Irradiance-Dependent Photobleaching and Pain in δ-Aminolevulinic Acid-Photodynamic Therapy of Superficial Basal Cell Carcinomas

Purpose: In superficial basal cell carcinomas treated with photodynamic therapy with topical δ-aminolevulinic acid, we examined effects of light irradiance on photodynamic efficiency and pain. The rate of singlet-oxygen production depends on the product of irradiance and photosensitizer and oxygen concentrations. High irradiance and/or photosensitizer levels cause inefficient treatment from oxygen depletion in preclinical models. Experimental Design: Self-sensitized photobleaching of protoporphyrin IX (PpIX) fluorescence was used as a surrogate metric for photodynamic dose. We developed instrumentation measuring fluorescence and reflectance from lesions and margins during treatment at 633 nm with various irradiances. When PpIX was 90% bleached, irradiance was increased to 150 mW/cm 2 until 200 J/cm 2 were delivered. Pain was monitored. Results: In 33 superficial basal cell carcinomas in 26 patients, photobleaching efficiency decreased with increasing irradiance above 20 mW/cm 2 , consistent with oxygen depletion. Fluences bleaching PpIX fluorescence 80% (D80) were 5.7 ± 1.6, 4.5 ± 0.3, 7.5 ± 0.8, 7.4 ± 0.3, 12.4 ± 0.3, and 28.7 ± 7.1 J/cm 2 , respectively, at 10, 20, 40, 50, 60 and 150 mW/cm 2 . At 20-150 mW/cm 2 , D80 doses required 2.5-3.5 min; times for the total 200 J/cm 2 were 22.2-25.3 min. No significant pain occurred up to 50 mW/cm 2 ; pain was not significant when irradiance then increased. Clinical responses were comparable to continuous 150 mW/cm 2 treatment. Conclusions: Photodynamic therapy with topical δ-aminolevulinic acid using ∼40 mW/cm 2 at 633 nm is photodynamically efficient with minimum pain. Once PpIX is largely photobleached, higher irradiances allow efficient, rapid delivery of additional light. Optimal fluence at a single low irradiance is yet to be determined.