Computational modelling of resistance and associated treatment response heterogeneity in metastatic cancers.

Computational modelling of resistance and associated treatment response heterogeneity in metastatic cancers. Phys Med Biol. 2019 Feb 21;: Authors: Turk M, Simoncic U, Roth A, Valentinuzzi D, Jeraj R Abstract Metastatic cancer patients invariably develop treatment resistance. Different levels of resistance lead to observed heterogeneity in treatment response. The main goal was to evaluate treatment response heterogeneity with computation model simulating dynamics of drug-sensitive and drug-resistant cells. Model parameters included proliferation, drug induced death, transition and proportion of intrinsically resistant cells. Model was benchmarked with imaging metric extracted from 39 metastatic prostate cancer patients who had 18F-NaF-PET/CT scans performed at baseline and three cycles into chemotherapy or hormonal therapy. Two initial model assumptions were evaluated: considering only inter-patient or both inter-patient and intra-patient heterogeneity in proportion of intrinsically resistant cells. Correlation between median proportion of intrinsically resistant cells and baseline patient-level imaging metrics was assessed with Spearman's rank correlation coefficient. Impact of model parameters on simulated treatment response was evaluated with sensitivity study. Treatment response after six, nine and twelve months was predicted with the model. Median predicted range of response for patients treated with both therapies was compared w...
Source: Physics in Medicine and Biology - Category: Physics Authors: Tags: Phys Med Biol Source Type: research