1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
3Department of Hospital Pathology, Yeouido St. Mary’s hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
4Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
5Department of Thoracic and Cardiovascular Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
6Department of Radiology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
7Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang, Korea
8Department of Radiation Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
9Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
10Division of Pulmonology, Chungnam National University College of Medicine, Daejeon, Korea
11Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
12Department of Pulmonary, Daegu Catholic University Medical Center, Daegu Catholic University School of Medicine, Daegu, Korea
13Department of Thoracic and Cardiovascular Surgery, Pusan National University Hospital, Busan, Korea
14Department of Pathology, Chonnam National University Medical School, Gwangju, Korea
15Department of Public Health Science, Graduate School of Public Healthy, Seoul National University, Seoul, Korea
16Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
17Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
Copyright © 2024 by the Korean Cancer Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
The study protocol was reviewed and approved by the Institutional Review Board at the National Cancer Center (NCC2018-0193), which waived the requirement for informed consent due to the retrospective nature of the study.
Author Contributions
Conceived and designed the analysis: Kim KY, Lim JU.
Collected the data: Kim HC, Kim TJ, Kim HK, Moon MH, Beck KS, Suh YG, Song CH, Ahn JS, Lee JE, Jeon JH, Jung CY, Cho JS, Hwang SS, Choi CM, Jang SH, Lim JU.
Contributed data or analysis tools: Kim KY, Kim HC, Kim TJ, Kim HK, Moon MH, Beck KS, Suh YG, Song CH, Ahn JS, Lee JE, Jeon JH, Jung CY, Cho JS, Hwang SS, Choi CM, Jang SH, Lim JU.
Performed the analysis: Kim KY.
Wrote the paper: Kim KY, Lim JU.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Values are presented as mean±SD or number (%). ALK, anaplastic lymphoma kinase; ALK positive, ALK immunohistochemistry or fluorescence in situ hybridization positive; DLco, diffusing capacity of the lungs for carbon monoxide; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; FEV1, forced expiratory volume exhaled in the first second; FVC, forced vital capacity; LN, lymph node; NOS, not otherwise specified; NSCLC, non–small cell lung cancer; PFT, pulmonary function test; SD, standard deviation.
Values are presented as mean±SD or number (%). The significance level of p-value was set after Bonferroni correction. ALK, anaplastic lymphoma kinase; ALK positive, ALK immunohistochemistry or fluorescence in situ hybridizationpositive; DLCO, diffusing capacity of the lungs for carbon monoxide; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; ERG, early recurrence group; FEV1, forced expiratory volume exhaled in the first second; FVC, forced vital capacity; LN, lymph node; LRG, late recurrence group; NOS, not otherwise specified; NRG, no recurrence group; NSCLC, non–small cell lung cancer; PFT, pulmonary function test; RT, radiotherapy; SD, standard deviation.
Characteristic | No. of patients (%) |
---|---|
Age (yr) | 62.54±9.97 |
≤ 65 | 511 (58.9) |
> 65 | 356 (41.1) |
Sex | |
Male | 338 (39.0) |
Female | 529 (61.0) |
Smoking status | |
Never | 592 (68.3) |
Ever | 272 (31.4) |
Unknown | 3 (0.3) |
ECOG | |
0-1 | 754 (87.0) |
≥ 2 | 19 (2.2) |
Unknown | 94 (10.8) |
PFT | |
FVC (L) | 3.23±0.83 |
FEV1 (L) | 2.46±0.65 |
DLCO (%) | 93.97±19.69 |
Pathologic T category | |
T1 | 494 (57.0) |
T2 | 331 (38.2) |
T3 | 36 (4.2) |
T4 | 4 (0.5) |
Unknown | 2 (0.2) |
Pathologic N category | |
N0 | 669 (77.2) |
N1 | 87 (10.0) |
N2 | 102 (11.8) |
N3 | 3 (0.3) |
Unknown | 6 (0.7) |
Surgery type | |
Wedge resection | 61 (7.0) |
Segmentectomy | 77 (8.9) |
Lobectomy | 712 (82.1) |
Pneumonectomy | 17 (2.0) |
Pathologic TNM stage | |
I | 652 (75.2) |
II | 97 (11.2) |
III | 102 (11.8) |
IV | 8 (0.9) |
Unknown | 8 (0.9) |
Histologic type | |
Squamous | 35 (4.0) |
Adenocarcinoma | 818 (94.3) |
Large cell carcinoma | 0 |
NSCLC, NOS | 1 (0.1) |
Adenosquamous | 8 (0.9) |
Carcinoid | 0 |
Others | 5 (0.6) |
Pleural invasion | |
None (PL0) | 637 (73.5) |
Visceral pleural invasion (PL1) | 167 (19.3) |
Invasion to the surface of the visceral pleura (PL2) | 45 (5.2) |
Extend to the parietal pleura (PL3) | 14 (1.6) |
Pleural invasion, NOS | 0 |
Unknown | 4 (0.5) |
Mediastinal LN resection | |
No | 43 (5.0) |
Sampling | 51 (5.9) |
Dissection | 768 (88.6) |
Unknown | 5 (0.6) |
ALK | |
Positive | 26 (3.0) |
Negative | 700 (80.7) |
Unknown | 141 (16.3) |
Recurrence | |
No recurrence | 702 (81.0) |
Late recurrence | 121 (14.0) |
Early recurrence (≤ 1 yr) | 44 (5.1) |
Death | |
No | 749 (86.4) |
Yes | 118 (13.6) |
Observation time (mo) | 36.56±10.97 |
Recurrence-free survival time (mo) | 33.02±13.52 |
Recurrence-free survival rate (%) | |
1-Year | 94.9 |
2-Year | 85.8 |
3-Year | 81.7 |
Characteristic | ERG (n=44) | LRG (n=121) | NRG (n=702) | p-value |
---|---|---|---|---|
Age (yr) | 63.20±10.22 | 61.94±11.18 | 62.61±9.74 | 0.778 |
≤ 65 | 24 (54.5) | 73 (60.3) | 414 (59.0) | |
> 65 | 20 (45.5) | 48 (39.7) | 288 (41.0) | |
Sex | ||||
Male | 20 (45.5) | 50 (41.3) | 268 (38.2) | 0.266 |
Female | 24 (54.5) | 71 (58.7) | 434 (61.8) | |
Smoking status | ||||
Never | 21 (47.7) | 78 (64.5) | 493 (70.2) | 0.015 |
Ever | 23 (52.3) | 42 (34.7) | 207 (29.5) | |
Unknown | 0 | 1 (0.8) | 2 (0.3) | |
ECOG | ||||
0-1 | 37 (84.1) | 107 (88.4) | 611 (87.0) | 0.555 |
≥ 2 | 4 (9.1) | 1 (0.8) | 14 (2.0) | |
Unknown | 3 (6.8) | 13 (10.7) | 77 (11.0) | |
PFT | ||||
FVC (L) | 3.22±0.84 | 3.22±0.80 | 3.24±0.83 | 0.968 |
FEV1 (L) | 2.38±0.63 | 2.45±0.59 | 2.46±0.66 | 0.690 |
DLCO (%) | 91.23±24.77 | 93.06±19.50 | 94.21±19.36 | 0.524 |
Pathologic T category | ||||
T1 | 14 (31.8) | 47 (38.8) | 433 (61.7) | < 0.001 |
T2 | 23 (52.3) | 66 (54.5) | 242 (34.5) | |
T3 | 6 (13.6) | 8 (6.6) | 22 (3.1) | |
T4 | 1 (2.3) | 0 | 3 (0.4) | |
Unknown | 0 | 0 | 2 (0.3) | |
Pathologic N category | ||||
N0 | 23 (52.3) | 68 (56.2) | 578 (82.3) | < 0.001 |
N1 | 8 (18.2) | 24 (19.8) | 55 (7.8) | |
N2 | 12 (27.3) | 28 (23.1) | 62 (8.8) | |
N3 | 0 | 1 (0.8) | 2 (0.3) | |
Unknown | 1 (2.3) | 0 | 5 (0.7) | |
Surgery type | ||||
Wedge resection | 3 (6.8) | 7 (5.8) | 51 (7.3) | 0.304 |
Segmentectomy | 2 (4.5) | 11 (9.1) | 64 (9.1) | |
Lobectomy | 38 (86.4) | 98 (81.0) | 576 (82.1) | |
Pneumonectomy | 1 (2.3) | 5 (4.1) | 11 (1.6) | |
Pathologic TNM stage | ||||
I | 15 (34.1) | 60 (49.6) | 577 (82.2) | < 0.001 |
II | 13 (29.5) | 24 (19.8) | 60 (8.5) | |
III | 13 (29.5) | 35 (28.9) | 54 (7.7) | |
IV | 2 (4.5) | 1 (0.8) | 5 (0.7) | |
Unknown | 1 (2.3) | 1 (0.8) | 6 (0.9) | |
Histologic type | ||||
Squamous | 4 (9.1) | 5 (4.1) | 26 (3.7) | 0.986 |
Adenocarcinoma | 40 (90.9) | 111 (91.7) | 667 (95.0) | |
Large cell carcinoma | 0 | 0 | 0 | |
NSCLC, NOS | 0 | 0 | 1 (0.1) | |
Adenosquamous | 0 | 4 (3.3) | 4 (0.6) | |
Carcinoid | 0 | 0 | 0 | |
Others | 0 | 1 (0.8) | 4 (0.6) | |
Pleural invasion | ||||
None (PL0) | 24 (54.5) | 63 (52.1) | 550 (78.3) | < 0.001 |
Visceral pleural invasion (PL1) | 13 (29.5) | 45 (37.2) | 109 (15.5) | |
Invasion to the surface of the visceral pleura (PL2) | 5 (11.4) | 11 (9.1) | 29 (4.1) | |
Extend to the parietal pleura (PL3) | 2 (4.5) | 1 (0.8) | 11 (1.6) | |
Pleural invasion, NOS | 0 | 0 | 0 | |
Unknown | 0 | 1 (0.8) | 3 (0.4) | |
Mediastinal LN resection | ||||
No | 3 (6.8) | 5 (4.1) | 35 (5.0) | 0.624 |
Sampling | 2 (4.5) | 7 (5.8) | 42 (6.0) | |
Dissection | 39 (88.6) | 107 (88.4) | 622 (88.6) | |
Unknown | 0 | 2 (1.7) | 3 (0.4) | |
ALK | ||||
Positive | 3 (6.8) | 5 (4.1) | 18 (2.6) | 0.549 |
Negative | 37 (84.1) | 94 (77.7) | 569 (81.1) | |
Unknown | 4 (9.1) | 22 (18.2) | 115 (16.4) | |
Chemotherapy | ||||
Adjuvant | 31 (70.5) | 82 (67.8) | 155 (22.1) | < 0.001 |
Neoadjuvant | 5 (11.4) | 5 (4.1) | 14 (2.0) | |
None | 8 (18.2) | 34 (28.1) | 533 (75.9) | |
RT | ||||
Adjuvant | 21 (47.7) | 41 (33.9) | 48 (6.8) | < 0.001 |
Neoadjuvant | 3 (6.8) | 4 (3.3) | 7 (1.0) | |
None | 20 (45.5) | 76 (62.8) | 647 (92.2) | |
Observation time (mo) | 32.69±11.10 | 37.21±7.89 | 36.69±11.38 | 0.05 |
Recurrence-free survival time (mo) | 10.56±7.37 | 24.48±9.04 | 35.90±12.49 |
Parameter | Univariate |
Multivariate |
||
---|---|---|---|---|
HR (95% CI) | p-value | HR (95% CI) | p-value | |
Sex | ||||
Female vs. male (Ref) | 0.75 (0.51-1.10) | 0.136 | 0.73 (0.53-1.00) | 0.053 |
Age (yr) | ||||
> 65 vs. ≤ 65 (Ref) | 1.46 (1.05-2.03) | 0.023 | 1.41 (1.02-1.94) | 0.037 |
BMI | 0.96 (0.91-1.00) | 0.074 | ||
Smoking | ||||
Ever vs. never (Ref) | 1.00 (0.67-1.48) | 0.994 | - | - |
ECOG | ||||
≥ 2 vs. 0-1 (Ref) | 0.67 (0.16-2.74) | 0.573 | ||
DLCO (per) | 0.99 (0.99-1.00) | 0.106 | 0.99 (0.99-1.00) | 0.080 |
pT | ||||
T3-4 vs. T1-2 | 1.42 (0.70-2.90) | 0.332 | - | - |
pN | ||||
N1 vs. N0 (Ref) | 2.08 (1.15-3.75) | 0.015 | 2.00 (1.12-3.56) | 0.019 |
N2 vs. N0 (Ref) | 2.68 (1.37-5.25) | 0.004 | 2.53 (1.31-4.91) | 0.006 |
pStage | ||||
Stage II vs. stage I (Ref) | 1.92 (1.07-3.45) | 0.028 | 1.93 (1.10-3.39) | 0.021 |
Stage III vs. stage I (Ref) | 1.34 (0.65-2.75) | 0.431 | 1.38 (0.71-2.71) | 0.345 |
Pleural invasion | ||||
Visceral pleural invasion vs. no pleural invasion (Ref) | 1.97 (1.37-2.83) | 0.000 | 1.89 (1.33-2.70) | < 0.001 |
Surgery type | ||||
Lobectomy vs. limited resection (Ref) | 0.64 (0.30-1.33) | 0.228 | 0.66 (0.32-1.37) | 0.264 |
Pneumonectomy vs. limited resection (Ref) | 0.45 (0.25-0.79) | 0.006 | 0.45 (0.26-0.79) | 0.006 |
Parameter | Univariate |
Multivariate |
||
---|---|---|---|---|
HR (95% CI) | p-value | HR (95% CI) | p-value | |
Sex | ||||
Female vs. male (Ref) | 0.48 (0.30-0.76) | 0.002 | 0.48 (0.32-0.71) | < 0.001 |
Age (yr) | ||||
> 65 vs. ≤ 65 (Ref) | 2.02 (1.35-3.00) | 0.001 | 1.99 (1.35-2.94) | 0.001 |
BMI | 0.94 (0.89-0.99) | 0.014 | 0.93 (0.89-0.99) | 0.012 |
Smoking | ||||
Ever vs. never (Ref) | 1.04 (0.65-1.65) | 0.877 | - | - |
ECOG | ||||
≥ 2 vs. 0-1 (Ref) | 2.88 (1.14-7.30) | 0.026 | 2.86 (1.14-7.19) | 0.026 |
DLCO (per) | 0.99 (0.98-1.00) | 0.002 | 0.98 (0.98-0.99) | 0.002 |
pT | ||||
T3-4 vs. T1-2 | 0.68 (0.32-1.45) | 0.318 | - | - |
pN | ||||
N1 vs. N0 (Ref) | 1.04 (0.51-2.15) | 0.911 | - | - |
N2 vs. N0 (Ref) | 1.29 (0.55-3.00) | 0.561 | - | - |
pStage | ||||
Stage II vs. stage I (Ref) | 2.77 (1.64-4.69) | 0.000 | 2.61 (1.58-4.31) | < 0.001 |
Stage III vs. stage I (Ref) | 5.27 (3.10-8.97) | 0.000 | 4.69 (2.85-7.71) | < 0.001 |
Pleural invasion | ||||
Visceral pleural invasion vs. no pleural invasion (Ref) | 3.84 (1.27-11.61) | 0.017 | 3.34 (1.33-8.40) | 0.010 |
Surgery type | ||||
Lobectomy vs. limited resection (Ref) | 0.71 (0.26-1.91) | 0.496 | - | - |
Pneumonectomy vs. limited resection (Ref) | 0.73 (0.33-1.64) | 0.448 | - | - |
Values are presented as mean±SD or number (%). ALK, anaplastic lymphoma kinase; ALK positive, ALK immunohistochemistry or fluorescence
Values are presented as mean±SD or number (%). The significance level of p-value was set after Bonferroni correction. ALK, anaplastic lymphoma kinase; ALK positive, ALK immunohistochemistry or fluorescence
BMI, body mass index; CI, confidence interval; DLCO, diffusing capacity of the lungs for carbon monoxide; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; HR, hazard ratio; NSCLC, non–small cell lung cancer.
BMI, body mass index; CI, confidence interval; DLCO, diffusing capacity of the lungs for carbon monoxide; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; HR, hazard ratio; NSCLC, non–small cell lung cancer.