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Quantitative dynamic contrast-enhanced parameters and intravoxel incoherent motion facilitate the prediction of TP53 status and risk stratification of early-stage endometrial carcinoma Cover

Quantitative dynamic contrast-enhanced parameters and intravoxel incoherent motion facilitate the prediction of TP53 status and risk stratification of early-stage endometrial carcinoma

Radiology and Oncology
Volume 57 (2023): Issue 2 (June 2023)
By:
Open Access
|Jun 2023

Figures & Tables

FIGURE 1.

Flowchart of the present study.EC = endometrial carcinoma
Flowchart of the present study.EC = endometrial carcinoma

FIGURE 2.

(A–I) A 53-year-old woman with low-risk endometrial carcinoma (EC) (arrowheads, endometrioid type, grade 2, stage IA, lymphovascular space invasion (LVSI) negative, and TP53-wild). (J–R) A 56-year-old woman with non-low-risk (intermediate) EC (arrowheads, endometrioid type, grade 1, stage IB, LVSI negative, and TP53-mutant). (A, J) Sagittal T2-weighted imaging maps; (B, K) Oblique axial pseudo colored maps of volume transfer constant (Ktrans); (C, L) Oblique axial pseudo colored maps of rate transfer constant (Kep); (D, M) Oblique axial pseudo colored maps of the volume of extravascular extracellular space per unit volume of tissue (Ve); (E, N) Oblique axial colored maps of true diffusion coefficient (D); (F, O) Oblique axial colored maps of pseudo-diffusion coefficient (D*); (G, P) Oblique axial colored maps of microvascular volume fraction (f), and (H, Q) Histopathological images (magnification = 100), and (I, R) Immunohistochemical image (magnification = 200).
(A–I) A 53-year-old woman with low-risk endometrial carcinoma (EC) (arrowheads, endometrioid type, grade 2, stage IA, lymphovascular space invasion (LVSI) negative, and TP53-wild). (J–R) A 56-year-old woman with non-low-risk (intermediate) EC (arrowheads, endometrioid type, grade 1, stage IB, LVSI negative, and TP53-mutant). (A, J) Sagittal T2-weighted imaging maps; (B, K) Oblique axial pseudo colored maps of volume transfer constant (Ktrans); (C, L) Oblique axial pseudo colored maps of rate transfer constant (Kep); (D, M) Oblique axial pseudo colored maps of the volume of extravascular extracellular space per unit volume of tissue (Ve); (E, N) Oblique axial colored maps of true diffusion coefficient (D); (F, O) Oblique axial colored maps of pseudo-diffusion coefficient (D*); (G, P) Oblique axial colored maps of microvascular volume fraction (f), and (H, Q) Histopathological images (magnification = 100), and (I, R) Immunohistochemical image (magnification = 200).

FIGURE 3.

Plots show individual data points, averages, and standard deviations of true diffusion coefficient (D) (A, G), pseudo-diffusion coefficient (D*) (B, H), microvascular volume fraction (f) (C, I), volume transfer constant (Ktrans) (D, J), the volume of extravascular extracellular space per unit volume of tissue (Ve) (E, K), and rate transfer constant (Kep) (F, L) in low-risk and non-low-risk groups (A–F), TP53-mutant and TP53-wild groups (G–L). Individual points are averages of values calculated by 2 readers. *P < 0.05, **P < 0.01, ***P < 0.001, and ● P > 0.005.
Plots show individual data points, averages, and standard deviations of true diffusion coefficient (D) (A, G), pseudo-diffusion coefficient (D*) (B, H), microvascular volume fraction (f) (C, I), volume transfer constant (Ktrans) (D, J), the volume of extravascular extracellular space per unit volume of tissue (Ve) (E, K), and rate transfer constant (Kep) (F, L) in low-risk and non-low-risk groups (A–F), TP53-mutant and TP53-wild groups (G–L). Individual points are averages of values calculated by 2 readers. *P < 0.05, **P < 0.01, ***P < 0.001, and ● P > 0.005.

FIGURE 4.

Receiver operating characteristic (ROC) curves, (A) shows each parameter and the combination of independent predictors for differentiation of TP53-mutant and TP53-wild early-stage endometrial carcinoma (EC); (B) shows each parameter and the combination of independent predictors for differentiation of low-risk and non-low-risk early-stage EC.
Receiver operating characteristic (ROC) curves, (A) shows each parameter and the combination of independent predictors for differentiation of TP53-mutant and TP53-wild early-stage endometrial carcinoma (EC); (B) shows each parameter and the combination of independent predictors for differentiation of low-risk and non-low-risk early-stage EC.

FIGURE 5.

In the prediction of TP53 status, receiver operating characteristic curves (A), calibration curves (B), and decision curve analysis (C) of the validation model.
In the prediction of TP53 status, receiver operating characteristic curves (A), calibration curves (B), and decision curve analysis (C) of the validation model.

FIGURE 6.

In the prediction of risk stratification, receiver operating characteristic curves (A), calibration curves (B), and decision curve analysis (C) of the validation model.
In the prediction of risk stratification, receiver operating characteristic curves (A), calibration curves (B), and decision curve analysis (C) of the validation model.

Clinicopathologic features of the patients

VariableData
Age (mean ± SD) (years)54.00 ± 7.91
Maximum diameter (mean ± SD) (mm)25.10 (13.76, 42.58)
FIGO stage n (%)
  IA44 (59.46)
  IB30 (40.54)
Histologic subtype n (%)
  Adenocarcinoma67 (90.54)
  Non-adenocarcinoma7 (9.46)
    Clear-cell3 (4.06)
    Undifferentiated carcinoma2 (2.70)
    Carcinosarcoma2 (2.70)
Lymphovascular space invasion n (%)
  Positive10 (6.76)
  Negative64 (93.24)
Histologic grade n (%)
  Grade 154 (72.98)
  Grade 210 (13.51)
  Grade 310 (13.51)
Risk stratification n (%)
  Low44 (59.46)
  Intermediate20 (27.03)
  High-intermediate0 (0.00)
  High10 (13.51)
TP53 expression
  Mutant21 (28.38)
  Wild25 (33.78)
  No result28 (37.84)

Comparison of different parameters

ParametersD (×10−3mm2/s)D* (×10−3mm2/s)f (%)Ktrans (min−1)VeKep(min−1)
Risk stratification
High-risk (n = 10)0.63 (0.40, 0.73)58.40 (40.10, 88.73)1.64 ± 0.600.35 (0.15, 0.43)0.30 ± 0.071.23 (0.48, 1.54)
High-intermediate-risk (n = 0)//////
Intermediate-risk (n = 20)0.55 (0.40, 0.81)52.00 (26.88, 74.33)1.74 ± 0.960.37 (0.29, 0.47)0.33 ± 0.141.24 (0.82, 1.98)
Low-risk (n = 44)0.86 (0.64, 1.16)44.35 (21.93, 95.33)2.43 ± 1.080.61 (0.43, 1.14)0.58 ± 0.251.53 (0.79, 2.21)
P-value0.033 a0.464 a0.012 a< 0.001 a< 0.001 a0.191 a
P-value (High vs Intermediate)0.880 b0.248 b0.735 c0.397 b0.532 c0.307 b
P-value (High vs Low)0.009 b0.238 b0.004 c< 0.001 b0.001 c0.099 b
P-value (Intermediate vs Low)0.001 b0.937 b0.014 c< 0.001 b< 0.001 c0.582
Low-risk (n = 44)0.86 (0.64, 1.16)44.35 (21.93, 95.33)2.43 ± 1.080.61 (0.43, 1.14)0.58 ± 0.251.53 (0.79, 2.21)
Non-low-risk (High + Intermediate, n = 30)0.58 (0.40, 0.77)55.25 (34.63, 72.78)1.71 ± 0.840.37 (0.28, 0.45)0.32 ± 0.121.23 (0.82, 1.87)
z/t value− 3.793−0.5233.234−5.1095.304−1.233
P-value< 0.001 b0.601 b0.002 c< 0.001 b< 0.001 c0.218 b
TP53 expression
  Mutant (n = 21)0.72 ± 0.3143.70 (16.30, 90.75)2.30 ± 1.090.67 (0.41, 1.14)0.32 (0.25, 0.91)1.67 (1.17, 2.09)
  Wild (n = 25)0.91 ± 0.2950.60 (26.90, 82.75)2.20 ± 1.020.43 (0.37, 0.49)0.49 (0.36, 0.76)0.90 (0.58, 1.55)
Z/t value−2.155−0.5180.321−2.073−0.783−3.165
P-value0.037 c0.604 b0.750 c0.038 b0.434 b0.002 b

Logistic regression analyses

ParametersUnivariate AnalysesP-valueMultivariate AnalysesP-value
OR for 1 SD (95% CI)OR for 1 SD (95% CI)
Low vs non-low risk
Age (year)1.462 (0.894–2.388)0.130//
Tumor size (mm)1.055 (1.003–1.110)0.0381.083 (0.979–1.197)0.123
TP53 mutant1.506 (0.407–5.578)0.540//
D (×10−3mm2/s)0.089 (0.021–0.373)0.0010.144 (0.015–1.334)0.088
D* (×10−3mm2/s)0.867 (0.533–1.412)0.567//
f (%)0.419 (0.226–0.776)0.0060.292 (0.093–0.921)0.036
Ktrans (min−1)0.009 (0.001–0.153)0.0010.001 (0.000–0.089)0.003
Ve0.173 (0.069–0.432)< 0.0010.130 (0.022–0.766)0.024
Kep (min−1)0.642 (0.367–1.126)0.122//
TP53 mutant vs wild
Age (year)0.855 (0.465–1.548)0.605//
Tumor size (mm)1.175 (0.649–2.127)0.594//
Subtype77.708 (0.001–100.5)0.999//
Grade2.099 (0.957–4.602)0.0641.961 (0.816–4.717)0.132
Risk stratification1.506 (0.407–5.578)0.540//
FIGO stage1.360 (0.739–2.505)0.323//
LVSI802.578 (0.001–1150.5)0.999//
D (×10−3mm2/s)2.063 (1.016–4.191)0.0458.274 (2.066–33.136)0.003
D* (×10−3mm2/s)1.020 (0.567–1.835)0.948//
f (%)0.906 (0.504–1.629)0.742//
Ktrans (min−1)0.487 (0.236–1.003)0.0510.155 (0.034–0.710)0.016
Ve1.008 (0.560–1.812)0.979//
Kep (min−1)0.501 (0.244–1.032)0.0611.172 (0.425–3.234)0.759

Imaging protocol parameters

ParametersT1WIT2WIDWIIVIMDCE-MRI
Sequence2D-FSE2D-FSE2D-SS-EPI2D-SS-EPI3D-LAVA
OrientationOblique AxialOblique AxialOblique AxialOblique AxialOblique Axial
TR/TE (ms)659/12.36000/953708/74.32000/80.73.5/1.7
FOV (cm2)40 × 4040 × 4040 × 4040 × 4036 × 36
Matrix288 × 192320 × 32096 × 128128 × 192288 × 192
Flip angle (°)160160909015
Slice thickness (mm)66666
No. of sections202020Based on lesion's size26
NEX111, 41, 1, 1, 1, 1, 1, 2, 4, 4, 60.73
Fat suppression/STIRSTIRSTIRFLEX
b-values (s/mm2)//0, 8000, 20, 40, 80, 160, 200, 400, 600, 800, 1000/
Respiratory compensationFreeFreeFreeFreeFree
Scan time1 min 56 s48 s1 min 04 s3~6min6 min 08 s (40 phases)

Predictive performance of different parameters

ParametersAUC (95% CI)P-valueCutoffSensitivitySpecificityComparison with combined diagnosis
Low vs non-low risk
D (×10−3mm2/s)0.761 (0.648–0.853)< 0.0010.69173.33%72.73%Z = 3.113, P = 0.002
D* (×10−3mm2/s)0.536 (0.416–0.653)0.598////
f (%)0.688 (0.569–0.790)0.0031.24036.67%93.18%Z = 4.317, P < 0.001
Ktrans (min−1)0.852 (0.750–0.924)< 0.0010.48790.00%68.18%Z = 2.713, P = 0.007
Ve0.808 (0.700–0.890)< 0.0010.40183.33%70.45%Z = 3.175, P = 0.002
Kep (min−1)0.585 (0.652–0.849)0.204////
Combined diagnosis 10.947 (0.869–0.986)< 0.001/83.33%93.18%/
TP53 mutant vs wild
D (×10−3mm2/s)0.694 (0.541–0.821)0.0190.60592.00%47.62%Z = 2.169, P = 0.030
D* (×10−3mm2/s)0.545 (0.391–0.692)0.498////
f (%)0.535 (0.382–0.648)0.388////
Ktrans (min−1)0.679 (0.525–0.809)0.0360.49980.00%61.90%Z = 2.572, P = 0.010
Ve0.568 (0.413–0.713)0.675////
Kep (min−1)0.773 (0.626–0.884)< 0.0011.55780.00%66.67%Z = 1.272, P = 0.203
Combined diagnosis 20.867 (0.734–0.949)< 0.001/92.00%80.95%/
DOI: https://doi.org/10.2478/raon-2023-0023 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099
Journal RSS Feed
Language: English
Page range: 257 - 269
Submitted on: Feb 9, 2023
Accepted on: Apr 6, 2023
Published on: Jun 21, 2023
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 times per year
Keywords:
early-stage endometrial carcinoma,
dynamic contrast-enhanced MRI,
intravoxel incoherent motion,
p53 status,
risk stratification
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Haematology, oncology,
Radiology

© 2023 Hongxia Wang, Ruifang Yan, Zhong Li, Beiran Wang, Xingxing Jin, Zhenfang Guo, Wangyi Liu, Meng Zhang, Kaiyu Wang, Jinxia Guo, Dongming Han, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

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