Dynamic Contrast-Enhanced and Intravoxel Incoherent Motion MRI Biomarkers Are Correlated to Survival Outcome in Advanced Hepatocellular Carcinoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. MRI Protocol
2.3. Image Analysis
2.3.1. IVIM Modeling of DWI
2.3.2. DCE-MRI
2.4. Statistical Analysis
3. Results
3.1. Participants’ Characteristics
3.2. Correlation of Tumor Size, DCE-MRI, and IVIM Parameters
3.3. Intraclass Correlation Coefficients of MR Quantitative Parameters
3.4. Comparison of MRI Parameters Derived for Participants with Short (≤8 Months) and Long (>8 Months) OS
3.5. Correlation of MRI Parameters with PFS and OS
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
DCE | dynamic contrast-enhanced |
IVIM DWI | intravoxel incoherent motion diffusion-weighted imaging |
HCC | hepatocellular carcinoma |
PFS | progression-free survival |
OS | overall survival |
ROIs | Regions of interest |
AUC | area under the curve |
ADC | apparent diffusion coefficient |
RECIST | response evaluation criteria in solid tumors |
References
- Bruix, J.; Sherman, M. Management of hepatocellular carcinoma: An update. Hepatology 2011, 53, 1020–1022. [Google Scholar] [CrossRef]
- Forner, A.; Reig, M.; Bruix, J. Hepatocellular carcinoma. Lancet 2018, 391, 1301–1314. [Google Scholar] [CrossRef]
- Cheng, A.L.; Kang, Y.K.; Chen, Z.; Tsao, C.J.; Qin, S.; Kim, J.S.; Luo, R.; Feng, J.; Ye, S.; Yang, T.S.; et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009, 10, 25–34. [Google Scholar] [CrossRef]
- Llovet, J.M.; Ricci, S.; Mazzaferro, V.; Hilgard, P.; Gane, E.; Blanc, J.F.; de Oliveira, A.C.; Santoro, A.; Raoul, J.L.; Forner, A.; et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008, 359, 378–390. [Google Scholar] [CrossRef] [PubMed]
- Yarchoan, M.; Agarwal, P.; Villanueva, A.; Rao, S.; Dawson, L.A.; Llovet, J.M.; Finn, R.S.; Groopman, J.D.; El-Serag, H.B.; Monga, S.P.; et al. Recent Developments and Therapeutic Strategies against Hepatocellular Carcinoma. Cancer Res. 2019, 79, 4326–4330. [Google Scholar] [CrossRef] [Green Version]
- Safran, H.; Charpentier, K.P.; Kaubisch, A.; Mantripragada, K.; Dubel, G.; Perez, K.; Faricy-Anderson, K.; Miner, T.; Eng, Y.; Victor, J.; et al. Lenalidomide for second-line treatment of advanced hepatocellular cancer: A Brown University oncology group phase II study. Am. J. Clin. Oncol. 2015, 38, 1–4. [Google Scholar] [CrossRef]
- Shao, Y.Y.; Chen, B.B.; Ou, D.L.; Lin, Z.Z.; Hsu, C.H.; Wang, M.J.; Cheng, A.L.; Hsu, C. Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: Exploration of biomarkers for treatment efficacy. Aliment. Pharmacol. Ther. 2017, 46, 722–730. [Google Scholar] [CrossRef] [Green Version]
- Chen, B.B.; Shih, T.T. DCE-MRI in hepatocellular carcinoma-clinical and therapeutic image biomarker. World J. Gastroenterol. 2014, 20, 3125–3134. [Google Scholar] [CrossRef]
- Chen, B.B.; Hsu, C.Y.; Yu, C.W.; Liang, P.C.; Hsu, C.; Hsu, C.H.; Cheng, A.L.; Shih, T.T. Early perfusion changes within 1 week of systemic treatment measured by dynamic contrast-enhanced MRI may predict survival in patients with advanced hepatocellular carcinoma. Eur. Radiol. 2017, 27, 3069–3079. [Google Scholar] [CrossRef] [PubMed]
- Hsu, C.; Yang, T.S.; Huo, T.I.; Hsieh, R.K.; Yu, C.W.; Hwang, W.S.; Hsieh, T.Y.; Huang, W.T.; Chao, Y.; Meng, R.; et al. Vandetanib in patients with inoperable hepatocellular carcinoma: A phase II, randomized, double-blind, placebo-controlled study. J. Hepatol. 2012, 56, 1097–1103. [Google Scholar] [CrossRef] [PubMed]
- Hsu, C.Y.; Shen, Y.C.; Yu, C.W.; Hsu, C.; Hu, F.C.; Hsu, C.H.; Chen, B.B.; Wei, S.Y.; Cheng, A.L.; Shih, T.T. Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict survival and response in hepatocellular carcinoma patients treated with sorafenib and metronomic tegafur/uracil. J. Hepatol. 2011, 55, 858–865. [Google Scholar] [CrossRef]
- Taouli, B.; Koh, D.M. Diffusion-weighted MR imaging of the liver. Radiology 2010, 254, 47–66. [Google Scholar] [CrossRef]
- Niekamp, A.; Abdel-Wahab, R.; Kuban, J.; Odisio, B.C.; Mahvash, A.; Hassan, M.M.; Qayyum, A.; Kaseb, A.; Sheth, R.A. Baseline Apparent Diffusion Coefficient as a Predictor of Response to Liver-Directed Therapies in Hepatocellular Carcinoma. J. Clin. Med. 2018, 7, 83. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhu, S.C.; Liu, Y.H.; Wei, Y.; Li, L.L.; Dou, S.W.; Sun, T.Y.; Shi, D.P. Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging for predicting histological grade of hepatocellular carcinoma: Comparison with conventional diffusion-weighted imaging. World J. Gastroenterol. 2018, 24, 929–940. [Google Scholar] [CrossRef] [PubMed]
- Shan, Q.; Chen, J.; Zhang, T.; Yan, R.; Wu, J.; Shu, Y.; Kang, Z.; He, B.; Zhang, Z.; Wang, J. Evaluating histologic differentiation of hepatitis B virus-related hepatocellular carcinoma using intravoxel incoherent motion and AFP levels alone and in combination. Abdom. Radiol. 2017, 42, 2079–2088. [Google Scholar] [CrossRef]
- Wu, L.F.; Rao, S.X.; Xu, P.J.; Yang, L.; Chen, C.Z.; Liu, H.; Huang, J.F.; Fu, C.X.; Halim, A.; Zeng, M.S. Pre-TACE kurtosis of ADCtotal derived from histogram analysis for diffusion-weighted imaging is the best independent predictor of prognosis in hepatocellular carcinoma. Eur. Radiol. 2019, 29, 213–223. [Google Scholar] [CrossRef] [PubMed]
- Wu, L.; Xu, P.; Rao, S.; Yang, L.; Chen, C.; Liu, H.; Fu, C.; Zeng, M. ADCtotal ratio and D ratio derived from intravoxel incoherent motion early after TACE are independent predictors for survival in hepatocellular carcinoma. J. Magn. Reson. Imaging 2017, 46, 820–830. [Google Scholar] [CrossRef]
- Eisenhauer, E.A.; Therasse, P.; Bogaerts, J.; Schwartz, L.H.; Sargent, D.; Ford, R.; Dancey, J.; Arbuck, S.; Gwyther, S.; Mooney, M.; et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur. J. Cancer 2009, 45, 228–247. [Google Scholar] [CrossRef] [PubMed]
- Luciani, A.; Vignaud, A.; Cavet, M.; Nhieu, J.T.; Mallat, A.; Ruel, L.; Laurent, A.; Deux, J.F.; Brugieres, P.; Rahmouni, A. Liver cirrhosis: Intravoxel incoherent motion MR imaging—Pilot study. Radiology 2008, 249, 891–899. [Google Scholar] [CrossRef]
- Kakite, S.; Dyvorne, H.A.; Lee, K.M.; Jajamovich, G.H.; Knight-Greenfield, A.; Taouli, B. Hepatocellular carcinoma: IVIM diffusion quantification for prediction of tumor necrosis compared to enhancement ratios. Eur. J. Radiol. Open 2016, 3, 1–7. [Google Scholar] [CrossRef] [Green Version]
- Zhu, L.; Wang, H.; Zhu, L.; Meng, J.; Xu, Y.; Liu, B.; Chen, W.; He, J.; Zhou, Z.; Yang, X. Predictive and prognostic value of intravoxel incoherent motion (IVIM) MR imaging in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy. Sci. Rep. 2017, 7, 11635. [Google Scholar] [CrossRef]
- Le Bihan, D.; Breton, E.; Lallemand, D.; Aubin, M.L.; Vignaud, J.; Laval-Jeantet, M. Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 1988, 168, 497–505. [Google Scholar] [CrossRef]
- Rosset, A.; Spadola, L.; Ratib, O. OsiriX: An open-source software for navigating in multidimensional DICOM images. J. Digit. Imaging 2004, 17, 205–216. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, B.B.; Hsu, C.Y.; Yu, C.W.; Liang, P.C.; Hsu, C.; Hsu, C.H.; Cheng, A.L.; Shih, T.T. Dynamic Contrast-enhanced MR Imaging of Advanced Hepatocellular Carcinoma: Comparison with the Liver Parenchyma and Correlation with the Survival of Patients Receiving Systemic Therapy. Radiology 2016, 281, 454–464. [Google Scholar] [CrossRef]
- Liang, P.C.; Ch’ang, H.J.; Hsu, C.; Chen, L.T.; Shih, T.T.; Liu, T.W. Perfusion parameters of dynamic contrast-enhanced magnetic resonance imaging predict outcomes of hepatocellular carcinoma receiving radiotherapy with or without thalidomide. Hepatol. Int. 2015, 9, 258–268. [Google Scholar] [CrossRef]
- Kim, K.A.; Park, M.S.; Ji, H.J.; Park, J.Y.; Han, K.H.; Kim, M.J.; Kim, K.W. Diffusion and perfusion MRI prediction of progression-free survival in patients with hepatocellular carcinoma treated with concurrent chemoradiotherapy. J. Magn. Reson. Imaging 2014, 39, 286–292. [Google Scholar] [CrossRef] [PubMed]
- Le Bihan, D. Intravoxel incoherent motion perfusion MR imaging: A wake-up call. Radiology 2008, 249, 748–752. [Google Scholar] [CrossRef]
- Woo, S.; Lee, J.M.; Yoon, J.H.; Joo, I.; Han, J.K.; Choi, B.I. Intravoxel incoherent motion diffusion-weighted MR imaging of hepatocellular carcinoma: Correlation with enhancement degree and histologic grade. Radiology 2014, 270, 758–767. [Google Scholar] [CrossRef]
- Lewin, M.; Fartoux, L.; Vignaud, A.; Arrive, L.; Menu, Y.; Rosmorduc, O. The diffusion-weighted imaging perfusion fraction f is a potential marker of sorafenib treatment in advanced hepatocellular carcinoma: A pilot study. Eur. Radiol. 2011, 21, 281–290. [Google Scholar] [CrossRef]
- Sahani, D.V.; Jiang, T.; Hayano, K.; Duda, D.G.; Catalano, O.A.; Ancukiewicz, M.; Jain, R.K.; Zhu, A.X. Magnetic resonance imaging biomarkers in hepatocellular carcinoma: Association with response and circulating biomarkers after sunitinib therapy. J. Hematol. Oncol. 2013, 6, 51. [Google Scholar] [CrossRef] [Green Version]
- Wei, Y.; Huang, Z.; Tang, H.; Deng, L.; Yuan, Y.; Li, J.; Wu, D.; Wei, X.; Song, B. IVIM improves preoperative assessment of microvascular invasion in HCC. Eur. Radiol. 2019, 29, 5403–5414. [Google Scholar] [CrossRef] [PubMed]
- Murtz, P.; Sprinkart, A.M.; Reick, M.; Pieper, C.C.; Schievelkamp, A.H.; Konig, R.; Schild, H.H.; Willinek, W.A.; Kukuk, G.M. Accurate IVIM model-based liver lesion characterisation can be achieved with only three b-value DWI. Eur. Radiol. 2018, 28, 4418–4428. [Google Scholar] [CrossRef] [PubMed]
- Gustafsson, O.; Montelius, M.; Starck, G.; Ljungberg, M. Impact of prior distributions and central tendency measures on Bayesian intravoxel incoherent motion model fitting. Magn. Reson. Med. 2018, 79, 1674–1683. [Google Scholar] [CrossRef] [PubMed]
- Lanzarone, E.; Mastropietro, A.; Scalco, E.; Vidiri, A.; Rizzo, G. A novel bayesian approach with conditional autoregressive specification for intravoxel incoherent motion diffusion-weighted MRI. NMR Biomed. 2020, 33, e4201. [Google Scholar] [CrossRef]
Sequence | TR (msec) | TE (msec) | Flip Angle (degrees) | Matrix | Field of View (mm) | Slice Thickness/Gap (mm) | NEX | Acquisition Time (min) |
---|---|---|---|---|---|---|---|---|
Coronal HASTE | 1400 | 93 | 160 | 640 × 640 | 320 × 320 | 5/0 | 1 | 0:59 |
Axial T1WI VIBE (in- and opposed-phase) | 4.2 | 2.5 | 10 | 512 × 416 | 350 × 284 | 3/0 | 1 | 0:52 |
Axial T2WI FS | 2610 | 96 | 123 | 640 × 440 | 340 × 234 | 6/0 | 1 | 1:04 |
DWI (b = 50, 500, 1000) | 7300 | 83 | 90 | 384 × 300 | 4000 × 313 | 6/0 | 2 | 4:08 |
IVIM (b = 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 1000) | 4438 | 77.2 | 180 | 182 × 150 | 385 × 317 | 6/0 | 2 | 14:06 |
DCE-MRI | 4.2 | 2.5 | 9 | 420 × 448 | 400 × 313 | 5/0 | 1 | 2:50 (25 sets) |
Axial T1WI postcontrast | 141 | 2.5 | 70 | 320 × 220 | 340 × 234 | 6/0 | 1 | 1:00 |
Characteristic | Value |
---|---|
Age (y) | 60.0 ± 11.6 |
Sex (men/women) | 39/5 |
Size (cm2) | 38.4 ± 44.4 |
ECOG (0/1) | 8/36 |
Child–Pugh score (5/6) | 23/21 |
HBsAg (+) | 29 (66) |
Anti-HCV (+) | 8 (18) |
Alcohol abuse † | 5 (11) |
Cirrhosis †† | 34 (77) |
Extrahepatic metastasis | 38 (86) |
Macroscopic vascular invasion | 24 (55) |
Serum AFP > 400 ng/mL | 29 (66) |
Prior treatment | |
Surgery | 20 (45) |
Ablation | 8 (18) |
TACE | 35 (80) |
Sorafenib | 44 (100) |
MRI Parameters | |
---|---|
Peak (%) | 27.5 ± 10.5 |
Slope (1/s) | 19.5 ± 7.8 |
AUC (/10 s) | 2635 ± 1101 |
Ktrans (min−1/1000) | 152 ± 146 |
Kep (min−1/1000) | 1252 ± 1248 |
Ve (%) | 10.7 ± 6.2 |
ADC (10−3 mm2/s) | 1.4 ± 0.3 |
D (10−3 mm2/s) | 1.1 ± 0.3 |
D* (10−3 mm2/s) | 65.1 ± 38 |
f (%) | 17.6 ± 10.6 |
Parameters | Short (n = 23) | Long (n = 21) | p Value |
---|---|---|---|
Peak (%) | 270 ± 101 | 280 ± 112 | 0.85 |
Slope (1/s) | 18.8 ± 7.2 | 20.4 ± 8.6 | 0.45 |
AUC (/10 s) | 2660 ± 1031 | 2607 ± 1199 | 0.83 |
Ktrans (min−1/1000) | 106 ± 75 | 203 ± 186 | 0.08 |
Kep (min−1/1000) | 943 ± 647 | 1591 ± 1630 | 0.10 |
Ve (%) | 9.6 ± 5.4 | 11.9 ± 7 | 0.36 |
ADC (10−3 mm2/s) | 1.28 ± 0.2 | 1.54 ± 0.4 | 0.02 * |
D (10−3 mm2/s) | 1.06 ± 0.2 | 1.14 ± 0.4 | 0.93 |
D* (10−3 mm2/s) | 65.6 ± 38.8 | 64.5 ± 38 | 0.87 |
f (%) | 14.6 ± 9.1 | 20.8 ± 11.5 | 0.02 * |
Parameters | Progression-Free Survival (PFS) | Overall Survival (OS) | |||||||
---|---|---|---|---|---|---|---|---|---|
Univariate | Multivariable | Univariate | Multivariable | ||||||
Cutoff | Hazard Ratio | p Value | Hazard Ratio | p Value | Hazard Ratio | p Value | Hazard Ratio | p Value | |
Age (y) | 60 | 1.0 (0.5–1.8) | >0.99 | 1.0 (0.6–1.9) | 0.89 | ||||
sex | M vs. F | 0.5 (0.2–1.3) | 0.18 | 1.0 (0.4–2.4) | 0.98 | ||||
Size (cm2) | 17.5 | 0.9 (0.5–1.7) | 0.82 | 0.4 (0.2–0.8) | 0.006 * | ||||
ECOG | 0 vs. 1 | 0.9 (0.4–2.1) | 0.89 | 1.0 (0.4–2.1) | 0.93 | ||||
Child | 5 vs. 6 | 1.1 (0.6–2.0) | 0.74 | 1.2 (0.7–2.3) | 0.48 | ||||
AFP (ng/mL) | 400 | 0.9 (0.5–1.7) | 0.78 | 0.8 (0.4–1.5) | 0.49 | ||||
Cirrhosis | No vs. yes | 0.7 (0.4–1.5) | 0.39 | 0.9 (0.4–1.8) | 0.71 | ||||
Macroscopic vascular invasion | No vs. yes | 0.99 (0.5–1.8) | 0.98 | 1.8 (1.0–3.4) | 0.06 | ||||
Extrahepatic spread | No vs. yes | 1.1 (0.4–2.8) | 0.89 | 1.0 (0.4–2.7) | 0.97 | ||||
PFS/OS | |||||||||
Peak (%) | 32.5/16.8 | 0.7 (0.4–1.4) | 0.35 | 0.6 (0.3–1.4) | 0.23 | ||||
Slope (1/s) | 21.4/22.4 | 0.5 (0.3–0.9) | 0.024 * | 0.6 (0.3–1.1) | 0.11 | 0.4 (0.2–0.8) | 0.01 * | 0.3 (0.2–0.7) | 0.003 * |
AUC (/10 s) | 1115/3689 | 0.5 (0.2–1.3) | 0.15 | 1.7 (0.8–3.7) | 0.19 | ||||
Ktrans (min−1/1000) | 51/21 | 0.8 (0.4–1.5) | 0.47 | 1.7 (0.5–5.5) | 0.42 | ||||
Kep (min−1/1000) | 370/1730 | 0.2 (0.1–0.5) | <0.001 * | 0.2 (0.1–0.5) | <0.001 * | 0.7 (0.3–1.5) | 0.3 | ||
Ve (%) | 6.5/11.1 | 0.7 (0.4–1.4) | 0.34 | 1.6 (0.9–3.0) | 0.11 | ||||
ADC (10−3 mm2/s) | 0.943/1.138 | 0.3 (0.1–0.7) | 0.018 * | 0.3 (0.1–0.7) | 0.009 * | 0.5 (0.2–0.9) | 0.015 * | 0.3 (0.1–0.8) | 0.009 * |
D (10−3 mm2/s) | 1.183/1.173 | 0.6 (0.2–1.3) | 0.2 | 0.6 (0.3–1.3) | 0.18 | ||||
D* (10−3 mm2/s) | 10.9/10.9 | 2.5 (0.8–8.4) | 0.1 | 3.1 (0.9–10.3) | 0.051 | ||||
f (%) | 28/23.4 | 0.6 (0.2–1.4) | 0.17 | 0.4 (0.2–0.8) | 0.012 * | 0.6 (0.3–1.1) | 0.1 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Chen, B.-B.; Shao, Y.-Y.; Lin, Z.-Z.; Hsu, C.-H.; Cheng, A.-L.; Hsu, C.; Liang, P.-C.; Shih, T.T.-F. Dynamic Contrast-Enhanced and Intravoxel Incoherent Motion MRI Biomarkers Are Correlated to Survival Outcome in Advanced Hepatocellular Carcinoma. Diagnostics 2021, 11, 1340. https://doi.org/10.3390/diagnostics11081340
Chen B-B, Shao Y-Y, Lin Z-Z, Hsu C-H, Cheng A-L, Hsu C, Liang P-C, Shih TT-F. Dynamic Contrast-Enhanced and Intravoxel Incoherent Motion MRI Biomarkers Are Correlated to Survival Outcome in Advanced Hepatocellular Carcinoma. Diagnostics. 2021; 11(8):1340. https://doi.org/10.3390/diagnostics11081340
Chicago/Turabian StyleChen, Bang-Bin, Yu-Yun Shao, Zhong-Zhe Lin, Chih-Hung Hsu, Ann-Lii Cheng, Chiun Hsu, Po-Chin Liang, and Tiffany Ting-Fang Shih. 2021. "Dynamic Contrast-Enhanced and Intravoxel Incoherent Motion MRI Biomarkers Are Correlated to Survival Outcome in Advanced Hepatocellular Carcinoma" Diagnostics 11, no. 8: 1340. https://doi.org/10.3390/diagnostics11081340
APA StyleChen, B. -B., Shao, Y. -Y., Lin, Z. -Z., Hsu, C. -H., Cheng, A. -L., Hsu, C., Liang, P. -C., & Shih, T. T. -F. (2021). Dynamic Contrast-Enhanced and Intravoxel Incoherent Motion MRI Biomarkers Are Correlated to Survival Outcome in Advanced Hepatocellular Carcinoma. Diagnostics, 11(8), 1340. https://doi.org/10.3390/diagnostics11081340