Skip to main content
SpringerLink
Log in

Effectiveness of Hepatic Artery Infusion (HAI) Versus Selective Internal Radiation Therapy (Y90) for Pretreated Isolated Unresectable Colorectal Liver Metastases (IU-CRCLM)

Annals of Surgical Oncology volume 25, pages 550–557 (2018)Cite this article

Abstract

Background

In the era of modern effective systemic chemotherapy, the comparative effectiveness of hepatic artery infusion (HAI) versus selective internal radiation therapy (yttrium-90 [Y90]) for pretreated patients with isolated unresectable colorectal liver metastasis (IU-CRCLM) remains unknown. This study sought to compare the overall survival (OS) after HAI versus Y90 for IU-CRCLM patients treated with modern chemotherapy and to perform a cost analysis of both regional methods.

Methods

This study retrospectively reviewed patients receiving HAI or Y90 in combination with modern chemotherapy as second-line therapy for IU-CRCLM. Overall survival was calculated from the time of IU-CRCLM diagnosis. Uni- and multivariate models were constructed to identify independent predictors of survival.

Results

The inclusion criteria were met by 97 patients (48 HAI patients and 49 Y90 patients). Both groups were similar in terms of age, gender, body mass index (BMI), synchronous disease, carcinoembryonic antigen (CEA), liver tumor burden, and chemotherapy-related characteristics including use of biologics and lines of chemotherapy (all p > 0.05). The HAI group had a better OS than the Y90 group (31.2 vs. 16.3 months; p < 0.001). A trend toward reduced cost favored the HAI group (median, $29,479 vs. $39,092; p = 0.296). The multivariate analysis showed that receipt of HAI (hazard ratio 0.465) and number of chemotherapy lines (HR 0.797) were associated with improved OS from the date of IU-CRCLM diagnosis.

Conclusions

This is the first study to evaluate the comparative effectiveness of HAI versus Y90 in the era of modern chemotherapy, and the findings suggests that HAI is associated with better survival than Y90 for patients with pretreated IU-CRCLM.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.

    Article  PubMed  Google Scholar 

  2. Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244:254–59.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64:104–17.

    Article  PubMed  Google Scholar 

  4. van Cutsem E, Bajetta E, Valle J, et al. Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma. J Clin Oncol. 2011;29:2004–10.

    Article  PubMed  Google Scholar 

  5. van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012;30:3499–506.

    Article  PubMed  Google Scholar 

  6. Grothey A, van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet London Engl. 2013;381:303–12.

    Article  CAS  Google Scholar 

  7. Bendell JC, Nemunaitis J, Vukelja SJ, et al. Randomized placebo-controlled phase II trial of perifosine plus capecitabine as second- or third-line therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2011;29:4394–400.

    Article  CAS  PubMed  Google Scholar 

  8. Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:4706–13.

    Article  CAS  PubMed  Google Scholar 

  9. Adam R, Wicherts DA, de Haas RJ, et al. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol. 2009;27:1829–35.

    Article  PubMed  Google Scholar 

  10. Alberts SR, Horvath WL, Sternfeld WC, et al. Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study. J Clin Oncol. 2005;23:9243–49.

    Article  CAS  PubMed  Google Scholar 

  11. Folprecht G, Gruenberger T, Bechstein WO, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010;11:38–47.

    Article  CAS  PubMed  Google Scholar 

  12. Masi G, Loupakis F, Pollina L, et al. Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann Surg. 2009;249:420–25.

    Article  PubMed  Google Scholar 

  13. Uetake H, Yasuno M, Ishiguro M, et al. A multicenter phase II trial of mFOLFOX6 plus bevacizumab to treat liver-only metastases of colorectal cancer that are unsuitable for upfront resection (TRICC0808). Ann Surg Oncol. 2015;22:908–15.

    Article  PubMed  Google Scholar 

  14. Wong R, Cunningham D, Barbachano Y, et al. A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol. 2011;22:2042–48.

    Article  CAS  PubMed  Google Scholar 

  15. Folprecht G, Gruenberger T, Bechstein W, et al. Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study). Ann Oncol. 2014;25:1018–25.

    Article  CAS  PubMed  Google Scholar 

  16. Dhir M, Jones HL, Shuai Y, et al. Hepatic arterial infusion in combination with modern systemic chemotherapy is associated with improved survival compared with modern systemic chemotherapy alone in patients with isolated unresectable colorectal liver metastases: a case-control study. Ann Surg Oncol. 2017;24:150–58.

    Article  PubMed  Google Scholar 

  17. D’Angelica MI, Correa-Gallego C, Paty PB, et al. Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes. Ann Surg. 2015;261:353–60.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kemeny N, Jarnagin W, Paty P, et al. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol. 2005;23:4888–96.

    Article  CAS  PubMed  Google Scholar 

  19. Kemeny NE, Melendez FDH, Capanu M, et al. Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2009;27:3465–71.

    Article  PubMed  PubMed Central  Google Scholar 

  20. McAuliffe JC, Qadan M, D’Angelica MI. Hepatic resection, hepatic arterial infusion pump therapy, and genetic biomarkers in the management of hepatic metastases from colorectal cancer. J Gastrointest Oncol. 2015;6:699–708.

    PubMed  PubMed Central  Google Scholar 

  21. Karanicolas PJ, Metrakos P, Chan K, et al. Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement. Curr Oncol. 2013;21:8.

    Article  Google Scholar 

  22. Sangha BS, Nimeiri H, Hickey R, Salem R, Lewandowski RJ. Radioembolization as a treatment strategy for metastatic colorectal cancer to the liver: what can we learn from the SIRFLOX trial? Curr Treat Options Oncol. 2016;17:26.

    Article  PubMed  Google Scholar 

  23. van Hazel GA, Heinemann V, Sharma NK, et al. SIRFLOX: randomized phase III trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2016;34:1723–31.

    Article  PubMed  Google Scholar 

  24. Ammori JB, D’Angelica MI, Fong Y, et al. Hepatic artery infusional chemotherapy in patients with unresectable colorectal liver metastases and extrahepatic disease. J Surg Oncol. 2012;106:953–8.

    Article  CAS  PubMed  Google Scholar 

  25. Kosmider S, Tan TH, Yip D, Dowling R, Lichtenstein M, Gibbs P. Radioembolization in combination with systemic chemotherapy as first-line therapy for liver metastases from colorectal cancer. JVIR J Vasc Intervent Radiol. 2011;22:780–6.

    Article  Google Scholar 

  26. Leal JN, Kingham TP. Hepatic artery infusion chemotherapy for liver malignancy. Surg Oncol Clin N Am. 2015;24:121–48.

    Article  PubMed  Google Scholar 

  27. Tohme S, Sukato D, Nace GW, et al. Survival and tolerability of liver radioembolization: a comparison of elderly and younger patients with metastatic colorectal cancer. HPB. 2014;16:1110–16.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bokemeyer C, Bondarenko I, Hartmann JT, et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol. 2011;22:1535–46.

    Article  CAS  PubMed  Google Scholar 

  29. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1065–75.

    Article  CAS  PubMed  Google Scholar 

  30. Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32:2240–47.

    Article  CAS  PubMed  Google Scholar 

  31. van Cutsem E, Köhne C-H, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal Cancer. N Engl J Med. 2009;360:1408–17.

    Article  PubMed  Google Scholar 

  32. Venook AP, Niedzwiecki D, Lenz H-J, et al. CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). ASCO Meet Abstr. 2014;32(15 Suppl):3.

    Google Scholar 

  33. Van Hazel G, Blackwell A, Anderson J, et al. Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol. 2004;88:78–85.

    Article  PubMed  Google Scholar 

  34. Hickey R, Lewandowski RJ, Prudhomme T, et al. 90Y Radioembolization of colorectal hepatic metastases using glass microspheres: safety and survival outcomes from a 531-patient multicenter study. J Nucl Med. 2016;57:665–71

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA

    Mashaal Dhir MD

  2. Department of Biostatistics and Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA

    Mazen S. Zenati MD, PhD

  3. Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Heather L. Jones PA, David L. Bartlett MD, M. Haroon A. Choudry MD, James F. Pingpank MD, Matthew P. Holtzman MD, Melissa E. Hogg MD, Herbert J. Zeh III MD, David A. Geller MD, J. Wallis Marsh MD, MBA & Allan Tsung MD

  4. Department of Medical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Nathan Bahary MD

  5. Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Amer H. Zureikat MD

Authors
  1. Mashaal Dhir MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mazen S. Zenati MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heather L. Jones PA
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David L. Bartlett MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Haroon A. Choudry MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. James F. Pingpank MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Matthew P. Holtzman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nathan Bahary MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Melissa E. Hogg MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Herbert J. Zeh III MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. David A. Geller MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J. Wallis Marsh MD, MBA
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Allan Tsung MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Amer H. Zureikat MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amer H. Zureikat MD.

Ethics declarations

Conflict of interest

There are no conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10434_2017_6265_MOESM1_ESM.tif

The 2-year overall survival after hepatic artery infusion (HAI) pump placement versus first yttrium-90 (Y90) treatment for patients with isolated unresectable colorectal liver metastasis (IU-CRCLM). Supplementary material 1 (TIFF 1735 kb)

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dhir, M., Zenati, M.S., Jones, H.L. et al. Effectiveness of Hepatic Artery Infusion (HAI) Versus Selective Internal Radiation Therapy (Y90) for Pretreated Isolated Unresectable Colorectal Liver Metastases (IU-CRCLM). Ann Surg Oncol 25, 550–557 (2018). https://doi.org/10.1245/s10434-017-6265-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-017-6265-9

Keywords

search

Navigation