Introduction
Materials and methods
Population
PET acquisition and reconstruction parameters
PET visual interpretation
Extraction of PET bone textural features
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First order metrics extracted from histogram: SkewnessH, KurtosisH, EntropyH and EnergyH.
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Second order metrics calculated from co-occurrence matrices: homogeneity, energy, contrast, correlation, entropy and dissimilarity. Index values were the average of indexes over the 13 directions in space.
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Third order metrics calculated from size-zone matrices: SZE (Short-Zone Emphasis), LZE (Long-Zone Emphasis), LGZE (Low Grey-level Zone Emphasis), HGZE (High Grey-LevelZone Emphasis), SZLGE (Short-Zone Low Grey-level Emphasis), SZHGE (Short-Zone High Grey-level Emphasis), LZLGE (Long-Zone Low Grey-level Emphasis), LZHGE (Long-Zone High Grey-level Emphasis), GLNU (Grey-Level Non-Uniformity for zone) ZLNU (Zone Length Non-Uniformity) and ZP (Zone Percentage). Index values were calculated using a single co-occurrence matrix taking into account all 13 spatial directions simultaneously [18, 19].
Statistical analysis
Results
Population characteristics
Characteristics | Total population (n = 82) | SkewnessH ≤1.26 (n = 53) | SkewnessH >1.26 (n = 29) | P value |
---|---|---|---|---|
Age (years), median (range) | 64 (20 – 88) | 63 (20 – 88) | 65.0 (43 – 80) | 0.2002 |
Sex, n (%) | ||||
Male | 44 (53.7) | 29 (54.7) | 15 (51.7) | 0.8206 |
Female | 38 (46.3) | 24 (45.3) | 14 (48.3) | |
B symptoms, n (%) | ||||
Yes | 17 (20.7) | 10 (18.9) | 7 (24.1) | 0.5810 |
No | 65 (79.3) | 43 (81.1) | 22 (75.9) | |
Ann Arbor stage, n (%) | ||||
I | 8 (9.8) | 8 (15.1) | 0 (0.0) | <0.0001 |
II | 18 (21.9) | 17 (32.1) | 1 (3.4) | |
III | 19 (23.2) | 15 (28.3) | 4 (13.8) | |
IV | 37 (45.1) | 13 (24.5) | 24 (82.8) | |
Bulky mass, n (%) | ||||
Yes | 34 (41.5) | 16 (30.2) | 18 (62.1) | 0.0093 |
No | 48 (58.3) | 37 (69.8) | 11 (37.9) | |
IPI score, n (%) | ||||
0 | 20 (24.4) | 20 (37.7) | 0 (0.0) | <0.0001 |
1 | 21 (25.6) | 16 (30.2) | 5 (17.2) | |
2 | 18 (22.0) | 10 (18.9) | 8 (27.6) | |
3 | 21 (25.6) | 6 (11.3) | 15 (51.7) | |
4 | 1 (1.2) | 1 (1.9) | 0 (0.0) | |
5 | 1 (1.2) | 0 (0.0) | 1 (3.5) | |
Hb (g/dL), mean (SD) | 12.6 (2.08) | 13.11 (2.15) | 11.54 (1.57) | 0.0003 |
WBC (G/L), mean (SD) | 7.45 (2.84) | 7.57 (2.94) | 7.21 (2.64) | 0.9150 |
Lymphocytes (G/L), mean(SD) | 1.41 (1.09) | 1.60 (1.25) | 1.05 (1.60) | 0.0158 |
LDH (UI/l), mean (SD) | 356.17 (254.78) | 308.5 (198.6) | 442.7 (323.0) | 0.0199 |
Diagnostic value of textural features for bone involvement at baseline staging
ROC analyses | Univariate OS analyses | Univariate PFS analyses | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Parameters | AUC | 95% CI | Youden index | Cut-off value | Sensitivity | Specificity | P value | HR | 95%CI | P value | HR | 95% CI | P value |
BMB/PET reference | |||||||||||||
Disease + * | – | – | – | – | – | – | – | 2.81 | 0.78-10.15 | 0.062 | 1.26 | 0.36-4.34 | 0.700 |
First Order metrics | |||||||||||||
SkewnessH | 0.821 | 0.721–0.897 | 0.6348 | >1.26 | 81.8 | 81.7 | <0.0001 | 3.78 | 1.15-12.44 | 0.019 | 3.17 | 1.00-10.04 | 0.032 |
KurtosisH | 0.813 | 0.712–0.891 | 0.6091 | >4.89 | 90.9 | 70.0 | <0.0001 | 3.47 | 1.12-10.79 | 0.047 | 2.77 | 0.93-8.26 | 0.077 |
EntropyH | 0.787 | 0.682–0.870 | 0.5545 | ≤1.32 | 95.4 | 60.0 | <0.0001 | 4.22 | 1.36-13.14 | 0.043 | 1.99 | 0.67-5.90 | 0.244 |
EnergyH | 0.800 | 0.697–0.880 | 0.5227 | >0.07 | 77.3 | 75.0 | <0.0001 | 3.18 | 0.99-10.16 | 0.046 | 2.71 | 0.88-8.34 | 0.068 |
Second Order metrics | |||||||||||||
Homogeneity | 0.542 | 0.429–0.653 | 0.1364 | ≤0.53 | 13.6 | 100.0 | 0.5739 | – | – | – | – | – | – |
Energy | 0.545 | 0.432–0.656 | 0.1197 | ≤0.02 | 13.6 | 98.3 | 0.5441 | – | – | – | – | – | – |
Contrast | 0.669 | 0.557–0.769 | 0.3424 | >2.88 | 40.9 | 93.3 | 0.0230 | 3.08 | 0.60-15.74 | 0.053 | 1.17 | 0.24-5.75 | 0.838 |
Correlation | 0.745 | 0.637–0.835 | 0.4394 | >0.75 | 77.3 | 66.7 | 0.0002 | 1.98 | 0.63-6.23 | 0.235 | 1.16 | 0.39-3.49 | 0.787 |
Entropy | 0.609 | 0.495–0.715 | 0.2227 | >1.45 | 77.3 | 45.0 | 0.1262 | – | – | – | – | – | – |
Dissimilarity | 0.606 | 0.492–0.713 | 0.2273 | >1.39 | 22.7 | 100.0 | 0.1583 | – | – | – | – | – | – |
Third Order metrics | |||||||||||||
SZE | 0.760 | 0.653–0.858 | 0.4667 | >0.50 | 50.0 | 96.7 | 0.0001 | 4.22 | 0.84-21.11 | 0.007 | 1.84 | 0.38-8.80 | 0.346 |
LZE | 0.631 | 0.517–0.735 | 0.2394 | ≤95,159.28 | 27.3 | 96.7 | 0.0681 | – | – | – | – | – | – |
LGZE | 0.581 | 0.467–0.690 | 0.1742 | ≤0.09 | 59.1 | 58.3 | 0.2695 | – | – | – | – | – | – |
HGZE | 0.768 | 0.662–0.854 | 0.5121 | >89.84 | 54.5 | 96.7 | <0.0001 | 4.05 | 0.83-19.75 | 0.009 | 1.72 | 0.37-7.95 | 0.402 |
SZLGE | 0.584 | 0.470–0.692 | 0.1379 | ≤0.03 | 45.4 | 68.3 | 0.2507 | – | – | – | – | – | – |
SZHGE | 0.778 | 0.673–0.862 | 0.4955 | >46.23 | 54.5 | 95.0 | <0.0001 | 3.42 | 0.77-15.31 | 0.025 | 2.21 | 0.51-9.51 | 0.174 |
LZLGE | 0.574 | 0.460–0.683 | 0.1848 | ≤38,867.89 | 81.8 | 36.7 | 0.3131 | – | – | – | – | – | – |
LZHGE | 0.687 | 0.575–0.785 | 0.3409 | ≤4,661,869.17 | 59.1 | 75.0 | 0.0068 | 1.40 | 0.42-4.62 | 0.566 | 1.76 | 0.55-5.60 | 0.302 |
GLNU | 0.542 | 0.428–0.652 | 0.1833 | ≤153.40 | 50.0 | 68.3 | 0.5944 | – | – | – | – | – | – |
ZLNU | 0.720 | 0.610–0.813 | 0.3924 | >694.77 | 40.9 | 98.3 | 0.0012 | 2.72 | 0.67-11.00 | 0.074 | 1.13 | 0.30-4.30 | 0.850 |
ZP | 0.628 | 0.514–0.732 | 0.3015 | >0.04 | 31.8 | 98.3 | 0.0782 | – | – | – | – | – | – |
ROC analyses | Univariate OS analyses | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Parameters | AUC | 95% CI | Youden index | Cut-off value | Sensitivity | Specificity | P value | HR | 95% CI | P value |
First Order metrics | ||||||||||
SkewnessH | 0.749 | 0.641–0.839 | 0.3952 | >1.50 | 66.7 | 72.9 | 0.0005 | 4.29 | 1.27-14.5 | 0.0094 |
KurtosisH | 0.753 | 0.645–0.842 | 0.4595 | >4.72 | 91.7 | 54.3 | <0.0001 | 10.35 | 3.34-32.12 | 0.0053 |
EntropyH | 0.749 | 0.641–0.838 | 0.4524 | ≤1.11 | 66.7 | 78.6 | 0.0001 | 5.60 | 1.55-20.22 | 0.0015 |
EnergyH | 0.749 | 0.641–0.838 | 0.4381 | >0.09 | 66.7 | 77.1 | <0.0001 | 5.21 | 1.47-18.45 | 0.0026 |
Second Order metrics | ||||||||||
Homogeneity | 0.514 | 0.401–0.626 | 0.1143 | ≤0.65 | 50.0 | 38.6 | 0.8847 | – | – | – |
Energy | 0.524 | 0.411–0.635 | 0.0714 | ≤0.04 | 50.0 | 57.14 | 0.8022 | – | – | – |
Contrast | 0.638 | 0.524–0.741 | 0.3429 | >2.63 | 50.0 | 84.3 | 0.1734 | – | – | – |
Correlation | 0.564 | 0.450–0.673 | 0.1810 | >0.74 | 66.7 | 51.4 | 0.5126 | – | – | – |
Entropy | 0.557 | 0.443–0.666 | 0.1833 | >1.53 | 58.3 | 60.0 | 0.5508 | – | – | – |
Dissimilarity | 0.587 | 0.473–0.695 | 0.2286 | >1.04 | 50.0 | 72.9 | 0.3660 | – | – | – |
Third Order metrics | ||||||||||
SZE | 0528 | 0.415–0.639 | 0.3024 | >0.50 | 41.7 | 88.6 | 0.8026 | – | – | – |
LZE | 0.540 | 0.427–0.651 | 0.1643 | ≤113,425.08 | 25.0 | 91.4 | 0.6808 | – | – | – |
LGZE | 0.595 | 0.480–0.702 | 0.1881 | ≤0.14 | 91.7 | 27.1 | 0.2746 | – | – | – |
HGZE | 0.683 | 0.571–0.782 | 0.3452 | >112.02 | 41.7 | 92.9 | 0.0264 | – | – | – |
SZLGE | 0.597 | 0.483–0.704 | 0.1786 | ≤0.04 | 75.0 | 42.9 | 0.2476 | – | – | – |
SZHGE | 0.692 | 0.580–0.789 | 0.3452 | >75.64 | 41.7 | 92.9 | 0.0149 | 6.24 | 0.97-40.22 | 0.0003 |
LZLGE | 0.555 | 0.441–0.665 | 0.1881 | ≤51,423.79 | 91.7 | 27.1 | 0.5290 | – | – | – |
LZHGE | 0.520 | 0.407–0.632 | 0.1916 | ≤3,741,969.49 | 33.3 | 82.9 | 0.8469 | – | – | – |
GLNU | 0.517 | 0.404–0.629 | 0.1690 | ≤160.4 | 58.3 | 58.6 | 0.8683 | – | – | – |
ZLNU | 0.613 | 0.499–0.719 | 0.2738 | >564.67 | 41.7 | 85.7 | 0.2705 | – | – | – |
ZP | 0.570 | 0.456–0.479 | 0.1786 | >0.04 | 25.0 | 92.9 | 0.4554 | – | – | – |
ROC analyses | Univariate PFS analyses | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Parameters | AUC | 95% CI | Youden index | Cut-off value | Sensitivity | Specificity | P value | HR | 95% CI | P value |
First Order metrics | ||||||||||
SkewnessH | 0.701 | 0.589–0.797 | 0.3735 | >1.16 | 69.2 | 68.1 | 0.0081 | 3.91 | 1.26-12.10 | 0.0142 |
KurtosisH | 0.676 | 0.563–0.775 | 0.3835 | >9.9 | 61.5 | 76.8 | 0.0353 | 4.35 | 1.27-14.81 | 0.0048 |
EntropyH | 0.651 | 0.537–0.753 | 03110 | ≤1.15 | 61.5 | 69.6 | 0.0836 | – | – | – |
EnergyH | 0.633 | 0.520–0.737 | 0.3255 | >0.08 | 61.5 | 71.0 | 0.1380 | – | – | – |
Second Order metrics | ||||||||||
Homogeneity | 0.552 | 0.439–0.662 | 0.1616 | >0.65 | 53.8 | 62.3 | 0.5766 | – | – | – |
Energy | 0.570 | 0.456–0.679 | 0.1572 | >0.05 | 46.1 | 69.6 | 0.4523 | – | – | – |
Contrast | 0.502 | 0.389–0.614 | 0.1761 | ≤1.54 | 53.8 | 63.8 | 0.9863 | – | – | – |
Correlation | 0.502 | 0.389–0.614 | 0.1226 | ≤0.74 | 38.5 | 49.3 | 0.9863 | – | – | – |
Entropy | 0.571 | 0.457–0.680 | 0.2441 | ≤1.4 | 46.1 | 78.3 | 0.4670 | – | – | – |
Dissimilarity | 0.552 | 0.439–0.662 | 0.1706 | ≤0.94 | 69.2 | 47.8 | 0.5721 | – | – | – |
Third Order metrics | ||||||||||
SZE | 0.556 | 0.442–0.666 | 0.1282 | >0.48 | 46.1 | 66.7 | 0.5403 | – | – | – |
LZE | 0.535 | 0.422–0.646 | 0.2879 | >533,174.76 | 46.1 | 82.6 | 0.7278 | – | – | – |
LGZE | 0.515 | 0.402–0.627 | 0.1728 | ≤0.18 | 76.9 | 5.8 | 0.8814 | – | – | – |
HGZE | 0.546 | 0.432–0.567 | 0.1817 | >77.99 | 38.5 | 79.7 | 0.6244 | – | – | – |
SZLGE | 0.504 | 0.392–0.617 | 0.1293 | >0.07 | 23.1 | 89.9 | 0.9636 | – | – | – |
SZHGE | 0.574 | 0.460–0.683 | 0.4166 | >42.90 | 38.5 | 82.6 | 0.4166 | – | – | – |
LZLGE | 0.536 | 0.423–0.647 | 0.7175 | >42,917.4 | 46.1 | 73.9 | 0.7175 | – | – | – |
LZHGE | 0.565 | 0.451–0.674 | 0.2040 | ≤5,919,722.88 | 76.9 | 43.5 | 0.4494 | – | – | – |
GLNU | 0.502 | 0.389–0.614 | 0.1839 | ≤141.57 | 7.7 | 73.9 | 0.9849 | – | – | – |
ZLNU | 0.511 | 0.398–0.623 | 0.1951 | ≤376.93 | 61.5 | 58.0 | 0.9059 | – | – | – |
ZP | 0.517 | 0.404–0.629 | 0.0624 | >0.10 | 7.7 | 98.6 | 0.8399 | – | – | – |
Prognostic value of bone textural features at baseline staging
Univariate analysis | Multivariate analysis* | |||||
---|---|---|---|---|---|---|
Characteristics | HR | 95% CI | P | HR | 95%CI | P |
SkewnessH >1.26 | 3.78 | 1.15-12.44 | 0.019 | ns | ||
Bulky mass | 2.12 | 0.67-6.74 | 0.188 | – | – | – |
IPI ≥ 2 | 5.31 | 1.62-17.40 | 0.016 | 5.34 | 1.16-24.55 | 0.032 |
Age > 60y | 2.22 | 0.71-6.98 | 0.219 | – | – | – |
Stage III/IV | 2.59 | 0.78-8.54 | 0.202 | – | – | – |
LDH+ | 9.22 | 2.24-38.03 | 0.0001 | – | – | – |
Hb < 12 g/dL | 4.23 | 1.26-14.21 | 0.010 | ns |
Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|
Characteristics | HR | 95% CI | P | HR | 95%CI | P |
SkewnessH >1.26 | 3.17 | 1.00-10.04 | 0.032 | – | – | – |
Bulky mass | 2.49 | 0.81-7.60 | 0.096 | – | – | – |
IPI ≥ 2 | 1.88 | 0.63-5.59 | 0.259 | – | – | – |
Age > 60y | 2.43 | 0.81-7.33 | 0.161 | – | – | – |
Stage III/IV | 1.65 | 0.52-5.25 | 0.439 | – | – | – |
LDH+ | 3.04 | 0.72-12.82 | 0.051 | – | – | – |
Hb < 12 g/dL | 2.61 | 0.80-8.46 | 0.073 | – | – | – |