Impact of primary tumour location on colorectal liver metastases: A systematic review

Table 1 Summary of characteristics of included studies

Ref.	Year	Country of study	Number of patients included	Median follow up (mo)	Primary tumour location (n)			Median age (yr)
					L	R	Rectum	L	R	Rectum
Zhou et al[27]	2017	China	295	24	89	94	112	57	59	61
Zhang et al[30]	2017	China	194	12	144	50		60	55.5
Makowiec et al[37]	2018	Germany	221		158	63		64	65
Chafai et al[29]	2005	Australia	398	26.8	277	71
Rougier et al[15]	1995	France	537		197	117	223
Wang et al[38]	2018	China	420	26	334	86		57	58.5
Gu et al[28]	2018	China	102		51	51		63	61.5
Gasser et al[12]	2019	Austria	259	38.1	200	59		64	66
de Haas et al[24]	2010	France	750	39	413	154	200
Marques et al[11]	2018	Brazil	151	42	124	27		57	61
Russolillo et al[21]	2019	Italy	686	81	364	322		63	66
Umeda et al[34]	2013	Japan	100	36	40	23	37
Zheng et al[31]	2018	China	318		233	85
Mavros et al[39]	2013	United States	97	26.4	44	24	27
Viganò et al[20]	2014	Italy	749	51.4	63	87	48
Connor et al[40]	2016	Canada	63	31.5	27	10	21
Eefsen et al[41]	2015	Denmark	254	44.6	125	51	78
Schirripa et al[33]	2015	Italy	309	45.6	138	87	82
Loosen et al[42]	2018	Germany	125		102	23
Amikura et al[32]	2018	Japan	342	52.7	236	106
Yamashita et al[26]	2018	United States	725	27/41	487	238		56	58
Dulundu et al[19]	2017	Turkey	108		40	24	44	58.5	63.2	63.8
Creasy et al[9]	2016	United States	907	132	578	329		62.4	65.4
Sasaki et al[23]	2016	United States	426	28.9	297	129
Palkovics et al[43]	2018	Hungary	319		114	72	133
Dupré et al[8]	2018	United Kingdom	364	41.8	290	74		65.1	68.6
Heise et al[22]	2017	Germany	160	21	113	47
Shigematsu et al[44]	2018	Japan	396	36.4	155	93	148
Rhu et al[45]	2017	South Korea	410	30.5	289	121		58.41	59.56
Lionti et al[25]	2018	Italy	63	40	22	23	18
Wang et al[46]	2017	China	159		130	29
Norén et al[18]	2015	Sweden	3125		1109	1092	924
Berardi et al[47]	2018	Belgium	62	24	11	4	47
Cremolini et al[16]	2018	Italy	159	42.1	40	64	52
McCracken et al[48]	2019	United States	612		388	226		55	62
McVey et al[49]	2019	United States	732	26.8	397	336		59	62
Imai et al[35]	2019	Japan	163	38.8	127	36
Koch et al[36]	2018	Germany	30		24	5	1
Liao et al[10]	2018	Taiwan	1442	58.	888	554		62.4	64.6
Adam et al[50]	2011	France	186	37	106	35	41
Wang et al[17]	2019	China	1508		557	593	358

De Haas et al[24]: Transverse colon grouped with left rather than right sided primaries; Yamashita et al[26]: Data for study and validation sets respectively, midgut vs hindgut not left vs right. L: Left; R: Right.

Table 2 Overall survival data

Ref.	Year	Median OS (mo)				5 Year OS (%)				OS Hazard ratio
		L	R	Rectum	P value	L	R	Rectum	P value	L	R	Rectum	P value
Zhou et al[27]	2017	35	33	32		27.5	23.1	23		0.85	1	1.02
Zhang et al[30]	2017	22	12		0.012a
		14	10
Makowiec et al[37]	2018					41	46
Chafai et al[29]	2005					22.5	9.9		< 0.001a	1	1.68		< 0.001a
Rougier et al[15]	1995	8.2	4.5	7.6	< 0.001a
		6.8	3.8	6.6	< 0.001a
Wang et al[38]	2018					38.3	46.5			1	1.08
Gu et al[28]	2018	40.3	29.4		0.042a					1	6.2		< 0.001a
Gasser et al[12]	2019	55.5	33.5	58.2						1	1.53		0.029a
de Haas et al[24]	2010					54	36	48	0.001a	1	1.5
Marques et al[11]	2018									1	2.1
Russolillo et al[21]	2019	63.3	35.7		0.002a					0.82	1		< 0.001a
Umeda et al[34]	2013									1.24	1	1.62
Zheng et al[31]	2018	29.5	21.9		< 0.001a					0.5	1		< 0.001a
Mavros et al[39]	2013									1	1.09
Viganò et al[20]	2014	41.3	58.3	47.4		43.1	44.7	41.3
Connor et al[40]	2016									1	2.4		0.0321a
Eefsen et al[41]	2015									0.63	1	0.57	0.045a
Schirripa et al[33]	2015	57.3	35.5	61.1	0.017a					1	1.59	0.95	0.017a
Loosen et al[42]	2018									1	2.32
Amikura et al[32]	2018					56.1	48.4			1	1.287
Yamashita et al[26]	2018					52	32		< 0.0001a	1	2.04		< 0.0001a
						78	55		0.003a	1	1.9		0.0009a
Dulundu et al[19]	2017	30.43	46.38	40.86		52.5	54.1	59
Creasy et al[9]	2016	62.4	43.2			50.4	38.5		0.028a	1	1.22		0.028a
Sasaki et al[23]	2016	55.3	44.1		0.033a	53.7	41.5			0.76	1		0.033a
Palkovics et al[43]	2018	39	36	40
Dupré et al[8]	2018	45.3	34.6		0.035a	37.5	25.4		0.010a	1	1.429		0.036a
Shigematsu et al[44]	2018									0.67	1	0.63
Rhu et al[45]	2017									0.862	1
Wang et al[46]	2017									0.75	1
Norén et al[18]	2015	61	57	48	0.02a	45.8	44.5	42.6	0.02a	0.75	1	0.73	< 0.001a
Cremolini et al[16]	2018									0.96	1
McCracken et al[48]	2019	75.6	54		< 0.001a					1	1.6		0.001a
McVey et al[49]	2019	43	44.2							1.108	1
		79.4	64.6		0.037a					0.629	0.788		0.024a
Imai et al[35]	2019					55.5	52.3			1	3.44		0.021a
Koch et al[36]	2018									0.66	1
Liao et al[10]	2018					75.2	61.7		0.005a
Adam et al[50]	2011					31	0	36	0.003a	1	2.2		0.003a
Wang et al[17]	2019					40.1	24.6		< 0.001a	1	1.75		< 0.001a

Zhang et al[30]: Top group: Overall population, bottom row: Patients who did not receive chemotherapy; Rougier et al[15]: Resection subgroup data presented in row above non-resection subgroup data; Yamashita et al[26]: Data for study set displayed above data for validation set; McVey et al[49]: R1 Resection data displayed over R0 Resection data. OS: Overall Survival.

^aP < 0.05. L: Left; R: Right.

Table 3 Disease free survival data

Ref.	Year	Median DFS (mo)				3 yr DFS (%)				DFS HR
		L	R	Rectum	P value	L	R	Rectum	P value	L	R	Rectum	P value
Wang et al[38]	2018					22.4	29.1
Gasser et al[12]	2019	12.6	9.1	9.6
Marques et al[11]	2018									1	1.1
Russolillo et al[21]	2019	32.7	20.8		0.002a
Connor et al[40]										1	1.6
Eefsen et al[41]										0.60	1	0.92
Schirripa et al[33]	2015					12.0	10.7	12.6		1	1.23	1.04
Amikura et al[32]	2018					35.4	32.3			1.09	1
Yamashita et al[26]	2018					27	15		0.001a	1	1.71		< 0.0001a
						41	21		0.001a	1	1.48		< 0.0001a
Creasy et al[9]	2016					37	29				1.14
Sasaki et al[23]	2016					20.2	28		0.001a
Heise et al[22]	2017									0.19	1		0.001a
Shigematsu et al[44]	2018									0.85	1	0.97
Wang et al[46]	2017									1.36	1
Berardi et al[47]	2018									1.06	1	1.63
Cremolini et al[16]	2018									0.81	1
Imai et al[35]	2019	22.9	21.3
Liao et al[10]	2018					70.9	66.5		0.033a

Yamashita et al[26]: Data for study set above data for validation set, midgut vs hindgut, not left vs right; Imai et al[35]: 5 Year DFS% not 3-year disease free survival.

^aP < 0.05. DFS: Disease free survival; L: Left; R: Right; HR: Hazard ratio.

Table 4 Progression free survival data

Ref.	Year	Median PFS (mo)				5 yr PFS (%)				PFS HR
		L	R	Rectum	P value	L	R	Rectum	P value	L	R	Rectum	P value
Zhou et al[27]	2017					12.5	7.1	11.5	0.012a	0.67	1	0.85	0.012a
de Haas et al[24]	2010					18	16	7	0.009a
Zheng et al[31]	2018	9.2	7.3		0.002a					0.75	1		0.002a
Lionti et al[25]	2018									0.5	1	1
Liao et al[10]	2018					70.9	66.5		0.033a

^aP < 0.05. PFS: Progression free survival; L: Left; R: Right; HR: Hazard ratio.