Fig. 3: Illustration of the three optimization strategies.

In the multi-step optimization strategy (a), patient-specific response is predicted for all candidate A/C schedules (light blue area represents the range of tumor volume, TV, predicted from various A/C schedules), with the schedule yielding the minimized TV_A/C identified as the optimal A/C schedule. Based on the minimized TV_A/C, patient-specific response is then predicted for all candidate T schedules (light green area), and the one yielding the minimal TV_T is identified as the optimal T schedule. Together, the optimal A/C and T schedules form the optimal NAC schedule (red area). In the simultaneous optimization strategy (b), patient-specific response is predicted for all candidate A/C and T schedules, with the one yielding the minimal TV_T identified as the optimal NAC schedule (red area). In the midway optimization strategy (c), the A/C schedule is fixed to the actual schedule (black curve). Based on the TV achieved from the actual A/C schedule, patient-specific response is predicted to all candidate T schedules, with the one yielding the minimal TV_T identified as the optimal T schedule.