Heat shock protein expression and injury optimization for laser therapy design

Background and Objectives: Hyperthermia can induce heat shock protein (HSP) expression in tumor regions where non-lethal temperature elevation occurs, enhancing cell viability and resistance to chemotherapy and radiation treatments typically employed in conjunction with thermal therapy. However, HSP expression control has not been incorporated into current thermal therapy design. Treatment planning models based on achieving the desired post-therapy HSP expression and injury distribution in the tumor and healthy surrounding tissue can enable design of more effective thermal therapies that maximize tumor destruction and minimize healthy tissue injury. Study Design/Materials and Methods: An optimization algorithm for prostate cancer laser therapy design was integrated into a previously developed treatment planning model, permitting prediction and optimization of the spatial and temporal temperature, HSP expression, and injury distributions in the prostate. This optimization method is based on dosimetry guidelines developed from measured HSP expression kinetics and injury data for normal and cancerous prostate cells and tumors exposed to hyperthermia Results: The optimization model determines laser parameters (wavelength, power, pulse duration, fiber position, and number of fibers) necessary to satisfy prescribed HSP expression and injury distributions in tumor and healthy tissue. Optimization based on achieving desired injury and HSP expression distributions within the tumor and normal tissue permits more effective tumor destruction and diminished injury to healthy tissue compared to temperature driven optimization strategies. Conclusions: Utilization of the treatment planning optimization model can permit more effective tumor destruction by mitigating tumor recurrence and resistance to chemotherapy and radiation arising from HSP expression and insufficient injury.