Table 1. Studies that analyze early ctDNA with treatment outcome in patients treated with chemotherapy.

C, cycle; DFS, disease-free survival; dPCR, digital polymerase chain reaction; GI, gastrointestinal; HR, hazard ratio; PDAC, pancreatic ductal adenocarcinoma; pts, patients; PR, partial response; Safe-SeqS, safe sequencing system; SCLC, small cell lung carcinoma; SD, stable disease; TTP, time to progression.

Author	N	Tumor	ctDNA method	Time point	Conclusions
		stage
Parikh et al. (101)	101 pts	GI tumors stage IV	ddPCR for mutations found in NGS on tumor	Baseline and 4 weeks	Percent change of ctDNA by 4 weeks predicted PR and clinical benefit (PR and SD).
					A decrease by 4 weeks ≥30% predicted a longer PFS.
Tie et al. (96)	53 pts	CRC stage IV	Safe-SeqS	Baseline and C2 (2 weeks after first dose)	Fold reduction in ctDNA predicts better radiological response than the absolute level of ctDNA.
					74% of patients who had a ≥10-fold reduction in ctDNA levels had a radiological response at the first radiological measurement.
Wei et al. (65)	17 pts	Pancreatic adeno- carcinoma stage IV	560-gene panel NGS	Baseline and C2 (2 weeks after first dose)	Relative changes in ctDNA prior cycle 2 predict radiological response as all patients with PD as best response had an increase in ctDNA, whereas 91% of patients with at least SD at first radiological assessment had a decrease in ctDNA.
Parkinson et al. (97)	32 pts	Relapsed high-grade serous ovarian carcinoma	dPCR for TP53 mutation	Baseline and C2 (21 to 28 days after first dose)	A percentage ctDNA decrease of ≥60% between baseline and cycle 2 predicted a longer TTP compared to those with a decrease of <60% irrespective of disease volume.
Kurtz et al. (102)	217 pts	Diffuse large B cell lymphoma	CAPP-seq	Baseline, mid cycle, cycle 2 (28 days), and cycle 3	ctDNA drop by midpoint of first cycle (6 to 16 days) predicts responders versus nonresponders.
					A 100-fold decrease (log2) drop by the start of cycle 2 and a log2.5 drop by cycle 3 were also predictive for a better event-free survival and OS irrespective other prognosis factors.
Osumi et al. (103)	29 pts	CRC stage IV	14-gene panel NGS	Baseline, weeks 2 and 8	Change in ctDNA levels at 2 weeks could be a possible predictor of PFS, while change in ctDNA levels at 8 weeks predicts independently PFS and OS.
Almodovar et al. (66)	25 pts	SCLC stage IV	14-gene panel NGS	Baseline, cycles 2 and 3	ctDNA decrease from baseline to cycle 2 or 3 predicts radiological response but not PFS or OS.
Perets et al. (104)	5 pts	PDAC stage IV	KRAS dPCR	Baseline and 4 weeks later	A significant negative correlation between the ctDNA slopes and survival times was found, suggesting that a deep fall in ctDNA over a short time correlates with longer OS, whereas a fast and marked rise in ctDNA predicted a shorter OS.