Fig. 4: Time to resistant population reduction, time to loss of control, and robustness to uncertainty in initial conditions are optimized under continuous adaptive therapy.
A Time to decrease resistant cell population to threshold (y = 0.01) when α < 1 and β > 1 under intermittent adaptive therapy (solid lines) and continuous adaptive therapy (dotted lines). (Model Parameters: α = 0.5, β = 2, rd = 0.1, rx = 0.03, ry = 0.02, A = 0.8., δ = 0.4) B Time to loss of control when α > 1 and β < 1 under intermittent adaptive therapy (solid lines) and continuous adaptive therapy (dotted lines). (Model Parameters: α = 1.5, β = 0.7, rd = 0.1, rx = 0.03, ry = 0.02, A = 0.8., δ = 0.4) C Phase planes corresponding to δ → 0 trajectories with the numerically computed separatrix delineating between initial conditions leading to resistant species extinction and those leading to sensitive species extinction. D Numerically computed separatrix for varying values of δ (Model Parameters: α = 0.5, β = 2, rd = 0.05, rx = 0.03, ry = 0.02). Theoretical computation of the separatrix is discussed in Supplemental Section 2.4 and has excellent concordance with numerical results.
