Advances in liver transplantation for unresectable colon cancer liver metastasis

Table 1 Published data on liver transplantation for colorectal cancer liver metastasis

Ref.	Year	Center	Period	Patients number	Survival time
Moore et al[12]	1964	Peter Bent Brigham Hospital, United States	September, 1963	1	11 d
Demirleau et al[58]	1964	Hospital St. Antonie, France	January, 1964	1	0 d (died of bleeding)
Andersen et al[59]	2012	Oslo University Hospital, Norway	1970	1	24 d (died of fuminating sepsis)
Penn[13]	1991	Cincinnati Medical Center, United States	September 1968-March 1991	8	Mortality 11% recurrence rate 70%
Pichlmayr et al[60]	1997	Hannover Medical School, German	1972-1995	4	11 mo, 8 d, 33 mo
Honoré et al[61]	2003	University of Liege, Belgium	1992	1	10 yr
Kappel et al[9]	2006	Medical University of Vienna, Austria	1983-1994	24	5-yr OS rate 12%-18%
Hoti et al[14]	2008	European Liver Transplant Registy	1968-1995	50 (including 24 above)	1- and 5-yr OS rate were 62% and 18%
Uskudar et al[62]	2011	The Mount Sinai Hospital, United States	2005, 2008	2	5 yr (no recurrence); 2 yr (no recurrence)
Kocman et al[63]	2011	University Hospital Mekur (Croatia)	2006	1	5 yr (no recurrence)
Hrehoreţ et al[64]	2013	University of Medicine and Phamarcy Caro Davila, Romania	January, 2012	1	20 mo post-operation (lung recurrence)
Line et al[46]	2015	Oslo University Hospital, Norway	2014-2017	3	40 d (died of complications); 5.5 yr (no recurrence); 2 yr (recurrent at 12 mo)
Caicedo et al[65]	2016	ICESI University, Colombia	November, 2014	1	19 mo (no recurrence)
Toso et al[66]	2017	Portugal, Paris, Geneva	1995-2015	12	5-yr OS 50% ± 16%, 5-yr PFS 38% ± 15%
Dueland et al[10]	2020	Olso University Hospital, Norway	2006-2012	23	5-yr OS 60%
Yang et al[67]	2019	Zhongnan Hospital of Wuhan University, China	2016	1	34 mo (recurrent at 4 mo)
Lerut et al[68]	2019	University Hospital Saint-Luc, Belgium	1985-2016	4	17 mo (recurrent at 6 mo), 64 mo (recurrent at 47 mo), 32 mo (no), 28 mo (recurrent at 4 mo)
Fernandes et al[69]	2019	Rio de Janeiro Federal University, Brazil	December, 2018	1	No prognosis information
Dueland et al[10]	2019	Oslo University Hospital, Norway	2012-2016	15	5-yr OS 83%
Smedman et al[25]	2019	Oslo University Hospital, Norway	2014-2018	10	Median OS 18 mo. Median DFS 4 mo
Coubeau et al[52]	2020	Cliniques Unviersitaires Saint-Luc	2019	1	180 d (no recurrence)

OS: Overall survival; DFS: Disease-free survival; PFS: Progression-free survival.

Table 2 Inclusion criteria in some prospective studies on liver transplantation for colorectal cancer liver metastasis

Study	SECA I	SECA II	LIVERTWOHEAL	TRANSMET	Toronto NCT02864485
Inclusion criteria	Primary tumor R0 resected; ECOG 0-1; More than 6 wk chemotherapy; No extrahepatic metastasis or recurrence confirmed by PET/CT, bone scan	Addition standard: No signs of extra hepatic metastatic disease (except resectable lung metastasis) or local recurrence according to coloscopy, CT or MRI within 12 mo; Chemotherapy response > 10%, If not, TACE or Y-90 response > 20%; More than 12 mo from diagnosis or adjuvant therapy	Unresectable CRLM without extrahepatic tumor burden, except resectable pulmonary metastases; Disease regresses or keeps stable after more than 8 wk chemotherapy	ECOG 0-1; BRAF wild type; Primary tumor R0 resected; No primary recurrence within 12 mo confirmed by coloscopy. Disease stable or regress more than 3 mo with chemotherapy; CEA < 80 ng/mL or decrease ≥ 50%; No extrahepatic metastasis confirmed by CT or PET-CT	ECOG 0-1; Primary tumor stage is ≤ T4a; More than 6 mo since liver resection; No major vascular invasion; More than 3 mo chemotherapy; Disease regression or stable more than 3 mo; Stable CEA value or decease at all time prior to LT
Outcome	OS	OS 10 yr	OS 3 yr	OS 5 yr	OS 5 yr; PFS 5 yr

TACE: Transcatheter arterial chemoembolization; Y-90: Yttrium; PET/CT: Positron emission tomography/computed tomography; MRI: Magnetic resonance imaging.

Table 3 Treatment for unresectable colorectal cancer liver metastasis prior to transplantation

Ref.	Year	Treatment prior to liver transplantation
		Liver resection	Local therapy	Systemic therapy
Moore et al[12]	1964	NR	NR	NR
Demirleau et al[58]	1964	NR	NR	NR
Andersen et al[59]	2012	NR	NR	NR
Penn[13]	1991	NR	NR	NR
Pichlmayr et al[60]	1997	NR	NR	NR
Honoré et al[61]	2003	Yes	No	No
Kappel et al[9]; Hoti et al[14]	2006; 2008	NR	NR	NR
Uskudar et al[62]	2011	Yes	Yes, TACE, HAI. Yes, HAI (causing liver failure)	Yes
Kocman et al[63]	2011	Yes (Two times)	No	Yes, 1/1
Hrehoreţ et al[64]	20I3	Yes (ALPPS one stage)	Yes, radio therapy	Yes, FOLFOX AND bevacizumab
Line et al[46]	2015	No; NR	No; NR	Yes, 3/3, FLIRI/cetuximab
Caicedo et al[65]	2016	No	Yes, 1/1 RFA	Yes, 1/1, FOFIRI + cetuximab
Toso et al[66]	2017	Yes, 10/12	1/12 RFA	11/12, irinotecan, oxaliplatin, cetuximab, bevacizumab
Dueland et al[10]	2020	Yes, 4/23	2/23	Yes, 23 (1st line, 10 patients; 2nd line, 9 patients; 3rd line, 4 patients)
Yang et al[67]	2019	No	Yes, 1/1; TACE + RFA	Yes, 1/1, mFOLFOX6 + bevacizumab
Lerut et al[68]	2019	No	No	Yes, 4/4, 5-FU, Oxaliplatin irinotecan, bevacizumab,
Fernandes et al[69]	2019	Yes	Yes	FOLFOX/FOLFIRI
Dueland et al[10]	2020	4/15	NR	Yes, 15/15
Smedman et al[25]	2019	2/10	2/10 RFA	Yes, 10 patients (1st line), 10 (2nd line), 3 (3rd line)
Coubeau et al[52]	2020	NAR	NAR	Yes, 1/1

NR: Not report; RFA: Radiofrequency ablation; mFOLFOX-6: Modified 5-fluorouracil/folinic acid and oxaliplatin; FOLFIRI: Fluorouracil, folinic acid, and irinotecan.

Table 4 Adjuvant therapy for recurrence after liver transplantation for unresectable colorectal cancer liver metastasis

Ref.	Overall survival (months)	Die/alive	Recurrence	Adjuvant therapy post recurrence after LT
Yang et al[67]	34	0/1	Yes	Chemotherapy
Lerut et al[68]	28	3/1	Yes, 4, 6, 47 mo	Chemotherapy
Toso et al[66]		6/6	Median DFS 6 mo	5 chemotherapy; 1 radiotherapy
Hagness[39]	27	6/15	Median DFS 19 mo	11 Chemotherapy; 1 TACE; 7 Radiation therapy; 11 Re-resection
Smedman et al[25]	18	5/5	Median DFS 8 mo	3 Chemotherapy combined radiation therapy; 2 Chemotherapy; 1 Radiation; 1 Surgery
Dueland et al[10]	36	2/13	Median DFS 8 mo	6 Surgery; 2 Surgery combined Radiation therapy; 2 Chemotherapy
Hrehoreţ et al[64]	20	0/1	Yes, 6 wk	Chemotherapy

LT: Liver transplantation.

Table 5 Ongoing clinical trials on liver transplantation for colorectal cancer liver metastasis

NCT number	Study name	Year	Type	Patients	Unit, country	Study aims
03494946	SECA III	2016-2027	RCT	25	Oslo University hospital, Norway	LT vs chemotherapy
02215889	No	2014-2028	Intervention	20	Oslo University hospital, Norway	Single arm (segment 2, 3 partial LT)
03488953	LIVERTWOHEAL	2018-2023	Intervention	40	Jena University Hospital, German	Single arm (Living donor liver transplantation with two-staged hepatectomy)
02597348	TRASMET	2015-2027	RCT	90	Hôpitaux de Paris, France	LT plus chemotherapy vs chemotherapy
03231722	COLT	2019-2024	Multi-center non-RCT		Fondazione IRCCS Istituto Nazionale dei Tumori, Italy	LT vs chemotherapy (parallel arm in TRIPLETE trial)
04161092	SOULMATE	2020-2030	Multi-center RCT	45	Vastra Gotaland Region, Sweden	LT (extended criteria graft) vs best alternative therapy

RCT: Randomized clinical trial; LT: Liver transplantation.