Systemic inflammation score: a novel risk stratification tool for postoperative outcomes after video-assisted thoracoscopic surgery lobectomy for early-stage non-small-cell lung cancer

Figures & data

Table 1 Patient characteristics^a

Characteristics^b	Total (N=1,025)	SIS=0 (N=470)	SIS=1 (N=413)	P1-value	SIS=2 (N=142)	P2-value
Median age (years)	62 (57–67)	61 (55–66)	63 (56–69)	0.004	66 (60–71)	<0.001
Gender
Male	530 (51.7%)	170 (36.2%)	256 (62.0%)	<0.001	104 (73.2%)	<0.001
Female	495 (48.3%)	300 (63.8%)	157 (38.0%)		38 (26.8%)
Median body mass index (kg/m^2)	23.3 (21.1–25.2)	23.2 (21.1–25.1)	23.4 (21.2–25.4)	0.090	22.9 (20.5–26.3)	0.92
Median FEV1%	83.8 (73.8–92.7)	87.3 (80.3–96.5)	80.8 (70.3–89.8)	<0.001	74.7 (64.9–86.8)	<0.001
Median FEV1/FVC (%)	79.0 (74.2–83.5)	81.3 (76.4–84.7)	77.9 (73.0–82.9)	<0.001	74.9 (66.8–79.4)	<0.001
Median neutrophil-to-lymphocyte ratio	1.9 (1.4–2.5)	1.5 (1.2–1.9)	2.3 (1.8–3.1)	<0.001	2.4 (1.7–3.1)	<0.001
Median platelet-to-lymphocyte ratio	91.5 (72.4–120.0)	82.7 (64.9–102.6)	101.6 (78.0–133.8)	<0.001	105.7 (81.6–162.7)	<0.001
Median hemoglobin (g/dL)	13.6 (12.8–14.6)	13.5 (12.9–14.5)	13.8 (12.9–14.8)	0.11	13.2 (12.1–14.2)	<0.001
Smoking history	380 (37.1%)	99 (21.1%)	198 (47.9%)	<0.001	83 (58.5%)	<0.001
Respiratory comorbidity	400 (39.0%)	146 (31.1%)	183 (44.3%)	<0.001	71 (50.0%)	<0.001
Cardio-cerebrovascular comorbidity	382 (37.3%)	134 (28.5%)	181 (43.8%)	<0.001	67 (47.2%)	<0.001
Diabetes mellitus	112 (10.9%)	36 (7.7%)	59 (14.3%)	0.002	17 (12.0%)	0.11
Renal insufficiency	89 (8.7%)	35 (7.4%)	38 (9.2%)	0.35	16 (11.3%)	0.15
Steroid use	31 (3.0%)	11 (2.3%)	14 (3.4%)	0.35	6 (4.2%)	0.23
Tumor location
Right upper lobe	334 (32.6%)	164 (34.9%)	136 (32.9%)	0.44	34 (23.9%)	0.25
Left upper lobe	261 (25.5%)	127 (27.0%)	99 (24.0%)		35 (24.6%)
Right lower lobe	193 (18.8%)	81 (17.2%)	78 (18.9%)		34 (23.9%)
Left lower lobe	149 (14.5%)	56 (11.9%)	65 (15.7%)		28 (19.7%)
Right middle lobe	88 (8.6%)	42 (8.9%)	35 (8.5%)		11 (7.7%)
Dense pleural adhesion
Absent	935 (91.2%)	429 (91.3%)	374 (90.6%)	0.71	132 (93.0%)	0.53
Present	90 (8.8%)	41 (8.7%)	39 (9.4%)		10 (7.0%)
Pulmonary fissure completeness
Complete	596 (58.1%)	285 (60.6%)	242 (58.6%)	0.54	69 (48.6%)	0.011
Incomplete	429 (41.9%)	185 (39.4%)	171 (41.4%)	73 (51.4%)
Median estimated intraoperative blood loss (mL)	50 (20–50)	30 (20–50)	50 (20–60)	0.053	50 (30–60)	<0.001
Median Operation time (mins)	100 (80–130)	100 (75–130)	105 (80–130)	0.016	120 (90–150)	<0.001
Histological subtypes
Adenocarcinoma	822 (80.2%)	386 (82.1%)	339 (82.1%)	0.99	97 (68.3%)	<0.001
Non-adenocarcinoma	203 (19.8%)	84 (17.9%)	74 (17.9%)		45 (31.7%)
Tumor invasion (T-stage)
T1	627 (61.2%)	322 (68.5%)	237 (57.4%)	0.001	68 (47.9%)	<0.001
T2-3	398 (38.8%)	148 (31.5%)	176 (42.6%)		74 (52.1%)
Lymph node metastasis (N-stage)
N0	966 (94.2%)	453 (96.4%)	389 (94.2%)	0.12	124 (87.3%)	0.001
N1-2	59 (5.8%)	17 (3.6%)	24 (5.8%)	18 (12.7%)

Notes: ^aP₁-value indicates demographic differences between patients with SIS=1 and with SIS=0. P₂-value indicates demographic differences between patients with SIS=2 and with SIS=0. ^bThe continuous data were presented as medians with 25th–75th percentile-intervals.

Abbreviations: FEV₁/FVC, FEV₁ to FVC ratio; SIS, Systemic inflammation score.

Table 2 Postoperative outcomes^a

Characteristics	Total (N=1,025)	SIS=0 (N=470)	SIS=1 (N=413)	P1-value	SIS=2 (N=142)	P2-value
Overall morbidity
Any morbidity	319 (31.1%)	124 (26.4%)	125 (30.3%)	0.20	70 (49.3%)	<0.001
Minor morbidity (Clavien-Dindo Grade II)	284 (27.7%)	111 (23.6%)	109 (26.4%)	0.34	64 (45.1%)	<0.001
Major morbidity (Clavien-Dindo Grade ≥III)	152 (14.8%)	54 (11.5%)	62 (15.0%)	0.12	36 (25.4%)	<0.001
In-hospital mortality	3 (0.3%)	1 (0.2%)	2 (0.5%)	0.60	0 (0.0%)	1.0
Individual complications
Prolonged air leak (>5 days)	152 (14.8%)	47 (10.0%)	65 (15.7%)	0.011	40 (28.2%)	<0.001
Pneumonia	118 (11.5%)	36 (7.7%)	48 (11.6%)	0.045	34 (23.9%)	<0.001
Atelectasis	95 (9.3%)	45 (9.6%)	35 (8.5%)	0.57	15 (10.6%)	0.73
Subcutaneous emphysema	73 (7.1%)	26 (5.5%)	28 (6.8%)	0.44	19 (13.4%)	0.002
Pneumothorax	49 (4.8%)	26 (5.5%)	17 (4.1%)	0.33	6 (4.2%)	0.54
Pleural effusion requiring chest tube drainage	30 (2.9%)	9 (1.9%)	5 (1.2%)	0.40	16 (11.3%)	<0.001
Hemoptysis requiring medical care	29 (2.8%)	11 (2.3%)	8 (1.9%)	0.68	10 (7.0%)	0.015
Sinus irregularity requiring medical care	17 (1.7%)	9 (1.9%)	4 (1.0%)	0.24	4 (2.8%)	0.75
Chylothorax	15 (1.5%)	2 (0.4%)	9 (2.2%)	0.019	4 (2.8%)	0.028
Atrial arrhythmia	11 (1.1%)	3 (0.6%)	6 (1.5%)	0.32	2 (1.4%)	0.33
Ventricular arrhythmia	3 (0.3%)	1 (0.2%)	0 (0.0%)	1.0	2 (1.4%)	0.14
Pulmonary artery embolism	8 (0.8%)	6 (1.3%)	2 (0.5%)	0.30	0 (0.0%)	0.35
Acute respiratory distress syndrome	4 (0.4%)	0 (0.0%)	4 (1.0%)	0.047	0 (0.0%)	—
Hemothorax	2 (0.2%)	0 (0.0%)	2 (0.5%)	0.22	0 (0.0%)	—
Bronchial fistula	1 (0.1%)	0 (0.0%)	1 (0.2%)	0.47	0 (0.0%)	—
Wound infection	4 (0.4%)	2 (0.4%)	2 (0.5%)	1.0	0 (0.0%)	1.0
Gastrointestinal discomforts requiring medical care	13 (1.3%)	5 (1.1%)	8 (1.9%)	0.28	0 (0.0%)	0.60
Urinary retention	7 (0.7%)	3 (0.6%)	2 (0.5%)	1.0	2 (1.4%)	0.33

Notes: ^aP₁-value indicates demographic differences between patients with SIS=1 and with SIS=0. P₂-value indicates demographic differences between patients with SIS=2 and with SIS=0.

Abbreviation: SIS, systemic inflammation score.

Figure 1 Overall, minor and major morbidity rates between 3 SIS groups.

Abbreviation: SIS, systemic inflammation score.

Figure 2 Incidences of five most frequent complications between 3 SIS groups.

Abbreviation: SIS, systemic inflammation score.

Table 3 Univariable analysis of predictors for overall morbidity

Characteristics^a	Total (N=1,025)	Without morbidity (N=706)	With morbidity			P-value^b
Overall (N=319)	Minor morbidity (N=284)	Major morbidity (N=152)
Median age (years)	62 (57–67)	62 (55–67)	63 (58–69)	63 (59–69)	63 (57–69)	<0.001
Gender
Male	530 (51.7%)	330 (46.7%)	200 (62.7%)	177 (62.3%)	100 (65.8%)	<0.001
Female	495 (48.3%)	376 (53.3%)	119 (37.3%)	107 (37.7%)	52 (34.2%)
Median body mass index (kg/m^2)	23.3 (21.1–25.2)	23.3 (21.4–25.1)	22.7 (20.4–25.6)	22.8 (20.5–25.8)	22.3 (19.7–25.6)	0.11
Median FEV1%	83.8 (73.8–92.7)	85.5 (76.5–94.7)	79.5 (67.5–89.8)	79.1 (65.8–90.0)	79.0 (65.6–90.2)	<0.001
Median FEV1/FVC (%)	79.0 (74.2–83.5)	79.4 (75.4–84.1)	77.9 (70.9–82.3)	77.3 (70.7–82.4)	77.3 (68.9–82.5)	<0.001
Median neutrophil-to-lymphocyte ratio	1.9 (1.4–2.5)	1.8 (1.4–2.5)	2.0 (1.6–2.5)	1.9 (1.6–2.4)	2.0 (1.6–2.7)	0.007
Median platelet-to-lymphocyte ratio	91.5 (72.4–120.0)	90.4 (70.2–117.0)	95.9 (77.4–126.7)	94.8 (77.2–125.5)	102.9 (86.6–134.4)	0.014
Median Hemoglobin (g/dL)	13.6 (12.8–14.6)	13.5 (12.8–14.5)	13.7 (12.9–14.8)	13.7 (12.9–14.7)	13.6 (12.8–14.8)	0.091
Systemic inflammation score
0	470 (45.9%)	346 (49.0%)	124 (38.9%)	111 (39.1%)	54 (35.5%)	<0.001
1	413 (40.3%)	288 (40.8%)	125 (39.2%)	109 (38.4%)	62 (40.8%)
2	142 (13.9%)	72 (10.2%)	70 (21.9%)	64 (22.5%)	36 (23.7%)
Smoking history	380 (37.1%)	235 (33.3%)	145 (45.5%)	130 (45.8%)	79 (52.0%)	<0.001
Respiratory comorbidity	400 (39.0%)	219 (31.0%)	181 (56.7%)	156 (54.9%)	101 (66.4%)	<0.001
Cardio-cerebrovascular comorbidity	382 (37.3%)	241 (34.1%)	141 (44.2%)	124 (43.7%)	74 (48.7%)	0.002
Diabetes mellitus	112 (10.9%)	78 (11.0%)	34 (10.7%)	28 (9.9%)	16 (10.5%)	0.85
Renal insufficiency	89 (8.7%)	56 (7.9%)	33 (10.3%)	30 (10.6%)	19 (12.5%)	0.21
Steroid use	31 (3.0%)	23 (3.3%)	8 (2.5%)	8 (2.8%)	7 (4.6%)	0.52
Tumor location
Right upper lobe	334 (32.6%)	217 (30.7%)	117 (36.7%)	107 (37.7%)	48 (31.6%)	0.060
Left upper lobe	261 (25.5%)	189 (26.8%)	72 (22.6%)	66 (23.2%)	39 (25.7%)
Right lower lobe	193 (18.8%)	124 (17.6%)	69 (21.6%)	59 (20.8%)	35 (23.0%)
Left lower lobe	149 (14.5%)	113 (16.0%)	36 (11.3%)	33 (11.6%)	15 (9.9%)
Right middle lobe	88 (8.6%)	63 (8.9%)	25 (7.8%)	19 (6.7%)	15 (9.9%)
Dense pleural adhesion
Absent	935 (91.2%)	654 (92.6%)	281 (88.1%)	250 (88.0%)	129 (84.9%)	0.017
Present	90 (8.8%)	52 (7.4%)	38 (11.9%)	34 (12.0%)	23 (15.1%)
Pulmonary fissure completeness
Complete	596 (58.1%)	433 (62.4%)	145 (45.5%)	127 (44.7%)	56 (36.8%)	<0.001
Incomplete	429 (41.9%)	255 (36.1%)	174 (54.5%)	157 (55.3%)	96 (63.2%)
Median estimated intraoperative blood loss (mL)	50 (20–50)	30 (20–50)	50 (30–100)	50 (30–100)	50 (30–100)	<0.001
Median operation time (mins)	100 (80–130)	95 (75–120)	120 (100–160)	120 (100–170)	130 (110–175)	<0.001
Histological subtypes
Adenocarcinoma	822 (80.2%)	559 (79.2%)	263 (82.4%)	234 (82.4%)	116 (76.3%)	0.22
Non-adenocarcinoma	203 (19.8%)	147 (20.8%)	56 (17.6%)	50 (17.6%)	36 (23.7%)
Tumor invasion (T-stage)
T1	627 (61.2%)	455 (64.4%)	172 (53.9%)	155 (54.6%)	79 (52.0%)	0.001
T2-3	398 (38.8%)	251 (35.6%)	147 (46.1%)	129 (45.4%)	73 (48.0%)
Lymph node metastasis (N-stage)
N0	966 (94.2%)	678 (96.0%)	288 (90.3%)	256 (90.1%)	135 (88.8%)	<0.001
N1-2	59 (5.8%)	28 (4.0%)	31 (9.7%)	28 (9.9%)	17 (11.2%)

Notes: ^aThe continuous data were presented as medians with 25th–75th percentile intervals. ^bP-value indicates demographic differences between patients with and without any Clavien-Dindo grade ≥II complication. FEV₁/FVC, FEV₁ to FVC ratio.

Table 4 Multivariable analysis of predictors for overall morbidity

Estimated factors	OR	95% CI	P-value
Age (per 1-year increase)	1.004	0.98–1.02	0.72
Gender (male vs female)	1.24	0.79–1.93	0.35
Body mass index (kg/m^2) (per unit decrease)	1.04	0.991–1.10	0.11
FEV1% (per unit decrease)	1.01	1.00–1.03	0.054
FEV1/FVC (%) (per unit decrease)	1.004	0.98–1.03	0.75
Systemic inflammation score (2 vs 0–1)	1.73	1.11–2.71	0.016
Neutrophil-to-lymphocyte ratio (per unit increase)	0.99	0.89–1.10	0.79
Platelet-to-lymphocyte ratio (per unit increase)	1.002	0.998–1.006	0.38
Hemoglobin (g/dL) (per unit decrease)	1.007	0.997–1.02	0.17
Smoking history	1.49	0.97–2.31	0.071
Respiratory comorbidity	2.13	1.56–2.91	<0.001
Cardio-cerebrovascular comorbidity	1.18	0.85–1.64	0.33
Right upper lobectomy	1.32	0.96–1.81	0.087
Pulmonary fissure completeness (incomplete vs complete)	1.69	1.25–2.29	0.001
Dense pleural adhesion (present vs absent)	1.33	0.78–2.25	0.30
Operation time (mins) (per 10 mins increase)	1.01	1.01–1.02	<0.001
Estimated intraoperative blood loss (mL) (per 10 mL increase)	1.002	1.00–1.004	0.083
Tumor invasion (T2-3vs.T1)	1.06	0.78–1.46	0.70
Lymph node metastasis	1.46	0.78–2.71	0.24

Note: FEV₁/FVC, FEV₁ to FVC ratio.

Figure 3 C-statistic revealing discriminative power of multivariable logistic-regression model for the prediction of overall morbidity.

Table S1 Multivariable analysis of predictors for minor morbidity (Clavien-Dindo Grade II complications)^a

Estimated factors	Odds ratio	95% CI	P-value
Age (year) (per 1-year increase)	1.006	0.98–1.03	0.59
Gender (male vs female)	1.25	0.81–1.93	0.32
FEV1% (per unit decrease)	1.01	0.999–1.03	0.064
FEV1/FVC (%) (per unit decrease)	1.005	0.98–1.03	0.68
Systemic inflammation score (2 vs 0-1)	1.79	1.15–2.80	0.011
Neutrophil-to-lymphocyte ratio (per unit increase)	0.98	0.88–1.10	0.72
Platelet-to-lymphocyte ratio (per unit increase)	1.001	0.997–1.006	0.51
Smoking history	1.40	0.89–2.22	0.14
Respiratory comorbidity	1.99	1.44–2.76	<0.001
Cardio-cerebrovascular comorbidity	1.08	0.77–1.52	0.66
Right upper lobectomy	1.46	1.05–2.01	0.024
Pulmonary fissure completeness (incomplete vs complete)	1.66	1.21–2.28	0.002
Dense pleural adhesion (present vs absent)	1.31	0.76–2.27	0.33
Operation time (mins) (per 10 mins increase)	1.01	1.009–1.02	<0.001
Estimated intraoperative blood loss (mL) (per 10 mL increase)	1.003	1.000–1.005	0.018
Tumor invasion (T2-3 vs T1)	1.004	0.72–1.39	0.98
Lymph node metastasis	1.51	0.80–2.84	0.20

Notes: ^aThe multivariable logistic-regression model was established based on 284 patients with minor morbidity and 706 patients without any morbidity to identify the risk factors for minor morbidity. The data for major morbidity (Clavien-Dindo Grade ≥III complications) were excluded. This multivariable logistic-regression model got a Hosmer–Lemeshow P=0.13 and a C-statistic of 0.75 (95% CI: 0.72-0.79; P<0.001). FEV1/FVC, FEV1 to FVC ratio.

Table S2 Multivariable analysis of predictors for major morbidity (Clavien-Dindo Grade ≥III complications)^a

Estimated factors	Odds ratio	95% CI	P-value
Age (year) (per 1-year increase)	0.992	0.97–1.02	0.53
Gender (male vs female)	1.45	0.83–2.54	0.20
Body mass index (kg/m^2) (per unit decrease)	1.07	1.005–1.14	0.036
FEV1% (per unit decrease)	1.01	0.994–1.03	0.19
FEV1/FVC (%) (per unit decrease)	1.02	0.98–1.05	0.34
Systemic inflammation score (2 vs 0-1)	1.87	1.09–3.20	0.023
Neutrophil-to-lymphocyte ratio (per unit increase)	0.92	0.79–1.08	0.29
Platelet-to-lymphocyte ratio (per unit increase)	1.006	1.001–1.01	0.017
Smoking history	1.44	0.79–2.63	0.23
Respiratory comorbidity	3.37	2.19–5.19	<0.001
Cardio-cerebrovascular comorbidity	1.58	1.01–2.45	0.044
Renal insufficiency	1.17	0.60–2.27	0.64
Pulmonary fissure completeness (incomplete vs complete)	2.40	1.58–3.66	<0.001
Dense pleural adhesion (present vs absent)	1.12	0.58–2.15	0.75
Operation time (mins) (per 10 mins increase)	1.02	1.01–1.03	<0.001
Estimated intraoperative blood loss (mL) (per 10 mL increase)	1.001	0.998–1.003	0.67
Tumor invasion (T2-3 vs T1)	1.12	0.73–1.72	0.60
Lymph node metastasis	1.27	0.55–2.95	0.57

Notes: ^aThe multivariable logistic-regression model was established based on 152 patients with major morbidity and 706 patients without any morbidity to identify the risk factors for major morbidity. The data for minor morbidity (Clavien-Dindo Grade II complications) were excluded. This multivariable logistic-regression model got a Hosmer–Lemeshow P=0.10 and a C-statistic of 0.82 (95% CI: 0.78-0.85; P<0.001). FEV1/FVC, FEV1 to FVC ratio.