Key points
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Nephrographic-phase CT radiomics is valuable in predicting the WHO/ISUP nuclear grade of CCRCC.
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Machine learning can noninvasively predict the WHO/ISUP nuclear grade of CCRCC.
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CT radiomics integrated with clinicoradiological parameters can facilitate differentiating between low- and high-grade CCRCCs with improved diagnostic efficacy.
Introduction
Materials and methods
Patient cohort
Nuclear grade and clinical characteristics
CT acquisition
Image analysis
Tumor segmentation
Radiomics feature extraction
Prediction model construction
Model evaluation
Statistical analysis
Results
Clinicoradiological characteristics between the low- and high-grade groups
Characteristics | Full cohort (n = 406) | Low grade (n = 330) | High grade (n = 76) | t value or χ2-value | p value |
---|---|---|---|---|---|
Age (years) | 57.48 ± 12.10 | 57.12 ± 11.94 | 59.07 ± 12.73 | 1.268 | 0.205 |
Gender, n (%) | |||||
Male | 240 (59.1%) | 189 (57.3%) | 51 (67.1%) | 2.471 | 0.116 |
Female | 166 (40.9%) | 141 (42.7%) | 25 (32.9%) | ||
BMI (kg/m2) | 24.30 ± 4.07 | 24.45 ± 4.04 | 23.69 ± 4.17 | 1.469 | 0.143 |
Smoking history, n (%) | 135 (33.3%) | 105 (31.8%) | 30 (39.5%) | 1.631 | 0.202 |
Hypertension, n (%) | 147 (36.2%) | 125 (37.9%) | 22 (28.9%) | 2.133 | 0.144 |
Diabetes, n (%) | 62 (15.3%) | 49 (14.8%) | 13 (17.1%) | 0.243 | 0.622 |
Tumor size (cm) | 4.51 ± 2.29 | 4.21 ± 2.02 | 5.82 ± 2.85 | 4.674 | < 0.001 |
Tumor bearing, n (%) | |||||
Left | 214 (52.7%) | 178 (53.9%) | 36 (47.4%) | 1.070 | 0.301 |
Right | 192 (47.3%) | 152 (46.1%) | 40 (52.6%) | ||
Operative method, n (%) | |||||
Partial | 213 (52.3%): | 192 (58.2%): | 20 (26.3%): | 25.140 | < 0.001 |
Radical | 194 (47.7%) | 138 (41.8%) | 56 (73.7%) | ||
Hematuria, n (%) | 49 (12.1%) | 34 (10.3%) | 15 (19.7%) | 5.180 | 0.023 |
Flank pain, n (%) | 63 (15.5%) | 48 (14.5%) | 15 (19.7%) | 1.270 | 0.260 |
Distant Metastasis, n (%) | 2 (0.5%) | 0 (0.0%) | 2 (2.6%) | – | 0.035 |
Intratumoral necrosis, n (%) | 192 (47.3%) | 135 (40.9%) | 57 (75.0%) | 28.802 | < 0.001 |
Cystic Degeneration, n (%) | 39 (9.6%) | 34 (10.3%) | 5 (6.6%) | 1.001 | 0.317 |
Calcification, n (%) | 24 (5.9%) | 12 (3.6%) | 12 (15.8%) | 14.292 | < 0.001 |
Violation of the Renal Capsule, n (%) | 64 (15.8%) | 35 (10.6%) | 29 (38.2%) | 35.314 | < 0.001 |
Angiogenesis, n (%) | 250 (61.6%) | 184 (55.8%) | 66 (86.8%) | 25.228 | < 0.001 |
Venous invasion, n (%) | 9 (2.2%) | 2 (0.6%) | 7 (9.2%) | 17.316 | < 0.001 |
Perinephric metastasis, n (%) | 42 (10.3%) | 18 (5.5%) | 24 (31.6%) | 45.456 | < 0.001 |
Clinicoradiological characteristics among the training, validation, and testing cohorts
Characteristics | Training cohort | Validation cohort | Testing cohort | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Low-grade | High-grade | t value or χ2-value | p value | Low-grade | High-grade | t value or χ 2-value | p value | Low-grade | High-grade | t value or χ2-value | p value | |
Full cohort, n (%) | ||||||||||||
406 (100%) | 184 (45.3%) | 43 (10.6%) | – | – | 46 (11.3%) | 11 (2.7%) | – | – | 100 (24.6%) | 22 (5.4%) | – | – |
Age (years) | 56.87 ± 12.09 | 60.33 ± 11.13 | 2.93 | 0.088 | 55.63 ± 10.74 | 59.64 ± 11.17 | 1.22 | 0.28 | 58.25 ± 12.19 | 56.32 ± 16.14 | 0.40 | 0.53 |
Gender, n (%) | ||||||||||||
Male | 109 (59.2%) | 27 (62.8%) | 0.183 | 0.669 | 25 (54.3%) | 7 (63.6%) | 0.31 | 0.58 | 55 (55.0%) | 17 (77.3%) | 3.70 | 0.05 |
Female | 75 (40.8%) | 16 (37.2%) | 21 (45.7%) | 4 (36.4%) | 45 (45.0%) | 5 (22.7%) | ||||||
BMI (kg/m2) | 24.25 ± 3.42 | 24.06 ± 5.00 | 0.087 | 0.768 | 24.18 ± 3.59 | 23.87 ± 2.19 | 0.08 | 0.78 | 24.93 ± 5.13 | 22.87 ± 2.96 | 3.30 | 0.07 |
Smoking history, n (%) | 57 (31.0%) | 18 (41.9%) | 1.87 | 0.17 | 11 (23.9%) | 4 (36.4%) | 0.71 | 0.40 | 37 (37.0%) | 8 (36.4%) | 0.003 | 0.96 |
Hypertension, n (%) | 67 (37.4%) | 12 (27.9%) | 1.11 | 0.29 | 17 (37.0%) | 3 (27.3%) | 0.37 | 0.55 | 41 (41.0%) | 7 (31.8%) | 0.64 | 0.43 |
Diabetes, n (%) | 21 (11.4%) | 9 (20.9%) | 2.75 | 0.097 | 9 (19.6%) | 0 (0.0%) | 2.56 | 0.11 | 19 (19%) | 4 (18.2%) | 0.008 | 0.93 |
Tumor size (cm) | 4.18 ± 1.86 | 5.76 ± 3.12 | 18.72 | < 0.001 | 4.06 ± 2.37 | 6.23 ± 1.67 | 8.20 | 0.006 | 4.32 ± 2.15 | 5.75 ± 2.87 | 6.95 | 0.009 |
Tumor location, n (%) | ||||||||||||
Left | 103 (56.0%) | 20 (46.5%) | 1.26 | 0.26 | 21 (45.7%) | 2 (20.0%) | 2.23 | 0.135 | 54 (54.0%) | 14 (63.6%) | 0.68 | 0.41 |
Right | 81 (44.0%) | 23 (53.5%) | 25 (54.3%) | 8 (80.0%) | 46 (46.0%) | 8 (36.4%) | ||||||
Operative method, n (%) | ||||||||||||
Partial | 109 (59.2%) | 11 (25.6%) | 15.85 | < 0.001 | 32 (69.6%) | 2 (18.2) | 9.74 | 0.002 | 51 (51.0%) | 7 (31.8%) | 2.66 | 0.10 |
Radical | 75 (40.8%) | 32 (74.4%) | 14 (30.4%) | 9 (81.8%) | 49 (49.0%) | 15 (68.2%) | ||||||
Hematuria, n (%) | 13 (7.1%) | 9 (20.9%) | 7.66 | 0.006 | 10 (21.7%) | 0 (0.0%) | 2.90 | 0.089 | 11 (11.0%) | 6 (27.3%) | 3.98 | 0.046 |
Flank pain, n (%) | 26 (14.1%) | 6 (14.0%) | 0.001 | 0.98 | 4 (8.7%) | 3 (27.3%) | 2.84 | 0.092 | 18 (18.0%) | 6 (27.3%) | 0.98 | 0.32 |
Distant Metastasis, n (%) | 0 (0.0%) | 1 (2.3%) | 4.30 | 0.038 | 0 (0.0%) | 1 (2.3%) | 4.30 | 0.038 | 0 (0.0%) | 1 (4.5%) | 4.58 | 0.032 |
Necrosis, n (%) | 76 (41.3%) | 31 (72.1%) | 13.26 | < 0.001 | 19 (41.3%) | 11 (100.0%) | 12.67 | < 0.001 | 40 (40.0%) | 15 (68.2%) | 5.79 | 0.016 |
Cystic Degeneration, n (%) | 19 (10.4%) | 4 (9.3%) | 0.044 | 0.83 | 5 (10.9%) | 1 (9.1%) | 0.03 | 0.863 | 10 (10.0%) | 0 (0.0%) | 2.40 | 0.12 |
Calcification, n (%) | 9 (4.9%) | 6 (14.0%) | 4.64 | 0.031 | 1 (2.2%) | 2 (18.2%) | 4.56 | 0.033 | 2 (2.0%) | 4 (18.2%) | 10.10 | 0.001 |
Violation of the Renal Capsule, n (%) | 25 (13.6%) | 19 (44.2%) | 20.89 | < 0.001 | 3 (6.5%) | 0 (0.0%) | 0.76 | 0.38 | 7 (7.0%) | 10 (45.5%) | 22.24 | < 0.001 |
Angiogenesis, n (%) | 101 (54.9%) | 36 (83.7%) | 12.11 | 0.001 | 23 (50.0%) | 10 (90.9%) | 6.10 | 0.014 | 60 (60.0%) | 20 (90.9%) | 7.63 | 0.006 |
Venous invasion, n (%) | 1 (0.5%) | 6 (14.0%) | 20.97 | < 0.001 | 0 (0.0%) | 0 (0.0%) | – | – | 1 (1.0%) | 1 (4.5%) | 1.41 | 0.24 |
Perinephric Metastasis, n (%) | 12 (6.5%) | 15 (34.9%) | 26.75 | < 0.001 | 2 (4.3%) | 2 (18.2%) | 2.60 | 0.11 | 4 (4.0%) | 7 (31.8%) | 17.01 | < 0.001 |
Characteristics | Training cohort | Validation cohort | Testing cohort | t value or χ2-value | p value |
---|---|---|---|---|---|
Full cohort, n (%) | |||||
406 (100%) | 227 (55.9%) | 57 (14.1%) | 122 (30.0%) | – | – |
Clinical characteristics | |||||
Age (years) | 57.52 ± 11.97 | 56.40 ± 10.84 | 57.90 ± 12.93 | 0.30 | 0.72 |
Gender, n (%) | |||||
Male | 136 (59.9%) | 32 (56.1%) | 72 (59.0%) | 0.27 | 0.87 |
Female | 91 (40.1%) | 25 (43.9%) | 50 (41.0%) | ||
BMI (kg/m2) | 24.21 ± 3.75 | 24.12 ± 3.35 | 24.56 ± 4.87 | 0.35 | 0.71 |
Smoking history, n (%) | 75 (33.0%) | 15 (26.3%) | 45 (36.9%) | 1.97 | 0.37 |
Hypertension, n (%) | 79 (34.8%) | 20 (35.1%) | 48 (39.3%) | 0.75 | 0.69 |
Diabetes, n (%) | 30 (13.2%) | 9 (15.8%) | 23 (18.9%) | 1.96 | 0.38 |
Tumor location, n (%) | |||||
Left | 123 (54.2%) | 24 (42.1%) | 68 (55.7%) | 3.69 | 0.16 |
Right | 104 (45.8%) | 33 (57.9%) | 54 (44.3%) | ||
Operative method, n (%) | |||||
Partial | 120 (52.9%) | 34 (59.6%) | 58 (47.5%) | 2.37 | 0.31 |
Radical | 107 (47.1%) | 23 (40.4%) | 64 (52.5%) | ||
Hematuria, n (%) | 22 (9.7%) | 10 (17.5%) | 17 (13.9%) | 3.22 | 0.20 |
Flank pain, n (%) | 32 (14.1%) | 7 (12.3%) | 24 (19.7%) | 2.41 | 0.30 |
Distant Metastasis, n (%) | 1 (0.4%) | 0 (0.0%) | 1 (0.8%) | 0.56 | 0.76 |
Imaging characteristics | |||||
Tumor size (cm) | 4.48 ± 2.24 | 4.48 ± 2.40 | 4.58 ± 2.35 | 0.083 | 0.92 |
Necrosis, n (%) | 107 (47.1%) | 30 (52.6%) | 55 (45.1%) | 0.89 | 0.64 |
Cystic Degeneration, n (%) | 23 (10.2%) | 6 (10.5%) | 10 (8.2%) | 0.42 | 0.81 |
Calcification, n (%) | 15 (6.6%) | 3 (5.3%) | 6 (4.9%) | 0.46 | 0.80 |
Violation of the Renal Capsule, n (%) | 44 (19.4%) | 3 (5.3%) * | 17 (13.9%) | 7.28 | 0.026 |
Angiogenesis, n (%) | 137 (60.4%) | 33 (57.9%) | 80 (65.6%) | 1.29 | 0.52 |
Venous invasion, n (%) | 7 (3.1%) | 0 (0.0%) | 2 (1.6%) | 2.27 | 0.32 |
Perinephric Metastasis, n (%) | 27 (11.9%) | 4 (7.0%) | 11 (9.0%) | 1.50 | 0.47 |
Clinicoradiological model construction
Characteristics | Kappa value | Univariate analysis | Multivariate analysis | ||||
---|---|---|---|---|---|---|---|
OR | 95% CI | p value | OR | 95% CI | p value | ||
Tumor size | 0.875 | 7.845 | 3.652–12.355 | < 0.001 | 0.992 | 0.852–1.155 | 0.918 |
Hematuria | 0.867 | 2.106 | 11.082–4.101 | 0.026 | 1.145 | 0.482–2.720 | 0.758 |
Distant metastasis | 0.831 | – | – | - | – | – | 0.999 |
Intratumoral necrosis | 0.854 | 4.465 | 2.543–7.838 | < 0.001 | 2.745 | 1.424–5.292 | 0.003 |
Calcification | 0.905 | 4.502 | 1.965–10.311 | < 0.001 | 4.293 | 1.629–11.314 | 0.003 |
Violation of renal capsule | 0.814 | 5.092 | 2.854–9.086 | < 0.001 | 1.642 | 1.642–3.446 | 0.190 |
Angiogenesis | 0.779 | 11.486 | 5.766–22.879 | < 0.001 | 3.805 | 1.741–8.313 | 0.001 |
Venous invasion | 0.923 | 16.400 | 3.336–80.624 | < 0.001 | 4.037 | 0.663–24.583 | 0.130 |
Perinephric metastasis | 0.867 | 7.849 | 3.989–15.446 | < 0.001 | 3.032 | 1.283–7.168 | 0.011 |
Radiomics feature extraction and radiomics model construction
Classifier | SVM-LASSO | SVM-RFE | SVM-ReliefF | ||||||
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Training cohort | Validation cohort | Testing cohort | Training cohort | Validation cohort | Testing cohort | Training cohort | Validation cohort | Testing cohort | |
AUC | 0.838 [0.721–0.934] | 0.795 [0.674–0.899] | 0.754 [0.652–0.889] | 0.842 [0.747–0.945] | 0.803 [0.687–0.904] | 0.761 [0.648–0.893] | 0.860 [0.759–0.963] | 0.824 [0.736–0.915] | 0.787 [0.710–0.892] |
Accuracy (%) | 76.70 [68.05–85.26] | 73.94 [73.49–89.75] | 68.78 [55.67–82.89] | 77.36 [65.35–86.25] | 74.11 [62.98–87.19] | 71.58 [59.87–83.74] | 83.61 [75.85–92.65] | 77.14 [69.38–86.05] | 73.42 [61.63–82.66] |
Sensitivity (%) | 77.57 [64.45–87.31] | 73.48 [60.67–86.48] | 70.07 [61.71–82.99] | 80.33 [69.35–89.79] | 75.47 [63.78–89.36] | 71.25 [61.36–80.74] | 84.78 [74.36–93.74] | 78.72 [64.35–91.48] | 82.15 [73.74–91.92] |
Specificity (%) | 81.22 [72.19–89.24] | 79.63 [61.34–70.49] | 80.30 [71.58–89.43] | 84.31 [73.74–92.18] | 83.04 [71.39–95.46] | 79.22 [66.57–88.34] | 82.67 [74.35–93.14] | 80.33 [69.74–92.26] | 76.48 [63.36–89.17] |
PPV (%) | 76.88 [62.38–85.69] | 73.86 [59.67–88.74] | 69.71 [60.98–78.35] | 79.46 [64.38–91.59] | 74.78 [62.88–86.74] | 72.98 [67.64–83.35] | 77.79 [69.16–85.97] | 75.98 [68.30–83.57] | 74.82 [65.87–83.64] |
NPV (%) | 84.12 [76.41–95.37] | 80.48 [71.70–92.26] | 79.25 [66.28–91.33] | 85.34 [75.65–96.43] | 83.92 [74.54–91.35] | 80.25 [72.36–92.17] | 83.90 [72.74–95.46] | 80.43 [71.32–89.91] | 82.62 [71.64–92.35] |
Comparison of the performance among clinicoradiological, radiomics, and combined models
Model | Combined model | Radiomics model | Clinicoradiological model | ||||||
---|---|---|---|---|---|---|---|---|---|
Training cohort | Validation cohort | Testing cohort | Training cohort | Validation cohort | Testing cohort | Training cohort | Validation cohort | Testing cohort | |
AUC | 0.887 [0.798–0.952] | 0.859 [0.748–0.935] | 0.828 [0.731–0.929] | 0.860 [0.759–0.963] | 0.824 [0.736–0.915] | 0.787 [0.710–0.892] | 0.752 [0.649–0.870] | 0.703 [0.592–0.844] | 0.637 [0.511–0.769] |
Accuracy (%) | 85.24 [76.75–90.14] | 82.76 [75.99–91.36] | 81.62 [74.18–92.45] | 83.61 [75.85–92.65] | 77.14 [69.38–86.05] | 73.42 [61.63–82.66] | 69.33 [56.54–83.76] | 62.87 [51.74–75.36] | 56.35 [42.48–69.49] |
Sensitivity (%) | 89.77 [80.63–96.98] | 84.94 [76.72–92.49] | 85.56 [77.82–91.58] | 84.78 [74.36–93.74] | 78.72 [64.35–91.48] | 82.15 [73.74–91.92] | 71.86 [59.43–83.82] | 73.89 [65.95–83.47] | 65.78 [46.89–80.87] |
Specificity (%) | 84.47 [72.60–91.65] | 83.42 [74.32–92.18] | 78.01 [69.45–85.74] | 82.67 [74.35–93.14] | 80.33 [69.74–92.26] | 76.48 [63.36–89.17] | 70.42 [61.36–83.47] | 66.86 [56.63–78.10] | 64.23 [52.36–80.62] |
PPV (%) | 82.34 [73.87–91.59] | 81.52 [73.67–87.59] | 78.36 [70.16–86.47] | 77.79 [69.16–85.97] | 75.98 [68.30–83.57] | 74.82 [65.87–83.64] | 68.24 [56.25–81.39] | 65.71 [52.63–78.78] | 60.99 [48.34–73.76] |
NPV (%) | 87.65 [79.48–97.86] | 86.77 [78.43–91.17] | 85.60 [79.98–90.35] | 83.90 [72.74–95.46] | 80.43 [71.32–89.91] | 82.62 [71.64–92.35] | 74.22 [65.61–86.34] | 70.98 [61.05–82.77] | 73.17 [60.05–87.47] |