Predictive Risk Factors for Early Recurrence of Stage pIIIA-N2 Non-Small Cell Lung Cancer

Figures & data

Figure 1 Flow chart of eligible patients enrolled in this study.

Table 1 Baseline Characteristics of All Patients

Variables		All Patients N=238	ER	NER	P value
			N=69	N=169
Gender, n (%)	Male	132 (55.5)	45 (65.2)	87 (51.5)	0.053
	Female	106 (44.5)	24 (34.8)	82 (48.5)
Age, n (%)	≤65	160 (67.2)	43 (62.3)	117 (69.2)	0.303
	>65	78 (32.8)	26 (37.3)	52 (30.8)
Smoking status, n (%)	Yes	82 (34.5)	32 (46.4)	50 (29.6)	0.013
	No	156 (65.5)	37 (53.6)	119 (70.4)
Body mass index, kg/m2, n (%)	<18.5	16 (6.7)	7 (10.1)	9 (5.3)	0.192
	18.5–25	178 (74.8)	53 (76.8)	125 (74.0)
	≥25	44 (18.5)	9 (13.0)	35 (20.7)
Tumor localization, n (%)	Left lung	95 (40.0)	26 (37.7)	69 (40.8)	0.653
	Right lung	143 (60.0)	43 (62.3)	100 (59.2)
Surgery type, n (%)	Open	83 (34.9)	32 (46.4)	51 (30.2)	0.017
	VATS	155 (65.1)	37 (53.6)	118 (69.8)
Extent of surgical resection, n (%)	Wedge resection	1 (0.4)	0 (0)	1 (0.6)	0.843
	Segmentectomy	1 (0.4)	0 (0)	1 (0.6)
	Lobectomy	226 (95.0)	66 (95.7)	160 (94.7)
	Pneumonectomy	10 (4.2)	3 (4.3)	7 (4.1)
Histological subtype, n (%)	AD	170 (71.4)	44 (63.8)	126 (74.6)	0.168
	SQ	60 (25.2)	21 (30.4)	39 (23.1)
	Other	8 (3.4)	4 (5.8)	4 (2.4)
Tumor size, cm, n (%)	≤2.95	104 (43.7)	17 (24.6)	87 (51.5)	0.0001
	>2.95	134 (56.3)	52 (75.4)	82 (48.5)
N status, n (%)	pN2a1	72 (30.3)	12 (17.4)	60 (35.5)	0.016
	pN2a2	46 (19.3)	18 (26.1)	28 (16.6)
	pN2b	120 (50.4)	39 (56.5)	81 (47.9)
The number of examined lymph nodes	≤10	65 (27.3)	14 (20.3)	51 (30.2)	0.120
	>10	173 (72.7)	55 (79.7)	118 (69.8)
LNR, n (%)	≤0.16	77 (32.4)	15 (21.7)	62 (36.7)	0.025
	>0.16	161 (67.6)	54 (78.3)	107 (63.3)
Adjuvant therapy, n (%)	No	62 (26.1)	22 (31.9)	40 (23.7)	0.213
	Chemotherapy	139 (58.4)	40 (58.0)	99 (58.6)
	Targeted therapy	37 (15.5)	7 (10.1)	30 (17.8)
NLR, n (%)	≤2.51	147 (61.8)	34 (49.3)	113 (66.9)	0.011
	>2.51	91 (38.2)	35 (50.7)	56 (33.1)
LMR, n (%)	≤3.54	119 (50)	40 (58.0)	79 (46.7)	0.116
	>3.54	119 (50)	29 (42.0)	90 (53.3)
PLR, n (%)	≤139	121 (50.8)	23 (33.3)	98 (58.0)	0.001
	>139	117 (49.2)	46 (66.7)	71 (42.0)
ALI, n (%)	≤42.44	119 (50.0)	44 (63.8)	75 (44.4)	0.007
	>42.44	119 (50.0)	25 (36.2)	94 (55.6)
SII, n (%)	≤327	63 (26.5)	8 (11.6)	55 (32.5)	0.001
	>327	175 (73.5)	61 (88.4)	114 (67.5)
PNI, n (%)	≤48.6	119 (50.0)	36 (52.2)	83 (49.1)	0.668
	>48.6	119 (50.0)	33 (47.8)	86 (50.9)

Abbreviations: ER, early recurrence; NER, non-early recurrence; VATS, video-assisted thoracoscopic surgery; AD, adenocarcinoma; SQ, squamous cell carcinoma; LNR, lymph node ratio; NLR, neutrophil-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; PLR, platelet-to-lymphocyte ratio; ALI, advanced lung cancer inflammation index; SII, systemic immune-inflammation index; PNI, prognostic nutritional index.

Table 2 Univariate Analyses of Risk Factors Associated with Early Recurrence

Variable		HR	95% CI	P value
Gender	Male vs Female	1.643	1.001–2.697	0.005
Age, years	>65 vs ≤65	1.269	0.78–2.065	0.338
Smoking status	Smoker vs Never smoker	1.881	1.172–3.021	0.009
Body mass index, kg/m2	18.5–25 vs <18.5	0.695	0.316–1.528	0.365
	≥25 vs <18.5	0.439	0.163–1.179	0.102
	18.5–25 vs ≥25	1.583	0.781–3.209	0.203
Histological subtype	SQ vs AD	1.421	0.845–2.39	0.186
	Other vs AD	2.4	0.861–6.686	0.094
	SQ vs.Other	0.592	0.203–1.725	0.337
Tumor size, cm	>2.95 vs ≤2.95	2.733	1.58–4.728	0.0001
Surgery type	VATS vs Open	0.566	0.352–0.908	0.018
Extent of surgical resection	Lobectomy vs Pneumonectomy	1.004	0.316–3.195	0.994
Tumor localization	Right vs Left	1.104	0.679–1.797	0.69
N status	pN2a2 vs pN2a1	2.584	1.244–5.365	0.011
	pN2b vs pN2a1	2.2	1.152–4.203	0.017
	pN2a2 vs pN2b	1.174	0.672–2.053	0.573
The number of examined lymph nodes	>10 vs ≤10	1.591	0.885–2.861	0.105
LNR	>0.16 vs ≤0.16	1.816	1.025–3.218	0.041
Adjuvant therapy	Chemotherapy vs No	0.77	0.458–1.296	0.325
	Targeted therapy vs No	0.463	0.198–1.084	0.076
	Chemotherapy vs Targeted therapy	1.664	0.745–3.715	0.214
NLR	>2.51 vs ≤2.51	1.853	1.156–2.972	0.01
LMR	>3.54 vs ≤3.54	0.699	0.433–1.127	0.142
PLR	>139 vs ≤139	2.426	1.47–4.006	0.001
ALI	>42.44 vs ≤42.44	0.524	0.32–0.856	0.01
SII	>327 vs ≤327	3.103	1.484–6.486	0.003
PNI	>48.6 vs ≤48.6	0.895	0.558–1.436	0.646

Abbreviations: ER, early recurrence; NER, non-early recurrence; VATS, video-assisted thoracoscopic surgery; AD, adenocarcinoma; SQ, squamous cell carcinoma; LNR, lymph node ratio; NLR, neutrophil-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; PLR, platelet-to-lymphocyte ratio; ALI, advanced lung cancer inflammation index; SII, systemic immune-inflammation index; PNI, prognostic nutritional index.

Table 3 Multivariate Analyses of Risk Factors Associated with Early Recurrence

Variable	HR	95% CI	P value	Risk Score
Smoking status (Smoker vs Never smoker)	1.895	1.178–3.048	0.008	2 vs 0
Tumor size (>2.95 vs ≤2.95)	2.511	1.43–4.409	0.001	3 vs 0
LNR (>0.16 vs ≤0.16)	2.098	1.178–3.738	0.012	2 vs 0
PLR (>139 vs ≤139)	1.962	1.173–3.28	0.01	2 vs 0

Abbreviations: HR, hazard ratio; CI, confidence interval; LNR, lymph node ratio; PLR, platelet-to-lymphocyte ratio.

Table 4 Sites of Recurrence After Curative Resection in the 178 Recurred Patients

Recurrence Site	ER Group	NER Group	P value
	N=69	N=109
Single site	56 (81.2%)	93 (85.3%)	0.464
Lung	14 (20.3%)	35 (20.7%)	0.085
Brain	7 (10.1%)	22 (13.0%)	0.077
Lymph node	10 (14.5%)	18 (10.7%)	0.718
Bone	18 (26.1%)	9 (5.3%)	0.001
Chest wall	1 (1.4%)	3 (1.8%)	0.568
Pleura	3 (4.3%)	1 (0.6%)	0.132
Liver	3 (4.3%)	2 (1.2%)	0.323
Other	0 (0%)	3 (1.8%)	0.165
Multiple sites	13 (18.8%)	16 (9.5%)	0.464

Abbreviations: ER, early recurrence; NER, non-early recurrence.

Figure 2 Kaplan–Meier survival curve for RFS (A and B) and OS (C and D) of overall patients and patients in ER and NER groups.

Figure 3 Kaplan–Meier survival curve for RFS (A) and OS (B) of patients with different risk groups.