(b) Uses of TMs at different clinical endpoints

Clinical endpoint	Prognostic
Use of clinical data	Correlate T0 levels with PFS/RFS and/or OS
Potential outcome	TM can be used in future trials as prognostic factor for risk stratification
Example for clinical implication	In “good risk patients”: consider less intensive treatment, or shorter duration
	In “poor risk patients”: consider maintenance after induction chemotherapy
Clinical endpoint	Response
Use of clinical data	Correlate change in T0 to T1 and T2 levels with response per RECIST on imaging at T2
Potential outcome	Early TM change at T1 predicts progression on first imaging at T2
	Early TM change at T2 predicts progression on 2nd imaging at T3 (i.e., in patients with stable disease on 1st imaging at T2)
Example for clinical implication	Randomized trial of continuation of same chemotherapy versus early change to different regimen based on early TM stratification; primary outcome could be ORR, PFS/RFS, or OS
Clinical endpoint	Treatment monitoring
Use of clinical data	Correlate change in T0 to T3 levels with best response per RECIST on imaging at T3
Potential outcome	Decline in TM panel correlates with response on imaging
Example for clinical implication	Fewer interval scans for patients with declining markers
Clinical endpoint	Detection of early relapse
Use of clinical data	Correlate change from nadir of TM at T3 with posttreatment at T4 and T5
Potential outcome	Increase in levels of TM at T4 compared to T3 will predict progression at T5
Example for clinical implication	Tailor surveillance imaging based on TM levels

T0 to T5, various time points for blood draw and/or imaging; PFS, progression-free survival; RFS, recurrence-free survival; OS, overall survival.