Irradiance, Photofrin^® Dose and Initial Tumor Volume are Key Predictors of Response to Interstitial Photodynamic Therapy of Locally Advanced Cancers in Translational Models

The objective of the present study was to develop a predictive model for Photofrin^®-mediated interstitial photodynamic therapy (I-PDT) of locally advanced tumors. Our finite element method was used to simulate 630-nm intratumoral irradiance and fluence for C3H mice and New Zealand White rabbits bearing large squamous cell carcinomas. Animals were treated with light only or I-PDT using the same light settings. I-PDT was administered with Photofrin^® at 5.0 or 6.6 mg kg⁻¹, 24 h drug-light interval. The simulated threshold fluence was fixed at 45 J cm⁻² while the simulated threshold irradiance varied, intratumorally. No cures were obtained in the mice treated with a threshold irradiance of 5.4 mW cm⁻². However, 20–90% of the mice were cured when the threshold irradiances were ≥8.6 mW cm⁻². In the rabbits treated with I-PDT, 13 of the 14 VX2 tumors showed either local control or were cured when threshold irradiances were ≥15.3 mW cm⁻² and fluence was 45 J cm⁻². No tumor growth delay was observed in VX2 treated with light only (n = 3). In the mouse studies, there was a high probability (92.7%) of predicting cure when the initial tumor volume was below the median (493.9 mm³) and I-PDT was administered with a threshold intratumoral irradiance ≥8.6 mW cm⁻².