Nuklearmedizin 2014; 53(02): 39-45
DOI: 10.3413/Nukmed-0622-13-09
Original article
Schattauer GmbH

Survival in patients with hepatocellular carcinoma treated with 90Y-microsphere radioembolization

Prediction by 18F-FDG PETRadioembolisation des hepatozellulären Karzinoms mit 90Y-MikrosphärenÜberlebensprädiktion durch 18F-FDG-PET
A. Sabet
1   Department of Nuclear Medicine, University Hospital, Bonn, Germany
,
H. Ahmadzadehfar
1   Department of Nuclear Medicine, University Hospital, Bonn, Germany
,
J. Bruhman
1   Department of Nuclear Medicine, University Hospital, Bonn, Germany
,
A. Sabet
1   Department of Nuclear Medicine, University Hospital, Bonn, Germany
,
C. Meyer
2   Department of Radiology, University Hospital, Bonn, Germany
,
J.-C. Wasmuth
3   Department of Internal Medicine, University Hospital, Bonn, Germany
,
C.-C. Pieper
2   Department of Radiology, University Hospital, Bonn, Germany
,
H.-J. Biersack
1   Department of Nuclear Medicine, University Hospital, Bonn, Germany
,
S. Ezziddin
1   Department of Nuclear Medicine, University Hospital, Bonn, Germany
› Author Affiliations
Further Information

Publication History

received: 13 September 2013

accepted in revised form: 05 November 2013

Publication Date:
02 January 2018 (online)

Summary

Aim: This retrospective study aims to evaluate the predictive value of FDG PET/CT in patients with unresectable hepatocellular carcinoma (HCC) undergoing radioembolization with yttrium-90 labeled microspheres (RE). Patients, methods: The study cohort comprised 33 patients who were treated with RE at our institution and underwent FDG PET/CT at baseline and four weeks after radioembolization. According to the baseline FDG metabolic status of the HCC lesions, patients were divided into two groups: FDG-negative (n = 12) and FDG-positive (n = 21) HCC. FDG-positive patients were further divided into early metabolic responders and non-re- sponders according to the relative change in SUVmax of the treated lesions. Survival analyses were performed with the Kaplan-Meier method (log-rank test, p < 0.05). Multivariate analysis was performed to assess the influence of prognostic factors on overall survival (OS). Results: FDG-negative patients had a significantly longer OS (13 months, 95%CI 7-19) than FDG-positive patients (9 months, 95%CI 7-11; p = 0.010). Among FDG- positive patients, metabolic responders survived significantly longer than metabolic non- responders (10 months, 95%CI 8-12 vs. 5 months, 95%CI 4-6; p = 0.003). From the other baseline factors (including performance status, hepatic tumour burden, presence of extra-hepatic disease, administered activity) only the BCLC stage had a significant impact on OS (p = 0.028). Conclusion: Pre- and post- therapeutic FDG PET independently predicts overall survival in patients with HCC undergoing radioembolization. Interestingly, early metabolic response seems to be assessable as early as four weeks post-treatment.

Zusammenfassung

Ziel: In dieser retrospektiven Studie wurde der prädiktive Wert der FDG-PET bei Patienten mit inoperablem hepatozellulärem Karzinom (HCC) untersucht, die sich einer Radioembolisation (RE) mit 90Y-Mikrosphären unterzogen. Patienten, Methoden: Das Studienkollektiv umfasste n = 33 RE-Patienten mit basaler sowie 4-Wo-post-therapeut. FDG-PET/ CT. Anhand des basalen FDG-Status der HCC- Tumore wurden FDG-negative (n = 12) und FDG-positive (n = 21) Patienten unterschieden. FDG-positive Patienten wurden des Weiteren anhand der relativen Abnahme des SUVmax der behandelten Läsionen in frühe metabolische Responder und Non-Responder unterteilt. Die Überlebensanalyse erfolgte mittels Kaplan-Meier Kurven (Log-rank-Test mit p > 0.05), die multivariate Analyse zur Ermittlung der Prädiktoren für das Gesamtüberleben (OS). Resultate: FDG-negative Patienten überlebten signifikant länger (median 13 Monate, 95%-CI: 7-19) als FDG-positive (median 9 Monate, 95%-CI: 7-11, p = 0.01). Unter den FDG-positiven Patienten überlebten die frühen metabolischen Responder (median 10 Monate, 95%-CI: 8-12) länger als die restlichen Patienten (median 5 Monate, 95%-CI: 4-6, p = 0.003). Von den anderen Ausgangsvariablen (inklusive Allgemeinzustand, intrahepatischer und extrahepatischer Tumorlast, applizierter Gesamtaktivität) zeigte lediglich das BCLC-Stadium einen signifikanten Einfluss auf das Gesamtüberleben (p = 0.028). Schlussfolgerung: Prä- und posttherapeutisches FDG-PET ist ein unabhängiger Prädiktor des Gesamtüberlebens nach Radio- embolisation von HCC-Patienten. Interessanterweise erscheint das metabolische Frühansprechen bereits vier Wochen nach SIRT bestimmbar zu sein.

 
  • References

  • 1 Ady N, Zucker JM, Asselain B. et al. A new 123I-MIBG whole body scan scoring method – application to the prediction of the response of metastases to induction chemotherapy in stage IV neuroblastoma. Eur J Cancer 1995; 31A: 256-261.
  • 2 Ahmadzadehfar H, Biersack HJ, Ezziddin S. Radioembolization of liver tumors with yttrium-90 microspheres. Semin Nucl Med 2010; 40: 105-121.
  • 3 Ahmadzadehfar H, Haslerud T, Reichmann K. et al. Residual activity after radioembolization of liver tumours with 90Y resin microspheres. A safe calculation method. Nuklearmedizin. 2013: 53.
  • 4 Bienert M. et al. 90Y microsphere treatment of unresectable liver metastases: changes in 18F-FDG uptake and tumour size on PET/CT. Eur J Nucl Med Mol Imaging 2005; 32: 778-787.
  • 5 Binderup T, Knigge U, Loft A. et al. 18F-fluorode-oxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res 2010; 16: 978-985.
  • 6 Bruix J. et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001; 35: 421-430.
  • 7 Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42: 1208-1236.
  • 8 Castaldi P. et al. Can „early” and „late” 18F-FDG PET-CT be used as prognostic factors for the clinical outcome of patients with locally advanced head and neck cancer treated with radio-chemotherapy?. Radiother Oncol 2012; 103: 63-68.
  • 9 Castellucci P. et al. Potential pitfalls of 18F-FDG PET in a large series of patients treated for malignant lymphoma: prevalence and scan interpretation. Nucl Med Commun 2005; 26: 689-694.
  • 10 Ferlay J, Shin HR, Bray F. et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-2917.
  • 11 Garin E, Le Jeune F, Devillers A. et al. Predictive value of 18F-FDG PET and somatostatin receptor scintigraphy in patients with metastatic endocrine tumors. J Nucl Med 2009; 50: 858-864.
  • 12 Geschwind JF, Salem R, Carr BI. et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology 2004; 127: S194-205.
  • 13 Haug AR. et al. 18F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with 90Y microspheres. Eur J Nucl Med Mol Imaging 2011; 38: 1037-1045.
  • 14 Haug AR, Tiega Donfack BP, Trumm C. et al. 18F-FDG PET/CT predicts survival after radioembolization of hepatic metastases from breast cancer. J Nucl Med 2012; 53: 371-377.
  • 15 Higashi T. 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: 468-482.
  • 16 Ibrahim SM, Lewandowski RJ, Sato KT. et al. Radioembolization for the treatment of unresectable hepatocellular carcinoma: a clinical review. World J Gastroenterol 2008; 14: 1664-1669.
  • 17 Jiao LR, Szyszko T, Al-Nahhas A. et al. Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours. Eur J Surg Oncol 2007; 33: 597-602.
  • 18 Juweid ME, Cheson BD. Positron emission tomography and assessment of cancer therapy. N Engl J Med 2006; 354: 496-507.
  • 19 Kennedy A, Nag S, Salem R. 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.
  • 20 Khan MA. et al. Positron emission tomography scanning in the evaluation of hepatocellular carcinoma. J Hepatol 2000; 32: 792-797.
  • 21 Khodjibekova M, Szyszko T, Khan S. et al. Selective internal radiation therapy with yttrium-90 for unresectable liver tumours. Rev Recent Clin Trials 2007; 2: 212-216.
  • 22 Kucuk ON, Soydal C, Araz M. et al. Prognostic importance of 18F-FDG uptake pattern of hepatocellular cancer patients who received SIRT. Clin Nucl Med 2013; 38: e283-289.
  • 23 Lencioni R, Llovet JM. Modified RECIST assessment for hepatocellular carcinoma. Semin Liver Dis 2010; 30: 52-60.
  • 24 Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362: 1907-1917.
  • 25 Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 2005; 25: 181-200.
  • 26 Salem R. et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol 2005; 16: 1627-1639.
  • 27 Salem R, Thurston KG. Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: Technical and methodologic considerations. J Vasc Interv Radiol 2006; 17: 1251-1278.
  • 28 Salem R, Lewandowski RJ, Mulcahy MF. et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 2010; 138: 52-64.
  • 29 Sangro B, Bilbao JI, Boan J. et al. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2006; 66: 792-800.
  • 30 Shiomi S, Nishiguchi S, Ishizu H. et al. Usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose for predicting outcome in patients with hepatocellular carcinoma. Am J Gastroenterol 2001; 96: 1877-1880.
  • 31 Smyth EC, Shah MA. Role of 18F 2-fluoro-2-deoxyglucose positron emission tomography in upper gastrointestinal malignancies. World J Gastroenterol 2011; 17: 5059-5074.
  • 32 Song P. et al. The management of hepatocellular carcinoma around the world: a comparison of guidelines from 2001 to 2011. Liver Int 2012; 32: 1053-1063.
  • 33 Szyszko T. et al. Assessment of response to treatment of unresectable liver tumours with 90Y microspheres: value of FDG PET versus computed tomography. Nucl Med Commun 2007; 28: 15-20.
  • 34 Therasse P, Arbuck SG, Eisenhauer EA. et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92: 205-216.
  • 35 Vallbohmer D. et al. [18F]-Fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemoradiation in esophageal cancer. Ann Surg 2009; 250: 888-894.
  • 36 Weber WA. Positron emission tomography as an imaging biomarker. J Clin Oncol 2006; 24: 3282-3292.
  • 37 Wong CY, Salem R, Raman S. et al. Evaluating 90Y-glass microsphere treatment response of unresectable colorectal liver metastases by [18F]FDG PET: a comparison with CT or MRI. Eur J Nucl Med Mol Imaging 2002; 29: 815-820.
  • 38 Zerizer I. et al. The role of early 18F-FDG PET/CT in prediction of progression-free survival after 90Y radioembolization: comparison with RECIST and tumour density criteria. Eur J Nucl Med Mol Imaging 2012; 39: 1391-1399.