Strategy

Median 2

Median 3

5 yr 2

5 yr 3

Cure 2

Cure 3


0: Current personalized medicine

585

720

35.8

29.6

23.0

10.8

Singlestep strategy 2.2

1170

1080

47.3

40.5

30.1

17.6

Multistep strategy 2.2

1215

1080

47.5

41.5

30.1

18.5

ALTOSMO

855

1035

44.7

41.8

34.3

17.9

ALTO

1260

1080

47.5

43.2

36.8

25.4

 Strategy 0 is the current personalized medicine strategy: treat with the best drug for the largest clone and continue to treat until tumor worsening or relapse, then rebiopsy and repeat. Strategy 2.2: select/adapt treatment every 45 days using evolutionary dynamic model to minimize the likelihood of forming a cell simultaneously resistant to all the therapies at a future reference timepoint, unless the estimated tumor burden is 10^{11} cells or more. Singlestep strategy 2.2: future reference timepoint for selecting treatments is 45 days, corresponding to the interval between treatment adaptations. Multistep strategy 2.2: future reference timepoint for selecting treatments is 225 days, or 5 times the interval between treatment adaptations (“thinking 5 steps ahead”). ALTO: Adaptive longterm optimization. ALTOSMO: Adaptive long term optimizationserial monotherapy only. Median 2: median survival days for twodrug cases. Median 3: median survival days for threedrug cases. 5 yr 2: percentage of twodrug cases with more than 5year survival time. 5 yr 3: percentage of threedrug cases with more than 5year survival time. Cure 2: percentage of twodrug cured cases. Cure 3: percentage of threedrug cured cases. Survival is defined as time before tumor grows to 10^{13} cells. This number is intended to represent the sum total of the cell numbers in a very large number of metastatic lesions, since most patients succumb to widespread metastatic disease. Cure is defined as total elimination of disease. Note that because the 3 drug simulation contains more states and allows doubly resistant cells at time zero, results from it cannot be directly compared to results from the two drug simulation