Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 1, pp 165–175

Prognostic implication of 18F FDG-PET in patients with extrahepatic metastatic hepatocellular carcinoma undergoing systemic treatment, a retrospective cohort study

  • Dong-Yeop Shin
  • Sae-Won Han
  • Do-Youn Oh
  • Seock-Ah Im
  • Tae-You Kim
  • Yung-Jue Bang
Original Article



The role of 18F FDG-PET in hepatocellular carcinoma (HCC) has not been firmly established. We conducted this study to investigate the clinical implication of SUVmax on 18F FDG-PET as a prognostic factor in patients with HCC, especially in the metastatic setting.


HCC patients with extrahepatic metastatic lesions were enrolled that were evaluated by 18F FDG-PET before palliative systemic therapy, between January 2002 and December 2009 at the Seoul National University Hospital. We retrospectively analyzed the clinical outcome and the value of the SUVmax.


A total of 25 patients (men, 88.0%) were enrolled. The response rate and disease control rate was 18.2% (95% CI: 2.1–34.3) and 32.0% (95% CI: 16.3–56.5), respectively. The progression-free survival (PFS) and overall survival (OS) were 2.3 months (95% CI: 1.1–3.4) and 14.2 months (95% CI: 9.1–19.2), respectively. The univariate analysis of OS showed that SUVmax and alphafetoprotein (AFP) were significant prognostic factors (P = 0.023 and P = 0.006, respectively). The multivariate analysis of OS showed that SUVmax and AFP were significant prognostic factors (P = 0.008 and P = 0.006, respectively). SUVmax and AFP were independent prognostic factors for PFS, too (P = 0.010 and P = 0.016, respectively). When the patients were divided according to the SUVmax and AFP, the patients with an SUVmax < 4.9 and an AFP ≤ 400 ng/ml showed longer OS and PFS than the patients with SUVmax ≥ 4.9 or AFP > 400 ng/ml (26.7 months vs. 9.3 months, P < 0.001 and 5.6 months vs. 1.7 months, P = 0.012, respectively).


The SUVmax of the 18F FDG-PET has a prognostic value for OS and PFS in patients with metastatic HCC undergoing systemic therapy. The combined analysis of the SUVmax with AFP might provide more detailed prognostic information.


Positron emission tomography Standardized uptake value Hepatocellular carcinoma Systemic therapy Prognostic factor 


  1. 1.
    Abe K, Baba S, Kaneko K, Isoda T, Yabuuchi H, Sasaki M, Sakai S, Yoshino I, Honda H (2009) Diagnostic and prognostic values of FDG-PET in patients with non-small cell lung cancer. Clin Imaging 33:90–95PubMedCrossRefGoogle Scholar
  2. 2.
    Fischer B, Lassen U, Mortensen J, Larsen S, Loft A, Bertelsen A, Ravn J, Clementsen P, Hogholm A, Larsen K, Rasmussen T, Keiding S, Dirksen A, Gerke O, Skov B, Steffensen I, Hansen H, Vilmann P, Jacobsen G, Backer V, Maltbaek N, Pedersen J, Madsen H, Nielsen H, Hojgaard L (2009) Preoperative staging of lung cancer with combined PET-CT. N Engl J Med 361:32–39PubMedCrossRefGoogle Scholar
  3. 3.
    Juweid ME, Wiseman GA, Vose JM, Ritchie JM, Menda Y, Wooldridge JE, Mottaghy FM, Rohren EM, Blumstein NM, Stolpen A, Link BK, Reske SN, Graham MM, Cheson BD (2005) Response assessment of aggressive non-Hodgkin’s lymphoma by integrated international workshop criteria and fluorine-18-fluorodeoxyglucose positron emission tomography. J Clin Oncol 23:4652–4661PubMedCrossRefGoogle Scholar
  4. 4.
    Wu D, Gambhir SS (2003) Positron emission tomography in diagnosis and management of invasive breast cancer: current status and future perspectives. Clin Breast Cancer 4(Suppl 1):S55–S63PubMedCrossRefGoogle Scholar
  5. 5.
    Choi M, Heilbrun LK, Venkatramanamoorthy R, Lawhorn-Crews JM, Zalupski MM, Shields AF (2010) Using 18F-fluorodeoxyglucose positron emission tomography to monitor clinical outcomes in patients treated with neoadjuvant chemo-radiotherapy for locally advanced pancreatic cancer. Am J Clin Oncol 33:257–261PubMedGoogle Scholar
  6. 6.
    Contractor KB, Aboagye EO (2009) Monitoring predominantly cytostatic treatment response with 18F-FDG PET. J Nucl Med 50(Suppl 1):97S–105SPubMedCrossRefGoogle Scholar
  7. 7.
    Hyun SH, Choi JY, Shim YM, Kim K, Lee SJ, Cho YS, Lee JY, Lee KH, Kim BT (2010) Prognostic value of metabolic tumor volume measured by 18F-fluorodeoxyglucose positron emission tomography in patients with esophageal carcinoma. Ann Surg Oncol 17:115–122PubMedCrossRefGoogle Scholar
  8. 8.
    Inohara H, Enomoto K, Tomiyama Y, Higuchi I, Inoue T, Hatazawa J (2010) Impact of FDG-PET on prediction of clinical outcome after concurrent chemoradiotherapy in hypopharyngeal carcinoma. Mol Imaging Biol 12:89–97PubMedCrossRefGoogle Scholar
  9. 9.
    Jung SY, Kim SK, Nam BH, Min SY, Lee SJ, Park C, Kwon Y, Kim EA, Ko KL, Park IH, Lee KS, Shin KH, Lee S, Kim SW, Kang HS, Ro J (2010) Prognostic impact of [18F] FDG-PET in operable breast cancer treated with neoadjuvant chemotherapy. Ann Surg Oncol 17:247–253PubMedCrossRefGoogle Scholar
  10. 10.
    Kato H, Nakajima M, Sohda M, Tanaka N, Inose T, Miyazaki T, Fukuchi M, Oriuchi N, Endo K, Kuwano H (2009) The clinical application of (18)F-fluorodeoxyglucose positron emission tomography to predict survival in patients with operable esophageal cancer. Cancer 115:3196–3203PubMedCrossRefGoogle Scholar
  11. 11.
    Sperti C, Pasquali C, Chierichetti F, Ferronato A, Decet G, Pedrazzoli S (2003) 18-Fluorodeoxyglucose positron emission tomography in predicting survival of patients with pancreatic carcinoma. J Gastrointest Surg 7:953–959 discussion 959-960PubMedCrossRefGoogle Scholar
  12. 12.
    Kong YH, Han CJ, Lee SD, Sohn WS, Kim MJ, Ki SS, Kim J, Jeong SH, Kim YC, Lee JO, Cheon GJ, Choi CW, Lim SM (2004) Positron emission tomography with fluorine-18-fluorodeoxyglucose is useful for predicting the prognosis of patients with hepatocellular carcinoma. Korean J Hepatol 10:279–287PubMedGoogle Scholar
  13. 13.
    Paudyal B, Paudyal P, Oriuchi N, Tsushima Y, Nakajima T, Endo K (2008) Clinical implication of glucose transport and metabolism evaluated by 18F-FDG PET in hepatocellular carcinoma. Int J Oncol 33:1047–1054PubMedGoogle Scholar
  14. 14.
    Eckel F, Herrmann K, Schmidt S, Hillerer C, Wieder HA, Krause BJ, Schuster T, Langer R, Wester HJ, Schmid RM, Schwaiger M, Buck AK (2009) Imaging of proliferation in hepatocellular carcinoma with the in vivo marker 18F-fluorothymidine. J Nucl Med 50:1441–1447PubMedCrossRefGoogle Scholar
  15. 15.
    Huo L, Wu Z, Zhuang H, Fu Z, Dang Y (2009) Dual time point C-11 acetate PET imaging can potentially distinguish focal nodular hyperplasia from primary hepatocellular carcinoma. Clin Nucl Med 34:874–877PubMedCrossRefGoogle Scholar
  16. 16.
    Yamamoto Y, Nishiyama Y, Kameyama R, Okano K, Kashiwagi H, Deguchi A, Kaji M, Ohkawa M (2008) Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F-FDG PET. J Nucl Med 49:1245–1248PubMedCrossRefGoogle Scholar
  17. 17.
    Yoon KT, Kim JK, Kim do Y, Ahn SH, Lee JD, Yun M, Rha SY, Chon CY, Han KH (2007) Role of 18F-fluorodeoxyglucose positron emission tomography in detecting extrahepatic metastasis in pretreatment staging of hepatocellular carcinoma. Oncology 72(Suppl 1):104–110PubMedCrossRefGoogle Scholar
  18. 18.
    Kawaoka T, Aikata H, Takaki S, Uka K, Azakami T, Saneto H, Jeong SC, Kawakami Y, Takahashi S, Toyota N, Ito K, Hirokawa Y, Chayama K (2009) FDG positron emission tomography/computed tomography for the detection of extrahepatic metastases from hepatocellular carcinoma. Hepatol Res 39:134–142PubMedCrossRefGoogle Scholar
  19. 19.
    Ho CL, Chen S, Yeung DW, Cheng TK (2007) Dual-tracer PET/CT imaging in evaluation of metastatic hepatocellular carcinoma. J Nucl Med 48:902–909PubMedCrossRefGoogle Scholar
  20. 20.
    Kaczynski J, Hansson G, Wallerstedt S (1995) Metastases in cases with hepatocellular carcinoma in relation to clinicopathologic features of the tumor. An autopsy study from a low endemic area. Acta Oncol 34:43–48PubMedCrossRefGoogle Scholar
  21. 21.
    Hatano E, Ikai I, Higashi T, Teramukai S, Torizuka T, Saga T, Fujii H, Shimahara Y (2006) Preoperative positron emission tomography with fluorine-18-fluorodeoxyglucose is predictive of prognosis in patients with hepatocellular carcinoma after resection. World J Surg 30:1736–1741PubMedCrossRefGoogle Scholar
  22. 22.
    Yang SH, Suh KS, Lee HW, Cho EH, Cho JY, Cho YB, Yi NJ, Lee KU (2006) The role of (18)F-FDG-PET imaging for the selection of liver transplantation candidates among hepatocellular carcinoma patients. Liver Transpl 12:1655–1660PubMedCrossRefGoogle Scholar
  23. 23.
    Kostakoglu L, Goldsmith SJ (2003) 18F-FDG PET evaluation of the response to therapy for lymphoma and for breast, lung, and colorectal carcinoma. J Nucl Med 44:224–239PubMedGoogle Scholar
  24. 24.
    Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236PubMedCrossRefGoogle Scholar
  25. 25.
    Sauerbrei W, Meier-Hirmer C, Benner A, Royston P (2006) Multivariable regression model building by using fractional polynomials: description of SAS, STATA and R programs. Comput Stat Data Anal 50:3464–3485CrossRefGoogle Scholar
  26. 26.
    Vora SR, Zheng H, Stadler ZK, Fuchs CS, Zhu AX (2009) Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist 14:717–725PubMedCrossRefGoogle Scholar
  27. 27.
    Tangkijvanich P, Anukulkarnkusol N, Suwangool P, Lertmaharit S, Hanvivatvong O, Kullavanijaya P, Poovorawan Y (2000) Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol 31:302–308PubMedCrossRefGoogle Scholar
  28. 28.
    Seo S, Hatano E, Higashi T, Hara T, Tada M, Tamaki N, Iwaisako K, Ikai I, Uemoto S (2007) Fluorine-18 fluorodeoxyglucose positron emission tomography predicts tumor differentiation, P-glycoprotein expression, and outcome after resection in hepatocellular carcinoma. Clin Cancer Res 13:427–433PubMedCrossRefGoogle Scholar
  29. 29.
    Park JW, Kim JH, Kim SK, Kang KW, Park KW, Choi JI, Lee WJ, Kim CM, Nam BH (2008) A prospective evaluation of 18F-FDG and 11C-acetate PET/CT for detection of primary and metastatic hepatocellular carcinoma. J Nucl Med 49:1912–1921PubMedCrossRefGoogle Scholar
  30. 30.
    Kawamura E, Habu D, Ohfuji S, Fukushima W, Enomoto M, Torii K, Kawabe J, Kondo K, Tamori A, Kawada N, Shiomi S (2008) Clinical role of FDG-PET for HCC: relationship of glucose metabolic indicator to Japan integrated staging (JIS) score. Hepatogastroenterology 55:582–586PubMedGoogle Scholar
  31. 31.
    Shiomi S, Nishiguchi S, Ishizu H, Iwata Y, Sasaki N, Tamori A, Habu D, Takeda T, Kubo S, Ochi H (2001) Usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose for predicting outcome in patients with hepatocellular carcinoma. Am J Gastroenterol 96:1877–1880PubMedCrossRefGoogle Scholar
  32. 32.
    Higashi T, Hatano E, Ikai I, Nishii R, Nakamoto Y, Ishizu K, Suga T, Kawashima H, Togashi K, Seo S, Kitamura K, Takada Y, Uemoto S (2010) FDG PET as a prognostic predictor in the early post-therapeutic evaluation for unresectable hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 37:468–482PubMedCrossRefGoogle Scholar
  33. 33.
    Nahmias C, Wahl LM (2008) Reproducibility of standardized uptake value measurements determined by 18F-FDG PET in malignant tumors. J Nucl Med 49:1804–1808PubMedCrossRefGoogle Scholar
  34. 34.
    Weber WA (2005) Use of PET for monitoring cancer therapy and for predicting outcome. J Nucl Med 46:983–995PubMedGoogle Scholar
  35. 35.
    Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25:579–586PubMedCrossRefGoogle Scholar
  36. 36.
    Berriolo-Riedinger A, Touzery C, Riedinger JM, Toubeau M, Coudert B, Arnould L, Boichot C, Cochet A, Fumoleau P, Brunotte F (2007) [18F]FDG-PET predicts complete pathological response of breast cancer to neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging 34:1915–1924PubMedCrossRefGoogle Scholar
  37. 37.
    Biersack HJ, Bender H, Palmedo H (2004) FDG-PET in monitoring therapy of breast cancer. Eur J Nucl Med Mol Imaging 31(Suppl 1):S112–S117PubMedCrossRefGoogle Scholar
  38. 38.
    Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019PubMedCrossRefGoogle Scholar
  39. 39.
    van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, Martens M, Webb A, Sciot R, Van Glabbeke M, Silberman S, Nielsen OS (2001) Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 358:1421–1423PubMedCrossRefGoogle Scholar
  40. 40.
    Lee DH, Kim SK, Lee HY, Lee SY, Park SH, Kim HY, Kang KW, Han JY, Kim HT, Lee JS (2009) Early prediction of response to first-line therapy using integrated 18F-FDG PET/CT for patients with advanced/metastatic non-small cell lung cancer. J Thorac Oncol 4:816–821PubMedCrossRefGoogle Scholar
  41. 41.
    Pillot G, Siegel BA, Govindan R (2006) Prognostic value of fluorodeoxyglucose positron emission tomography in non-small cell lung cancer: a review. J Thorac Oncol 1:152–159PubMedCrossRefGoogle Scholar
  42. 42.
    Lee KH, Lee SH, Kim DW, Kang WJ, Chung JK, Im SA, Kim TY, Kim YW, Bang YJ, Heo DS (2006) High fluorodeoxyglucose uptake on positron emission tomography in patients with advanced non-small cell lung cancer on platinum-based combination chemotherapy. Clin Cancer Res 12:4232–4236PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Dong-Yeop Shin
    • 1
  • Sae-Won Han
    • 1
    • 2
  • Do-Youn Oh
    • 1
    • 2
  • Seock-Ah Im
    • 1
    • 2
  • Tae-You Kim
    • 1
    • 2
  • Yung-Jue Bang
    • 1
    • 2
  1. 1.Department of Internal MedicineSeoul National University Hospital, Seoul National University College of MedicineSeoulKorea
  2. 2.Cancer Research InstituteSeoul National University College of MedicineSeoulKorea

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