Pennathur, MD, and James D.
  Luketich, MD Heart, Lung, and Esophageal Surgery
  Institute, University of Pittsburgh School of
  Medicine, University of Pittsburgh Medical
  Center, Pittsburgh, Pennsylvania 15213 Lasers in
  Surgery and Medicine 38396402 (2006)
• Tumor Ablation with Photodynamic Therapy
  Introduction to Mechanism and Clinical
  Applications
• Paul Harrod-Kim, MD J Vasc Interv Radiol 2006
  1714411448
• Local Physiological Changes During Photodynamic
  Therapy
• Theresa M. Busch, PhD Department of Radiation
  Oncology, School of Medicine, University of
  Pennsylvania, Philadelphia, Pennsylvania
  19104-6072
• UpTodate

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Thank you for your attention!