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

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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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References

  1. 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.

    Article  PubMed  Google Scholar 

  2. Liver EAFTSOT, Research EOF, Cancer TO. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.

    Article  Google Scholar 

  3. 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 8

    Article  PubMed  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. 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.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. Fluss R, Faraggi D, Reiser B. Estimation of the Youden index and its associated cutoff point. Biom J. 2005;47:458–72.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 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.

    Article  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  CAS  PubMed  Google Scholar 

  17. Kaibori M, Ishizaki M, Matsui K, Kwon AH. Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol. 2010;102:462–8.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. Royston P, Altman DG, Sauerbrei W. Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med. 2006;25:127–41.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  Google Scholar 

  23. 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.

    Article  Google Scholar 

  24. 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.

    Article  Google Scholar 

  25. 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.

    Article  PubMed  Google Scholar 

  26. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by the Korean Society of Nuclear Medicine Clinical Trial Network (KSNM CTN) working group funded by the Korean Society of Nuclear Medicine (KSNM-CTN-2014-02-1), the Korea University Guro Hospital Grant (O1700461), and the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (No. 2014R1A5A2010008).

Funding

This research was supported by the Korean Society of Nuclear Medicine Clinical Trial Network (KSNM CTN) working group funded by the Korean Society of Nuclear Medicine (KSNM-CTN-2014-02-1), the Korea University Guro Hospital Grant (O1700461), and the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (No. 2014R1A5A2010008).

Author information

Author notes

  1. Seung Hyup Hyun and Jae Seon Eo contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Seung Hyup Hyun

  2. Department of Nuclear Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea

    Jae Seon Eo

  3. Department of Nuclear Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea

    Bong-Il Song

  4. Department of Nuclear Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon, South Korea

    Jeong Won Lee

  5. Department of Nuclear Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea

    Sae Jung Na

  6. Department of Nuclear Medicine, Kyung Hee University Hospital, School of Medicine, Kyung Hee University, Seoul, South Korea

    Il Ki Hong

  7. Department of Nuclear Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea

    Jin Kyoung Oh & Yong An Chung

  8. Department of Nuclear Medicine, Research Institute and Hospital, National Cancer Center, Goyang, South Korea

    Tae-Sung Kim

  9. Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea

    Mijin Yun

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  1. Seung Hyup Hyun
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Corresponding authors

Correspondence to Bong-Il Song or Mijin Yun.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

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Hyun, S.H., Eo, J.S., Song, BI. et al. Preoperative prediction of microvascular invasion of hepatocellular carcinoma using 18F-FDG PET/CT: a multicenter retrospective cohort study. Eur J Nucl Med Mol Imaging 45, 720–726 (2018). https://doi.org/10.1007/s00259-017-3880-4

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  • DOI: https://doi.org/10.1007/s00259-017-3880-4

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