PHOTODYNAMIC THERAPY FOR PREMALIGNANT LESIONS IN DMBA-TREATED HAMSTERS - A PRELIMINARY-STUDY

Purpose: Photodynamic therapy (PDT) involves the selective destruction of neoplastic cells through the activation of a photosensitizer by li ght. We have previously shown that the photosensitizer Photofrin (porf imer sodium) is selectively accumulated in transformed lesions destine d to become malignant, but not yet definable histologically as precanc ers. The aim of this investigation was to determine if this premaligna nt tissue could be selectively destroyed by systemically administered Photofrin activated by 630 nm red light via an argon dye laser. Materi als and Methods: The carcinogenic model used was the DMBA (9, 10 dimet hyl 1,2 benzanthracene)-treated hamster cheek pouch. The animals were treated with 0.5% DMBA in acetone thrice weekly for 6 weeks (experimen t I, premalignant lesions), or 12 weeks (experiment II, malignant lesi ons). Ten animals were in experiment I; nine animals were in experimen t II. These were divided into experimental and control subgroups. The 6-week experimental group received PDT and CO2 laser incision into the DMBA-treated area. The CO2 laser was used as a promoter of neoplasia in a field that had already undergone initiation from the DMBA treatme nt. The control groups received either CO2 laser incision alone into t he DMBA-treated field or CO2 laser incision and argon pumped dye laser treatment (without Photofrin). The 12-week experimental group receive d PDT after CO2 laser excision of tumors. The controls received CO2 ex cision alone, or CO2 excision combined with postoperative hyperthermia . Results: One hundred percent (three of three) of cheeks in experimen t I receiving PDT developed necrosis of the treated area within 24 to 48 hours, but 0% (0 of three) subsequently developed tumors. No necros is was seen in control cheeks receiving Photofrin without irradiation (0 of four) or irradiation without Photofrin (0 of six), and 56% (five of nine) of cheeks exposed to identical carcinogenic stimulus, withou t PDT, developed tumors (n = 9). In experiment II, 0% (0 of six) of ch eeks receiving postoperative PDT developed tumor recurrence. In experi ment II controls, 50% (three of six) of cheeks that underwent excision and hyperthermia developed tumor recurrence. In cheeks treated only w ith CO2 laser excision of tumors, a recurrence rate of 67% (four of si x) was noted. These results were found to be statistically significant by the Student t-test on the binomial distribution (P < .01). One ani mal was treated with DMBA for 6 weeks, administered Photofrin, and the right cheek was irradiated and the animal was left for 30 weeks. The irradiated cheek epithelium necrosed but no cancer developed, whereas the positive control cheek developed a large cancer.Conclusion: These results suggest that photodynamic therapy possesses significant potent ial in elimination of premalignant tissue. This could be beneficial in treating potentially premalignant lesions such as oral leukoplakia, a nd useful as adjunctive therapy in removal of areas of field canceriza tion adjacent to surgical sites.