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Table 1 Studies investigating inflammation scores as prognostic biomarkers in small cell lung cancer patients (n = 33)

From: Inflammation scores as prognostic biomarkers in small cell lung cancer: a systematic review and meta-analysis

Author
Year
Country
Inclusion period Study design
N
Age, median (range)
Clinical stage Treatment Female (%) Current/ever smoker (%) ECOG PS < 2 (%) Inflammation score and cut-offs applied Median follow-up, months (range) Overall survival
U/M
HR (95% CI) or log-rank p value
Adjustment variables Quality Score
Bernhardt
2008
Germany [16]
1999–2017 Retrospective
N = 350
Median: 64 years (37–93)
LD: 350 (100) Concurrent TCR: 350 (100) 137 (39) NR Median KPS: 80 (50–100) NLR: 2.65 and 4.0 NR U:
2.65: 0.86 (0.64–1.15)
4.0: 0.92 (0.71–1.19)
  Low quality
Cao
2017
China [48]
January 2008–January 2010 Retrospective
N = 707
Mean: 56 ± 10.15 years
LD: 419 (59)
ED: 288 (41)
Platinum and etoposide: 707 (100)
Thoracic RT: 294 (42)
253 (36) 442
(63)
KPS:
> 80 point 543 (77)
≤ 80 points 164 (23)
NLR: 3.18a
PLR: 176.5a
LMR: 2.615a
562 (79%) events during follow-up U:
PLR not significant
NLR p = 0.002
LMR p = 0.008
M:
NLR: 1.030 (0.837–1.267)
LMR: 1.053 (0.848-1.307)
Age, sex, KPS, smoking history, anaemia, lymphocyte count, NLR, PLR, LMR, LDH, ALP, surgery, thoracic irradiation, number of chemo cycles, number of metastatic sites, stage Moderate quality
Deng
2017
China [21]
March 2007–December 2014 Retrospective
N = 320
Median: 58 years (24–81)
LD: 122 (38)
ED: 198 (62)
Surgery: 27 (8)
Thoracic RT: 135 (42)
PCI: 77 (24)
81 (25) 215 (63) 0: 104 (33)
≥ 1: 216 (67)
NLR: 2.65a
PLR: 125a
39.1 (3.2–85.4) U:
NLR < 0.001
PLR = 0.099
M:
NLR: 1.35 (1.02–1.79)
NR Low quality
Gioulbasanisb
2012
Greece [22]
February 2006–March 2008 Retrospective
N = 96 (SCLC N = 46)
Median: 63 years (32–83)
NR Platinum-based doublet CT: 96 (100) 12 (13) NR 66 (69) mGPS: 0/1/2 NR U: SCLC: p = 0.008
M: no data for SCLC alone
  Low quality
He
2015
China [23]
June 2006–December 2011 Retrospective
N = 365
Median: 59 years (22–82)
LD: 201 (55)
ED: 164 (45)
Etoposide-based CT: 191 (52)
Irinotecan-based CT: 171 (47)
Thoracic RT: 139 (38)
PCI: 86 (24)
55 (15) 291 (80) 338 (93) ALI: 19.5a Last follow-up date September 2014 M: 1.617 (1.160 2.254) Clinical stage, PS and LDH Moderate quality
Hong
2015 [24]
China
January 2000–December 2012 Retrospective
N = 919
Median: 56 years (16–84)
LD: 552 (60)
ED: 367 (40)
Surgery, RT, CT: 760 (83)
No treatment: 159 (17)
284 (30) 567 (62) 760 (83) NLR: 5 PLR: 250
SII: 1600
Last follow up data December 2014 U:
NLR: p = 0.007
PLR: p = 0.004
SII: p < 0.001
M:
NLR: 0.908 (0.721–1.144)
PLR: 0.975 (0.783–1.215)
SII: 1.377 (1.024–1.852)
Sex, age, smoking history, PS, stage, BMI, response to treatment, platelet count, HGB, MCV, MPV, PNI, LDH Low quality
Kang
2014
Korea [25]
July 2006–October 2013 Retrospective
N = 187
Median: 68 years (43–84)
LD: 67 (36)
ED: 120 (64)
Platinum-based CT 25 (13) 172 (92) 163 (87) NLR: 4a
PLR: 160a
40.28 (2.60–89.26) U:
NLR: p = 0.019
PLR: p = 0.467
M:
NLR: 1.465 (1.012–2.119)
PLR: 0.896 (0.628–1.280)
Stage and LDH Moderate quality
Käsmann
2017
Germany [26]
2006–2014 Retrospective
N = 65
≤ 65 years: 36 (55%)
> 65 years: 29 (45%)
LD: 65 (100) Concurrent TCR: 35 (54)
PCI: 47 (72)
25 (38) 18 (28) 47 (72) NLR: 4 PLR: 180 NR U:
NLR: p = 0.001
PLR: non-significant
M:
NLR: 2.05 (1.06–3.95)
PS, pathologic lymph node, smoking, and PCI Low quality
Kim
2016
Korea [27]
January 2010–October 2015 Retrospective
N = 186
Mean: 69 years ± 9.4
LD: 64 (34)
ED: 122 (66)
CT: 94 (50)
TRC: 59 (32)
Chest RT: 2 (1)
Supportive care only 31 (17)
30 (16) 166 (89) 132 (71) ALI: 31.1a 29.0 (19.7–38.3)
141 (83.5%) events during follow up
U:
2.10 (1.50–2.94)
M:
1.67 (1.17–2.37)
NR Low quality
Kim
2019
Korea
[28]
2010–2016 Retrospective
N = 157
Mean: 66 years ± 9.0
LD: 67 (43)
ED: 90 (57)
NR 29 (19) NR NR NLR: 2.48a
PLR: 110.43a
NR U:
Low NLR vs high NLR: 27.6 months vs 19.3 months, p = 0.151
Low PLR vs high PLR: 31.1 vs 19.3 months, p = 0.155
  Low quality
Kurishima
2017
Japan [29]
April 1999–July 2016 Retrospective
N = 319
Median: 71 years (49–94)
LD: 103 (32)
ED: 216 (68)
CT: 276 (87)
Supportive care: 43 (13)
46 (14) 304 (95) 192 (78) (PS 0–2) mGPS: 0/1/2 NR M:
Score 1 vs 0: 1.23 (0.86–1.74) (N = 54)
Score 2 vs 0: 2.04 C1.51–2.78) (N = 73)
NR Low quality
Liu
2017
China [30]
January 2009–October 2013 Retrospective
N = 139
Mean: 58 years ± 10.5
LD: 55 (39)
ED: 83 (60)
NR: 1 (1)
CT: 120 (86)
RT: 61 (44)
32 (23) 100 (72) NR NLR:4.55a PLR:148a NR
Follow up for at least 12 months
U:
NLR: 3.309 (2.088–5.244)
PLR: 1.813 (1.200–2.738)
M:
NLR: 2.093 (1.079–4.063)
PLR: not significant, p = 0.332
Stage, metastatic disease, liver metastasis, adrenal metastasis, RT, CT, RBC, HGB, albumin, LDH Low quality
Lohinai
2019
Hungary/Italy/Russia [31]
1999–2013, 3 centres Retrospective
N = 155
Median: 58 years (Range NR)
I: 60
II: 29
III: 40
Unknown: 26
Surgery, adjuvant
CT: 100 (65)
41 (26) 141 (91) NR NLR: 2.258a
PLR: 111.253a
NR
Last follow up date: April
2017
U:
NLR: 1.621 (1.036–2.537)
Low PLR vs. high PLR, median OS, 73.6 vs. 40.4 months, respectively, p = 0.084
M:
NLR: 1.582 (1.010–2.478)
Surgery, pathologic lymph node, stage Moderate quality
Minami
2017
Japan [32]
November 2007–June 2016 Retrospective
N = 97
Mean: 71 years ± 8.7
IIIB: 18 (19)
IV:79 (81)
Platinum-based CT: 97 (100)
palliative RT: 4 (4)
20 (21) 67 (69) 66 (68) mGPS: 0/1/2 NR
78 (80%) events during follow up
mGPS 0, 1 vs 2
U: 1.92 (1.19–3.07)
M: 2.34 (1.27–4.31)
Brain metastasis, liver metastasis, bone metastasis, adrenal metastasis, PS, BMI, haemoglobin, creatinine clearence, sodium, LDH, ALP, CRP High quality
Mirili
2018
Turkey
May 2007–February
2017
Retrospective
N = 112
Median: 58 years (38–83)
LD: 26 (23)
ED: 86 (77)
TCR: 35 (31)
Platinum-based doublet CT: 62 (55)
No treatment: 15 (13)
20 (18) 106 (95) 69 (62) NLR: 3 / 4 8.4 (0.03–69.8)
89 (79.5%) events during follow-up
M:
beta coef: 0.151 SE = 0.077
Whole body total lesion glycolysis, age, sex, stage Low quality
Pan
2019
China [33]
January 2014–May 2016 Retrospective
N = 73
Mean: 62 years (39–83)
LD: 29 (40)
ED: 37 (51)
Unknown: 7 (9)
Etoposide/carboplatin: 18 (25)
etoposide/cisplatin: 40 (55)
Other CT: 15 (21)
local RT: 34 (47)
4 (6) 44/66 (67) 34/66 (52) NLR: 3.8a NR
Last follow-up date: August 31, 2017
60 (82%) events during follow-up
U:
high-NLR (n = 26) vs low-NLR groups (n = 34): 13.73 ± 1.87 vs. 13.22 ± 2.18 months; P = 0.785
  Low quality
Sakin
2019
Turkey [34]
2012–2018 Retrospective. N = 113
Median: 61 years (35–83)
ED 113 (100) Platinum/etoposide: 98 (87)
Etoposide: 6 (1)
Best supportive care: 9 (1)
21 (19) 113 (100) 72 (64) NLR:3.0a
PLR: 150a
MLR:0.367a
6 (1–33)
92 (81%) events during follow-up
U:
NLR: 2.23 (1.42–3.32)
PLR: 1.69 (1.08–2.26)
MLR: 0.61 (0.40–0.94)
M:
NLR: 2.26 (1.25–4.10)
PLR and MLR: NR
NR Low quality
Sakin
2019
Turkey [34]
1997–2017 Retrospective. N = 90
Median: 59 years (42–83)
LD: 90 (100) Platinum/etoposide: 90 (100) 18 (20) 86 (96) PS: 0–2: 77 (86) NLR:3.0a
PLR: 150a
MLR:0.367a
NR
53 (59%) events during follow-up
U:
NLR: 0.98 (0.89–1.08)
PLR: 1.0 (0.99–1.00)
MLR: 1.19 (0.41–3.43)
M:
NLR, PLR and MLR: NR
  Low quality
Sedef
2018 [35]
Turkey
September 2011–December 2017 Retrospective. N = 117
Median: 61 years (39–83)
ED: 117 (100) Platinum/etoposide: 117 (100) 12 (10) NR NR NLR: 3.28a
PLR: 139.8a
12 (range NR)
95 (81%) events during follow up
U:
High NLR: 12 months vs low NLR 14 months p = 0.013
High PLR 13 months vs low PLR 13 months p = 0.66
  Low quality
Shao
2015
China [36]
January 2000–March 2009 Retrospective. N = 112
Median: 62 years (45–82)
LD: 39 (35)
ED: 73 (65)
Platinum/etoposide: 84 (75%)
Platinum/irinotecan: 28 (25%)
14 (13) 105 (94) 103 (92) NLR: 4.15a
PLR:150a
68.5 (range NR) U:
NLR: p = 0.001
PLR: p = 0.101
M:
NLR: 1.56 (1.16–1.96)
PLR: NR
Stage, PS Moderate quality
Shen
2019
China [37]
September 2015–May 2019 Retrospective. N = 178
Mean: 61 ± 9.27
LD: 50 (28)
ED: 128 (72)
Platinum/etoposide: 178 (100%) 36 (20) NR NR HALP: 25.8a NR NR NR Low quality
Sonehara
2019
Japan [38]
January 2005–December 2018 Retrospective. N = 83.
Median: 72 years (43–86)
ED: 83 (100) Platinum/irinotecan: 33 (40%)
Platinum/etoposide: 46 (55%)
Etoposide 1 (1%)
Best supportive care: 3 (4%)
13 (16) 79 (95) 60 (72) mGPS:
0 / 1 / 2
PLR: 200
NR U:
mGPS 0 vs 1:
1.83 (1.06–3.15)
mGPS 0 vs 2:
2.28 (1.21–4.30)
PLR: 1.52
(0.94–2.47)
M:
mGPS 0 vs. 1:
1.31 (0.72–2.34)
mGPS 0 vs. 2:
2.34 (1.16–4.73)
PLR: 0.91 (0.35–1.56)
Age, PS, LDH, bone metastasis, lever metastasis Low quality
Suzuki
2018
USA [39]
May 1998–September 2015 Retrospective
N = 252
Median: 63 years (IQR 56–69)
ED: 252 (100) Platinum: 240 (95)
TRT ≥ 45Gy: 113 (45)
PCI: 49 (19)
133 (53) 247 (98) 185 (73) NLR: 4
PLR: 194.7
NR U:
NLR: 1.64 (1.27–2.11)
PLR: 1.20 (0.93–1.55)
M:
NLR: 1.52 (1.17–1.98)
PLR: non-significant, data not reported
Age, sex, PS, number of chemo cycles, TRT ≥ 45 Gy, PCI Moderate quality
Suzuki
2019
Japan [40]
2002–2015 Retrospective. N = 122
Median: 65 years (Range NR)
LD: 122 (100) Platinum/etoposide: 122 (100%) 61 (50) 111 (91) 118 (97) NLR: 2.9a
PLR: 140.1a
NR U:
NLR: 1.68 (1.06–2.66)
PLR: 1.85 (1.16–2.96)
M:
NLR: 1.86 (1.15–3.01)
PLR: 1.72 (1.06–2.82)
Age, number of chemo cycles, stage Moderate quality
Wang
2020
China [41]
January 2008–December 2009 Retrospective. N = 653
Median: 56 years (23–75)
LD: 384 (59)
ED: 269 (41)
Platinum/etoposide: 653 (100%)
RT: 267 (41%)
Surgery: 22 (3%)
231 (35) 408 (63) NR SII:748.51a NR U:
Low SII were associated with a prolonged OS 17 vs 12 months p < 0.001
M:
1.55 (1.30–1.86)
Age, sex, smoking, stage, LDH, distant metastasis, CRT, surgery + adjuvant CT Low quality
Wang
2019
China [42]
March 2009–August 2015 Retrospective. N = 228
Median: 58 (39–71)
LD: 114(50)
ED: 114 (50)
TRC platinum/etoposide 228 (100%) 69 (30) 181 (79) KPS ≥ 80 186 (82) SII: 479a
NLR: 2.3a
PLR: 125a
LMR: 6.08a
46 (range NR) U:
SII: 4.80 (3.42–6.74)
PLR: 3.17 (2.15–4.66)
NLR: 2.53 (1.84–3.48)
LMR: 1.96 (1.40–2.75)
M:
SII: 2.67 (1.67–4.28)
PLR: 1.95 (1.26–3.00)
NLR: 1.38 (0.93–2.05)
LMR: 1.32 (0.92–1.89)
Initial therapeutic response, extrapulmonary lesion, stage Low quality
Wang
2014
China [17]
January 2005–December 2010 Retrospective. N = 114
Mean: 59 years
LD: 68 (60)
ED: 46 (40)
Platinum/etoposide: 92 (80%) 25 (22) NR 45 (39) NLR: 3.0
PLR: 150
NR U:
NLR: chi2 = 5.641, P = 0.018
PLR: NR
M:
NLR: 1.70 (1.05–2.75)
PLR: NR
PS, stage Moderate quality
Wen
2017
China [43]
January 2005–December 2010 Retrospective. N = 452
Median: 56 years (27–82)
LD: 452 (100) Platinum/etoposide: 376 (83%) Platinum/irinotecan: 76 (17%) 112 (25) 322 (71) 357 (79) NLR: 4.0
PLR: NR
35 (range NR)
NR
U:
NLR: p = 0.004
PLR: p = 0.016
M:
NLR: 2.04 (1.02–4.10)
PLR: NR
Number of cycles, treatment modality, LDH, NSE, platinum status, response to treatment Moderate quality
Wu
2020 [44]
China
January 2008–October 2018 Retrospective. N = 146
Mean: 57 years (19–74)
LD: 59 (40)
ED: 87 (60)
Platinum/etoposide: 146 (100%) 32 (22) 108 (74) 146 (100) NLR: 3.0
PLR: 165
14 (5–138)
140 events during follow-up
U:
NLR: 1.57 (1.08–2.29)
PLR: 1.46 (1.02–2.11)
  Moderate quality
Xie
2015
USA [45]
January 1997–December 2012 Retrospective.
N = 938
Median: 68 years (27–91)
LD: 383 (41)
ED: 555 (59)
CT: 777 (83%) 438 (47) 921 (99) 730 (78) NLR: 5.0
PLR: 210a
10.8 (range NR)
856 (91%)events during follow-up
U:
PLR p < 0.0001
NLR p < 0.0001
RDW p < 0.0001
M: LD
PLR: 1.60 (1.18–2.18)
Loge (NLR): 1.16 (0.96–1.42)
Loge (RDW):
0.84 (0.24–2.94)
M: ED
Loge (RDW): 2.81 (1.32–6.01)
Loge (NLR): 1.41 (1.24–1.59)
PLR: 0.83 (0.67–1.02)
Age, sex, PS, chest irradiation, CT, liver metastasis, number of metastatic sites Low quality
Zhang
2019
China [46]
January 2012–September 2015 Retrospective. N = 286
< 65 years: 220 (77%)
LD:
I: 20 (7)
II: 48 (17)
III: 218 (76)
Platinum/etoposide: 236 (83%)
Other not specified: 50 (17%)
84 (29) 161 (56) NR PLR: 152.1a 40 (4–74)
221 (77%) events during follow-up
U:
p = 0.002
M:
1.33 (1.01–1.74)
Age, stage, treatment, initial treatment regimen, PCI Low quality
Zheng
2018
China [47]
January 2010–December 2016 Retrospective. N = 153
Median: 59 years (23–80)
LD:
I: 4 (3)
II: 13 (8)
III: 136 (89)
Platinum/etoposide: 153 (100%) 49 (32) 84 (55) 139 (90) NLR: 2.55a
PLR: 125.7a
42.5 (5.8–93.2)
88 (52%) events during follow-up
U:
NR
M:
NLR: 2.14 (95%CI NR)
PLR: NR
NR Low quality
Zhou
2014
China
January 2009–December 2011 Retrospective. N = 359
Median: 60 years (22–82)
LD: 163 (45)
ED:
196 (55)
Platinum / irinotecan: 174 (47%)
Platinum / etoposide: 185 (53%)
55 (15) NR 341 (95) mGPS:
0 / 1 / 2
NR
180 (50.1%) events during follow-up
U:
0 v 1 v 2: p < 0.001
M:
0 v 1 (n = 238v 110):
1.52 (1.08–2.13)
0 v 2 (N = 238 v 11):
5.23 (2.63–11.58)
PS, sex, stage High quality
  1. ALI, advanced lung cancer inflammation index (body mass index × albumin/NLR ); ALP, alkaline phosphate; CT, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group performance status; HALP, haemoglobin × albumin × lymphocytes/platelet count; HGB, haemoglobin; KPS, Karnofsky performance scale; LDH, lactate dehydrogenase; LMR, lymphocyte-to-monocyte ratio; M, multivariate; MCV, mean cell volume; MLR, monocyte-to-lymphocyte ratio; mGPS, modified Glasgow Prognostic Score (CRP ≤ 10 mg/L and albumin ≥ 35 g/L: score 0; CRP > 10 mg/L and ≥ 35 g/L: score 1; CRP < 10 mg/L and ≤ 35 g/L: score 1; CRP > 10 mg/L and albumin < 35 g/L: score 2); MPV, mean platelet volume; PCI, prophylactic cranial irradiation; PLR, platelet-to-lymphocyte ratio; PNI, prognostic nutritional index; RBC, red blod cell count; RT, radiotherapy; SII, systemic immune-inflammation index (= platelet count × neutrophil count/lymphocyte count); TCR, thoracic chemo-radiotherapy; U, univariate
  2. aData-dependent cut point
  3. bIn the original paper, the score is named Glasgow prognostic score. However, the score is calculated as the mGPS and therefore evaluated as mGPS in this study