CardioVascular and Interventional Radiology

, Volume 35, Issue 5, pp 1066–1073

Matched-Pair Comparison of Radioembolization Plus Best Supportive Care Versus Best Supportive Care Alone for Chemotherapy Refractory Liver-Dominant Colorectal Metastases

  • Ricarda Seidensticker
  • Timm Denecke
  • Patrick Kraus
  • Max Seidensticker
  • Konrad Mohnike
  • Jörg Fahlke
  • Erika Kettner
  • Bert Hildebrandt
  • Oliver Dudeck
  • Maciej Pech
  • Holger Amthauer
  • Jens Ricke
Clinical Investigation



This study was designed to evaluate overall survival after radioembolization or best supportive care (BSC) in patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer (mCRC).


This was a matched-pair comparison of patients who received radioembolization plus BSC or BSC alone for extensive liver disease. Twenty-nine patients who received radioembolization were retrospectively matched with a contemporary cohort of >500 patients who received BSC from 3 centers in Germany. Using clinical databases, patients were initially matched for prior treatments and tumor burden and then 29 patients were consecutively identified with two or more of four matching criteria: synchronous/metachronous metastases, tumor burden, increased ALP, and/or CEA >200 U/ml. Survival was calculated from date of progression before radioembolization or BSC by using Kaplan–Meier analysis.


Of 29 patients in each study arm, 16 pairs (55.2%) matched for all four criteria, and 11 pairs (37.9%) matched three criteria. Patients in both groups had a similar performance status (Karnofsky index, median 80% [range, 60–100%]). Compared with BSC alone, radioembolization prolonged survival (median, 8.3 vs. 3.5 months; P < 0.001) with a hazard ratio of 0.3 (95% confidence interval, 0.16–0.55; P < 0.001) in a multivariate Cox proportional hazard model. Treatment-related adverse events following radioembolization included: grade 1–2 fatigue (n = 20, 69%), grade 1 abdominal pain/nausea (n = 14, 48.3%), and grade 2 gastrointestinal ulceration (n = 3, 10.3%). Three cases of grade 3 radiation-induced liver disease were symptomatically managed.


Radioembolization offers a promising addition to BSC in treatment-refractory patients for whom there are limited options. Survival was prolonged and adverse events were generally mild-to-moderate in nature and manageable.


Radioembolization Yttrium-90 Liver metastases Colorectal cancer Salvage therapy 


  1. 1.
    Europe against Colorectal Cancer Declaration of Brussels 9 May 2007. Accessed July 2009
  2. 2.
    Lepage C, Remontet L, Launoy G et al (2008) French network of cancer registries (FRANCIM). Trends in incidence of digestive cancers in France. Eur J Cancer Prev 17:13–17PubMedCrossRefGoogle Scholar
  3. 3.
    Manfredi S, Lepage C, Hatem C et al (2006) Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 244:254–259PubMedCrossRefGoogle Scholar
  4. 4.
    Golfinopoulos V, Salanti G, Pavlidis N, Ioannidis JP (2007) Survival and disease-progression benefits with treatment regimens for advanced colorectal cancer: a meta-analysis. Lancet Oncol 8:898–911PubMedCrossRefGoogle Scholar
  5. 5.
    Folprecht G, Grothey A, Alberts S et al (2005) Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol 16:1311–1319PubMedCrossRefGoogle Scholar
  6. 6.
    Nordlinger B, Sorbye H, Glimelius B et al (2008) Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 371:1007–1016PubMedCrossRefGoogle Scholar
  7. 7.
    Grothey A, Sugrue MM, Purdie DM et al (2008) Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BriTE). J Clin Oncol 26:5326–5334PubMedCrossRefGoogle Scholar
  8. 8.
    Tol J, Koopman M, Cats A et al (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360:563–572PubMedCrossRefGoogle Scholar
  9. 9.
    Gervais DA, Goldberg SN, Brown DB et al (2009) Society of interventional radiology position statement on percutaneous radiofrequency ablation for the treatment of liver tumors. J Vasc Interv Radiol 20(7 Suppl):S342–S347PubMedCrossRefGoogle Scholar
  10. 10.
    Popescu I, Alexandrescu S, Croitoru A, Boros M (2009) Strategies to convert to resectability the initially unresectable colorectal liver metastases. Hepatogastroenterology 56:739–744PubMedGoogle Scholar
  11. 11.
    Ricke J, Wust P, Wieners G et al (2005) Liver malignancies: CT-guided interstitial brachytherapy in patients with unfavourable lesions for thermal ablation. J Vasc Interv Radiol 15:1279–1286CrossRefGoogle Scholar
  12. 12.
    Denecke T, Lopez, Hänninen E (2008) Brachytherapy of liver metastases. Recent Results Cancer Res 177:95–104PubMedCrossRefGoogle Scholar
  13. 13.
    Kennedy A, Coldwell D, Nutting C et al (2006) Resin 90Y microsphere brachytherapy for unresectable colorectal metastases: modern USA experience. Int J Radiat Oncol Biol Phys 65:412–425PubMedCrossRefGoogle Scholar
  14. 14.
    Cosimelli M, Golfieri R, Cagol PP et al (2010) Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases. Br J Cancer 103:324–331PubMedCrossRefGoogle Scholar
  15. 15.
    Jakobs TF, Hoffmann RT, Dehm K et al (2008) Hepatic yttrium-90 radioembolization of chemotherapy-refractory colorectal cancer liver metastases. J Vasc Interv Radiol 19:1187–1195PubMedCrossRefGoogle Scholar
  16. 16.
    Hoffmann RT, Jakobs TF, Kubisch C et al (2010) Radiofrequency ablation after selective internal radiation therapy with Yttrium90 microspheres in metastatic liver disease–is it feasible? Eur J Radiol 74:199–205PubMedCrossRefGoogle Scholar
  17. 17.
    Van den Eynde M, Flamen P, El Nakadi I et al (2008) Inducing resectability of chemotherapy refractory colorectal liver metastasis by radioembolization with yttrium-90 microspheres. Clin Nucl Med 33:697–699PubMedCrossRefGoogle Scholar
  18. 18.
    Denecke T, Rühl R, Hildebrandt B et al (2008) Planning transarterial radioembolization of colorectal liver metastases with Yttrium 90 microspheres: evaluation of a sequential diagnostic approach using radiologic and nuclear medicine imaging techniques. Eur Radiol 18:892–902PubMedCrossRefGoogle Scholar
  19. 19.
    Saltz L, Meropol N, Loehrer P et al (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201–1208PubMedCrossRefGoogle Scholar
  20. 20.
    Sangro B, Gil-Alzugaray B, Rodriguez J et al (2008) Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer 112:1538–1546PubMedCrossRefGoogle Scholar
  21. 21.
    Hendlisz A, Van den Eynde M, Peeters M et al (2010) Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol 28:3687–3694PubMedCrossRefGoogle Scholar
  22. 22.
    Dawood O, Mahadevan A, Goodman KA (2009) Stereotactic body radiation therapy for liver metastases. Eur J Cancer 45:2947–2959PubMedCrossRefGoogle Scholar
  23. 23.
    Jonker DJ, O’Callaghan CJ, Karapetis CS et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040–2048PubMedCrossRefGoogle Scholar
  24. 24.
    Van Cutsem E, Peeters M, Siena S et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664PubMedCrossRefGoogle Scholar
  25. 25.
    van Hazel G, Blackwell A, Anderson J et al (2004) Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol 88:78–85PubMedCrossRefGoogle Scholar
  26. 26.
    Sharma R, van Hazel G, Morgan B et al (2007) Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol 25:1099–1106PubMedCrossRefGoogle Scholar
  27. 27.
    van Hazel GA, Pavlakis N, Goldstein D et al (2009) Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using Yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy. J Clin Oncol 27:4089–4095PubMedCrossRefGoogle Scholar
  28. 28.
    Kuebler JP (2009) Radioembolization of liver metastases in patients with colorectal cancer: A nonsurgical treatment with combined modality potential. J Clin Oncol 27:4041–4042PubMedCrossRefGoogle Scholar
  29. 29.
    Rose SC, Gulec SA (2009) Yttrium 90 radiomicrosphere therapy: ongoing clinical trials. J Interv Oncol 2:72–83Google Scholar

Copyright information

© Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2011

Authors and Affiliations

  • Ricarda Seidensticker
    • 1
  • Timm Denecke
    • 2
  • Patrick Kraus
    • 1
  • Max Seidensticker
    • 1
  • Konrad Mohnike
    • 1
  • Jörg Fahlke
    • 3
  • Erika Kettner
    • 4
  • Bert Hildebrandt
    • 5
  • Oliver Dudeck
    • 1
  • Maciej Pech
    • 1
  • Holger Amthauer
    • 1
  • Jens Ricke
    • 1
  1. 1.Universitätsklinikum Magdeburg, Klinik für Radiologie & NuklearmedizinMagdeburgGermany
  2. 2.Universitätsmedizin BerlinBerlinGermany
  3. 3.Universitätsklinikum Magdeburg, Klinik für Allgemein-, Viszeral- und GefäßchirurgieMagdeburgGermany
  4. 4.Klinikum MagdeburgKlinik für Hämatologie/OnkologieMagdeburgGermany
  5. 5.Universitätsmedizin BerlinBerlinGermany

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