Clinical implications and mechanism of histopathological growth pattern in colorectal cancer liver metastases

Table 1 Studies on stratification value of histopathological growth pattern in colorectal cancer liver metastasis

Year	Factors	Prediction	Distribution of HGPs	Ref.
Survival stratification
2018-2019	dHGP and rHGP (based on radiomics)	dHGP vs rHGP and mixed HGP: longer PFS (no detail)	119 patients: dHGP (206 lesions), rHGP (140 lesions)	Wei et al[43]
2004-2019	Pushing GP and infiltrative GP	Infiltrative GP vs pushing GP: Worse OS (50.2 mo vs 92 mo) and DFS (10.5 mo vs 21.5 mo), higher intrahepatic recurrence (75% vs 20%)	266 patients: Infiltrative (n = 182, 68.4%) and pushing (n = 84, 31.6%)	Jayme et al[16]
2005-2017	dHGP and non-dHGP group; metabolic-clinical risk score	dHGP vs non-dHGP: Longer 5 yr OS (83.3% vs 34.3%) and 10 yr OS (62.5% vs 22.8%) and DFS (14.4 mo vs 8.3 mo)	108 patients: dHGP (26, 20%), non-dHGP (38, 35%)	Bohlok et al[23]
2000-2015	dHGP and non-dHGP; positive resection margins (R1) and negative resection margins(R0)	Non-dHGP vs dHGP: worse OS (50 mo vs 80 mo), higher risk of positive resection margins (76.6% vs 23.4%)	1302 patients: dHGP (305, 23%) and non-dHGP (997, 77%); R1 (170, 13%) and R0 (1132, 87%)	Nierop et al[9]
2004-2017	dHGP and non-dHGP, clinical risk score, the immunoscore	dHGP vs non-dHGP: Higher immunoscore (51.9% vs 33%), longer relapse free survival (32 mo vs 12 mo) and OS (not reached vs 40 mo)	166 patients: dHGP (54, 32.5%), non-dHGP (112, 67.5%)	Liang et al[4]
2012-2017	Expanding GP, infiltrating GP; low tumor budding score, and Crohn's disease-like response	Expanding GP in primary CRC: dHGP liver metastasis and better OS (no detail); infiltrating GP in primary carcinoma: rHGP liver metastasis and worse OS (no detail)	29 patients; primary CRC: expanding GP (11, 37.9%) and infiltrating GP (18, 62.1%); liver metastasis: dHGP (15, 51.7%) and rHGP (14, 48.2%)	Wu et al[19]
2000-2015	dHGP and non-dHGP	dHGP vs non-dHGP: More liver-limited disease recurrence (43% vs 31%); less frequently experience multi-organ recurrence (19% vs 34%)	690 patients: dHGP (173, 25%) and non-dHGP (517, 75%)	Nierop et al[17]
2000-2009	Infiltrative and pushing tumor margin	Infiltrative margin vs pushing margin: poorer 5 yr DFS (20.2% vs 40.5%)	91 patients: infiltrative margin (54, 59.3%) and pushing margin (37, 40.7%)	Pinheiro et al[12]
2007-2011	dHGP, rHGP, pHGP, mixed HGP	rHGP vs dHGP, pHGP and mixed HGP: Poorer OS (22.8 mo vs > 60 mo, 44.2 mo and 40.3 mo)	217 patients: pHGP(33%), dHGP(32%), rHGP(11%) and mixed HGP(24%)	Nielsen et al[8]
1997-2005	dHGP, rHGP, pHGP, mixed HGP	pHGP vs dHGP, rHGP and mixed HGP: Poorer 2 yr OS (43.8% vs 72.5%, 70.2%, and 54.3%)	205 patients: pHGP (15.6%), dHGP (34.6%), rHGP (27.8%) and mixed HGP (17.6 %)	Van den Eynden et al[13]
Therapy response stratification
2000-2016	dHGP and non-dHGP	Non-dHGP: Superior response to adjuvant systemic chemotherapy on improving OS and DFS but only in patients that were not treated with chemotherapy	1236 patients; 580 not pretreated patients (46.9%): dHGP (91, 15.6%) and non-dHGP (489, 84.4%); 656 pretreated patients (53.1%), dHGP (189, 28.8%) and non-dHGP (467, 71.2%).	Buisman et al[27]
2000-2015	dHGP and non-dHGP	dHGP vs non-dHGP: Better 5-year PFS (50% vs 19%) and 5 yr OS (70% vs 37%) but only in chemo-naive patients with resecting CRCLM	732 patients; in the chemo-naive patient cohort (n = 367), dHGP (68, 19%) and non-dHGP (299, 81%); in the neoadjuvantly treated patient cohort (n = 365), dHGP (109, 30%) and non-dHGP (256, 70%)	Galjart et al[6]
2010-2013	dHGP, rHGP, pHGP, mixed HGP	pHGP: Worse OS and DFS; significantly associated with Oxaliplatin-based chemotherapy	110 patients: pHGP (33, 30%), dHGP (23, 21%), rHGP (19, 18%) and mixed HGP (34, 31%)	Falcao et al[11]

HGP: Histopathological growth pattern; GP: Growth pattern; dHGP: Desmoplastic histopathological growth pattern; rHGP: Replacement histopathological growth pattern; pHGP: Pushing histopathological growth pattern; OS: Overall survival; DFS: Disease-free survival; PFS: Progression-free survival.