Introduction
Materials and methods
Patients and inclusion criteria
18F–FDG PET/CT acquisition and analysis
ALK Ventana immunohistochemistry (IHC)
EGFR mutation analysis
IHC analysis
Statistical analysis
Results
Patient and tumor characteristics
Characteristics | EGFR Mutant | EGFR Wild-Type | Total |
p value | ALK Positive | ALK Negative | Total |
p value |
---|---|---|---|---|---|---|---|---|
Age (years), Mean ± SD (range) | 58.7 ± 9.8 (30–83) | 58.7 ± 10.5 (25–85) | 58.7 (25–85) | 0.908 | 50.5 ± 9.7 (31–69) | 58.8 ± 9.6 (29–85) | 58.2 ± 9.8 (29–85) | 0.001 |
Sex | <0.001 | 0.615 | ||||||
Male | 165 (35.3%) | 303 (64.7%) | 468 (57.9%) | 8 (6.6%) | 114 (93.4%) | 122 (54.7%) | ||
Female | 206 (60.6%) | 134 (39.4) | 340 (42.1%) | 9 (8.9%) | 92 (91.1%) | 101 (45.3%) | ||
Smoking status | <0.001 | 0.299 | ||||||
Never smoker | 278 (55.8%) | 220 (44.2%) | 498 (61.6%) | 13 (9.4%) | 126 (90.6%) | 139 (62.3%) | ||
Ever smoker | 93 (30%) | 217 (70%) | 310 (38.4%) | 4 (4.8%) | 80 (93.5%) | 84 (37.7%) | ||
Tumor size, Mean ± SD | 3.2 ± 1.6 | 3.7 ± 2.0 | 0.021 | 4.2 ± 2.6 | 3.8 ± 2.1 | 0.445 | ||
pSUVmax, Mean ± SD | 8.7 ± 4.8 | 10.7 ± 6.2 | <0.001 | 9.4 ± 4.2 | 10.4 ± 5.4 | 0.745 | ||
nSUVmax, Mean ± SD | 7.3 ± 4.2 | 9.3 ± 5.5 | <0.001 | 10.6 ± 3.5 | 8.6 ± 4.9 | 0.091 | ||
mSUVmax, Mean ± SD | 8.0 ± 4.9 | 9.5 ± 5.7 | 0.005 | 9.9 ± 6.1 | 8.8 ± 6.1 | 0.575 | ||
Nodal involvement | 0.030 | 0.652 | ||||||
0 | 149 (52.1%) | 137 (47.9%) | 286 (35.4%) | 5 (6.7%) | 70 (93.3%) | 75 (33.6%) | ||
1 | 20 (43.5%) | 26 (56.5%) | 46 (0.57%) | 0 (0.0%) | 9 (100.0%) | 9 (4.0%) | ||
2 | 74 (47.1) | 83 (52.9%) | 157 (19.4%) | 3 (6.2%) | 45 (93.8%) | 48 (21.5%) | ||
3 | 128 (40.1%) | 191 (59.9%) | 319 (39.5%) | 9 (9.9%) | 82 (90.1%) | 891 (40.8%) | ||
Metastasis | 0.618 | 0.009 | ||||||
0 | 163 (47.0%) | 184 (53.0%) | 347 (42.9%) | 2 (2.1%) | 94 (97.9%) | 96 (43.0%) | ||
1 | 208 (45.1%) | 253 (54.9%) | 461 (57.1%) | 15 (13.4%) | 112 (86.6%) | 127 (57.0%) | ||
Stage | <0.001 | 0.060 | ||||||
I | 87 (61.3%) | 55 (38.7%) | 142 (17.5%) | 1 (2.5%) | 39 (97.5%) | 40 (17.9%) | ||
II | 16 (32.7%) | 33 (67.3%) | 49 (6.4%) | 0 (0.0%) | 11 (100.0%) | 11 (4.9%) | ||
III | 61 (38.9%) | 96 (61.1%) | 157 (19.4%) | 1 (2.2%) | 44 (97.8%) | 45 (20.2%) | ||
IV | 207 (45.0%) | 253 (55.0%) | 460 (56.8%) | 15 (11.8%) | 112 (88.2%) | 127 (57.0%) | ||
Histology | <0.001 | 0.083 | ||||||
Adenocarcinoma | 367 (50.2%) | 364 (49.8%) | 731 (90.5%) | 17 (8.9%) | 173 (91.9%) | 190 (85.2%) | ||
Non-adenocarcinoma | 7 (9.1%) | 70 (90.9%) | 77 (9.5%) | 0 (0.0%) | 33 (100.0%) | |||
Squamous cell carcinoma | 5 (8.6%) | 53 (91.4%) | 58 (7.2%) | 0 (0.0%) | 25 (100.0%) | 25 (11.2%) | ||
Large cell carcinoma | 1 (25%) | 3 (75%) | 4 (0.5%) | 0 (0.0%) | 1 (100.0%) | 1 (0.4%) | ||
Undefined NSCLC | 1 (6.7%) | 14 (93.3%) | 15 (1.9%) | 0 (0.0%) | 7 (100.0%) | 7 (3.1%) | ||
TTF-1 | <0.001 | 0.046 | ||||||
Negative | 13 (14.1%) | 79 (85.9%) | 92 (17.2%) | 0 (0.0%) | 1541 (100.0%) | 41 (19.8%) | ||
Positive | 212 (47.7%) | 232 (52.3% | 444 (82.8%) | 16 (9.9%) | 150 (90.9%) | 166 (80.2%) | ||
NaspinA | <0.001 | 0.037 | ||||||
Negative | 15 (16.5%) | 76 (83.5%) | 91 (25.9%) | 0 (0.0%) | 44 (100.0%) | 44 (27.3%) | ||
Positive | 119 (45.8%) | 141 (54.2%) | 260 (74.1%) | 12 (10.4%) | 105 (89.6%) | 117 (72.7%) | ||
CK7 | 0.005 | 0.362 | ||||||
Negative | 2 (8.7%) | 21 (91.3%) | 23 (5.8%) | 0 (0.0%) | 15 (100.0%) | 15 (10.1%) | ||
Positive | 142 (37.9%) | 233 (62.1%) | 375 (94.2%) | 14 (10.4%) | 120 (89.6%) | 134 (89.9%) | ||
Ki67 score, Mean ± SD | 22.4 ± 21.2 | 33.4 ± 22.1 | 0.002 | 16.9 ± 9.6 | 38.4 ± 26.1 | <0.001 |
Association between clinical characteristics and EGFR mutations
Characteristics | EGFR Mutant | EGFR Wild-Type | Total |
p value | ALK Positive | ALK Negative | Total |
p value |
---|---|---|---|---|---|---|---|---|
Age (years), Mean ± SD (range) | 58.6 ± 9.8 (30–83) | 58.0 ± 10.5 (25–85) | 58.3 ± 10.1 (25–85) | 0.367 | 50.5 ± 9.7 (31–69) | 58.3 ± 9.5 (29–85) | 57.6 ± 9.7 (29–85) | 0.001 |
Sex | <0.001 | 0.803 | ||||||
Male | 159 (39.4%) | 245 (60.6%) | 404 (55.3%) | 8 (8.2%) | 89 (91.8%) | 97 (51.1%) | ||
Female | 205 (62.7%) | 122 (37.3) | 327 (44.7%) | 9 (9.7%) | 84 (90.3%) | 93 (48.9%) | ||
Smoking status | <0.001 | 0.589 | ||||||
Never smoker | 275 (58.4%) | 198 (41.6%) | 473 (64.7%) | 13 (10.2%) | 115 (89.8%) | 128 (67.4%) | ||
Ever smoker | 89 (34.5%) | 169 (65.5%) | 258 (35.3%) | 4 (6.5%) | 58 (93.5%) | 62 (32.6%) | ||
Tumor size, Mean ± SD | 2.9 ± 1.8 | 3.1 ± 2.0 | 0.302 | 3.5 ± 2.1 | 3.6 ± 2.0 | 0.349 | ||
pSUVmax, Mean ± SD | 8.6 ± 4.7 | 10.0 ± 6.0 | <0.001 | 9.4 ± 5.3 | 9.7 ± 4.8 | 0.852 | ||
nSUVmax, Mean ± SD | 7.3 ± 4.1 | 9.3 ± 5.5 | <0.001 | 10.6 ± 3.5 | 8.2 ± 4.7 | 0.046 | ||
mSUVmax, Mean ± SD | 7.9 ± 5.0 | 9.4 ± 5.7 | 0.010 | 9.9 ± 6.1 | 8.2 ± 5.3 | 0.353 | ||
Nodal involvement | 0.033 | 0.708 | ||||||
0 | 146 (55.7%) | 116 (44.3%) | 262 (35.8%) | 5 (7.9%) | 58 (92.1%) | 63 (33.2%) | ||
1 | 20 (48.8%) | 21 (51.2%) | 41 (5.6%) | 0 (0.0%) | 7 (100.0%) | 7 (3.7%) | ||
2 | 73 (52.1%) | 67 (47.9%) | 140 (19.2%) | 3 (7.5%) | 37 (92.5%) | 40 (21.1%) | ||
3 | 125 (43.4%) | 163 (56.6%) | 288 (39.4%) | 9 (11.3%) | 71 (88.8%) | 80 (42.1%) | ||
Metastasis | 0.223 | 0.010 | ||||||
0 | 160 (52.5%) | 145 (47.5%) | 305 (41.7%) | 2 (2.6%) | 76 (97.4%) | 78 (41.1%) | ||
1 | 204 (47.9%) | 222 (52.1%) | 426 (58.3%) | 15 (13.4%) | 97 (86.6%) | 112 (58.9%) | ||
Stage | 0.010 | 0.083 | ||||||
I | 85 (62.5%) | 51 (37.5%) | 136 (18.6%) | 1 (2.9%) | 34 (97.1%) | 35 (18.4%) | ||
II | 16 (42.1%) | 22 (57.9%) | 38 (5.2%) | 0 (0.0%) | 7 (100.0%) | 7 (3.7%) | ||
III | 60 (45.5%) | 72 (54.5%) | 132 (18.1%) | 1 (2.8%) | 35 (97.2%) | 36 (18.9%) | ||
IV | 203 (47.8%) | 222 (52.2%) | 425 (58.1%) | 15 (13.4%) | 97 (86.6%) | 112 (58.9%) | ||
TTF-1 | <0.001 | 0.376 | ||||||
Negative | 6 (13.6%) | 38 (86.4%) | 44 (9.1%) | 0 (0.0%) | 15 (100.0%) | 15 (8.5%) | ||
Positive | 212 (48.3%) | 227 (51.7%) | 439 (90.9%) | 16 (9.9%) | 145 (90.9%) | 161 (91.5%) | ||
NaspinA | <0.001 | 0.363 | ||||||
Negative | 10 (17.5%) | 47 (82.5%) | 57 (18.1%) | 0 (0.0%) | 15 (100.0%) | 15 (22%) | ||
Positive | 119 (46.1%) | 139 (53.9%) | 258 (81.9%) | 12 (10.4%) | 103 (89.6%) | 115 (78%) | ||
CK7 | 0.225 | 1.000 | ||||||
Negative | 0 (0.0%) | 2 (100.0%) | 2 (0.6%) | 0 (0.0%) | 1 (100.0%) | 1 (0.8%) | ||
Positive | 138 (39.4%) | 212 (60.6%) | 350 (99.4%) | 14 (11.5%) | 108 (88.5%) | 122 (99.2%) | ||
Ki67 score, Mean ± SD | 20.9 ± 18.8 | 31.1 ± 22.7 | 0.005 | 16.9 ± 9.6 | 31.9 ± 24.6 | 0.006 |
Association between clinical characteristics and ALK status
Prediction of the EGFR mutation status
Characteristics | Univariate Analysis OR (95% CI) |
p value | Multivariate Analysis OR (95% CI) |
p value |
---|---|---|---|---|
Age | 1.00 (0.99–1.01) | 0.908 | ||
Sex | <0.001 | 0.003 | ||
Male | Reference | Reference | ||
Female | 2.82 (2.12–3.77) | 1.83 (1.23–2.73) | ||
Smoking status | <0.001 | 0.006 | ||
Never smoker | 2.95 (2.18–3.98) | 1.79 (1.18–2.72) | ||
Ever smoker | Reference | Reference | ||
Histology | <0.001 | <0.001 | ||
Adenocarcinoma | 9.92 (4.50–21.86) | 7.09 (2.93–17.17) | ||
Non-adenocarcinoma | Reference | Reference | ||
Primary tumor SUVmax
| Reference | 0.001 | 0.041 | |
< 7.0 | 1.68 (1.25–2.26) | 1.48 (1.02–2.16) | ||
≥ 7.0 | Reference | Reference | ||
Tumor size | 0.92 (0.86–0.99) | 0.021 | 0.862 | |
Nodal involvement | 0.031 | 0.246 | ||
0 | ||||
1 | 0.71 (0.38–1.33) | 0.279 | ||
2 | 0.8 (0.56–1.21) | 0.318 | ||
3 | 0.62 (0.45–0.85) | 0.003 | ||
Distant metastasis | 0.601 | 1.000 | ||
0 | Reference | |||
1 | 0.93 (0.70–1.23) | |||
Stage | <0.001 | 0.347 | ||
I | Reference | |||
II | 0.31 (0.15–0.60) | 0.001 | ||
III | 0.40 (0.25–0.64) | <0.001 | ||
IV | 0.52 (0.35–0.76) | 0.001 |
Characteristics | Univariate Analysis OR (95% CI) |
p value | Multivariate Analysis OR (95% CI) |
p value |
---|---|---|---|---|
Age | 1.01 (0.99–1.02) | 0.366 | ||
Sex | <0.001 | 0.002 | ||
Male | Reference | Reference | ||
Female | 2.59 (1.92–3.50) | 1.91 (1.29–2.87) | ||
Smoking status | <0.001 | 0.010 | ||
Never smoker | 2.64 (1.93–3.61) | 1.74 (1.14–2.66) | ||
Ever smoker | Reference | Reference | ||
Primary tumor SUVmax
| 0.006 | 0.036 | ||
< 7.0 | 1.53 (1.13–2.09) | 1.51 (1.03–2.21) | ||
≥ 7.0 | Reference | Reference | ||
Tumor size | 0.96 (0.89–1.04) | 0.302 | ||
Nodal involvement | 0.034 | 0.250 | ||
0 | ||||
1 | 0.76 (0.39–1.46) | 0.407 | ||
2 | 0.87 (0.57–1.31) | 0.492 | ||
3 | 0.61 (0.44–0.85) | 0.004 | ||
Metastasis | 0.223 | 1.000 | ||
0 | Reference | |||
1 | 0.83 (0.62–1.12) | |||
Stage | 0.011 | 0.547 | ||
I | Reference | |||
II | 0.44 (0.21–0.91) | 0.026 | ||
III | 0.50 (0.31–0.81) | 0.005 | ||
IV | 0.55 (0.37–0.82) | 0.003 |
Prediction for ALK status
Characteristics | Univariate Analysis OR (95% CI) |
p value | Multivariate Analysis OR (95% CI) |
p value |
---|---|---|---|---|
Age | 0.92 (0.88–0.97) | 0.001 | 0.93 (0.88–0.99) | 0.014 |
Sex | 0511 | 0.528 | ||
Male | Reference | Reference | ||
Female | 1.39 (0.52–3.76) | 1.51 (0.42–5.40) | ||
Smoking status | 0.219 | 0.594 | ||
Never smoker | 2.06 (0.65–6.6) | 0.67 (0.16–2.88) | ||
Ever smoker | Reference | Reference | ||
Histology | 0.117 | 0.998 | ||
Adenocarcinoma | 5.13 (0.66–39.65) | |||
Non-adenocarcinoma | Reference | |||
Primary tumor SUVmax
| 0.96 (0.87–1.06) | 0.455 | 0.97 (0.86–1.10) | 0.615 |
Nodal metastasis SUVmax
| 1.08 (0.97–1.22) | 0.173 | ||
Distant metastasis SUVmax
| 1.03 (0.94–1.13) | 0.561 | ||
Tumor size | 1.09 (0.87–1.38) | 0.445 | ||
Nodal involvement | 0.846 | |||
0 | Reference | |||
1 | 0.76 (0.17–3.37) | 0.999 | ||
2 | 0.933 (0.21–4.01) | 0.927 | ||
3 | 1.54 (0.49–4.80) | 0.460 | ||
Metastasis | 0.058 | 0.071 | ||
0 | Reference | Reference | ||
1 | 1.66 (0.98–2.81) | 4.23 (0.89–20.20) | ||
Stage | 0.234 | |||
I | Reference | |||
II | 1.53 (0.43–5.45) | 0.508 | ||
III | 1.58 (0.62–4.08) | 0.340 | ||
IV | 2.24 (0.98–5.11) | 0.056 |
Characteristics | Univariate Analysis OR (95% CI) |
p value | Multivariate Analysis OR (95% CI) |
p value |
---|---|---|---|---|
Age | 0.92 (0.90–0.95) | <0.001 | 0.93 (0.89–0.99) | 0.014 |
Sex | 0.174 | 0.583 | ||
Male | Reference | Reference | ||
Female | 1.45 (0.85–2.48) | 0.70 (0.19–2.54) | ||
Smoking status | 0.213 | 0.647 | ||
Never smoker | 1.45 (0.81–2.61) | 1.41 (0.32–6.16) | ||
Ever smoker | Reference | Reference | ||
Primary tumor SUVmax
| 1.02 (0.98–1.07) | 0.332 | 0.97 (0.86–1.09) | 0.615 |
Tumor size | 1.04 (0.90–1.19) | 0.611 | ||
Nodal involvement | 0.225 | |||
0 | ||||
1 | 0.48 (0.06–3.76) | 0.487 | ||
2 | 1.58 (0.75–3.31) | 0.225 | ||
3 | 1.77 (0.94–3.33) | 0.079 | ||
Metastasis | 0.158 | 0.071 | ||
0 | Reference | Reference | ||
1 | 1.49 (0.86–2.58) | 4.22 (0.88–20.0) | ||
Stage | 0.235 | |||
I | Reference | |||
II | 1.99 (0.47–8.36) | 0.350 | ||
III | 2.37 (0.87–6.42) | 0.091 | ||
IV | 2.52 (1.04–6.11) | 0.041 |