Inclusion criteria for liver transplantation in patients with colorectal liver metastases: How to make the best selection?

Table 1 Inclusion criteria reported in the studies registered in ClinicalTrials.gov focused on liver transplantation for colorectal cancer liver metastases

NCT	Location	Criteria
Demographic parameters
NCT02215889	Oslo, Norway	ECOG 0-1
NCT05186116	Modena, Italy	Age ≥ 18, ECOG 0-2
NCT05750329	RenJi Hospital, Shanghai, China	Age 18-75
NCT04870879	Padua, Italy	Age ≥ 18 and < 70, ECOG 0-1
NCT05248581	Rochester, NY, United States	Age ≥ 18
NCT03803436	Milan, Italy	ECOG 0
NCT03488953	Jena, Germany	Age ≥ 18
NCT05398380	Barcelona, Spain	Age 18-70, ECOG 0-1
NCT06069960	RenJi Hospital, Shanghai, China	Age 18-75, ECOG 0-1
NCT04742621	NY, United States	Age 18-65, ECOG 0-1
NCT05185245	Bologna, Italy	ECOG 0-1
NCT03494946	Oslo, Norway	ECOG 0-1
NCT01479608	Oslo, Norway	ECOG 0-1
NCT04616495	Valencia, Spain	Age ≥ 18, ECOG 0-1
NCT02864485	Toronto, Canada	ECOG 0-1
NCT02597348	Villejuif, France	Age ≥ 18 and ≤ 65, ECOG 0-1
NCT04865471	Padua, Italy	Age ≥ 18 and < 70, ECOG 0-1
NCT04161092	Gothenburg, Sweden	Age ≥ 18, ECOG 0-1
Biochemical markers
NCT02215889	Oslo, Norway	Hb > 10 g/dL, neutrophils > 1.0, TRC > 75, bilirubin < 2 × ULN, AST/ALT < 5 × ULN, creatinine < 1.25 × ULN, albumin > LLN
NCT04870879	Padua, Italy	Hb > 10 g/dL, neutrophils > 1.0, bilirubin < 2 × ULN, AST/ALT < 5 × ULN, creatinine and albumin normal
NCT03803436	Milan, Italy	Hb > 10 g/dL, neutrophils > 1.0, TRC > 75, bilirubin < 2 × ULN, AST/ALT < 5 × ULN, creatinine < 1.25 × ULN
NCT05398380	Barcelona, Spain	Creatinine ≤ 1.25 × ULN or eGFR ≥ 60, platelets ≥ 80 × 109/L, neutrophils ≥ 2.5 × 109/L
NCT04742621	NY, United States	Hb > 10 g/dL, ANC > 1000/μL, platelets > 100000/μL, bilirubin < 2 × ULN, AST/ALT < 5 × ULN, creatinine < 1.25 × ULN, albumin > LLN
NCT05185245	Bologna, Italy	Neutrophils > 1.0
NCT03494946	Oslo, Norway	Hb > 10 g/dL, neutrophils > 1.0, TRC > 75, bilirubin < 1.5 × ULN, AST/ALT < 5 × ULN, creatinine < 1.25 × ULN, albumin > LLN
NCT01479608	Oslo, Norway	Hb > 10 g/dL, neutrophils > 1.0, TRC > 75, bilirubin < 2 × ULN, AST/ALT < 5 × ULN, creatinine < 1.25 × ULN, albumin > LLN
NCT02597348	Villejuif, France	Platelet count > 80000/mm³, WBC > 2500/mm³, normal renal function
NCT04865471	Padua, Italy	Creatinine normal, platelets > 60000/mm³, WBC > 2500/mm³
NCT04161092	Gothenburg, Sweden	Hb ≥ 90 g/L, WBC > 3.0 ×109/L, ANC ≥ 1.5 ×109/L, PLT > 75, bilirubin < 2 × ULN, AST/ALT < 5 × ULN, creatinine clearance ≥ 50 mL/minute
CEA
NCT04870879	Padua, Italy	CEA < 100 ng/mL
NCT03803436	Milan, Italy	CEA < 50 ng/mL
NCT05398380	Barcelona, Spain	CEA ≤ 80 μg/L
NCT06069960	RenJi Hospital, Shanghai, China	CEA ≤ 80 μg/L or ≥ 50% reduction after treatment
NCT04742621	NY, United States	CEA < 200 μg/L
NCT05185245	Bologna, Italy	CEA < 80 μg/L or ≥ 50% reduction
NCT01479608	Oslo, Norway	CEA < 100 ng/mL (subset)
NCT02597348	Villejuif, France	CEA < 80 μg/L or ≥ 50% decrease
NCT04865471	Padua, Italy	CEA stable or decreasing
Tumor characteristics
NCT02215889	Oslo, Norway	Unresectable CRLM, no extrahepatic disease except 1-3 resectable lung lesions < 15 mm, no local recurrence (confirmed by MR and colonoscopy)
NCT05186116	Modena, Italy	Unresectable CRLM, pT1-3, pN0/pN1 (< 4 nodes), no mucinous > 50%, R0 resection, BRAF wild-type
NCT05750329	RenJi Hospital, Shanghai, China	Unresectable HCC or CRLM, tumor shrinkage or stable after chemo, no abdominal metastases or ≤ 3 resectable lung metastases
NCT04870879	Padua, Italy	Unresectable CRLM, no extrahepatic disease, no lesion > 10 cm before chemo, < 10% chemo response accepted if 20% response after TACE/90Y
NCT03803436	Milan, Italy	Non-mucinous colon adenocarcinoma, pT1-3 pN0/1 (< 4 nodes), R0 resection, BRAF and RAS wild-type, MSS
NCT05398380	Barcelona, Spain	Bilateral, liver-limited unresectable CRLM, R0 resection of primary, stage ≤ T3N1 (or T4 if ≥ 2 years interval)
NCT06069960	RenJi Hospital, Shanghai, China	CRLM limited to liver or bilateral, unresectable, T ≤ T3N1 or T4N0/T4N2 if ≥ 2 years
NCT04742621	NY, United States	No extrahepatic disease or local recurrence, liver metastases stable/regressed for ≥ 6 months
NCT05185245	Bologna, Italy	Unresectable CRLM, p ≤ T4a, R0 resection, no extrahepatic disease
NCT03494946	Oslo, Norway	Liver metastases not resectable, No extrahepatic disease except resectable lung lesions < 15 mm
NCT01479608	Oslo, Norway	Histologically confirmed CRC, no extrahepatic disease or recurrence, ≥ 6 liver metastases (part A), pN0 (part B), metachronous liver metastases
NCT02597348	Villejuif, France	Confirmed unresectable CRLM, BRAF wild-type, no local recurrence
NCT04865471	Padua, Italy	Unresectable CRLM, no extrahepatic disease except resectable lung/hilar metastases
NCT04161092	Gothenburg, Sweden	Unresectable CRLM, R0 resection of primary, no extrahepatic disease, measurable liver metastases
Treatment history
NCT02215889	Oslo, Norway	≥ 8 weeks of chemotherapy
NCT05186116	Modena, Italy	Objective response to 1st-line (≥ 4 months) or stable disease during 2nd-line (≥ 4 months)
NCT05750329	RenJi Hospital, Shanghai, China	6-8 weeks of 1st-line chemotherapy
NCT04870879	Padua, Italy	≥ 3 months chemotherapy, RECIST response or SD, response after TACE/90Y if poor initial response
NCT03803436	Milan, Italy	1st or 2nd-line chemo response ≥ 4 months, max 2 lines
NCT03488953	Jena, Germany	≥ 8 weeks of systemic chemotherapy, SD or regression
NCT05398380	Barcelona, Spain	≥ 3 months chemotherapy, max 2 lines, response per RECIST within 3 months before screening
NCT06069960	RenJi Hospital, Shanghai, China	6-8 weeks 1st-line chemo, stable or partial regression
NCT04742621	NY, United States	≥ 6 months chemotherapy
NCT05185245	Bologna, Italy	≥ 3 months of at least 1 line, PR or SD per mRECIST
NCT03494946	Oslo, Norway	Progressive disease or intolerance to 1st-line, randomized before evaluation 8-12 weeks after 2nd-line
NCT01479608	Oslo, Norway	≥ 3 cycles chemotherapy (6 weeks), 10% response to chemo before progression (varies by subgroup)
NCT02597348	Villejuif, France	≥ 3 months tumor control on last chemo line, ≤ 3 lines total
NCT02864485	Toronto, Canada	≥ 3 months chemo with FOLFOX/FOLFIRI +/- bevacizumab, stable or regressing LM
NCT04865471	Padua, Italy	≥ 3 months chemotherapy, ≥ 8 weeks SD or PR per RECIST 11
NCT04161092	Gothenburg, Sweden	≥ 2 months chemotherapy, no progression at last RECIST evaluation
Other criteria
NCT02215889	Oslo, Norway	Imaging within 4 weeks prior to LT meeting, colonoscopy/CT colography ≤ 12 months
NCT05186116	Modena, Italy	Confirmed R0 resection, multi-modal imaging (CT + MRI + PET)
NCT04870879	Padua, Italy	≥ 10 months from CRC resection to LT listing
NCT05398380	Barcelona, Spain	≥ 12 months from primary CRC resection to transplant, TNM staging required, no contraindications from prior hepatic resection
NCT06069960	RenJi Hospital, Shanghai, China	≥ 3 months from CRC resection to transplant, MDT confirmation, imaging via PET/CT + MRI
NCT04742621	NY, United States	≥ 1 year from CRC diagnosis and ≥ 6 months from resection to LT
NCT01479608	Oslo, Norway	Signed informed consent, standard oncologic surgery with CRM ≥ 2 mm, study includes special subgroups (A-D)
NCT02597348	Villejuif, France	R0 resection, no extrahepatic localization (CT/PET), normal renal function, nephrologist evaluation
NCT02864485	Toronto, Canada	Living donor identified, ABO compatible, no major vascular invasion
NCT04865471	Padua, Italy	≥ 6 months from CRC resection to LT list, validation committee approval
NCT04161092	Gothenburg, Sweden	≥ 1 year from CRC diagnosis to inclusion, imaging within 4 weeks, colonoscopy < 12 months

ECOG: Eastern Cooperative Oncology Group; Hb: Hemoglobin; TRC: Tanned red cell; ULN: Upper limit of normal; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LLN: Lower limit of normal; ANC: Absolute neutrophil count; WBC: White blood cell; CEA: Carcinoembryonic antigen; CRLM: Colorectal cancer liver metastases; MR: Magnetic resonance; HCC: Hepatocellular carcinoma; TACE: Transcatheter arterial chemoembolization; MSS: Micro satellite stability; CRC: Colorectal cancer; PR: Partial response; SD: Stable disease; LT: Liver transplantation; CT: Computed tomography; MRI: Magnetic resonance imaging; PET: positron emission tomography; TNM: Tumor node metastasis; MDT: Multi-disciplinary treatment; CRM: Circumferential resection margin; eGFR: Estimated glomerular filtration rate.