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Table 1 Overview of the studies that have addressed risk factors of the metachronous liver metastasis of CRC

From: Which patients are prone to suffer liver metastasis? A review of risk factors of metachronous liver metastasis of colorectal cancer

Tool citations

Sample size

Population/sample

Dates of data collection

Duration of follow-up

Final variables in model

Cheng et al. [126]

1969

CRC treated with surgery

2000–2013

8–163.4 months (median 36.3 months)

Patients with the BRAFV600E mutation are prone to non-regional lymph node metastasis and peritoneal metastasis, not liver metastasis

Feng et al. [121]

281

Primary tumor resections (R0)

2002–2008

In metachronous metastasis group, the median follow-up time was 87 months

Sex, primary tumor location, primary N stage and KRAS codon 13 mutations were independent factors for metachronous distant metastasis

Cho et al. [117]

147

Confirmed CRC by pathology and imaging studies confirmed metastatic disease

2007–2014

Unknown

KRAS and BRAF mutation have no correlation with liver metastasis of colorectal cancer and non-CEA producers are associated with RAS mutations

Margonis et al. [123]

849

Patients underwent resections with curative intent

2000–2016

28.3 months (median follow-up)

Mutbraf/wtkras genotype were also significantly more likely to be right-sided, more advanced T stage and metachronous liver metastasis

Colloca et al. [48]

425

Patients who diagnosed with relapsed or metastatic CRC

2006–2011

Unknown

1. Patients with synchronous metastasis: older, more frequent liver involvement, more right-sided primary tumors. 2. High CEA levels were related with synchronous liver metastasis

Tsai et al. [19]

155

Only CRC patients whose metastasis were resectable on presentation were included

1995–2004

Mean 28.5 ± 2.0 months

1. The metachronous group: the mean age was higher. 2. No significant difference between the synchronous and metachronous groups in terms of tumor location, tumor size, tumor staging, tumor grading and metastasis to regional lymph nodes

Mekenkamp et al. [14]

550

Only patients with a prior resection of the primary tumor were considered

2003–2005

Follow-up after completion of treatment was performed every 3 months until death. The primary endpoint was overall survival

Tumors of patients with synchronous metastasis had larger diameters, a higher T and N stage, absent or little lymphoid reaction and more frequently a diffuse infiltration pattern than patients with metachronous disease

Khan et al. [39]

434

Patients with histologically proven rectal carcinoma

2005–2015

5 years

The risk factors of metachronous group: tumor depth (T stage), lymph node metastasis, post-op serum CEA levels and complete tumor response on histopathology

Chuang et al. [20]

1099

Patients with histologically proven CRC receiving surgical treatment

2001–2007

Mean follow-up time of 39.0 ± 24.2 months

 > 65 years, reoperative serum CEA level > 5/ml, tumor depth of T3–4 invasion, positive LN metastasis, positive vascular invasion, and positive perineural invasion are related to metachronous liver metastasis

Zheng et al. [22]

161

Colorectal adenocarcinoma determined by pathologic evidence

2008–2014

Unknown

1. Metachronous group: elder

2. Synchronous group: larger in size, poorly differentiated, more frequently local advanced and lymph node positive, result in more and larger metastatic lesions

Laubert et al. [52]

920/120

Patients who underwent surgery for colorectal cancer

1993–2008

5 years

Factors related to metachronous group: aneuploidy and elevated CEA

Amara et al. [76]

124 /35

CRC

1995–2011

The duration of follow-up was calculated from the date of surgery to death

SDF-1/CXCR4 may enhance the liver metastasis causing poor prognosis

Schøler et al. [34]

23

Liver metastasis patients treated with curative intent

2015–2016

3 years

CtDNA detected within 3 months post-surgery is associated with a very high relapse risk of liver metastasis

Huang et al. [110]

205

Histologically proven synchronous or metachronous mCRC who received surgical treatment

2002–2012

The median follow-up time for the 205 patients was 30.2 ± 20.9 months

1. Positive EGFR expression has prognostic value only for patients with metachronous liver metastasis

2. KRAS mutation did not have prognostic value in patients with metachronous or synchronous CRC

Pantal et al. [109]

18

Fresh tissue specimens from liver metastasis of 18 patients who had undergone liver surgery

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1. EGFR was overexpressed in metachronous group

2. COX-2 gene was over expressed in synchronous group

Pan et al. [140]

20

Blood samples

/

/

1. HER2 is an independent predictive factor for synchronous liver metastasis

2. HER2 may also be a risk factor for metachronous liver metastasis

Styczen et al. [141]

208

Cancer samples and tissue samples

/

/

HER2 and HER3 expression status in primary tumors, is closely associated with metachronous liver metastasis

  1. CRC colorectal cancer; CEA carcinoembryonic antigen; COX-2 cyclooxygenase-2; mir-200c micrornas-200c; ctDNA circulating tumor DNA; EGFR epidermal growth factor receptor; BRAF B-type RAF kinase