Systematic Reviews
Copyright ©The Author(s) 2022.
World J Clin Oncol. Oct 24, 2022; 13(10): 822-834
Published online Oct 24, 2022. doi: 10.5306/wjco.v13.i10.822
Table 1 Patient demographics, neutrophil to lymphocyte ratio cut-off value, follow-up time and time of sample acquisition for patients after hepatectomy
Ref.
Number of patients
Sex
Mean age (years)
NLR threshold
Follow up (mo), mean (range)
Sample acquisition
Erstad et al[13]15184 M, 67 F58541.3 ± 36.7 (2-186)Within 6 mo prior to surgery and prior to chemotherapy
Halazun et al[14]440289 M, 151 F64 (32-88)524 (11-97)1 d prior to surgery
Kishi et al[15]290Resection group 132 M, 68 F; non resection group 61 M, 29 FResection, 57; non resection, 56528 (2-102)Resection group: Before chemotherapy and before resection
Neal et al[16]302192 M, 110 F64.8 (26-85)529.5 (4-96)Prior to surgery
Hand et al[17]322205 M, 117 F252 p < 70 yr; 70 p > 70 yr541On admission; the night prior to or on the morning of surgery
Peng et al[18]15097 M, 53 F58 (20-82)4.6336 (2-126)Within 7 d prior to surgery
Kim et al[19]8362 M, 21 F59.51.94NSWithin 1 wk prior to surgery
Mao et al[20]183123 M, 60 F67 p > 60 yr2.336.3Within 10 d before chemotherapy and surgery
Neofytou et al[21]14088 M, 52 F78% < 70 yr2.433 (1-103)Within 10 d prior to surgery
Giakoustidis et al[22]169104 Μ, 65 F135 p < 70 yr, 34 p > 40 yr2.534.610 d prior to surgery - after preoperative chemotherapy
Dupré et al[23]343236 M, 107 F65.8 ± 10.9 2.5, 2.6 and 7.26149Within 1 wk prior to surgery
Hamada et al[24]2920 M, 9 F63 ± 11.6 (41-83)4.151 (2-97)NS
Zeman et al[25]13070 M, 60 F60 (33-82)539.3NS
Table 2 Survival and disease characteristics
Ref.
Median Survival
5-year OS
5-year DFS
Extrahepatic Disease
Primary Tumor
Chemotherapy
Erstad et al[13]3.1 yr, NLR > 5; 6.3 yr NLR < 528.7%, NLR > 5; 59.6%, NLR < 5NSΝοPrevious resection of rectum or colonNeoadjuvant
Halazun et al[14]NS22%, NLR > 5; 43%, NLR < 512%, NLR > 5; 42%, NLR < 5No disseminated or unresectable EHDPreviously resectedNeoadjuvant
Kishi et al[15]34 mo, NLR > 5; 45 mo, NLR < 526%, NLR > 5; 36%, NLR < 5NSNoPreviously resectedNeoadjuvant, n = 200; Without resection, n = 90
Neal et al[16]27.8 mo, NLR > 5; 39.8 mo, NLR < 518.5% NLR > 5; 30.6% NLR < 5 22.3%, NLR > 5; 35.2%, NLR < 52NSRectum n = 149, Colon n = 153Adjuvant, n = 126
Hand et al[17]59 moChemotherapy group, 50.8%; No chemotherapy group, 42.5%NSNSNoNeoadjuvant, n = 202
Peng et al[18]NS18.8%, NLR > 4.63; 46.7%, NLR < 4.63NSNo58% colon, 42% rectumNeoadjuvant, n = 59
Kim et al[19]NSNSNSNoNSNeoadjuvant, n = 24
Mao et al[20]31.1 mo NLR > 2.3 43.1 mo NLR < 2.3NSNSNoColon n = 104 Neoadjuvant, n = 183
Neofytou et al[21]55 mo, NLR > 2.4; Not reached, NLR < 2.442%, NLR > 2.4; 69%, NLR < 2.4Total 27%. 14%, NLR > 2.4; 40%, NLR < 2.4ΝοResection prior to hepatectomy in 81%Neoadjuvant
Giakoustidis et al[22]75 mo51%, NLR > 2.5; 74% NLR < 2.5NSNoSynchronous resection, n = 26; ‘liver first’, n = 7Neoadjuvant, n = 169
Dupré et al[23]50.3, NLR < 2.5; 38.4, NLR > 2.5; 44.8, NLR < 7.26; 25.4, NLR > 7.26NS 11.6, NLR < 2.5; 9.7, NLR > 2.5; 10.3, NLR < 7.26; 6.3, NLR > 7.261Resectable EHD in 36 patientsSynchronous, n = 169; Right colon, n = 73; Left colon, n = 126; Rectum, n = 142; Multiple, n = 2Neoadjuvant, n = 198
Hamada et al[24]NSNSNSYes, n = 5NSAdjuvant, n = 15
Zeman et al[25]Resection group, 56 mo46.6%, resection group; 9.5%, RFA group30.5%, resection group, 21 mo medianNoRectum n = 60, colon n = 70Adjuvant, n = 25
Table 3 Univariate and multivariate analysis results after hepatectomy
Ref.
Univariate analysis
Multivariate analysis
Erstad et al[13]NLR > 5 was significantly associated with reduced OS (P = 0.001)NLR > 5 associated with reduced OS (P = 0.032)
Halazun et al[14]NLR > 5 was associated with reduced OS (P < 0.0001); NLR > 5 was the sole positive predictor of recurrence (P < 0.0001)NLR > 5 was associated with reduced OS (P < 0.0001)
Kishi et al[15]NLR > 5 predicted worse survival (P = 0.011)NLR > 5 predicted worse survival using variables available before surgery (P = 0.016) and after surgery (P = 0.048)
Neal et al[16]NLR > 5 was significantly associated with worse OS (P = 0.001) and CSS (P < 0.001) following metastasectomyNLR > 3 was associated with shorter survival (P < 0.001); NLR > 3 was associated with adverse outcomes regarding CSS (P < 0.001)
Hand et al[17]Following index hepatectomy, patients with NLR > 5 had a median survival of 55 mo vs 70 mo when NLR < 5 (P = 0.027); Following neoadjuvant chemotherapy, no association between NLR and survival was demonstrated (P = 0.93); NLR > 5 had no impact on prognosis following repeat hepatectomyThere is an independent association between elevated preoperative neutrophil count and shortened overall survival (P = 0.001); no such association was found for NLR
Peng et al[18]Patients with NLR > 4.63 were more likely to present multiple hepatic metastases than those with low NLR (68.8% vs 40.3%, P = 0.030); 5-year RFS and OS for high NLR were significantly inferior to those for low NLR (RFS: 12.5% vs 38.5%, P = 0.015; OS: 18.8% vs 46.7%, P = 0.004)NLR was not identified as an independent inflammatory factor for better RFS
Kim et al[19]NLR > 1.94 was a prognostic factor for poor OS (P = 0.035) and DFS; High NLR was associated with recurrence (P = 0.031)NLR > 1.94 was an independent prognostic factor for OS (P = 0.01) and prognostic factor for poor DFS; High NLR was associated with recurrence (P = 0.006)
Mao et al[20]Pre- and post-chemotherapy NLR > 2.3 was associated with decreased OS (P = 0.012)NLR > 2.3 was a significant predictor both for worse OS (P < 0.001) and for RFS (P = 0.017)
Neofytou et al[21]NLR > 2.4 was associated with decreased DFS (P = 0.033) and OS (P = 0.007)No significant correlation was found between NLR and OS/DFS
Giakoustidis et al[22]NLR > 2.5 was associated with decreased OS (P = 0.009) and decreased DFS (P = 0.09)High NLR remained a significant prognostic factor for poor OS (P = 0.012)
Dupré et al[23]NLR of 2.5 was an independent prognostic factor for OS and PFSHigh NLR was significantly associated with decreased OS (P < 0.002)
Hamada et al[24]NLR > 4.1 was significantly correlated with better CSS (P = 0.026)Only univariate analysis was performed
Zeman et al[25]NLR > 5 was significantly associated with DFS (P = 0.044); OS was significantly affected by the preoperative number of leukocytes (P = 0.0014) and neutrophils (P = 0.0036) but not by the NLR.NLR > 5 was significantly associated with DFS (P = 0.03); Leukocyte number was significantly associated with OS (P = 0.0014); no effect of NLR was demonstrated on OS
Table 4 Patient demographics, NLR cut-off value, follow up and time of sample acquisition for patients treated with radio-frequency ablation, radioembolization or solely chemotherapy
Ref.
Number of patients and procedure
Sex
Mean age (yr)
NLR threshold
Follow up (mo)
Sample acquisition
Tohme et al[29]104 RE69 M, 35 F60.8 ± 12.2, NLR > 5, 66.4 ± 12.2, NLR < 55100 patients died during follow upSame day before RE
Chang et al[26]98 RFA56 M, 42 F62 (28-92)2.535.2 ± 21.891 d before RFA - 1 mo after RFA
Zhang et al[27]92 RFA51 M, 41 F59 (43-78)527.1 ± 9.8 (range 5-62)Preoperatively as part of the routine workup. 1-3 d before RFA
Weiner et al[28]131 RE84 M, 47 F595117 deaths during follow upNS
Kishi et al[15]90 chemotherapy61 M, 29 F56528 (2-102)
Wu et al[31]55 chemotherapy35 M, 20 F594Complete clinical records (no exact mention)Preoperatively and before 2nd cycle of chemotherapy
Philips et al[30]71--5--
Table 5 Survival and disease characteristics of patients that were treated with radio-frequency ablation, radioembolization or solely chemotherapy
Ref.
Median Survival
5-year OS
5-year DFS
Extrahepatic disease
Primary tumor
Chemotherapy
Tohme et al[29]5.6 m high NLR 10.6 m low NLR--40 (less than 10% of tumor burden)Some patients had undergone CRC resection (number not mentioned)All patients
Chang et al[26]--(Preoperative NLR) 11.1% high NLR 22.6% low NLR (NLR increase after RFA 8.6%) (No postoperative NLR increase 22.2%)NoAll patients had undergone CRC resectionNo mention
Zhang et al[27]-18,4% high NLR 41.7% low NLR9.5% high NLR 26.7% low NLRNoAll patients had undergone CRC resectionIf necessary after primary tumor resection (number not mentioned)
Weiner et al[28]7.9 m high NLR 13 low NLR--5979% had undergone primary CRC resectionAll patients
Kishi et al[15]11 m high NLR 21 m low NLR0% high NLR 14% low NLR-NoAll patients had undergone CRC resectionAll patients
Wu et al[31]24 m high NLR 56 m low NLR--NoAll patients had undergone CRC resectionAll patients
Philips et al[30]14.7 m high NLR 31.9 m low NLR--Liver dominant diseaseNot mentionedAll patients
Table 6 Univariate and multivariate analysis outcomes for patients treated with radio-frequency ablation, radioembolization or solely chemotherapy
Ref.
Univariate analysis
Multivariate analysis
Tohme et al[29]High NLR associated with decreased OS P < 0.001High NLR associated with decreased OS (HR = 1.927, 95%CI: 1.202-3.089, P = 0.006)
Chang et al[26]Preoperative high NLR and postoperative increase in NLR were associated with decreased DFS (P = 0.044 and P = 0.022, respectively)Only postoperative NLR increase was associated with decreased DFS (P = 0.029)
Zhang et al[27]High NLR associated with decreased OS (P = 0.007) and DFS (P = 0.007)High NLR associated with decreased OS (P = 0.039, HR = 3.59, 95%CI: 1.54-9.67) and DFS (P = 0.022, HR = 3.19, 95%CI: 1.87-8.24).
Weiner et al[28]High NLR associated with decreased OS (HR = 2.18, 95%CI: 1.45-3.28, P = 0.0002)High NLR associated with decreased OS (HR = 2.22, 95%CI: 1.46-3.38, P = 0.0002)
Kishi et al[15]High NLR associated with decreased OS (HR = 3.1, 95%CI: 1.7-5.9, P < 0.001)High NLR associated with decreased OS (HR = 2.9, 95%CI: 1.5-5.5, P = 0.001).
Wu et al[31]High NLR (HR = 3.182, 95%CI: 1.277-7.933, P = 0.013) associated with decreased OS and DFS (HR = 2.284, 95%CI: 1.156-4.498, P = 0.017). Patients with normalization of NLR had better DFS than those with high NLR that did not decrease (P = 0.002).No association between NLR and survival
Philips et al[30]High NLR associated with decreased OS P = 0.067 (statistically significant)No association between NLR and survival