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Photodynamic therapy

ISSN 2398-2977

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Synonym(s): PDT

Introduction

  • Photodynamic therapy (PDT) describes a method of cancer therapy using interactions of a photosensitizing agent, light and oxygen.
  • PDT is a promising method of treating superficial squamous cell carcinomas (SCC) Skin: neoplasia - squamous cell carcinoma that is non-invasive, provides good cosmesis and carries minimal risk of toxicity.
  • It may also be a useful adjunctive treatment for small sarcoids Sarcoid, especially following surgical removal.
  • The photosensitizer is quite expensive, so for large areas, this may prove a financially prohibitive limitation.

Indications

  • Treatment of superficial carcinomas, where surgery is not feasible, or may not provide good cosmetic outcome, eg superficial SCC.
  • Adjunctive treatment of squamous cell carcinomas and sarcoids, in combination with incomplete surgical excision.

Principles

  • Certain agents, eg porphyrins and their derivatives are preferentially distributed into malignant tissues rather than normal tissues.
  • These agents can be 'excited' by light of appropriate wavelength causing reactive oxygen species (ROS) stress and producing cytotoxic free radicals, killing the cell and stimulating a local inflammatory response.

History and background

  • PDT was first investigated in the 1970's when it was found that porphyrins were preferentially distributed into malignant tissues rather than normal tissues.
  • The technique was slow to gain acceptance because the 'first generation' photodynamic agents were slow to clear from normal cells with the result that treated human patients had to remain out of bright light, eg sunlight, for several weeks to avoid severe skin reactions.
  • The potential for the technique was demonstrated however on laboratory animals and on some human patients with locally advanced carcinomas of the head and neck, bladder, esophagus and bronchus.
  • The availability of hematoporphyrin derivatives with faster tissue clearance times stimulated more interest in PDT and a number of human and veterinary clinical trials were published with encouraging results.
  • Photodynamic therapy has become established as a safe, minimally invasive and effective method of treatment of certain human cancers and is offered at several major cancer centers in the UK and Europe.
  • It is used in the treatment of head and neck cancers because of its excellent cosmetic results.
  • PDT can also be used in any hollow organ accessible to a fiber optic for light delivery, thus it is often used in human prostate, bladder and esophageal cancer.

Veterinary clinical results

  • In animals, PDT has been used to treat squamous cell carcinoma and as an adjunctive treatment for small or incompletely removed sarcoids in various locations.
  • Photodynamic therapy using 5-aminolevulinic acid (5-ALA) applied topically to superficial tumors and illuminated by a light-emitting diode (LED) light source of 635 nm has been used in horses.
  • The present technique is limited however by depth of penetration of the topically applied 5-ALA cream, such that only tumors <2 mm deep are suitable for this type of PDT. The response of the tumor following PDT usually includes an immediate erythema and edema which resolves over 3-5 days:
    • The tumor then dries up, often forming a scab over the surface which may slough between 2-6 weeks following treatment to expose a bed of granulation tissue which eventually re-epithelializes.
    • Normal tissue toxicity appears to be minimal.
    • Local effects such as inflammatory reactions, swelling and necrosis of normal tissues adjacent to the tumor site have been reported and local infections requiring antibiotic treatment have occurred in some cases.
    • Intense local irritation may occur at the tumor site immediately following treatment but this usually resolves within 2-4 days as the inflammatory response subsides.
    • Bone necrosis and sequestration have been reported in 3 of 5 patients whose tumors were located adjacent to the bone of the maxilla or mandible.

Conclusion and future directions

  • There is no doubt that PDT has the ability to kill tumor cells and normal tissues.
  • The preferential distribution of HpD and other photodynamic agents in tumors, and the accuracy with which laser light can be controlled and the development of multi-fiber optic systems for light delivery mean that this technique has potential clinical value in the treatment of non-resectable, superficial tumors or tumors sited in hollow organs such as the upper respiratory tract, esophagus, bladder and large bowel.
  • The recent development of agents that can be applied topically offers some advantages in reduction of systemic effects. However, large bulky tumors are not likely to be amenable to treatment by this method.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Golding J P, Kemp-Symonds J G & Dobson J M (2017) Glycolysis inhibition improves photodynamic therapy response rates for equine sarcoids. Vet Comp Oncol 15 (4), 1543-1552 PubMed.
  • Buchholz J & Walt H (2013) Veterinary photodynamic therapy: a review. Photodiagnosis Photodynamic Therapy 10 (4), 342-347 PubMed.
  • Martens A, Moor A D E, Waelkens E, Merlevede W & De Witte P (2000) In vitro and in vivo evaluation of hypericin for photodynamic therapy of equine sarcoids. The Vet J 159 (1), 77-84 PubMed.