A cell kinetics model for prostate cancer and its application to clinical data and individual patients.
A cell kinetics model is developed to describe the evolution of prostate cancer (PC) from diagnosis to PC specific death. Such a model can be used to estimate an individual's eventual outcome and thus to inform decisions about therapy. To describe the observed clinical progression, the model must postulate three PC cell populations that are (1) local to the prostate and sensitive to hormones, (2) regional and hormone sensitive, and (3) systemic and hormone resistant. A set of coupled first-order differential equations describes the exponential growth of a PC tumor as well as its transformation from a local to systemic disease. The time dependence of the solutions is scaled to the doubling time of the prostate specific antigen (PSADT) because it characterizes the tumor growth for the individual. The conversion from local to systemic cell populations is described with a parameter alpha that can be associated with the Gleason score. The model also has three critical cell populations that describe (1) the initiation of the non-local populations, (2) the saturation level of the local tumor, and (3) the cell count likely to cause PC specific death. These parameters are calibrated by reproducing published PC clinical data and survival tables. The model is then applied to individuals with complete PC diagnostic data in order to calculate the progression to PC specific death. One man has early stage PC as described in the 'vignette' patient of Walsh et al. (2007. N. Engl. J. Med. 357, 2696-2705). The second man has a more serious condition and has undergone both local and systemic treatments. Unfortunately, I am that patient.
Dimonte
Guy
G
Los Alamos National Laboratory, Los Alamos, NM 87545, USA. dimonte@lanl.gov
D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D018450:Disease Progression; D006801:Humans; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009367:Neoplasm Staging; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000628:therapy*; D018570:Risk Assessment / Q000379:methods; D013997:Time Factors
D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen