18F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with 90Y microspheres

  • Alexander R. Haug
  • Volker Heinemann
  • Christiane J. Bruns
  • Ralf Hoffmann
  • Tobias Jakobs
  • Peter Bartenstein
  • Marcus Hacker
Original Article



90Y radioembolization has emerged as a valuable therapy for intrahepatic cholangiocellular carcinomas (ICC). We aimed to evaluate the prognostic power of FDG PET/CT and that of pretherapeutic scintigraphy with 99mTc-labelled macroagglutinated albumin (MAA), an index of tumour vascularization.


The study group comprised 26 consecutive patients suffering from nonresectable ICC. Before treatment with radioembolization, all patients underwent MRI of the liver, as well as MAA scintigraphy, which was followed immediately by SPECT(/CT) to quantify the liver–lung shunt fraction. Using image fusion, regions of interest were drawn around the tumours and the entire liver, and the tumour-to-liver quotient was calculated. In addition, FDG PET/CT was performed at baseline and 3 months after radioembolization, and the percentage changes in peak (ΔSUVmax) and mean (ΔSUVmean) FDG uptake and in metabolic tumour volume (ΔVol2SD) relative to baseline were calculated. Treatment response at 3 months was also assessed using contrast-enhanced MRI and CT on the basis of standard criteria.


Of 23 patients in whom follow-up MRI was available, 5 (22%) showed a partial response, 15 (65%) stable disease and 3 (13%) progressive disease. The change in all FDG values significantly predicted survival by Kaplan-Meier analysis after radioembolization; ΔVol2SD responders had a median survival of 97 weeks versus 30 weeks in nonresponders (P = 0.02), whereas ΔSUVmax and ΔSUVmean responders had a median survival of 114 weeks (responder) versus 19 weeks (nonresponder) and 69 weeks in patients with stable disease (P < 0.05). Pretherapeutic MAA scintigraphy or MRI did not predict survival, nor did the presence of extrahepatic metastases, or prior therapies. Only ΔVol2SD was significantly associated with survival by univariate analysis (hazard ratio 0.25; P = 0.04) and multivariate analysis (hazard ratio 0.20, P = 0.04).


FDG PET/CT was able to predict patient outcome after radioembolization treatment, with the change in metabolically active tumour volume at 3 months being the best independent predictor. High tumour vascularization, as indicated by MAA scintigraphy, was not a prerequisite for successful radioembolization and was even associated with a tendency towards shorter survival.


Radioembolization Intrahepatic cholangiocellular carcinoma FDG PET/CT MAA scintigraphy 


  1. 1.
    Shaib YH, Davila JA, McGlynn K, El-Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol. 2004;40:472–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology. 2001;33:1353–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Shaib YH, Davila JA, Henderson L, McGlynn KA, El-Serag HB. Endoscopic and surgical therapy for intrahepatic cholangiocarcinoma in the United States: a population-based study. J Clin Gastroenterol. 2007;41:911–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson CD, Pinson CW, Berlin J, Chari RS. Diagnosis and treatment of cholangiocarcinoma. Oncologist. 2004;9:43–57.PubMedCrossRefGoogle Scholar
  5. 5.
    Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet. 2005;366:1303–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Alberts SR, Gores GJ, Kim GP, Roberts LR, Kendrick ML, Rosen CB, et al. Treatment options for hepatobiliary and pancreatic cancer. Mayo Clin Proc. 2007;82:628–37.PubMedCrossRefGoogle Scholar
  7. 7.
    Park I, Lee JL, Ryu MH, Kim TW, Sook Lee S, Hyun Park D. Prognostic factors and predictive model in patients with advanced biliary tract adenocarcinoma receiving first-line palliative chemotherapy. Cancer. 2009;115:4148–55.PubMedCrossRefGoogle Scholar
  8. 8.
    Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.PubMedCrossRefGoogle Scholar
  9. 9.
    Vente MA, Wondergem M, van der Tweel I, van den Bosch MA, Zonnenberg BA, Lam MG, et al. Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis. Eur Radiol. 2009;19:951–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Ibrahim SM, Mulcahy MF, Lewandowski RJ, Sato KT, Ryu RK, Masterson EJ, et al. Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer. 2008;113:2119–28.PubMedCrossRefGoogle Scholar
  11. 11.
    Saxena A, Bester L, Chua TC, Chu FC, Morris DL. Yttrium-90 radiotherapy for unresectable intrahepatic cholangiocarcinoma: a preliminary assessment of this novel treatment option. Ann Surg Oncol. 2010;17:484–91.PubMedCrossRefGoogle Scholar
  12. 12.
    Flamen P, Vanderlinden B, Delatte P, Ghanem G, Ameye L, Van Den Eynde M, et al. Multimodality imaging can predict the metabolic response of unresectable colorectal liver metastases to radioembolization therapy with Yttrium-90 labeled resin microspheres. Phys Med Biol. 2008;53:6591–603.PubMedCrossRefGoogle Scholar
  13. 13.
    de Geus-Oei LF, van Laarhoven HW, Visser EP, Hermsen R, van Hoorn BA, Kamm YJ, et al. Chemotherapy response evaluation with FDG-PET in patients with colorectal cancer. Ann Oncol. 2008;19:348–52.PubMedCrossRefGoogle Scholar
  14. 14.
    Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med. 2006;354:496–507.PubMedCrossRefGoogle Scholar
  15. 15.
    Weber WA, Ott K, Becker K, Dittler HJ, Helmberger H, Avril NE, et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol. 2001;19:3058–65.PubMedGoogle Scholar
  16. 16.
    Kostakoglu L, Coleman M, Leonard JP, Kuji I, Zoe H, Goldsmith SJ. PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. J Nucl Med. 2002;43:1018–27.PubMedGoogle Scholar
  17. 17.
    Ott K, Weber WA, Lordick F, Becker K, Busch R, Herrmann K, et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol. 2006;24:4692–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Goin JE, Salem R, Carr BI, Dancey JE, Soulen MC, Geschwind JF, et al. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. J Vasc Interv Radiol. 2005;16:205–13.PubMedGoogle Scholar
  19. 19.
    Ho S, Lau WY, Leung TW, Chan M, Johnson PJ, Li AK. Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer. Eur J Nucl Med. 1997;24:293–8.PubMedGoogle Scholar
  20. 20.
    Kennedy A, Nag S, Salem R, Murthy R, McEwan AJ, Nutting C, et al. Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the Radioembolization Brachytherapy Oncology Consortium. Int J Radiat Oncol Biol Phys. 2007;68:13–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Dancey JE, Shepherd FA, Paul K, Sniderman KW, Houle S, Gabrys J, et al. Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres. J Nucl Med. 2000;41:1673–81.PubMedGoogle Scholar
  22. 22.
    Salem R, Thurston KG, Carr BI, Goin JE, Geschwind JF. Yttrium-90 microspheres: radiation therapy for unresectable liver cancer. J Vasc Interv Radiol. 2002;13:S223–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.PubMedCrossRefGoogle Scholar
  24. 24.
    Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50 Suppl 1:122S–50S.PubMedCrossRefGoogle Scholar
  25. 25.
    Farley DR, Weaver AL, Nagorney DM. "Natural history" of unresected cholangiocarcinoma: patient outcome after noncurative intervention. Mayo Clin Proc. 1995;70:425–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Kim YS, Lee MK, Kim SJ, Kim IJ, Kim YK, Jo WS, et al. Prognostic stratification using F-18 FDG PET/CT in patients with advanced stage (stage III and IV) non-small cell lung cancer. Neoplasma. 2010;57:241–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Farrag A, Ceulemans G, Voordeckers M, Everaert H, Storme G. Can 18F-FDG-PET response during radiotherapy be used as a predictive factor for the outcome of head and neck cancer patients? Nucl Med Commun. 2010;31:495–501PubMedGoogle Scholar
  28. 28.
    Jingu K, Kaneta T, Nemoto K, Takeda K, Ogawa Y, Ariga H, et al. (18)F-fluorodeoxyglucose positron emission tomography immediately after chemoradiotherapy predicts prognosis in patients with locoregional postoperative recurrent esophageal cancer. Int J Clin Oncol. 2010;15:184–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Higashi T, Hatano E, Ikai I, Nishii R, Nakamoto Y, Ishizu K, et al. FDG PET as a prognostic predictor in the early post-therapeutic evaluation for unresectable hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2010;37:468–82.PubMedCrossRefGoogle Scholar
  30. 30.
    Zhu AX, Meyerhardt JA, Blaszkowsky LS, Kambadakone AR, Muzikansky A, Zheng H, et al. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol. 2010;11:48–54.PubMedCrossRefGoogle Scholar
  31. 31.
    Dunfee BL, Riaz A, Lewandowski RJ, Ibrahim S, Mulcahy MF, Ryu RK, et al. Yttrium-90 radioembolization for liver malignancies: prognostic factors associated with survival. J Vasc Interv Radiol. 2010;21:90–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138:52–64.PubMedCrossRefGoogle Scholar
  33. 33.
    Kennedy AS, Nutting C, Coldwell D, Gaiser J, Drachenberg C. Pathologic response and microdosimetry of (90)Y microspheres in man: review of four explanted whole livers. Int J Radiat Oncol Biol Phys. 2004;60:1552–63.PubMedCrossRefGoogle Scholar
  34. 34.
    Sato KT, Omary RA, Takehana C, Ibrahim S, Lewandowski RJ, Ryu RK, et al. The role of tumor vascularity in predicting survival after yttrium-90 radioembolization for liver metastases. J Vasc Interv Radiol. 2009;20:1564–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Dhabuwala A, Lamerton P, Stubbs RS. Relationship of 99mtechnetium labelled macroaggregated albumin (99mTc-MAA) uptake by colorectal liver metastases to response following Selective Internal Radiation Therapy (SIRT). BMC Nucl Med. 2005;5:7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Alexander R. Haug
    • 1
    • 5
  • Volker Heinemann
    • 2
  • Christiane J. Bruns
    • 3
  • Ralf Hoffmann
    • 4
  • Tobias Jakobs
    • 4
  • Peter Bartenstein
    • 1
  • Marcus Hacker
    • 1
  1. 1.Department of Nuclear MedicineLudwig-Maximilians-UniversityMunichGermany
  2. 2.Department of Internal Medicine IIILudwig-Maximilians-UniversityMunichGermany
  3. 3.Department of SurgeryLudwig-Maximilians-UniversityMunichGermany
  4. 4.Institute of Clinical RadiologyLudwig-Maximilians-UniversityMunichGermany
  5. 5.Department of Nuclear MedicineKlinikum GrosshadernMunichGermany

Personalised recommendations