Skip to main content

Advertisement

SpringerLink
Log in

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

  • Clinical Investigation
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Europe against Colorectal Cancer Declaration of Brussels 9 May 2007. http://www.future-health-2007.com/fileadmin/user_upload/Brussels_Declaration.pdf. Accessed July 2009

  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 17:13–17

    Article  PubMed  Google Scholar 

  3. Manfredi S, Lepage C, Hatem C et al (2006) Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 244:254–259

    Article  PubMed  Google Scholar 

  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 8:898–911

    Article  PubMed  CAS  Google Scholar 

  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 16:1311–1319

    Article  PubMed  CAS  Google Scholar 

  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 371:1007–1016

    Article  PubMed  CAS  Google Scholar 

  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 26:5326–5334

    Article  PubMed  CAS  Google Scholar 

  8. Tol J, Koopman M, Cats A et al (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360:563–572

    Article  PubMed  CAS  Google Scholar 

  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–S347

    Article  PubMed  Google Scholar 

  10. Popescu I, Alexandrescu S, Croitoru A, Boros M (2009) Strategies to convert to resectability the initially unresectable colorectal liver metastases. Hepatogastroenterology 56:739–744

    PubMed  Google Scholar 

  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 15:1279–1286

    Article  Google Scholar 

  12. Denecke T, Lopez, Hänninen E (2008) Brachytherapy of liver metastases. Recent Results Cancer Res 177:95–104

    Article  PubMed  CAS  Google Scholar 

  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 65:412–425

    Article  PubMed  CAS  Google Scholar 

  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 103:324–331

    Article  PubMed  CAS  Google Scholar 

  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 19:1187–1195

    Article  PubMed  Google Scholar 

  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 74:199–205

    Article  PubMed  CAS  Google Scholar 

  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 33:697–699

    Article  PubMed  Google Scholar 

  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 18:892–902

    Article  PubMed  Google Scholar 

  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 22:1201–1208

    Article  PubMed  CAS  Google Scholar 

  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 112:1538–1546

    Article  PubMed  Google Scholar 

  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 28:3687–3694

    Article  PubMed  CAS  Google Scholar 

  22. Dawood O, Mahadevan A, Goodman KA (2009) Stereotactic body radiation therapy for liver metastases. Eur J Cancer 45:2947–2959

    Article  PubMed  Google Scholar 

  23. Jonker DJ, O’Callaghan CJ, Karapetis CS et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040–2048

    Article  PubMed  CAS  Google Scholar 

  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 25:1658–1664

    Article  PubMed  Google Scholar 

  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 88:78–85

    Article  PubMed  Google Scholar 

  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 25:1099–1106

    Article  PubMed  CAS  Google Scholar 

  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 27:4089–4095

    Article  PubMed  Google Scholar 

  28. Kuebler JP (2009) Radioembolization of liver metastases in patients with colorectal cancer: A nonsurgical treatment with combined modality potential. J Clin Oncol 27:4041–4042

    Article  PubMed  CAS  Google Scholar 

  29. Rose SC, Gulec SA (2009) Yttrium 90 radiomicrosphere therapy: ongoing clinical trials. J Interv Oncol 2:72–83

    Google Scholar 

Download references

Acknowledgments

The authors thank the patients who participated in this study. We also thank Rae Hobbs for her editorial assistance on this manuscript, courtesy of Sirtex Medical Ltd. This trial was supported in part by Sirtex Medical Limited, Sydney, Australia. Ricarda Seidensticker and Max Seidensticker received travel fees. Jens Ricke and Maciej Pech received research grants and consultant fees from Sirtex Medical Limited, Sydney, Australia.

Conflict of interest

All other authors disclose any actual or potential conflict of interest.

Author information

Authors and Affiliations

  1. Universitätsklinikum Magdeburg, Klinik für Radiologie & Nuklearmedizin, Leipzigerstr. 44, 39120, Magdeburg, Germany

    Ricarda Seidensticker, Patrick Kraus, Max Seidensticker, Konrad Mohnike, Oliver Dudeck, Maciej Pech, Holger Amthauer & Jens Ricke

  2. Universitätsmedizin Berlin, Campus Virchow Charité Centrum 6, Klinik für Strahlenheilkunde, Berlin, Germany

    Timm Denecke

  3. Universitätsklinikum Magdeburg, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Magdeburg, Germany

    Jörg Fahlke

  4. Klinikum Magdeburg, Klinik für Hämatologie/Onkologie, Magdeburg, Germany

    Erika Kettner

  5. Universitätsmedizin Berlin, Campus Virchow Charité Centrum 14 für Tumormedizin Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Berlin, Germany

    Bert Hildebrandt

Authors
  1. Ricarda Seidensticker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timm Denecke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick Kraus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Max Seidensticker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Konrad Mohnike
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jörg Fahlke
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Erika Kettner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bert Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Oliver Dudeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maciej Pech
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Holger Amthauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jens Ricke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ricarda Seidensticker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seidensticker, R., Denecke, T., Kraus, P. et al. Matched-Pair Comparison of Radioembolization Plus Best Supportive Care Versus Best Supportive Care Alone for Chemotherapy Refractory Liver-Dominant Colorectal Metastases. Cardiovasc Intervent Radiol 35, 1066–1073 (2012). https://doi.org/10.1007/s00270-011-0234-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-011-0234-7

Keywords

Search

Navigation