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Published in: European Journal of Nuclear Medicine and Molecular Imaging 5/2018

01-05-2018 | Original Article

Preoperative prediction of microvascular invasion of hepatocellular carcinoma using 18F-FDG PET/CT: a multicenter retrospective cohort study

Authors: Seung Hyup Hyun, Jae Seon Eo, Bong-Il Song, Jeong Won Lee, Sae Jung Na, Il Ki Hong, Jin Kyoung Oh, Yong An Chung, Tae-Sung Kim, Mijin Yun

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2018

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Abstract

Purpose

The aim of this study was to assess the potential of tumor 18F-fluorodeoxyglucose (FDG) avidity as a preoperative imaging biomarker for the prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC).

Methods

One hundred and fifty-eight patients diagnosed with Barcelona Clinic Liver Cancer stages 0 or A HCC (median age, 57 years; interquartile range, 50–64 years) who underwent 18F-FDG positron emission tomography with computed tomography (PET/CT) before curative surgery at seven university hospitals were included. Tumor FDG avidity was measured by tumor-to-normal liver standardized uptake value ratio (TLR) of the primary tumor on FDG PET/CT imaging. Logistic regression analysis was performed to identify significant parameters associated with MVI. The predictive performance of TLR and other clinical variables was assessed using receiver operating characteristic (ROC) curve analysis.

Results

MVI was present in 76 of 158 patients with HCCs (48.1%). Multivariable logistic regression analysis revealed that TLR, serum alpha-fetoprotein (AFP) level, and tumor size were significantly associated with the presence of MVI (P < 0.001). Multinodularity was not significantly associated with MVI (P = 0.563). The area under the ROC curve (AUC) for predicting the presence of MVI was best with TLR (AUC = 0.704), followed by tumor size (AUC = 0.685) and AFP (AUC = 0.670). We were able to build an improved prediction model combining TLR, tumor size, and AFP by using multivariable logistic regression modeling (AUC = 0.756).

Conclusions

Tumor FDG avidity measured by TLR on FDG PET/CT is a preoperative imaging biomarker for the prediction of MVI in patients with HCC.
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Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed
2.
go back to reference Liver EAFTSOT, Research EOF, Cancer TO. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.CrossRef Liver EAFTSOT, Research EOF, Cancer TO. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.CrossRef
3.
go back to reference Zimmerman MA, Ghobrial RM, Tong MJ, Hiatt JR, Cameron AM, Hong J, et al. Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg. 2008;143:182–8. discussion 8CrossRefPubMed Zimmerman MA, Ghobrial RM, Tong MJ, Hiatt JR, Cameron AM, Hong J, et al. Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg. 2008;143:182–8. discussion 8CrossRefPubMed
4.
go back to reference Renzulli M, Brocchi S, Cucchetti A, Mazzotti F, Mosconi C, Sportoletti C, et al. Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? Radiology. 2016;279:432–42.CrossRefPubMed Renzulli M, Brocchi S, Cucchetti A, Mazzotti F, Mosconi C, Sportoletti C, et al. Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? Radiology. 2016;279:432–42.CrossRefPubMed
5.
go back to reference Eo JS, Paeng JC, Lee DS. Nuclear imaging for functional evaluation and theragnosis in liver malignancy and transplantation. World J Gastroenterol. 2014;20:5375–88.CrossRefPubMedPubMedCentral Eo JS, Paeng JC, Lee DS. Nuclear imaging for functional evaluation and theragnosis in liver malignancy and transplantation. World J Gastroenterol. 2014;20:5375–88.CrossRefPubMedPubMedCentral
6.
go back to reference Lee JW, Paeng JC, Kang KW, Kwon HW, Suh KS, Chung JK, et al. Prediction of tumor recurrence by 18F-FDG PET in liver transplantation for hepatocellular carcinoma. J Nucl Med. 2009;50:682–7.CrossRefPubMed Lee JW, Paeng JC, Kang KW, Kwon HW, Suh KS, Chung JK, et al. Prediction of tumor recurrence by 18F-FDG PET in liver transplantation for hepatocellular carcinoma. J Nucl Med. 2009;50:682–7.CrossRefPubMed
7.
go back to reference Lee JD, Yun M, Lee JM, Choi Y, Choi YH, Kim JS, et al. Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography. Eur J Nucl Med Mol Imaging. 2004;31:1621–30.CrossRefPubMed Lee JD, Yun M, Lee JM, Choi Y, Choi YH, Kim JS, et al. Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography. Eur J Nucl Med Mol Imaging. 2004;31:1621–30.CrossRefPubMed
8.
go back to reference Kobayashi T, Aikata H, Honda F, Nakano N, Nakamura Y, Hatooka M, et al. Preoperative fluorine 18 Fluorodeoxyglucose positron emission tomography/computed tomography for prediction of microvascular invasion in small hepatocellular carcinoma. J Comput Assist Tomogr. 2016;40:524–30.CrossRefPubMed Kobayashi T, Aikata H, Honda F, Nakano N, Nakamura Y, Hatooka M, et al. Preoperative fluorine 18 Fluorodeoxyglucose positron emission tomography/computed tomography for prediction of microvascular invasion in small hepatocellular carcinoma. J Comput Assist Tomogr. 2016;40:524–30.CrossRefPubMed
9.
go back to reference Ahn SY, Lee JM, Joo I, Lee ES, Lee SJ, Cheon GJ, et al. Prediction of microvascular invasion of hepatocellular carcinoma using gadoxetic acid-enhanced MR and (18)F-FDG PET/CT. Abdom Imaging. 2015;40:843–51.CrossRefPubMed Ahn SY, Lee JM, Joo I, Lee ES, Lee SJ, Cheon GJ, et al. Prediction of microvascular invasion of hepatocellular carcinoma using gadoxetic acid-enhanced MR and (18)F-FDG PET/CT. Abdom Imaging. 2015;40:843–51.CrossRefPubMed
10.
go back to reference Kornberg A, Küpper B, Thrum K, Katenkamp K, Steenbeck J, Sappler A, et al. Increased 18F-FDG uptake of hepatocellular carcinoma on positron emission tomography independently predicts tumor recurrence in liver transplant patients. Transplant Proc. 2009;41:2561–3.CrossRefPubMed Kornberg A, Küpper B, Thrum K, Katenkamp K, Steenbeck J, Sappler A, et al. Increased 18F-FDG uptake of hepatocellular carcinoma on positron emission tomography independently predicts tumor recurrence in liver transplant patients. Transplant Proc. 2009;41:2561–3.CrossRefPubMed
11.
go back to reference Fluss R, Faraggi D, Reiser B. Estimation of the Youden index and its associated cutoff point. Biom J. 2005;47:458–72.CrossRefPubMed Fluss R, Faraggi D, Reiser B. Estimation of the Youden index and its associated cutoff point. Biom J. 2005;47:458–72.CrossRefPubMed
12.
go back to reference DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.CrossRefPubMed DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.CrossRefPubMed
13.
go back to reference Mlynarsky L, Menachem Y, Shibolet O. Treatment of hepatocellular carcinoma: steps forward but still a long way to go. World J Hepatol. 2015;7:566–74.CrossRefPubMedPubMedCentral Mlynarsky L, Menachem Y, Shibolet O. Treatment of hepatocellular carcinoma: steps forward but still a long way to go. World J Hepatol. 2015;7:566–74.CrossRefPubMedPubMedCentral
14.
go back to reference TH W, Hatano E, Yamanaka K, Seo S, Taura K, Yasuchika K, et al. A non-smooth tumor margin on preoperative imaging predicts microvascular invasion of hepatocellular carcinoma. Surg Today. 2016;46:1275–81.CrossRef TH W, Hatano E, Yamanaka K, Seo S, Taura K, Yasuchika K, et al. A non-smooth tumor margin on preoperative imaging predicts microvascular invasion of hepatocellular carcinoma. Surg Today. 2016;46:1275–81.CrossRef
15.
go back to reference Mizuguchi T, Kawamoto M, Meguro M, Okita K, Ota S, Ishii M, et al. Impact of aging on morbidity and mortality after liver resection: a systematic review and meta-analysis. Surg Today. 2015;45:259–70.CrossRefPubMed Mizuguchi T, Kawamoto M, Meguro M, Okita K, Ota S, Ishii M, et al. Impact of aging on morbidity and mortality after liver resection: a systematic review and meta-analysis. Surg Today. 2015;45:259–70.CrossRefPubMed
16.
go back to reference Zhao WC, Fan LF, Yang N, Zhang HB, Chen BD, Yang GS. Preoperative predictors of microvascular invasion in multinodular hepatocellular carcinoma. Eur J Surg Oncol. 2013;39:858–64.CrossRefPubMed Zhao WC, Fan LF, Yang N, Zhang HB, Chen BD, Yang GS. Preoperative predictors of microvascular invasion in multinodular hepatocellular carcinoma. Eur J Surg Oncol. 2013;39:858–64.CrossRefPubMed
17.
go back to reference Kaibori M, Ishizaki M, Matsui K, Kwon AH. Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol. 2010;102:462–8.CrossRefPubMed Kaibori M, Ishizaki M, Matsui K, Kwon AH. Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol. 2010;102:462–8.CrossRefPubMed
18.
go back to reference Kim BK, Han KH, Park YN, Park MS, Kim KS, Choi JS, et al. Prediction of microvascular invasion before curative resection of hepatocellular carcinoma. J Surg Oncol. 2008;97:246–52.CrossRefPubMed Kim BK, Han KH, Park YN, Park MS, Kim KS, Choi JS, et al. Prediction of microvascular invasion before curative resection of hepatocellular carcinoma. J Surg Oncol. 2008;97:246–52.CrossRefPubMed
19.
go back to reference Kornberg A, Freesmeyer M, Bärthel E, Jandt K, Katenkamp K, Steenbeck J, et al. 18F-FDG-uptake of hepatocellular carcinoma on PET predicts microvascular tumor invasion in liver transplant patients. Am J Transplant. 2009;9:592–600.CrossRefPubMed Kornberg A, Freesmeyer M, Bärthel E, Jandt K, Katenkamp K, Steenbeck J, et al. 18F-FDG-uptake of hepatocellular carcinoma on PET predicts microvascular tumor invasion in liver transplant patients. Am J Transplant. 2009;9:592–600.CrossRefPubMed
20.
go back to reference Royston P, Altman DG, Sauerbrei W. Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med. 2006;25:127–41.CrossRefPubMed Royston P, Altman DG, Sauerbrei W. Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med. 2006;25:127–41.CrossRefPubMed
21.
go back to reference Rodriguez-Peralvarez M, Luong TV, Andreana L, Meyer T, Dhillon AP, Burroughs AKA. Systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol. 2013;20:325–39.CrossRefPubMed Rodriguez-Peralvarez M, Luong TV, Andreana L, Meyer T, Dhillon AP, Burroughs AKA. Systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol. 2013;20:325–39.CrossRefPubMed
22.
go back to reference Zhao H, Hua Y, Dai T, He J, Tang M, Fu X, et al. Development and validation of a novel predictive scoring model for microvascular invasion in patients with hepatocellular carcinoma. Eur J Radiol. 2017;88:32–40.CrossRefPubMed Zhao H, Hua Y, Dai T, He J, Tang M, Fu X, et al. Development and validation of a novel predictive scoring model for microvascular invasion in patients with hepatocellular carcinoma. Eur J Radiol. 2017;88:32–40.CrossRefPubMed
23.
go back to reference Huang YQ, Liang HY, Yang ZX, Ding Y, Zeng MS, Rao SX. Value of MR histogram analyses for prediction of microvascular invasion of hepatocellular carcinoma. Medicine (Baltimore). 2016;95:e4034.CrossRef Huang YQ, Liang HY, Yang ZX, Ding Y, Zeng MS, Rao SX. Value of MR histogram analyses for prediction of microvascular invasion of hepatocellular carcinoma. Medicine (Baltimore). 2016;95:e4034.CrossRef
24.
go back to reference Zhao J, Li X, Zhang K, Yin X, Meng X, Han L, et al. Prediction of microvascular invasion of hepatocellular carcinoma with preoperative diffusion-weighted imaging: a comparison of mean and minimum apparent diffusion coefficient values. Medicine (Baltimore). 2017;96:e7754.CrossRef Zhao J, Li X, Zhang K, Yin X, Meng X, Han L, et al. Prediction of microvascular invasion of hepatocellular carcinoma with preoperative diffusion-weighted imaging: a comparison of mean and minimum apparent diffusion coefficient values. Medicine (Baltimore). 2017;96:e7754.CrossRef
25.
go back to reference Cucchetti A, Qiao GL, Cescon M, Li J, Xia Y, Ercolani G, et al. Anatomic versus nonanatomic resection in cirrhotic patients with early hepatocellular carcinoma. Surgery. 2014;155:512–21.CrossRefPubMed Cucchetti A, Qiao GL, Cescon M, Li J, Xia Y, Ercolani G, et al. Anatomic versus nonanatomic resection in cirrhotic patients with early hepatocellular carcinoma. Surgery. 2014;155:512–21.CrossRefPubMed
26.
go back to reference Liu M, Wang L, Zhu H, Rong W, Wu F, Liang S, et al. A preoperative measurement of serum microRNA-125b may predict the presence of microvascular invasion in hepatocellular carcinomas patients. Transl Oncol. 2016;9:167–72.CrossRefPubMedPubMedCentral Liu M, Wang L, Zhu H, Rong W, Wu F, Liang S, et al. A preoperative measurement of serum microRNA-125b may predict the presence of microvascular invasion in hepatocellular carcinomas patients. Transl Oncol. 2016;9:167–72.CrossRefPubMedPubMedCentral
27.
go back to reference Vitale A, Cucchetti A, Qiao GL, Cescon M, Li J, Morales RR, et al. Is resectable hepatocellular carcinoma a contraindication to liver transplantation? A novel decision model based on “number of patients needed to transplant” as measure of transplant benefit. J Hepatol. 2014;60:1165–71.CrossRefPubMed Vitale A, Cucchetti A, Qiao GL, Cescon M, Li J, Morales RR, et al. Is resectable hepatocellular carcinoma a contraindication to liver transplantation? A novel decision model based on “number of patients needed to transplant” as measure of transplant benefit. J Hepatol. 2014;60:1165–71.CrossRefPubMed
Metadata
Title
Preoperative prediction of microvascular invasion of hepatocellular carcinoma using 18F-FDG PET/CT: a multicenter retrospective cohort study
Authors
Seung Hyup Hyun
Jae Seon Eo
Bong-Il Song
Jeong Won Lee
Sae Jung Na
Il Ki Hong
Jin Kyoung Oh
Yong An Chung
Tae-Sung Kim
Mijin Yun
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3880-4

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