Table 1.
Studies investigating inflammation scores as prognostic biomarkers in small cell lung cancer patients (n = 33)
| 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 |
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
aData-dependent cut point
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