World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 13, Number 5, October 2022, pages 259-271

Distinct Prognostic Factors of Ground Glass Opacity and Pure-Solid Lesion in Pathological Stage I Invasive Lung Adenocarcinoma

Figure 1. (a) OS for patients with pure-GGOs, part-GGOs and pure-solid nodules. (b) DFS for patients with pure-GGOs, part-GGOs and pure-solid nodules. OS: overall survival; DFS: disease-free survival; GGO: ground-glass opacity.

Figure 2. (a) OS for patients with different grade of CTR. (b) DFS for patients with different grade of CTR. OS: overall survival; DFS: disease-free survival; CTR: consolidation-tumor-ratio.

Figure 3. (a) OS for patients with sublobectomy and lobectomy or others. (b) DFS for patients with sublobectomy and lobectomy or others. OS: overall survival; DFS: disease-free survival.

**Table 1.** Patient Characteristics
Characteristics	Radiologic characteristic on CT	P value	P value
VATS: video-assisted thoracoscopic surgery; EGFR: epidermal growth factor receptor; ALK: anaplastic lymphoma kinase; CT: computed tomography; GGO: ground-glass opacity. ^aThe P value was calculated excluded the patients with unknown EGFR or ALK status.
Gender					0.008	0.033
Male	56 (41.8)	266 (49.3)	223 (56.3)	545 (50.9)
Female	78 (58.2)	274 (50.7)	173 (43.7)	525 (49.1)
Age (year)	56.5 ± 9.0	59.9 ± 9.1	61.0 ± 9.4	59.8 ± 9.3	< 0.001	0.087
Pathological tumor size (cm)	1.4 ± 0.6	2.3 ± 0.8	2.3 ± 0.8	2.2 ± 0.8	< 0.001	0.357
Solid tumor size (cm)	0	1.6 ± 1.0	2.2 ± 0.9	1.6 ± 1.0	< 0.001	< 0.001
Smoking history					< 0.001	0.028
No	107 (79.9)	353 (65.4)	231 (58.3)	691 (64.6)
Yes or ever	27 (20.1)	187 (34.6)	165 (41.7)	379 (35.4)
8th TNM stage					< 0.001	< 0.001
IA	115 (85.8)	318 (58.9)	187 (47.2)	620 (57.9)
IB	19 (14.2)	222 (41.1)	209 (52.8)	450 (42.1)
Differentiation degree					< 0.001	< 0.001
Well	61 (45.5)	52 (9.6)	20 (5.1)	133 (12.4)
Moderate	67 (50.0)	352 (65.2)	226 (57.1)	645 (60.3)
Poor	6 (4.5)	136 (25.2)	150 (37.9)	292 (27.3)
Visceral pleura invasion					< 0.001	0.009
Negative	116 (86.6)	383 (70.9)	249 (62.9)	748 (69.9)
Positive	18 (13.4)	157 (29.1)	147 (37.1)	322 (30.1)
Vascular invasion					0.028	0.579
Negative	133 (99.3)	508 (94.1)	369 (93.2)	1,010 (94.4)
Positive	1 (0.7)	32 (5.9)	27 (6.8)	60 (5.6)
Number of N2 station examined	2.7 ± 1.5	3.2 ± 1.4	3.2 ± 1.4	3.2 ± 1.4	< 0.001	0.938
Number of N1 station examined	2.8 ± 1.2	2.7 ± 1.2	2.7 ± 1.2	2.7 ± 1.2	0.442	0.568
Surgical approach					< 0.001	0.022
Sublobectomy	23 (17.2)	36 (6.7)	13 (3.3)	72 (6.7)
Lobectomy and others	111 (82.8)	504 (93.3)	383 (96.7)	998 (93.3)
Thoracotomy or VATS					< 0.001	0.608
Thoracotomy	31 (23.1)	216 (40.0)	165 (41.7)	412 (38.5)
VATS	103 (76.9)	324 (60.0)	231 (58.3)	658 (61.5)
EGFR gene mutation					0.222^a	0.084^a
Negative	34 (25.4)	158 (29.3)	131 (33.1)	323 (30.2)
Positive	47 (35.1)	236 (43.7)	149 (37.6)	432 (40.4)
Unknown	53 (39.6)	146 (27.0)	116 (29.3)	315 (29.4)
ALK rearrangement					0.755^a	0.955^a
Negative	73 (54.5)	317 (58.7)	229 (57.8)	619 (57.9)
Positive	1 (0.7)	10 (1.9)	7 (1.8)	18 (1.7)
Unknown	60 (44.8)	213 (39.4)	160 (40.4)	433 (40.5)

Table 1. Patient Characteristics

Characteristics

Radiologic characteristic on CT

P value

Pure-GGO (n = 134)

Part-GGO (n = 540)

Pure-solid (n = 396)

Overall (n = 1,070)

Part-solid vs. pure-solid

VATS: video-assisted thoracoscopic surgery; EGFR: epidermal growth factor receptor; ALK: anaplastic lymphoma kinase; CT: computed tomography; GGO: ground-glass opacity. ^aThe P value was calculated excluded the patients with unknown EGFR or ALK status.

Gender

0.008

0.033

Male

56 (41.8)

266 (49.3)

223 (56.3)

545 (50.9)

Female

78 (58.2)

274 (50.7)

173 (43.7)

525 (49.1)

Age (year)

56.5 ± 9.0

59.9 ± 9.1

61.0 ± 9.4

59.8 ± 9.3

< 0.001

0.087

Pathological tumor size (cm)

1.4 ± 0.6

2.3 ± 0.8

2.2 ± 0.8

< 0.001

0.357

Solid tumor size (cm)

1.6 ± 1.0

2.2 ± 0.9

1.6 ± 1.0

< 0.001

Smoking history

< 0.001

0.028

107 (79.9)

353 (65.4)

231 (58.3)

691 (64.6)

Yes or ever

27 (20.1)

187 (34.6)

165 (41.7)

379 (35.4)

8th TNM stage

< 0.001

115 (85.8)

318 (58.9)

187 (47.2)

620 (57.9)

19 (14.2)

222 (41.1)

209 (52.8)

450 (42.1)

Differentiation degree

< 0.001

Well

61 (45.5)

52 (9.6)

20 (5.1)

133 (12.4)

Moderate

67 (50.0)

352 (65.2)

226 (57.1)

645 (60.3)

Poor

6 (4.5)

136 (25.2)

150 (37.9)

292 (27.3)

Visceral pleura invasion

< 0.001

0.009

Negative

116 (86.6)

383 (70.9)

249 (62.9)

748 (69.9)

Positive

18 (13.4)

157 (29.1)

147 (37.1)

322 (30.1)

Vascular invasion

0.028

0.579

Negative

133 (99.3)

508 (94.1)

369 (93.2)

1,010 (94.4)

Positive

1 (0.7)

32 (5.9)

27 (6.8)

60 (5.6)

Number of N2 station examined

2.7 ± 1.5

3.2 ± 1.4

< 0.001

0.938

Number of N1 station examined

2.8 ± 1.2

2.7 ± 1.2

0.442

0.568

Surgical approach

< 0.001

0.022

Sublobectomy

23 (17.2)

36 (6.7)

13 (3.3)

72 (6.7)

Lobectomy and others

111 (82.8)

504 (93.3)

383 (96.7)

998 (93.3)

Thoracotomy or VATS

< 0.001

0.608

Thoracotomy

31 (23.1)

216 (40.0)

165 (41.7)

412 (38.5)

VATS

103 (76.9)

324 (60.0)

231 (58.3)

658 (61.5)

EGFR gene mutation

0.222^a

0.084^a

Negative

34 (25.4)

158 (29.3)

131 (33.1)

323 (30.2)

Positive

47 (35.1)

236 (43.7)

149 (37.6)

432 (40.4)

Unknown

53 (39.6)

146 (27.0)

116 (29.3)

315 (29.4)

ALK rearrangement

0.755^a

0.955^a

Negative

73 (54.5)

317 (58.7)

229 (57.8)

619 (57.9)

Positive

1 (0.7)

10 (1.9)

7 (1.8)

18 (1.7)

Unknown

60 (44.8)

213 (39.4)

160 (40.4)

433 (40.5)

**Table 2.** LASSO and Cox Regression Analyses for All Patients
Factors	Univariate analysis	LASSO analysis	Multivariate analysis
LASSO: the least absolute shrinkage and selection operator; HR: hazard ratio; CI: confidence interval; OS: overall survival; DFS: disease-free survival; VATS: video-assisted thoracoscopic surgery; GGO: ground-glass opacity.
Analysis of OS
Gender	< 0.001	-0.463	0.509 (0.327 - 0.793)	0.003
Age (year)	< 0.001	0.038	1.042 (1.017 - 1.067)	0.001
Pathological tumor size (cm)	0.008	0.17	1.207 (0.923 - 1.580)	0.179
Smoking history	0.001	0.144	1.165 (0.670 - 2.028)	0.588
8th TNM stage (IA versus IB)	0.017
Differentiation degree		0.289
Well	Reference			Reference
Moderate	0.594		0.950 (0.436 - 2.069)	0.897
Poor	0.021		1.538 (0.697 - 3.395)	0.287
Visceral pleura invasion	0.011	0.465	1.748 (1.153 - 2.652)	0.009
Vascular invasion	0.301
Operative approach	0.256
Number of N2 stations examined	0.045	-0.083	0.905 (0.776 - 1.057)	0.207
Number of N1 stations examined	< 0.001	-0.145	0.851 (0.709 - 1.021)	0.083
Presence of GGO component		-0.334
Pure - solid	Reference			Reference
Part GGO	0.053		0.753 (0.495 - 1.146)	0.185
Pure GGO	0.023		0.114 (0.016 - 0.834)	0.032
Thoracotomy or VATS	0.785
Analysis of DFS
Gender	0.001	-0.321	0.664 (0.493 - 0.894)	0.007
Age (year)	0.185
Pathological tumor size (cm)	< 0.001	0.332	1.451 (1.205 - 1.747)	< 0.001
Smoking history	0.003	0.026	1.035 (0.694 - 1.543)	0.866
8th TNM stage (IA versus IB)	< 0.001		0.782 (0.437 - 1.398)	0.406
Differentiation degree		0.132
Well	Reference			Reference
Moderate	0.078		1.177 (0.645 - 2.145)	0.595
Poor	0.002		1.359 (0.724 - 2.551)	0.339
Visceral pleura invasion	< 0.001	0.495	1.698 (1.265 - 2.279)	< 0.001
Vascular invasion	0.043	0.339	1.543 (0.890 - 2.677)	0.122
Operative approach	0.371
Number of N2 stations examined	0.209
Number of N1 stations examined	0.008	-0.147	0.844 (0.742 - 0.960)	0.010
Presence of GGO component		-0.481
Pure - solid	Reference			Reference
Part GGO	< 0.001		0.605 (0.449 - 0.815)	0.001
Pure GGO	< 0.001		0.252 (0.101 - 0.629)	0.003
Thoracotomy or VATS	0.381

Table 2. LASSO and Cox Regression Analyses for All Patients

Factors

Univariate analysis

LASSO analysis

Multivariate analysis

P value

Coefficient

HR (95% CI)

P value

LASSO: the least absolute shrinkage and selection operator; HR: hazard ratio; CI: confidence interval; OS: overall survival; DFS: disease-free survival; VATS: video-assisted thoracoscopic surgery; GGO: ground-glass opacity.

Analysis of OS

Gender

< 0.001

-0.463

0.509 (0.327 - 0.793)

0.003

Age (year)

< 0.001

0.038

1.042 (1.017 - 1.067)

0.001

Pathological tumor size (cm)

0.008

0.17

1.207 (0.923 - 1.580)

0.179

Smoking history

0.001

0.144

1.165 (0.670 - 2.028)

0.588

8th TNM stage (IA versus IB)

0.017

Differentiation degree

0.289

Well

Reference

Moderate

0.594

0.950 (0.436 - 2.069)

0.897

Poor

0.021

1.538 (0.697 - 3.395)

0.287

Visceral pleura invasion

0.011

0.465

1.748 (1.153 - 2.652)

0.009

Vascular invasion

0.301

Operative approach

0.256

Number of N2 stations examined

0.045

-0.083

0.905 (0.776 - 1.057)

0.207

Number of N1 stations examined

< 0.001

-0.145

0.851 (0.709 - 1.021)

0.083

Presence of GGO component

-0.334

Pure - solid

Reference

Part GGO

0.053

0.753 (0.495 - 1.146)

0.185

Pure GGO

0.023

0.114 (0.016 - 0.834)

0.032

Thoracotomy or VATS

0.785

Analysis of DFS

Gender

0.001

-0.321

0.664 (0.493 - 0.894)

0.007

Age (year)

0.185

Pathological tumor size (cm)

< 0.001

0.332

1.451 (1.205 - 1.747)

< 0.001

Smoking history

0.003

0.026

1.035 (0.694 - 1.543)

0.866

8th TNM stage (IA versus IB)

< 0.001

0.782 (0.437 - 1.398)

0.406

Differentiation degree

0.132

Well

Reference

Moderate

0.078

1.177 (0.645 - 2.145)

0.595

Poor

0.002

1.359 (0.724 - 2.551)

0.339

Visceral pleura invasion

< 0.001

0.495

1.698 (1.265 - 2.279)

< 0.001

Vascular invasion

0.043

0.339

1.543 (0.890 - 2.677)

0.122

Operative approach

0.371

Number of N2 stations examined

0.209

Number of N1 stations examined

0.008

-0.147

0.844 (0.742 - 0.960)

0.010

Presence of GGO component

-0.481

Pure - solid

Reference

Part GGO

< 0.001

0.605 (0.449 - 0.815)

0.001

Pure GGO

< 0.001

0.252 (0.101 - 0.629)

0.003

Thoracotomy or VATS

0.381

**Table 3.** LASSO and Cox Regression Analyses for Patients With Part-GGOs
Factors	Univariate analysis	LASSO analysis	Multivariate analysis
LASSO: the least absolute shrinkage and selection operator; HR: hazard ratio; CI: confidence interval; CTR: consolidation-tumor-ratio; OS: overall survival; DFS: disease-free survival; VATS: video-assisted thoracoscopic surgery; GGO: ground-glass opacity.
Analysis of OS
Gender	0.001	-1.021	0.329 (0.170 - 0.635)	0.001
Age (year)	0.391
Solid tumor size (cm)	< 0.001	0.042	1.138 (0.711 - 1.820)	0.590
Smoking history	0.008	0.013	1.052 (0.497 - 2.226)	0.894
8th TNM stage (IA versus IB)	0.011	0.073	1.131 (0.383 - 3.341)	0.823
Differentiation degree
Well	Reference
Moderate	0.537
Poor	0.320
Visceral pleura invasion	0.013	0.495	1.894 (1.029 - 3.485)	0.040
Vascular invasion	0.272
Operative approach	0.988
Number of N2 stations examined	0.169
Number of N1 stations examined	0.054
CTR	0.001	3.081	1.401 (1.096 – 1.792)	0.007
Thoracotomy or VATS	0.387
Analysis of DFS
Gender	< 0.001	-0.896	0.381 (0.236 – 0.613)	< 0.001
Age (year)	0.477
Solid tumor size (cm)	< 0.001	0.357	1.773 (1.372 - 2.290)	< 0.001
Smoking history	0.005
8th TNM stage (IA versus IB)	< 0.001
Differentiation degree
Well	Reference
Moderate	0.964
Poor	0.135
Visceral pleura invasion	< 0.001	0.645	2.022 (1.296 - 3.154)	0.002
Vascular invasion	0.049	0.573	1.935 (0.930 - 4.028)	0.078
Operative approach	0.515
Number of N2 stations examined	0.428
Number of N1 stations examined	0.495
CTR	< 0.001	1.051	2.530 (0.261 - 24.481)	0.493
Thoracotomy or VATS	0.760

Table 3. LASSO and Cox Regression Analyses for Patients With Part-GGOs

Factors

Univariate analysis

LASSO analysis

Multivariate analysis

P value

Coefficient

HR (95% CI)

P value

LASSO: the least absolute shrinkage and selection operator; HR: hazard ratio; CI: confidence interval; CTR: consolidation-tumor-ratio; OS: overall survival; DFS: disease-free survival; VATS: video-assisted thoracoscopic surgery; GGO: ground-glass opacity.

Analysis of OS

Gender

0.001

-1.021

0.329 (0.170 - 0.635)

0.001

Age (year)

0.391

Solid tumor size (cm)

< 0.001

0.042

1.138 (0.711 - 1.820)

0.590

Smoking history

0.008

0.013

1.052 (0.497 - 2.226)

0.894

8th TNM stage (IA versus IB)

0.011

0.073

1.131 (0.383 - 3.341)

0.823

Differentiation degree

Well

Reference

Moderate

0.537

Poor

0.320

Visceral pleura invasion

0.013

0.495

1.894 (1.029 - 3.485)

0.040

Vascular invasion

0.272

Operative approach

0.988

Number of N2 stations examined

0.169

Number of N1 stations examined

0.054

CTR

0.001

3.081

1.401 (1.096 – 1.792)

0.007

Thoracotomy or VATS

0.387

Analysis of DFS

Gender

< 0.001

-0.896

0.381 (0.236 – 0.613)

< 0.001

Age (year)

0.477

Solid tumor size (cm)

< 0.001

0.357

1.773 (1.372 - 2.290)

< 0.001

Smoking history

0.005

8th TNM stage (IA versus IB)

< 0.001

Differentiation degree

Well

Reference

Moderate

0.964

Poor

0.135

Visceral pleura invasion

< 0.001

0.645

2.022 (1.296 - 3.154)

0.002

Vascular invasion

0.049

0.573

1.935 (0.930 - 4.028)

0.078

Operative approach

0.515

Number of N2 stations examined

0.428

Number of N1 stations examined

0.495

CTR

< 0.001

1.051

2.530 (0.261 - 24.481)

0.493

Thoracotomy or VATS

0.760

Table 4. LASSO and Cox Regression Analyses for Patients With Pure-Solid

Factors

Univariate analysis

LASSO analysis

Multivariate analysis

P value

Coefficient

HR (95% CI)

P value

Analysis of OS

Gender

0.675

Age (year)

< 0.001

0.068

1.073 (1.035 - 1.112)

< 0.001

Pathological tumor size (cm)

0.800

Smoking history

0.117

8th TNM stage (IA versus IB)

0.906

Differentiation degree

Well

Reference

Moderate

0.822

Poor

0.640

Visceral pleura invasion

0.518

Vascular invasion

0.929

Operative approach

0.003

1.382

4.118 (1.455 - 11.657)

0.008

Number of N2 stations examined

0.108

Number of N1 stations examined

0.184

Thoracotomy or VATS

0.385

Analysis of DFS

Gender

0.535

Age (year)

0.164

Pathological tumor size (cm)

0.024

0.312

1.377 (1.074 - 1.766)

0.012

Smoking history

0.949

8th TNM stage (IA versus IB)

0.121

Differentiation degree

Well

Reference

Moderate

0.909

Poor

0.735

Visceral pleura invasion

0.065

Vascular invasion

0.649

Operative approach

0.002

1.104

3.150 (1.401 - 7.081)

0.005

Number of N2 stations examined

0.258

Number of N1 stations examined

0.004

-0.175

0.517 (0.317 - 0.842)

0.008

Thoracotomy or VATS

0.744