Table 2.

Discordant samples

	ID	qPCR (SoC) tumor	BEAMing plasma	BEAMing tumor	Additional (SoC) tumorc	Historical (SoC) tumorc	Codon	MAF (BEAMing plasma)	adjMAF (BEAMing tumor)	Tissue source	Tissue tumor area (%)	Time tissue- plasma (month)	Previous chemo lines	Previous treatment receivedd	Anti-EGFR after plasma collection and best response	Possible explanation
Group Aa	1	WT	MUT	MUT	MUT	WT	NRAS Q61	0.43	0.072	Primary	15	8	1	Capox adyuvant	FOLFIRI+ Panitumumab 1L (PR)	SoC sensitivity
	2	WT	MUT	MUT	MUT	WT	KRAS A146	0.0065	0.25	Primary	95	1	0		FOLFOX+ Cetuximab 1L (SD)
	3	WT	MUT	MUT	NA	NA	KRAS A146	0.0061	0.29	Primary	50	7	0		No
	4	WT	MUT	MUT	NA	MUT	KRAS G12	0.0006	0.058	Primary	20	108	2	5FU adyuvant, FOLFIRI 1L	No
	5	WT	MUT	MUT	NA	MUT	NRAS Q61	0.0005	0.085	Primary	75	2	0		No
	6	WT	MUT	WT	NA	WT	KRAS G12	0.0005		Metastasis	45	4	1	FOLFIRI+BVZ 1L	FOLFIRI+ Panitumumab 2L (PR)	Molecular heterogeneity
	7	WT	MUT	WT	NA	WT	KRAS G12	0.0008		Primary	70	3	0		No
	8	WT	MUT	WT	WT	WT	KRAS Q61	0.0015		Primary	70	1	0		FOLFIRI+ Cetuximab 1L (PR)
	9	WT	MUT	WT	NA	WT	NRAS Q61	0.0005		Primary	100	10	1	FOLFIRI 1L	FOLFIRI+ Panitumumab 2L (PD)
Group Bb	10	MUT	WT	MUT	MUTe	MUT	KRAS G12		0,27	Primary	50	1	0		No	Low tumor burden?
	11	MUT	WT	MUT	MUT	MUT	KRAS G12		0,14	Primary	40	33	2	FOLFOX 1L, FOLFIRI 2L	No
	12	MUT	WT	MUT	NA	MUT	KRAS G12		0,12	Primary	95	3	0	In course FOLFOX 1L (PR)	No	Chemotherapy effect?
	13	NA	WT	MUT	NA	MUT	NRAS G13		NA	Primary	70	8	0	In course FOLFOX + BVZ 1L (SD)	No
	14	NA	WT	MUT	NA	MUT	NRAS Q61		NA	Primary	70	4	0	In course FOLFOX 1L (PD)	No
	15	MUT	WT	WT	NA	MUTf	KRAS Q61			Primary	60	3	0		No	Technical issues?

^aGroup A: mutations detected in plasma but not in tissue by SoC.

^bGroup B: mutation detected in tissue by SoC but not in plasma.

^cSupplementary Table S2, available at Annals of Oncology online.

^dIn those patients with plasma extraction during chemotherapy immediate response after extraction is reported between brackets.

^eCodon NRAS A59.

^fCodon KRAS G13.

SoC, standard of care; MAF, mutant allele fraction; adjMAF, adjusted mutant allele fraction; Chemo, chemotherapy (adyuvant and/or metastatic setting); MUT, mutation; NA, not available; PR, partial response; SD, stable disease; PD, progression disease; 1L, frontline metastatic therapy; 2L, second line metastatic therapy; Capox, Capecitabine + oxaliplatin; 5FU, 5-fluorouracil; BVZ, Bevacizumab; FOLFIRI, 5FU + leucovorin + irinotecan; FOLFOX, 5FU + leucovorin + oxaliplatin.