Optimal frequency of scans for patients on cancer therapies: A population kinetics assessment

Background: Optimal frequency of follow-up scans for patients receiving systemic therapies is poorly defined. Progression-free survival (PFS) generally follows first-order kinetics. We used exponential decay nonlinear regression analysis to calculate half-lives for 887 published PFS curves. Method: We used the Excel formula x = EXP(-t_n*0.693/t_1/2) to calculate proportion of residual patients remaining progression-free at different times, where t_n is the interval in weeks between scans (eg, 6 weeks), * indicates multiplication, 0.693 is the natural logarithm of 2, and t_1/2 is the PFS half-life in weeks. Results: Proportion of residual patients predicted to remain progression-free at each subsequent scan varied with scan intervals and regimen PFS half-life. For example, with a 4-month half-life (17.3 weeks) and scans every 6 weeks, 21% of patients would progress by the first scan, 21% of the remaining patients would progress by the second scan at 12 weeks, etc With 2, 6- and 12-month half-lives (for example), the proportion of remaining patients progressing at each subsequent scan if repeated every 3 weeks would be 21%, 8% and 4%, respectively, while with scans every 12 weeks it would be 62%, 27% and 15%, respectively. Furthermore, optimal scan frequency can be calculated for populations comprised of distinct rapidly and slowly progressing subpopulations, as well as with convex curves arising from treatment breaks, where optimal scan frequency may differ during therapy administration vs during more rapid progression after therapy interruption. Conclusions: A population kinetics approach permits a regimen- and tumor-specific determination of optimal scan frequency for patients on systemic therapies.