Clinical outcomes of patients with metachronous second primary lung adenocarcinomas

Figures & data

Table 1 Perioperative characteristics of the second intervention (N=115)

Variables	First resection, n (%)	Second resection, n (%)
Sex (%)
Male		55 (47.8)
Female		60 (52.2)
Age (years)
Median (range)		60.0 (36–78)
Smoking history
Never		80 (69.6)
Ever		35 (30.4)
FEV1 (%)
≤60		17 (14.8)
>60		98 (85.2)
Tumor-free interval (years)
<2		63 (54.8)
≥2		52 (45.2)
Surgical approach
Thoracotomy		28 (24.3)
Video-assisted thoracoscopic surgery		87 (75.7)
Adjuvant chemotherapy after first/second resection
Yes	32 (27.8)	40 (34.8)
No	83 (72.2)	75 (65.2)
ECOG PS before second resection
0–1	80 (69.6)
2	35 (30.4)
Location
Ipsilateral	39 (33.9)
Contralateral	76 (66.1)
Computed tomography morphology
GGO-p	46 (40)	73 (63.5)
Solid-p	69 (60)	42 (36.5)
Type of resection
Sublobar resection	21 (18.3)	58 (50.4)
Wedge	18 (15.7)	37 (32.2)
Segmentectomy	3 (2.6)	21 (18.3)
Lobar resection	94 (81.7)	57 (49.6)
Lobectomy	88 (76.5)	56 (48.7)
Extended lobectomy	3 (2.6)	1 (0.9)

Abbreviations: ECOG, Eastern Cooperative Oncology Group; FEV₁, forced expiratory volume in 1 s; GGO-p, ground glass opacity predominant; PS, performance status; Solid-p, solid predominant.

Table 2 Histology of first and second resections

Histology	First resection, n (%)	Second resection, n (%)
Same/similar	93 (80.9)
AIS	1 (0.9)	6 (5.2)
MIA	8 (7.0)	19 (16.5)
Lepidic	7 (6.1)	9 (7.8)
Acinar	38 (33.0)	38 (33.0)
Papillary	30 (26.1)	25 (21.7)
Solid	6 (5.2)	9 (7.8)
Micropapillary	1 (0.9)	2 (1.7)
Mucinous	2 (1.7)	7 (6.1)
Different	22 (19.1)
SCC–AC	13 (11.3)
AS–AC	6 (5.2)
LC–AC	3 (1.7)
T stage
T1a	36 (31.3)	54 (47.0)
T1b	25 (21.7)	13 (11.3)
T2a	49 (42.6)	44 (38.3)
T2b	2 (1.7)	2 (1.7)
T3	3 (2.6)	2 (1.7)
N stage
N0	91 (79.1)	87 (75.7)
N1	27 (20.9)	16 (13.9)
N2	0	12 (10.4)
TNM stage
Ia	57 (49.6)	71 (61.7)
Ib	31 (27.0)	18 (15.7)
IIa	22 (19.1)	11 (9.6)
IIb	5 (4.3)	2 (1.7)
IIIa	0	13 (11.3)

Abbreviations: AC, adenocarcinoma; AIS, adenocarcinoma in situ; AS, adenosquamous carcinoma; LC, large cell carcinoma; MIA, minimally invasive adenocarcinoma; SCC, squamous cell carcinoma; TNM, tumor, node, and metastasis.

Table 3 Correlation of the predominant histologic subtype with pathologic stage and survival

Group	Total	VPI	N0	N1	N2	Ia	Ib	IIa	IIb	IIIa	5-year OS
Low grade	25	0	25	0	0	25	0	0	0	0	–*
AIS	6	0	6	0	0	6	0	0	0	0
MIA	19	0	19	0	0	19	0	0	0	0
Intermediate grade	72	16	54	11	7	42	14	6	2	8	70.1%
Lepidic	9	3	4	3	2	3	1	3	0	2
Acinar	38	8	30	5	3	25	8	2	0	3
Papillary	25	5	20	3	2	14	5	1	2	3
High grade	18	8	8	5	5	4	4	5	0	5	33.0%
Solid	9	5	4	2	3	1	3	2	0	3
Micropapillary	2	1	1	1	0	0	1	1	0	0
Mucinous	7	2	3	2	2	3	0	2	0	2

Notes:

* All data are censored. –, Not applicable, as more than half the number of patients were still alive.

Abbreviations: AIS, adenocarcinoma in situ; MIA, minimally invasive adenocarcinoma; VPI, visceral pleural invasion; OS, overall survival.

Table 4 Univariate analysis of various potential prognostic factors for OS in patients with SPLAC

Variable	Patients (n)	Median OS (months)	P-value
Gender			0.628
Male	55	91.0±15.3
Female	60	81.0±11.7
Age (years)			0.679
≤60	61	81.0±16.2
>60	54	96.0±31.2
Smoking history			0.824
Never	80	81.0±12.7
Ever	35	91.0±13.5
Interval (months)			0.888
≤24	63	96.0±33.7
>24	52	81.0±12.6
ECOG PS			0.054
0–1	80	91.0±17.7
2	35	66.0±11.0
Type of the first resection			0.072
Sublobar resection	58	81.0±12.9
Lobar resection	57	91.0±18.6
Type of the second resection			0.206
Sublobar resection	57	81.0±15.5
Lobar resection	58	91.0±17.7
TNM stage of the primary tumor			<0.001a
Stage I		101.0±5.8
Stage II		48.0±7.1
CT morphology of SPLAC			0.001a
GGO-p	73	–b
Solid-p	42	59.0±8.0
Location			0.308
Ipsilateral	39	67.0±27.5
Contralateral	76	81.0
Histologic classification			0.001a
Similar/same	93	96.0±6.3
Different	22	48.0±7.2
TNM stage of SPLAC			<0.001a
I	83	–b
II	19	66.0±11.2
IIIa	13	32.0±7.6
Histologic grade of SPLAC			0.001a
Low	25	101.0
Intermediate	72	91.0±15.7
High	18	51.0±11.0

Notes:

a Statistically significant.

b Median survival unable to be estimated. Data presented as mean ± standard deviation. –, Not applicable, as more than half the number of patients were still alive.

Abbreviations: CT, computed tomography; ECOG, Eastern Cooperative Oncology Group; GGO-p, ground glass opacity predominant; MPLC, multiple primary lung cancer; OS, overall survival; PS, performance status; Solid-p, solid predominant; SPLAC, second primary lung adenocarcinoma; TNM, tumor, node, and metastasis.

Figure 1 Survival comparisons according to tumor computed tomography morphologies of the second primary adenocarcinomas.

Abbreviations: GGO-p, ground glass opacity predominant; HR, hazard ratio; Solid-p, solid predominant.

Figure 2 Survival comparisons based on the tumor, node, and metastasis stage of the second primary adenocarcinomas.

Abbreviation: HR, hazard ratio.

Figure 3 Survival comparisons based on the histologic classification.

Abbreviation: HR, hazard ratio.

Figure 4 Survival comparisons according to histologic grade of the second primary adenocarcinomas.

Abbreviation: HR, hazard ratio.

Table 5 Cox proportional hazards model of factors associated with survival in patients with SPLAC

Characteristics	Overall survival
	HR	95% CI	P-value
CT morphology of SPLAC
GGO-p	0.42	0.19–0.94	0.036
Solid-p		Ref
Histology of MPLC
Similar/same	0.06	0.02–0.18	<0.001
Different		Ref
Pathologic stage of primary tumor
I	0.25	0.08–0.76	0.015
II		Ref
Pathologic stage of SPLAC			0.006
I	0.21	0.08–0.56	0.002
II	0.53	0.20–1.38	0.192
IIIa		Ref
Histologic grade			0.019
Low	0.05	0.01–0.58	0.016
Intermediate	0.37	0.15–0.89	0.027
High		Ref

Abbreviations: CI, confidence interval; CT, computed tomography; GGO-p, ground glass opacity predominant; HR, hazard ratio; MPLC, multiple primary lung cancer; Ref, reference; Solid-p, solid predominant; SPLAC, second primary lung adenocarcinoma.