TABLE 3.
Lung EpiCheck performance by sensitivity and specificity
| Training set | European validation set | Chinese validation set | ||||||||||
| LCO EpiScore=60 | HCO EpiScore=70 | LCO EpiScore=60 | HCO EpiScore=70 | LCO EpiScore=60 | HCO EpiScore=70 | |||||||
| Cases/controls | 102/265 | 179/137 | 30/15 | |||||||||
| AUC (95% CI) | 0.890 (0.848–0.932) | 0.882 (0.846–0.918) | 0.899 (0.809–0.989) | |||||||||
| Overall sensitivity | 86/102 | 84.3 (75.8–90.8) | 75/102 | 73.5 (63.9–81.8) | 156/179 | 87.2 (81.3–91.7) | 133/179 | 74.3 (67.2–80.5) | 23/30 | 76.7 (59.1–88.2) | 17/30 | 56.7 (39.2–72.6) |
| Overall specificity | 206/265 | 77.7 (72.2–82.6) | 248/265 | 93.6 (89.9–96.2) | 88/137 | 64.2 (55.6–72.2) | 124/137 | 90.5 (84.3–94.9) | 14/15 | 93.3 (68.0–99.9) | 15/15 | 100.0 (78.1–100.0) |
| Sensitivity by histological subtype | Overall§ p=0.075 NSCLC versus SCLC p=0.213 |
Overall§ p=0.051 NSCLC versus SCLC p=0.278 |
Overall§ p=0.250 NSCLC versus SCLC p=0.224 |
Overall§ p=0.311 NSCLC versus SCLC p=0.120 |
p=0.029 | p<0.001 | ||||||
| Adenocarcinoma | 34/45 | 75.6 (60.5–87.1) | 27/45 | 60.0 (44.3–74.3) | 73/82 | 89.0 (80.2–94.9) | 59/82 | 72.0 (60.9–81.3) | 12/19 | 63.2 (38.4–83.7) | 6/19 | 31.6 (12.6–56.6) |
| Squamous cell carcinoma# | 35/38 | 92.1 (78.6–98.3) | 32/38 | 84.2 (68.7–94.0) | 61/74 | 82.4 (71.8–90.3) | 53/74 | 71.6 (59.9–81.5) | 11/11 | 100.0 (71.5–100.0) | 11/11 | 100.0 (71.5–100.0) |
| Other NSCLC | 2/3 | 66.7 (9.4–99.2) | 2/3 | 66.7 (9.4–99.2) | 5/6 | 83.3 (35.9–99.6) | 5/6 | 83.3 (35.9–99.6) | ||||
| All NSCLC | 71/86 | 82.6 (72.9–89.9) | 61/86 | 70.9 (60.1–80.2) | 139/162 | 85.8 (79.5–90.8) | 117/162 | 72.2 (64.7–79.0) | 23/30 | 76.7 (57.7–90.1) | 17/30 | 56.7 (37.4–74.5) |
| Small cell carcinoma | 10/10 | 100.0 (69.2–100.0) | 9/10 | 90.0 (55.5–99.7) | 15/15 | 100.0 (78.2–100.0) | 14/15 | 93.3 (68.1–99.8) | ||||
| Other/unknown | 5/6 | 83.3 (35.9–99.6) | 5/6 | 83.3 (35.9–99.6) | 2/2 | 100.0 (15.8–100.0) | 2/2 | 100.0 (15.8–100.0) | ||||
| Sensitivity by NSCLC stage | p=0.075 | p=0.012 | p=0.089 | p=0.187 | p=0.193 | p=0.018 | ||||||
| Stage I | 18/26 | 69.2 (48.2–85.7) | 13/26 | 50.0 (29.9–70.1) | 29/37 | 78.4 (61.8–90.2) | 23/37 | 62.2 (44.8–77.5) | 7/10 | 70.0 (34.8–93.3) | 3/10 | 30.0 (6.7–65.2) |
| Stage II | 17/21 | 81.0 (58.1–94.6) | 14/21 | 66.7 (43.0–85.4) | 24/28 | 85.7 (67.3–96.0) | 20/28 | 71.4 (51.3–86.8) | 3/6 | 50.0 (11.8–88.2) | 2/6 | 33.3 (4.3–77.7) |
| Stage III | 17/20 | 85.0 (62.1–96.8) | 16/20 | 80.0 (56.3–94.3) | 53/59 | 89.8 (79.2–96.2) | 44/59 | 74.6 (61.6–85.0) | 10/11 | 90.9 (58.7–99.8) | 10/11 | 90.9 (58.7–99.8) |
| Stage IV | 17/17 | 100.0 (80.5–100.0) | 16/17 | 94.1 (71.3–99.9) | 33/37 | 89.2 (74.6–97.0) | 30/37 | 81.1 (64.8–92.0) | 3/3 | 100.0 (29.2–100.0) | 2/3 | 66.7 (9.4–99.2) |
| Unstaged | 2/2 | 100.0 (15.8–100.0) | 2/2 | 100.0 (15.8–100.0) | 0/1 | 0.0 (0.0–97.5) | 0/1 | 0.0 (0.0–97.5) | ||||
| Sensitivity by tumour size (largest diameter), NSCLC only | p<0.001ƒ | p<0.0001ƒ | p=0.584 | p=0.043 | ||||||||
| ≤20 mm | 11/16 | 68.8 (41.3–89.0) | 7/16 | 43.8 (19.8–70.1) | 3/5 | 60.0 (14.7–94.7) | 1/5 | 20.0 (0.5–71.6) | ||||
| 21–30 mm | 14/22 | 63.6 (40.7–82.8) | 10/22 | 45.5 (24.4–67.8) | 4/6 | 66.7 (22.3–95.7) | 2/6 | 33.3 (4.3–77.7) | ||||
| 31–50 mm | 46/49 | 93.9 (83.1–98.7) | 38/49 | 77.6 (63.4–88.2) | 11/14 | 78.6 (49.2–95.3) | 9/14 | 64.3 (35.1–87.2) | ||||
| >50 mm | 47/50 | 94.0 (83.5–98.7) | 44/50 | 88.0 (75.7–95.5) | 5/5 | 100.0 (47.8–100.0) | 5/5 | 100.0 (47.8–100.0) | ||||
| Unknown¶ | 23/27 | 85.2 (66.3–95.8) | 20/27 | 74.1 (53.7–88.9) | ||||||||
| Sensitivity by tumour size (largest diameter), stage I NSCLC only | p=0.003 | p=0.020 | p=0.700 | p=0.200 | ||||||||
| ≤20 mm | 4/7 | 57.1 (18.4–90.1) | 3/7 | 42.9 (9.9–81.6) | 2/4 | 50.0 (6.8–93.2) | 0/4 | 0.0 (0.0–60.2) | ||||
| 21–30 mm | 6/11 | 54.5 (23.4–83.3) | 4/11 | 36.4 (10.9–69.2) | 3/3 | 100.0 (29.2–100.0) | 1/3 | 33.3 (0.8–90.6) | ||||
| >30 mm | 19/19 | 100.0 (82.4–100.0) | 16/19 | 84.2 (60.4–96.6) | 2/3 | 66.7 (9.4–99.2) | 2/3 | 66.7 (9.4–99.2) | ||||
| Sensitivity by stage group, NSCLC only | p=0.058 | p=0.008 | p=0.641 | p=0.465 | p=0.290 | p=0.196 | ||||||
| Early stages (I, II and IIIA) | 45/59 | 76.3 (63.4–86.4) | 36/59 | 61.0 (47.4–73.5) | 86/101 | 85.1 (76.7–91.4) | 71/101 | 70.3 (60.4–79.0) | 17/24 | 70.8 (48.9–87.4) | 12/24 | 50.0 (29.1–70.9) |
| Advanced stages (IIIB and IV)+ | 24/25 | 96.0 (79.6–99.9) | 23/25 | 92.0 (74.0–99.0) | 53/60 | 88.3 (77.4–95.2) | 46/60 | 76.7 (64.0–86.6) | 6/6 | 100.0 (54.0–100.0) | 5/6 | 83.3 (35.9–99.6) |
| Sensitivity by SCLC stage | p=1.000 | p=0.300 | p=1.000 | p=1.000 | ||||||||
| Limited | 3/3 | 100.0 (29.2–100.0) | 2/3 | 66.7 (9.4–99.2) | 6/6 | 100.0 (54.1–100.0) | 6/6 | 100.0 (54.1–100.0) | ||||
| Extensive | 7/7 | 100.0 (59.0–100.0) | 7/7 | 100.0 (59.0–100.0) | 9/9 | 100.0 (66.4–100.0) | 8/9 | 88.9 (51.8–99.7) | ||||
Data are presented as n/N or % (95% CI), unless otherwise stated. LCO: low cut-off; HCO: high cut-off; AUC: area under the curve; NSCLC: nonsmall cell lung cancer; SCLC: small cell lung cancer. In the cases of complete or quasi-complete separation, exact p-values were calculated. #: patients with adenosquamous carcinoma histology were grouped with the squamous cell carcinoma histology subtype; ¶: tumour sizes were missing or unmeasurable for n=3 stage II, n=14 stage III and n=10 stage IV; +: stage III tumours without stage IIIA/IIIB classification were included in the advanced stages group; §: p-value calculation for the comparison of histological subtypes did not include the “unknown” group; ƒ: p-value calculation for the comparison by tumour size did not include the “unknown” group.