Table 1.

Studies reporting on association between pre-ablation circulating DNA and treatment response, recurrence, and/or survival.

First author	Year	Metastatic site	Treatment modality	Analytical method	Circulating DNA marker	Cutoff	Time of sampling	n	Circulating DNA marker statistically significantly associated with				Ref
					Genetic mutation unless otherwise specified				Treatment response	Recurrence	RFS	OS
Diehl	2008	Liver, lung, oment, stomach	Resection, RFA	BEAMing	Tumor-informed (APC, KRAS, PIK3CA, TP53)	Detection	On the day of surgery	16	NR	D	NR	NR	14
Shin	2017	NR	Resection	MassArray	Tumor specific KRAS mutation	Detection	On the day of surgery	NR	NR	NR	NR	Yes	40
Boysen	2018	Liver	DEBIRI-TACE	DFA	cfDNA-level	75th percentile	Baseline	NR	No	NR	NR	D	38
Narayan	2019	Liver	Resection	Targeted sequencing	9 genes/cfDNA level	Detection/levelc	During surgery before resection	59	NR	NR	No	No/Yesh	17
Bidard	2019	Liver	Resection	ddPCR	KRAS	Detection	Before neo-adjuvant CT	NR	NR	NR	NR	Yes	12
							After 1 month of neo- adjuvant CT		NR	NR	NR	No
							Before liver surgery		NR	NR	NR	Yes
He	2020	Liver	Resection	Targeted sequencing	41 genes/cfDNA level	High versus low levelc	Within 7 days before surgery	19	NR	NR	Yes	NR	18
Beagan	2020	Peritoneal, liver, lnn	CRS-HIPEC, resection	ddPCR	Tumor-informed (48 genes) and KRAS	Detection	During surgery before resection	24	NR	Noe	Yesf/Nog	NR	19
Polivka	2020	Liver	Resection	ddPCR	KRAS	Detection/FA = 3.33%/percentage increment	Preoperative	30	NR	NR	No	No/Yesh	20
Boysen	2020B	Liver	HAI	DFA	cfDNA-level	75th percentile	Before first HAI	NR	Yes	NR	NR	Yes	16
Kobayashi	2021	Liver	Resection	Targeted sequencing	74 genes	Detection	Within a month of Liver resection	40	NR	Yes	Yes	No	21
Nakamura	2021	Liver, lung, lnn	PBT, SBRT	Targeted sequencing	18 genes	Detection/MaxAF = 1%/clonal versus multiclonal	Before ablative radiotherapy	20	NR	NR	No/Yesh	NR	22
Tie	2021	Liver	Resection	Targeted sequencing	Tumor-informed (15 genes)	Detection	Before possible neo-adjuvant CT and surgery	54	NR	NR	No	No	23
Lee	2021	Liver, lung, peritoneum, lnn, rectum	Resection	Targeted sequencing	Tumor-informed	Detection	Before resection	58	NR	D	No	No	24
Wang	2021	Liver	Resection	Targeted sequencing	451 genes	Detection	At diagnosis before treatment	NR	NR	NR	No	NR	25
							Before resection		NR	NR	No	NR
Pellini	2021	Liver and others	Resection	Targeted sequencing	197 genes	Detection	On the day of surgery	24	NR	Noe	No	NR	26
Parikh	2021	NR	NR	Targeted sequencing	Multiple analytical features	Detection	Preoperatively	15	NR	Noe	NR	NR	27
Reinerta	2022	Liver	Resection	ddPCR	Tumor-informed (APC, BRAF, KRAS, NRAS, PIK3CA, TP53)b	Detection	Prior to liver resection	68	NR	No	NR	NR	28
Øgaarda	2022	Liver	Resection	ddPCR	TriMeth	Positived	Prior to liver resection	NR	NR	No	No	NR	29

Studies included in at least one meta-analysis are indicated in bold type. For some outcomes, n may be lower.

^aSame study group.

^bPreoperative plasma samples from two patients, where no liver metastasis tissue was available.

^cNo cutoff reported.

^dSamples were classified as ‘TriMeth positive’ if two out of three TriMeth markers showed >1 positive droplet.

^eFisher’s exact test applied.

^fAll patients.

^gPatients without liver metastases.

^hDifferent associations for different markers of circulating DNA.

cfDNA, circulating cell-free DNA; CRS-HIPEC, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy; CT, chemotherapy; D, descriptively with no statistical test; ddPCR, droplet digital polymerase chain reaction; DEBIRI-TACE, transarterial chemoembolization with irinotecan loaded beads; DFA, direct flourescent assay; FA, fractional abundance; HAI, hepatic artery infusion; lnn, lymph nodes; MaxAF, maximum allele frequency; n, number of patients with reported association between pre-ablation circulating DNA and at least one outcome; NR, not reported; PBT, proton beam therapy; Ref, reference; RFA, radiofrequency ablation; SBRT, stereotactic body radiation therapy; OS, overall survival; RFS, recurrence-free survival.