Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate cancer.

BACKGROUND AND OBJECTIVES: Interstitial photodynamic therapy (PDT) is an emerging modality for the treatment of solid organ disease. Our group at the University of Pennsylvania has performed extensive studies that demonstrate the feasibility of interstitial PDT for prostate cancer. Our preclinical and clinical experience is herein detailed. STUDY DESIGN/MATERIALS AND METHODS: We have treated 16 canines in preclinical studies, and 16 human subjects in a Phase I study, using motexafin lutetium-mediated PDT for recurrent prostate adenocarcinoma. Dosimetry of light fluence, drug level and oxygen distribution for these patients were performed. RESULTS: We demonstrate the safe and comprehensive treatment of the prostate using PDT. However, there is significant variability in the dose distribution and the subsequent tissue necrosis throughout the prostate. CONCLUSIONS: PDT is an attractive option for the treatment of prostate adenocarcinoma. However, the observed variation in PDT dose distribution translates into uncertain therapeutic reproducibility. Our future focus will be on the development of an integrated system that is able to both detect and compensate for dose variations in real-time, in order to deliver a consistent overall PDT dose distribution.

Comparative treatment planning between proton and X-ray therapy in pancreatic cancer.

With the utilization of new biologic agents and experimental chemotherapy in the treatment of pancreatic cancer, the issue of local-regional control will become increasingly important. This study was undertaken to determine the feasibility of dose escalation using proton therapy, as compared to conventional 3-dimensional conformal radiation, by minimizing the dose to normal tissues. The photon treatment plans of 4 patients with unresectable pancreatic cancer treated on a biologic therapy trial were utilized. Each patient was treated using a 3- or 4-field photon plan with 45 Gy to the clinical target volume (CTV), followed by a boost of 14.4 Gy to the gross target volume (GTV). Using a Helax treatment planning system, proton plans were generated to encompass the same CTV and GTV to the same prescribed dose. Dose-volume histograms (DVHs) were generated for the GTV, CTV, spinal cord, liver, and right and left kidneys. Each DVH was compared between the photon and proton plans. Proton plans utilized either a 2- or 3-field technique. Available energies included 130 or 180 MeV. Range modulators and bolus were used as needed to conform to the target volume. With the CTV and GTV receiving the same dose from the proton and photon plans, all individual proton plans were superior to the photon plans in reduction of normal tissue dose. For the 4 patients, the average dose reduction to 50% of the organ at risk was 78% to spinal cord (p = 0.003), 73% to left kidney (p = 0.025), 43% to right kidney (p = 0.059), and 55% to liver (p = 0.061). These comparative treatment plans show proton therapy results in significant reductions of dose to normal tissue compared to conventional photons while treating the same target volumes. This allows for the design of dose-escalation protocols using protons in combination with new biologic therapies and chemotherapy.