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Dosimetric and technical considerations for interstitial adenoviral gene therapy as applied to prostate cancer
Shidong Li1, Jonathon Simons, Nicholas Detorie
1Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. lish@jhmi.edu
Purpose:
To introduce a simple and specific dosimetric model and an adenoviral delivery technique for interstitial adenoviral gene therapy of prostate cancer.
Methods And Materials:
CG7060, a PSA-specific, replication-competent adenovirus, was used in a Phase I study in the treatment of 20 patients with locally recurrent prostate cancer. The virus was delivered directly into the prostate via transperineal needles under real-time transrectal ultrasonography guidance. Up to 80 aliquots of 0.1-mL viral solution were injected into the prostate. The injection pattern, effective treatment volume (V(eff)), and viral dose distribution were determined according to a simple dosimetric model in which the local dose of virus was defined as the concentration of the delivered virion uniformly distributed in a sphere of 5-mm radius per injection. The initial dosimetric parameters were measured through scans of contrast solutions in dog prostate glands. The biochemical response (the reduction of serum PSA) as a function of the viral dose and tumor volume coverage was analyzed.
Results:
A 0.1-mL solution injected into the dog prostate gland spreads via 4-mm mechanical flow plus 1-mm molecular diffusion. Multiple injections into the prostate of patients resulted in considerable enlargement of the prostate gland. The biochemical response probability for patients treated with CG7060 may be estimated by 1 - alpha * exp[-[beta + gamma (PTV/V(eff)) P/A] * P], where alpha, beta, and gamma are constants; A is the number of aliquots, and P is the integral dose of initial viruses.
Conclusion:
A simple dosimetric model based on results from our recently reported Phase I study can quantify the biochemical response of patients treated with CG7060 adenoviral therapy. The model predicts that outcome is influenced by the integral dose of delivered virus and the target volume coverage. This first dosimetric model for interstitial adenoviral therapy will serve as a basis for quantitative analysis for ongoing and future studies.