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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