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Photodynamic therapy

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A treatment requiring a single injection of drug followed after ... 1903- eosin topically to BCC prior to illumination (von Tappeiner ... Gastroenterology. 1995; ... – PowerPoint PPT presentation

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Title: Photodynamic therapy


1
Photodynamic therapy
4B Ri ???
Slide 001
2
  • A treatment requiring a single injection of drug
    followed after a certain time interval
    (drug-light interval) by single illumination.

3
History of PDT
4
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

5
Mechanism of PDT
Singlet molecular oxygen
6
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

7
  • 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

8
  • 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

9
  • Tumor drug dose were relative high (?)
  • Plasma concentration (vascular?)
  • Complete shutdown of vessels
  • ? long term cure
  • Vasoconstriction decrease tumor response
  • ?vascular integrity difference!!

10
  • 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

11
Mechanism of PDT
Singlet molecular oxygen
12
  • Photosensitizer
  • Light
  • Oxygen

13
Photosensitizers
  • Preferential uptake in tumor
  • Rapid clearance
  • Strong absorption peak at light gt630nm (longer!)

14
Light Application
  • Conventional, broad-spectrum light sources
  • Lasers
  • LED
  • Optical fiber technology
  • Delivery, homogeneous light distribution
  • Superficial / hollow organ
  • Balloon-centering device

15
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

16
  • Bladder cancer
  • Skin cancer
  • Head and Neck cancer
  • Esophageal cancer
  • Barretts Esophagus
  • Endobronchial cancer
  • Cholangiocarcinoma
  • Pituitary tumors
  • debuling surgery
  • Prostate cancer
  • Pancreatic cancer

17
In unresectable Esophageal and lung cancer
  • Barretts esophagus
  • Esophageal cancer?
  • 50 have metastasis or unresectable
  • Dysphagia, malnutrition and bleeding
  • Lung cancer
  • Endobronchial obstruction

18
  • 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

19
Side effects
  • Sunburns
  • Perforation
  • Stricture
  • Candida esophagitis
  • Symptomatic pleural effusions

20
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

21
PDT in Esophageal Cancer
22
PDT in Esophageal CancerComplications
23
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.

24
PDT in Endobronchial tumors
  • Useful in palliation of late stage NSCLC.
  • Improve symptoms cough,
  • obstruction,
  • Ventilation
  • performance status 6-8 weeks after treatment

25
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

26
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

27
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

28
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