Comparing PET metabolic parameters with clinicopathological factors in predicting onset of early recurrence in recently diagnosed hepatocellular carcinoma

Document Type : Original Article

Authors

1 Amrita School of Medicine, Amrita Vishwa Vidyapeetham, Ponekkara Post, Cochin, Kerala, India

2 Department of Nuclear Medicine and Molecular Imaging, Amrita Institute of Medical Sciences, Ponekkara Post, Cochin, Kerala, India

Abstract

Introduction: Early recurrence of hepatocellular carcinoma (HCC) is a major risk factor affecting survival even after hepatectomy. Many clinical, biochemical parameters and pathological grading like fibrosis 1 index have been used for risk stratifying HCC. However not many studies have combined all of them. It is therefore important to risk stratify HCC especially with newer PET based metabolic parameters to see if they match with existing clinicopathological parameters to achieve better clinical outcome. The objectives of this study were twofold; firstly, to evaluate [18F]FDG PET as a prognostic biomarker to predict tumour recurrence. Secondly, if clinicopathological parameters combined with PET indices increase the risk correlate in predicting HCC disease recurrence.
Methods: Records of 200 adult HCC patients were analysed, (6:1, Male: Female; mean age ± SD, 52 ± 2 year). All underwent [18F]FDG PET (PET MR: PET CT = 168:32) and subsequent therapy. Patients had a follow up for at least 15 months or onset of first recurrence, whichever was earlier. Clinicopathological data, alpha-fetoprotein (AFP) titres, SUVmax and few other PET indices were documented along with details of first recurrence. Statistical analysis was also performed.
Results: In a multivariate analysis of various prognostic factors including T (SUVmax)/ L (SUVmax), serum alpha-fetoprotein, T stage, size of tumour, and vascular invasion of tumour, T (SUVmax)/ L (SUVmax) was the most significant with a cut off value of 1.9. Only vascular invasion of tumour and AFP titres had additional significance. 16% ( 32/200 patients) developed recurrence (OR 1.673). Comparing the low and high AFP titres by Kaplan Meir curve, P was found to be 0.039 that predicted a worse prognosis in patients with higher AFP titres. Similarly patients with higher SUV T/L: ratio of tumour SUVmax to liver (> 1.9) also revealed higher recurrence rate. Cut-off SUVmax was 3.03 g/ml in our series (range 2.5 - 23.8 g/ml) and found to be strongly associated with AFP, tumour size, number, and histological grade of tumour.
Conclusion: Our study shows that PET based metabolic indices are effective robust tools to predict tumour recurrence in aggressive HCC. Secondly, when clinicopathological parameters are combined with PET based indices there is better prediction of HCC recurrence and one can reclassify HCC patients into mild, moderate, and high-risk groups. We found it very useful in predicting poor clinical outcome especially in high-risk HCC patients; so that stricter surveillance measures can be recommended to identify early recurrence and offer appropriate therapy. The strength of this study lies in the fact that the observed associations between the combined parameters were found to be stronger than those reported in the past.

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References

  1. Nandennavar MI, Karpurmath SV, Mandakalatur G, Prasad AE. Clinical profile of hepatocellular carcinoma and experience with sorafenib from a tertiary cancer centre in Southern India. Int J Res Med Sci. 2017;5(2):379-83.
  2. Bhattacharya GS, GovindBabu K, Malhotra H, Ranade AA, Murshed S, Datta D.  Hepatocellular carcinoma in India. Chin Clin Oncol. 2013 Dec;2(4):41.
  3. Bosch FX, Ribes J, Borras J. Epidemiology of primary liver cancer. Semin Liver Dis. 1999;19(3):271-85.
  4. Ferlay J, Colombet M, Soerjomataram I , Mathers C , Parkin D M , Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCON sources and methods. Int J Cancer. 2019 Apr 15;144(8):1941-1953.
  5. Llovet JM, Ducreux M, Lencioni R, Bisceglie AMD, Galle PR, Dufour JF, Greten TF, Raymond E, Roskams T, Baere TD, Ducreux M, Mazzaferro V. European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012;56:908-943.
  6. Galle P R, Forner A, Llovet J M, Mazzaferro V, Piscaglia F, Raoul JL, Schirmacher P, Vilgrain V. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69:182-236.
  7. Zhang XF, Qi X, Meng B, Liu C, Yu L, Wang B, Lv Y. Prognosis evaluation in alpha-fetoprotein negative hepatocellular carcinoma after hepatectomy: comparison of five staging systems. Eur J Surg Oncol. 2010;36:718-24.
  8. Agopian VG, Harlander-Locke MP, Markovic D, Zarrinpar A, Kaldas FM, Cheng EY, Yersiz H, Farmer DG, Hiatt JR, Busuttil RW. Evaluation of patients with hepatocellular carcinomas that do not produce α-fetoprotein. JAMA Surg 2017;152:55-64.
  9. Carr BI, Pancoska P, Branch RA. Low alpha-fetoprotein hepatocellular carcinoma. J Gastroenterol Hepatol. 2010 Sep;25(9):1543-9. 
  10. Shah SA, Cleary SP, Wei AC, Yang I, Taylor BR, Hemming AW, Langer B, Grant DR, Greig PD, Gallinger S. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery. 2007 Mar;141(3):330-9.  
  11. Edmondson HA, Steiner PE. Primary carcinoma of the liver. A study of 100 cases among 48,900 necropsies. Cancer. 1954 May;7(3):462-503.
  12. Shirabe K, Toshima T, Kimura K, Yamashita Y, Ikeda T, Ikegami T, Yoshizumi T, Abe K, Aishima S, Maehara Y. New scoring system for prediction of microvascular invasion in patients with hepatocellular carcinoma. Liver Int. 2014 Jul;34(6):937-41. 
  13.  Lee JW, Paeng JC, Kang KW, Kwon HW, Suh KS, Chung JK, Lee MC, Lee DS. Prediction of tumor recurrence by 18F-FDG PET in liver transplantation for hepatocellular carcinoma. J Nucl Med. 2009 May;50(5):682-687.
  14. Li P, Wang SS, Liu H, Li N, McNutt MA, Li G, Ding HG. Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma. World J Gastroenterol. 2011 Nov 7;17(41):4563-71.
  15. Carrie NG, Nahon P. Hepatocellular carcinoma in the setting of alcohol-related liver disease. J Hepatol. 2019;70:284-93.
  16. Lu Y, Zhu M, Li W, Lin B, Dong X, Chen Y, Xie X, Guo J, Li M. Alpha fetoprotein plays a critical role in promoting metastasis of hepatocellular carcinoma cells. J Cell Mol Med. 2016;20(3):549-58.  
  17. Sun P, Chen S, Li Y. The association between pretreatment serum alkaline phosphatase and prognosis in hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore). 2020 Mar;99(11):e19438.   
  18. Toso C, Meeberg G, Hernandez-Alejandro R, Dufour JF, Marotta P, Majno P, Kneteman NM. Total tumor volume and alpha‐fetoprotein for selection of transplant candidates with hepatocellular carcinoma: A prospective validation.  Hepatology. 2015 Jul;62(1):158-65.
  19. Pawlik TM, Delman KA, Vauthey JN, Nagorney DM, Ng IO, Ikai I, Yamaoka Y, Belghiti J, Lauwers GY, Poon RT, Abdalla EK. Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl. 2005;11:1086-1092.
  20. Lin YL, Li Y. Study on the hepatocellular carcinoma model with metastasis. Genes Dis. 2020 Sep; 7(3): 336–350.
  21. Gao YS, Chen XP, Li KY, Wu ZD. Nude mice model of human hepatocellular carcinoma via orthotopic implantation of histologically intact tissue. World J Gastroenterol. 2004;10(21):3107-3111.
  22. Kwak MS, Chung GE, Yang JI, Yim JY. Long-term outcomes of HBsAg/anti-HBs double-positive versus HBsAg single-positive patients with chronic hepatitis B. Sci Rep. 2019 Dec 19;9(1):19417.
  23. Jurado-García J, Muñoz García-Borruel M, Rodríguez-Perálvarez ML, Ruíz-Cuesta P, Poyato-González A, Barrera-Baena P, Fraga-Rivas E, Costán-Rodero G, Briceño-Delgado J, Montero-Álvarez JL, de la Mata-García M. Impact of MELD allocation system on waiting list and early post-liver transplant mortality. PLoS One. 2016 Jun 14;11(6):e0155822.
  24. Al-Freah MAB, Moran C, Foxton MR, Agarwal K, Wendon JA, Heaton ND, Heneghan MA. Impact of comorbidity on waiting list and post-transplant outcomes in patients undergoing liver retransplantation. World J Hepatol. 2017 Jul 18;9(20):884-895.
  25. Feng J, Zhu R, Feng D, Yu L, Zhao D, Wu J, Yuan C, Chen J, Zhang Y, Zheng X. Prediction of early recurrence of solitary hepatocellular carcinoma after orthotopic liver transplantation. Sci Rep. 2019;9(1):15855.
  26. Li M, Zhao Y, Liu X, Z Shuan, Jiang Y, Yang Z. Early risk warning system for distant metastasis of hepatitis B virus‑associated hepatocellular carcinoma with portal vein tumor thrombus. Oncol Lett. 2020 Apr; 19(4): 3249–3257.  
  27. Kong E, Chun KA, Cho IH. Quantitative assessment of simultaneous F-18 FDG PET/MRI in patients with various types of hepatic tumors: correlation between glucose metabolism and apparent diffusion coefficient. PLoS One. 2017;12(7) e0180184.
  28. Ong LC, Jin Y, Song IC, Yu S, Zhang K, Chow PK. 2-[18F]-2-deoxy-D-glucose (FDG) uptake in human tumor cells is related to the expression of GLUT-1 and hexokinase II. Acta Radiol. 2008 Dec;49(10):1145-53.
  29. Lee SM, Kim HS, Lee S, Lee JW. Emerging role of 18F-fluorodeoxyglucose positron emission tomography for guiding management of hepatocellular carcinoma. World J Gastroenterol. 2019;25(11):1289-1306.

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