Secondary hepatic resection as a therapeutic goal in advanced colorectal cancer

Table 1 Outcomes related to secondary hepatic resection in patients treated with oxaliplatin-based chemotherapy

Study	n	Regimen	Response rate (%)	Resection rate (%)	R0 rate (%)	MS (mo)
Unselected populations
GERCOR[14]	111	FOLFOX6	54.0	22.0	13.0	NYR
Tournigand et al[24]	311	FOLFOX4	58.5	17.7	11.3	38.9
Tournigand et al[24]	309	FOLFOX71	59.2	15.2	9.4	43.0
Colucci et al[23]	182	FOLFOX4	34.0	4.4	NR	NR
Liver metastases only
Alberts et al[25]	44	FOLFOX4	60.0	40.0	33.3	NR

¹FOLFOX7 × 6 cycles, followed by treatment without oxaliplatin × 12 cycles, followed by FOLFOX7 until PD. MS: Median survival in resected patients; FOLFOX: Oxaliplatin plus infusional 5-fluorouracil/leucovorin (5-FU/LV); NYR: Not yet reached; NR: Not reported.

Table 2 Outcomes related to secondary hepatic resection in patients treated with irinotecan-based chemotherapy

Study	n	Regimen	Response rate (%)	Resection rate (%)	R0 rate (%)	MS (mo)
Unselected populations
Tournigand et al[14]	109	FOLFIRI	61.0	9.0	7.0	47
Colucci et al[23]	178	FOLFIRI	36.0	5.1	NR	NR
Liver metastases only
Pozzo et al[26]	40	5-FU/LV, irinotecan	47.5	40.0	32.5	NYR
Zelek et al[27]	31	5-FU/LV, irinotecan, and HAI of pirarubicin	48.0	35.0	29.0	NYR
Ho et al[28]	40	5-FU/LV, irinotecan	55.0	10.0	NR	NR

HAI: Hepatic arterial infusion.

Table 3 Randomized trials comparing first-line chemotherapy with or without cetuximab or bevacizumab that report secondary resection rates

Study	n	Regimen	Response rate (%)	Resection rate (%)	R0 rate (%)	R0 rate in liver-only disease (%)	PFS (mo)
Cetuximab
CRYSTAL[37]	559	FOLFIRI	38.7	2.5	1.5	4.5	8.0
	559	FOLFIRI + cetuximab	46.9	6.0	4.3	9.8	8.9
Bevacizumab
Hurwitz et al[38]	411	IFL	34.8	< 2%	NR	NR	6.2
	402	IFL + bevacizumab	44.8	< 2%	NR	NR	10.6
NO16966[3940]	701	CT1	49.0	4.9	NR	11.5	8.0
	699	CT1 + bevacizumab	47.0	6.3	NR	12.3	9.4

¹FOLFOX4 or XELOX. PFS: Progression-free survival in the study arm; FOLFIRI: Irinotecan plus infusional 5-fluorouracil/leucovorin (5-FU/LV); IFL: Irinotecan, fluorouracil, and leucovorin; CT: Chemotherapy.

Table 4 Liver injury by chemotherapy regimen[12]

Regimen	Sinusoidal dilation1 (n = 22)			Steatosis > 30% (n = 36)			Steatohepatitis2 (n = 34)
	Yes (%)	No (%)	P value3	Yes (%)	No (%)	P value3	Yes (%)	No (%)	P value3
No CT	2	98		9	91		4	96
FU	0	100	NS	17	83	NS	5	95	NS
IRI	4	96	NS	11	89	NS	20	80	0.001
OX	19	81	0.00001	4	96	NS	6	94	NS
Other	0	100	NS	8	92	NS	0	100	NS

¹Rubbia: Brandt grade 2 or 3;

²Kleiner score ≥ 4;

³Presence of liver injury characteristic; comparison of each chemotherapy group vs no chemotherapy. FU: Fluorouracil; IRI: Irinotecan; OX: Oxaliplatin; NS: Not significant.

Table 5 Secondary resection in patients with initially unresectable liver metastases

Improve patient selection through early and continued consultation in a multidisciplinary team approach, including close cooperation among a radiologist, medical oncologist, and surgeon with experience in liver resection

Conduct surgical evaluation at baseline and, if disease is initially unresectable, reevaluation at intervals during therapy to determine if conversion to resectability has been achieved

Set appropriate goals of therapy (best response, conversion to resectable disease, or palliation)

Determine length of therapy, with consideration for the risk of potential toxicities

Consider the safety profile of individual agents and the risks of overtreatment, including hepatotoxicity

If the treatment goal is conversion to resection, treat to resectability and not to best response