ARTICLES

Dr. L. Sarangi, M. S
Indian Railways Cancer Institute & Research Centre,
Varanasi

In recent years a lot of interest has been generated on application of photodynamic therapy (POT) in both diagnosis and treatment of neoplastic lesions. POT is an anticancer technique that has been known for a century and which is increasingly applied in dermatology, urology, gastro-enterology, ophthalmology and neuro surgery. Now it is breaking new grounds in oncological surgery,(1)

Photodynamic therapy is systemic administration of a photosensitiser, which is preferentially taken up by tissues of strong mitotic activity and pathological stroma.(2) Photosensitisers develop no spontaneous toxicity; they must be excited by photons to produce cytotoxic free radicals, such as singlet oxygen and superoxide radicals. These radicals selectivelv destroy the neoplastic cells having strong mitotic activities. Secondly excitation of the photosensitisers by an incident photon produces re-emission of a fluorescent photon, which can be used to demonstrate small tumour deposits, micro-metastasis, extent of the primary disease as well as incomplete excision and extent of the residual disease left after radical surgery. So POT may represent the technique which can be applied for both diagnosis, detection and destruction of micrometastases and residual disease. It has the potential for use as an adjuvant per-operative treatment.

The first full clinical report of POT dates from 1976. Haematoporphyrin derivatives, a complex mixture of porphyrins, was initially used as a photo-sensitiser. An enriched fraction (Porfimer sodium) is now the most commonly used clinical agent. After systemic administration, porphyrins bind to albumin and lipoproteins that accumulate mainly in tumours and organs of reticulo-endotheliol systems.(3) The light of an argon dye laser can be turned to the appropriate wavelength and delivered either superficially, interstitially and interluminally. Light distribution can be assessed by using a radiation transport model and tissue optical properties, or direct measurement with ligHt detectors.

Various photo sensitisers that are in experimental stage besides Porfimer sodium are:- Photolocyanines, Chlorins, Purpurins, Bacterochlorins, Verdins or Protoporphyrin IX endogenously produced from aminolevulinic acid (ALA)4. The ideal properties of a photosenstiser are :- Clinical purity, minimal dark toxicityty, significant absorption at wavelengths above 650 nm, high quantum yields for generation of desired photochemical reactions, preferential tumour localisation and rapid clearance from normal tissue. Amongst the above enumerated photosensitisers, ALA induced photosensitisation is most promissing for selective photodynamic therapy.

Various laser systems that are being used are Argon dye laser, KTP laser, Diode laser. The Argon dye laser is expensive and clinically not easy to handle. KTP laser is relatively complex and large. Diode laser is somewhat suitable, though it has its own disadvantages. The main advantage of Diode laser are low capital cost, negligible running cost, high reliability and portable in nature. .

The effects of PDT depend in a complex way on charactristics, tissue concentration and localisation of the photosensitisers; the target tissue optical properties and oxygenation; activation wavelength; power density and treatment regimen.

Although it has been clearly demonstrated that PDT can cause significant tumour destruction, most clinical studies to date have involved patients who have failed other standard therapies. The likelihood of tumour control in these patients is accordingly low. It is being applied as phase II & III trials in advanced cancers of oral cavity, esophagas, bronchus, colon, pancreas, skin (5,6,7,8). Attempts have been made to apply PDT intra-operatively mainly in advanced malignancy of pancreas, ovary as an adjuvant to radical surgery. By this approach the residual disease and micrometastases can be detected intra-operatively and selectively destroyed. However, large scale randomised clinical trials are required to provide a clear evaluation of the potential curative and palliative role of POT.

Suggested readings:-

1. Hillegersberg R. V., Kort W.J., Paul Wilson J.H.: Current status of photodynamic therapy in Oncology: Drugs 1994;48(4): 510-527.

2. Bugelski PJ, Porter CW, Dougherty T J: Autorodiographic distribution of hematoporphyrin derivative in normal and tumour tissue of the Mouse Cancer. Res 1981; 41: 4606-12.

3. Gomer CJ, Dougherty T J: Determination of hematoporphyrin derivative distribution in malignant and normal tissue cancer. Res 1979; 39: 146-51.

4. Kreimer-Birnbaum M, Modified porphynins. chlorins, phtalocyarins, and purpurins: Second generation photosensitisers for photodynamic therapy: Semin Hematol1989; 26: 157-73.

5. Pass HI. Photodynamic therapy in oncology: Mechanisms and clinical use. J Natl Cancer Inst. 1993; 85: 443-56.

6. Dougherty T J. Photodynamic therapy. Photochem PhotobioI1993;58: 895-900.

7. PuolakkainenP., SchroderT. Photodynamic therapy of gastroentestinal tumours: a review. Dig. Dis 1992; 10: 53-60.

8. Evrad S. Aprahamian M, Marescaux J. Intra- abdominal photodynamic therapy: From theory to feasibility. Br. J. Surg. 1903; 80: 293-303.