Clinicopathological Factors Related to Recurrence Patterns of Resected Non-Small Cell Lung Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Characteristics
2.2. Pathological Evaluation
2.3. Follow-Up
2.4. Statistical Analysis
3. Results
3.1. Organ-specific Recurrence
3.2. Location (Local vs. Distant) and Numbers (Single vs. Multiple) of Recurrence Sites
3.3. Time to Recurrence
3.4. Survival after Recurrence
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Factors | All Cases n = 688 (%) | Recurrence Cases n = 223 (%) |
---|---|---|
sex male/female | 408/280 (59/41) | 145/78 (65/35) |
age median (range) | 71 (19–91) | 69 (19–87) |
observation period mean months (range) | 57.3 (4–194) | 58.5 (4−194) |
smoking ever/never | 482/206 (70/30) | 164/59 (74/36) |
surgery lobectomy/bilobectomy/pneumonectomy | 653/30/5 (95/4/1) | 208/12/3 (93/5/2) |
histological type AD/SQ/ADSQ/LA/LCNEC/others | 470/163/14/11/13/17 (68/24/2/2/2/2) | 154/45/6/3/5/10 (69/20/3/1/2/5)) |
invasive size <3cm/3–5cm/5–7cm/7cm> | 409/202/55/22 (59/30/8/3) | 85/96/28/14 (38/43/13/6) |
lymphatic permeation present/absent | 307/381 (45/55) | 120/103 (54/46) |
vascular invasion present/absent | 386/302 (56/44) | 175/48 (78/22) |
pleural invasion present/absent | 143/545 (21/79) | 130/93 (58/42) |
pulmonary metastasis present/absent | 41/647 (6/94) | 18/205 (8/92) |
lymph node metastasis N0/N1/N2 | 496/90/102 (72/13/15) | 107/44/72 (48/20/32) |
adjuvant therapy performed/undone | 170/518 (25/75) | 88/135 (39/61) |
pathological stage IA/IB/IIA/IIB/IIIA/IIIB | 228/151/44/128/99/38 (33/22/6/19/14/6) | 22/41/13/59/58/30 (10/18/6/26/26/14) |
Mediastinal Lymph Node Metastasis | |||||||||
---|---|---|---|---|---|---|---|---|---|
Factors | All Cases | Recurrence Cases | |||||||
Initial Recurrence | Final Recurrence | Initial Recurrence | Final Recurrence | ||||||
HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | ||
Sex | male | 1.92 (1.03–3.56) | 0.004 | - | 2.11 (1.11–4.05) | 0.025 | - | ||
female | 1 | 1 | |||||||
Pleural invasion | present | 3.01 (1.72–5.26) | 0.001 | 3.48 (2.05–5.92) | 0.001 | - | - | ||
absent | 1 | 1 | |||||||
Invasive size | >3 cm | 1.81 (1.02–3.21) | 0.043 | 1.94 (1.14–3.30) | 0.014 | - | - | ||
≤3 cm | 1 | 1 | |||||||
Lymph node metastasis | present | 5.46 (3.09–9.62) | 0.001 | 4.59 (2.70–7.81) | 0.001 | 2.98 (1.62–5.50) | 0.001 | 2.45 (1.38–4.35) | 0.002 |
absent | 1 | 1 | 1 | 1 |
Lung Metastasis | |||||||||
---|---|---|---|---|---|---|---|---|---|
Factors | All Cases | Recurrence Cases | |||||||
Initial Recurrence | Final Recurrence | Initial Recurrence | Final Recurrence | ||||||
HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | ||
Vascular invasion | present | - | - | 0.49 (0.26–0.96) | 0.037 | - | |||
absent | 1 | ||||||||
Pleural invasion | present | 6.62 (3.91–11.2) | 0.001 | 7.46 (4.61–12.1) | 0.001 | - | - | ||
absent | 1 | 1 | |||||||
Pulmonary metastasis | present | 2.11 (1.01–4.88) | 0.042 | 2.01 (1.01–4.46) | 0.044 | 2.80 (1.04–2.80) | 0.041 | 2.82 (1.02–7.81) | 0.046 |
absent | 1 | 1 | 1 | 1 | |||||
Invasive size | >3 cm | 2.33 (1.35–4.03) | 0.002 | 2.03 (1.25–3.30) | 0.004 | - | - | ||
≤3 cm | 1 | 1 |
Brain Metastasis | |||||||||
---|---|---|---|---|---|---|---|---|---|
Factors | All Cases | Recurrence Cases | |||||||
Initial Recurrence | Final Recurrence | Initial Recurrence | Final Recurrence | ||||||
HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | ||
Age | ≥70 | 0.42 (0.22–0.81) | 0.010 | 0.51 (0.29–0.87) | 0.017 | 0.44 (0.22–0.88) | 0.021 | 0.48 (0.26–0.88) | 0.017 |
<70 | 1 | 1 | 1 | 1 | |||||
Pathology | AD | 2.65 (1.18–5.96) | 0.018 | 4.37 (2.10–9.06) | 0.001 | 2.45 (1.05–5.68) | 0.038 | 4.77 (2.20–10.1) | 0.001 |
others | 1 | 1 | 1 | 1 | |||||
Vascular invasion | present | 6.45 (2.42–17.2) | 0.001 | 4.27 (2.02–9.01) | 0.001 | 3.09 (1.12–8.48) | 0.029 | 3.07 (1.38–6.80) | 0.006 |
absent | 1 | 1 | 1 | 1 | |||||
Pleural invasion | present | 2.68 (1.40–5.13) | 0.003 | 4.41 (2.53–7.69) | 0.001 | - | - | ||
absent | 1 | 1 | |||||||
Pathological stage | II–III | - | 2.11 (1.13–3.96) | 0.010 | - | - | |||
I | 1 |
Bone Metastasis | |||||||||
---|---|---|---|---|---|---|---|---|---|
Factors | All Cases | Recurrence Cases | |||||||
Initial Recurrence | Final Recurrence | Initial Recurrence | Final Recurrence | ||||||
HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | ||
Vascular invasion | present | 2.95 (1.08–8.07) | 0.037 | 2.45 (1.21–4.95) | 0.013 | - | - | ||
absent | 1 | 1 | |||||||
Pleural invasion | present | 5.32 (2.53–11.2) | 0.001 | 4.00 (2.24–7.14) | 0.001 | - | - | ||
absent | 1 | 1 |
Liver Metastasis | |||||||||
---|---|---|---|---|---|---|---|---|---|
Factors | All Cases | Recurrence Cases | |||||||
Initial Recurrence | Final Recurrence | Initial Recurrence | Final Recurrence | ||||||
HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | ||
Vascular invasion | present | 9.85 (3.90–58.6) | 0.001 | 7.58 (1.74–33.3) | 0.007 | 5.85 (1.86–12.5) | 0.001 | 2.59 (0.96–7.45) | 0.055 |
absent | 1 | 1 | 1 | 1 | |||||
Pleural invasion | present | 3.257 (1.33–7.94) | 0.010 | 2.70 (1.20–6.06) | 0.016 | - | - | ||
absent | 1 | 1 |
Adrenal Gland Metastasis | |||||||||
---|---|---|---|---|---|---|---|---|---|
Factors | All Cases | Recurrence Cases | |||||||
Initial Recurrence | Final Recurrence | Initial Recurrence | Final Recurrence | ||||||
HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | ||
Vascular invasion | present | 8.86 (3.14–53.5) | 0.001 | 7.99 (3.42–40.5) | 0.001 | 6.86 (2.15–13.5) | 0.001 | 7.95 (3.23–20.5) | 0.001 |
absent | 1 | 1 | 1 | 1 | |||||
Pleural invasion | present | 3.32 (1.03–10.6) | 0.044 | 3.45 (1.28–9.35) | 0.014 | - | - | ||
absent | 1 | 1 |
Factors | Initial Recurrence | Final Recurrence | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Location | Number | Number | ||||||||
Local (%) | Distant (%) | p | Single (%) | Multiple (%) | p | Single (%) | Multiple (%) | p | ||
Sex | male | 64 (44) | 81 (56) | 0.079 | 97 (67) | 48 (33) | 0.580 | 59 (41) | 86 (59) | 0.891 |
female | 25 (32) | 53 (68) | 55 (71) | 23 (29) | 31 (40) | 47 (60) | ||||
Age | ≥70 | 48 (44) | 62 (56) | 0.262 | 72 (65) | 38 (35) | 0.392 | 51 (46) | 59 (54) | 0.071 |
<70 | 41 (36) | 72 (64) | 80 (71) | 33 (29) | 39 (35) | 74 (65) | ||||
Smoking | ever | 63 (38) | 101 (62) | 0.447 | 112 (68) | 52 (32) | 0.944 | 68 (41) | 96 (59) | 0.575 |
never | 26 (44) | 33 (56) | 40 (68) | 19 (32) | 22 (37) | 37 (63) | ||||
Pathology | AD | 56 (36) | 98 (64) | 0.106 | 103 (67) | 51 (33) | 0.540 | 52 (34) | 102 (66) | 0.003 |
others | 33 (48) | 36 (52) | 49 (71) | 20 (29) | 38 (55) | 31 (45) | ||||
Lymphatic permeation | present | 46 (38) | 74 (62) | 0.604 | 78 (65) | 42 (35) | 0.274 | 40 (33) | 80 (67) | 0.021 |
absent | 43 (42) | 60 (58) | 74 (72) | 29 (28) | 50 (49) | 53 (51) | ||||
Vascular invasion | present | 65 (37) | 110 (63) | 0.107 | 115 (66) | 60 (34) | 0.134 | 68 (39) | 107 (61) | 0.383 |
absent | 24 (50) | 24 (50) | 37 (77) | 11 (23) | 22 (46) | 26 (54) | ||||
Pleural invasion | present | 53 (41) | 77 (59) | 0.757 | 89 (68) | 41 (32) | 0.909 | 55 (42) | 75 (58) | 0.483 |
absent | 36 (39) | 57 (61) | 63 (68) | 30 (32) | 35 (38) | 58 (62) | ||||
Pulmonary metastasis | present | 6 (33) | 12 (67) | 0.552 | 8 (44) | 10 (56) | 0.024 | 5 (28) | 13 (72) | 0.256 |
absent | 83 (40) | 122 (60) | 144 (70) | 61 (30) | 85 (41) | 120 (59) | ||||
Invasive size | >3cm | 54 (39) | 84 (61) | 0.762 | 91 (66) | 47 (34) | 0.365 | 59 (43) | 79 (57) | 0.353 |
≤3cm | 35 (41) | 50 (59) | 61 (72) | 24 (28) | 31 (50) | 31 (50) | ||||
Lymph node metastasis | present | 46 (40) | 70 (60) | 0.935 | 74 (64) | 42 (36) | 0.145 | 51 (48) | 56 (52) | 0.033 |
absent | 43 (40) | 64 (60) | 78 (73) | 29 (27) | 39 (34) | 77 (66) | ||||
Adjuvant therapy | performed | 53 (60) | 35 (40) | 0.973 | 60 (68) | 28 (32) | 0.996 | 34 (39) | 54 (61) | 0.672 |
undone | 81 (60) | 54 (40) | 92 (68) | 43 (32) | 56 (41) | 79 (59) | ||||
Pathological stage | II–III | 65 (41) | 95 (59) | 0.728 | 100 (63) | 60 (38) | 0.004 | 59 (37) | 101 (63) | 0.091 |
I | 24 (38) | 39 (62) | 52 (83) | 11 (17) | 31 (49) | 32 (51) |
Factors | Multiple Metastasis | ||||
---|---|---|---|---|---|
Initial Recurrence | Final Recurrence | ||||
HR (95% CI) | p | HR (95% CI) | p | ||
Pathology | AD | - | 2.06 (1.14–3.69) | 0.016 | |
Others | 1 | ||||
Lymphatic permeation | Present | - | 1.75 (1.00–3.03) | 0.048 | |
absent | 1 | ||||
Pathological stage | II–III | 2.57 (1.23–5.36) | 0.012 | - | |
I | 1 |
Multivariate Analysis | ||||||||
---|---|---|---|---|---|---|---|---|
Factors | n | Time to Recurrence | Survival after Recurrence | |||||
Median Months (Range) | HR (95% CI) | p | Median Months (Range) | HR (95% CI) | p | |||
Age | ≥70 | 110 | 12 (1–95) | - | 13 (0–83) | 1.99 (1.39–2.85) | 0.001 | |
<70 | 113 | 12 (1–119) | 25 (0–182) | 1 | ||||
Pathology | AD | 154 | 17 (1–119) | - | 23.5 (0–180) | 0.51 (0.36–0.74) | 0.001 | |
others | 69 | 10 (1–95) | 10 (1–182) | 1 | ||||
Vascular invasion | present | 175 | 11 (1–107) | 1.56 (1.12–2.17) | 0.008 | 17 (0–182) | 1.61 (1.00–2.36) | 0.048 |
absent | 48 | 24 (1–119) | 1 | 21 (1–121) | 1 | |||
Invasive size | >3 cm | 138 | 11 (1–119) | 1.37 (1.03–1.82) | 0.028 | 17 (0–182) | - | |
≤3 cm | 85 | 19 (1–107) | 1 | 21 (0–121) | ||||
Pathological stage | II–III | 160 | 11 (1–80) | 1.43 (1.04–1.96) | 0.027 | 17 (0–182) | - | |
I | 63 | 23 (3–119) | 1 | 21 (1–115) |
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Shimizu, R.; Kinoshita, T.; Sasaki, N.; Uematsu, M.; Sugita, Y.; Shima, T.; Harada, M.; Hishima, T.; Horio, H. Clinicopathological Factors Related to Recurrence Patterns of Resected Non-Small Cell Lung Cancer. J. Clin. Med. 2020, 9, 2473. https://doi.org/10.3390/jcm9082473
Shimizu R, Kinoshita T, Sasaki N, Uematsu M, Sugita Y, Shima T, Harada M, Hishima T, Horio H. Clinicopathological Factors Related to Recurrence Patterns of Resected Non-Small Cell Lung Cancer. Journal of Clinical Medicine. 2020; 9(8):2473. https://doi.org/10.3390/jcm9082473
Chicago/Turabian StyleShimizu, Reiko, Tomomari Kinoshita, Naomichi Sasaki, Mao Uematsu, Yusuke Sugita, Toshiyuki Shima, Masahiko Harada, Tsunekazu Hishima, and Hirotoshi Horio. 2020. "Clinicopathological Factors Related to Recurrence Patterns of Resected Non-Small Cell Lung Cancer" Journal of Clinical Medicine 9, no. 8: 2473. https://doi.org/10.3390/jcm9082473