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Chemoembolization and Radioembolization for Metastatic Disease to the Liver: Available Data and Future Studies

  • Gastrointestinal Cancers (AB Benson, Section Editor)
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Opinion statement

Hepatic metastatic disease includes tumors from colorectal, neuroendocrine, breast, melanocytes, kidney, and other primary sites. Tumor characteristic, liver function, and performance status are factors that need to be considered while deciding on treatment. Surgery offers the most optimal therapeutic option for such patients. However, due to the diffuse nature of disease and large tumor burden, a majority of the patients are not operable. Moreover, because the morbidity and mortality is associated with hepatic metastatic disease, it is intuitive to investigate and develop treatment options that target the tumor locally, thereby minimizing systemic toxicities. Transarterial locoregional therapies, such as chemoembolization and radioembolization, have been widely investigated during the past decade for the treatment of hepatic metastatic disease and have generated encouraging outcomes in term of survival, response, and quality of life. Moreover, these options are applicable in many clinical scenarios, because they are less limited by tumor characteristics. Currently, a large number of trials are investigating the combination of locoregional and systemic therapies, and the results are expected to benefit the treating physicians and patients alike.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance•• Of major importance

  1. Norton JA. Surgical treatment of neuroendocrine metastases. Best Pract Res Clin Gastroenterol. 2005;19(4):577–83.

    Article  PubMed  Google Scholar 

  2. Tomlinson JS, Jarnagin WR, DeMatteo RP, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80.

    Article  PubMed  Google Scholar 

  3. Sasson AR, Sigurdson ER. Surgical treatment of liver metastases. Semin Oncol. 2002;29(2):107–18.

    Article  PubMed  Google Scholar 

  4. Ingold JA, Reed GB, Kaplan HS, Bagshaw MA. Radiation hepatitis. Am J Roentgenol Radium Ther Nucl Med. 1965;93:200–8.

    PubMed  CAS  Google Scholar 

  5. Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol. 1954;30(5):969–77.

    PubMed  CAS  Google Scholar 

  6. Liu DM, Salem R, Bui JT, et al. Angiographic considerations in patients undergoing liver-directed therapy. J Vasc Interv Radiol. 2005;16(7):911–35.

    Article  PubMed  Google Scholar 

  7. Lewandowski RJ, Sato KT, Atassi B, et al. Radioembolization with (90)y microspheres: angiographic and technical considerations. Cardiovasc Intervent Radiol. 2007;30(4):571–92.

    Article  PubMed  Google Scholar 

  8. Salem R, Lewandowski RJ, Sato KT, et al. Technical aspects of radioembolization with 90Y microspheres. Tech Vasc Interv Radiol. 2007;10(1):12–29.

    Article  PubMed  Google Scholar 

  9. Salem R, Lewandowski RJ, Kulik L, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011;140(2):497–507 e492. This is the first large study comparing matched cohorts of HCC patients treated with radioembolization and transarterial chemoembolization and suggests that patients treated with radioembolization demonstrate lower toxicity and longer time-to-progression

    Article  PubMed  Google Scholar 

  10. 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(1):52–64.

    Article  PubMed  CAS  Google Scholar 

  11. Lewandowski RJ, Mulcahy MF, Kulik LM, et al. Chemoembolization for hepatocellular carcinoma: comprehensive imaging and survival analysis in a 172-patient cohort. Radiology. 2010;255(3):955–65.

    Article  PubMed  Google Scholar 

  12. Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734–9.

    Article  PubMed  Google Scholar 

  13. Memon K, Kulik L, Lewandowski RJ, et al. Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times. Gastroenterology. 2011;141(2):526–35. e522. This study identifies radiologic response as a reliable predictor of survival outcomes in HCC patients treated with locoregional therapies and suggests adopting response as a surrogate of survival in clinical trials

    Article  PubMed  Google Scholar 

  14. Coldwell DM, Stokes KR, Yakes WF. Embolotherapy: agents, clinical applications, and techniques. Radiographics. 1994;14(3):623–43. quiz 645-6.

    PubMed  CAS  Google Scholar 

  15. Soulen MC. Chemoembolization of hepatic malignancies. Oncology (Williston Park). 1994;8(4):77–84. discussion 84, 89-90 passim.

    CAS  Google Scholar 

  16. Solomon B, Soulen MC, Baum RA, Haskal ZJ, Shlansky-Goldberg RD, Cope C. Chemoembolization of hepatocellular carcinoma with cisplatin, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol: prospective evaluation of response and survival in a U.S. population. J Vasc Interv Radiol. 1999;10(6):793–8.

    Article  PubMed  CAS  Google Scholar 

  17. Albert M, Kiefer MV, Sun W, et al. Chemoembolization of colorectal liver metastases with cisplatin, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol. Cancer. 2011;117(2):343–52. This study analyzes survival and response after TACE in 121 patients with hepatic colorectal metastases and demonstrates survival advantage for those patients treated with TACE earlier in the course of treatment and in the era of biologic therapy with bevacizumab

    Article  PubMed  CAS  Google Scholar 

  18. Vogl TJ, Gruber T, Balzer JO, Eichler K, Hammerstingl R, Zangos S. Repeated transarterial chemoembolization in the treatment of liver metastases of colorectal cancer: prospective study. Radiology. 2009;250(1):281–9. This study evaluated three chemoembolization protocols (mitomycin C alone, mitomycin C with gemcitabine, and mitomycin C with irinotecan) in 463 patients of hepatic metastases with colorectal cancer and found similar results among the three protocols.

    Article  PubMed  Google Scholar 

  19. Tellez C, Benson 3rd AB, Lyster MT, et al. Phase II trial of chemoembolization for the treatment of metastatic colorectal carcinoma to the liver and review of the literature. Cancer. 1998;82(7):1250–9.

    Article  PubMed  CAS  Google Scholar 

  20. Geschwind J, Hong K, Georgiades C. Utility of transcatheter arterial chemoembolization for liver dominant colorectal metastatic adenocarcinoma in the salvage setting. American Society of Clinical Oncology Gastrointestinal Cancers Symposium. San Francisco, CA, January 26-28, 2006.

  21. Liapi E, Geschwind J-F, Vossen JA, et al. Functional MRI evaluation of tumor response in patients with neuroendocrine hepatic metastasis treated with transcatheter arterial chemoembolization. Am J Roentgenol. 2008;190(1):67–73.

    Article  Google Scholar 

  22. Dong XD, Carr BI. Hepatic artery chemoembolization for the treatment of liver metastases from neuroendocrine tumors: a long-term follow-up in 123 patients. Med Oncol. 2011;28(Suppl 1):S286-90. Epub 2010 Nov 24. This is one of the few large studies investigating the role of chemoembolization in 123 patients with hepatic metastases from neuroendocrine tumors.

  23. Vogl TJ, Gruber T, Naguib NN, Hammerstingl R, Nour-Eldin NE. Liver metastases of neuroendocrine tumors: treatment with hepatic transarterial chemotherapy using two therapeutic protocols. AJR Am J Roentgenol. 2009;193(4):941–7.

    Article  PubMed  Google Scholar 

  24. Giroux MF, Baum RA, Soulen MC. Chemoembolization of liver metastasis from breast carcinoma. J Vasc Interv Radiol. 2004;15(3):289–91.

    Article  PubMed  Google Scholar 

  25. Buijs M, Kamel IR, Vossen JA, Georgiades CS, Hong K, Geschwind JF. Assessment of metastatic breast cancer response to chemoembolization with contrast agent enhanced and diffusion-weighted MR imaging. J Vasc Interv Radiol. 2007;18(8):957–63.

    Article  PubMed  Google Scholar 

  26. Patel K, Sullivan K, Berd D, et al. Chemoembolization of the hepatic artery with BCNU for metastatic uveal melanoma: results of a phase II study. Melanoma Res. 2005;15(4):297–304.

    Article  PubMed  Google Scholar 

  27. Mavligit GM, Charnsangavej C, Carrasco CH, Patt YZ, Benjamin RS, Wallace S. Regression of ocular melanoma metastatic to the liver after hepatic arterial chemoembolization with cisplatin and polyvinyl sponge. JAMA. 1988;260(7):974–6.

    Article  PubMed  CAS  Google Scholar 

  28. Bedikian AY, Legha SS, Mavligit G, et al. Treatment of uveal melanoma metastatic to the liver: a review of the M.D. Anderson Cancer Center experience and prognostic factors. Cancer. 1995;76(9):1665–70.

    Article  PubMed  CAS  Google Scholar 

  29. Vogl T, Eichler K, Zangos S, et al. Preliminary experience with transarterial chemoembolization (TACE) in liver metastases of uveal malignant melanoma: local tumor control and survival. J Cancer Res Clin Oncol. 2007;133(3):177–84.

    Article  PubMed  CAS  Google Scholar 

  30. Leyvraz S, Spataro V, Bauer J, et al. Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy. J Clin Oncol. 1997;15(7):2589–95.

    PubMed  CAS  Google Scholar 

  31. Xia J, Ren Z, Ye S, et al. Study of severe and rare complications of transarterial chemoembolization (TACE) for liver cancer. Eur J Radiol. 2006;59(3):407–12.

    Article  PubMed  Google Scholar 

  32. Kim HK, Chung YH, Song BC, et al. Ischemic bile duct injury as a serious complication after transarterial chemoembolization in patients with hepatocellular carcinoma. J Clin Gastroenterol. 2001;32(5):423–7.

    Article  PubMed  CAS  Google Scholar 

  33. Belli L, Magistretti G, Puricelli GP, Damiani G, Colombo E, Cornalba GP. Arteritis following intra-arterial chemotherapy for liver tumors. Eur Radiol. 1997;7(3):323–6.

    Article  PubMed  CAS  Google Scholar 

  34. Hong K, Georgiades CS, Geschwind JF. Technology insight: Image-guided therapies for hepatocellular carcinoma–intra-arterial and ablative techniques. Nat Clin Pract Oncol. 2006;3(6):315–24.

    Article  PubMed  Google Scholar 

  35. Martin R, Joshi J, Robbins K, et al. Hepatic intra-arterial injection of drug-eluting bead, Irinotecan (DEBIRI) in unresectable colorectal liver metastases refractory to systemic chemotherapy: results of multi-institutional study. Ann Surg Oncol. 2011;18(1):192–8. This is one of few multi-institutional studies investigating the role of drug eluting beads loaded with irinotecan (DEBIRI) in patients with hepatic colorectal metastases and reports that DEBIRI is safe and effective for treatment of metastatic colorectal cancer refractory to multiple lines of systemic chemotherapy.

    Article  PubMed  Google Scholar 

  36. Bower M, Metzger T, Robbins K, et al. Surgical downstaging and neo-adjuvant therapy in metastatic colorectal carcinoma with irinotecan drug-eluting beads: a multi-institutional study. HPB (Oxford). 2010;12(1):31–6.

    Article  Google Scholar 

  37. de Baere T, Deschamps F, Teriitheau C, et al. Transarterial chemoembolization of liver metastases from well-differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results. J Vasc Interv Radiol. 2008;19(6):855–61.

    Article  PubMed  Google Scholar 

  38. Martin RC, Robbins K, Fages JF, et al. Optimal outcomes for liver-dominant metastatic breast cancer with transarterial chemoembolization with drug-eluting beads loaded with doxorubicin. Breast Cancer Res Treat. 2012;132(2):753–63. Epub 2011 Dec 27.

    Article  PubMed  CAS  Google Scholar 

  39. Brown RE, Gibler KM, Metzger T, et al. Imaged guided transarterial chemoembolization with drug-eluting beads loaded with doxorubicin (DEBDOX) for hepatic metastases from melanoma: early outcomes from a multi-institutional registry. Am Surg. 2011;77(1):93–8.

    PubMed  Google Scholar 

  40. Vogl TJ, Lammer J, Lencioni R, et al. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: results from the PRECISION V randomized trial. AJR Am J Roentgenol. 2011;197(4):W562–70.

    Article  PubMed  Google Scholar 

  41. Geschwind JF, Salem R, Carr BI, et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S194–205.

    Article  PubMed  CAS  Google Scholar 

  42. 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(9 Pt 2):S223–9.

    Article  PubMed  Google Scholar 

  43. Wong CY, Salem R, Raman S, Gates VL, Dworkin HJ. Evaluating 90Y-glass microsphere treatment response of unresectable colorectal liver metastases by [18 F]FDG PET: a comparison with CT or MRI. Eur J Nucl Med Mol Imaging. 2002;29(6):815–20.

    Article  PubMed  CAS  Google Scholar 

  44. Wong CY, Salem R, Qing F, et al. Metabolic response after intraarterial 90Y-glass microsphere treatment for colorectal liver metastases: comparison of quantitative and visual analyses by 18 F-FDG PET. J Nucl Med. 2004;45(11):1892–7.

    PubMed  CAS  Google Scholar 

  45. Goin JE, Dancey JE, Hermann GA, Sickles CJ, Roberts CA, MacDonald JS. Treatment of unresectable metastatic colorectal carcinoma to the liver with intrahepatic Y-90 microspheres: a dose-ranging study. World J of Nuc Med. 2003;2:216–25.

    Google Scholar 

  46. Wong CY, Qing F, Savin M, et al. reduction of metastatic load to liver after intra-arterial hepatic yttrium-90 radioembolization as evaluated by [18 F]fluorodeoxyglucose positron emission tomographic imaging. J Vasc Interv Radiol. 2005;16(8):1101–6.

    Article  PubMed  Google Scholar 

  47. Mulcahy MF, Lewandowski RJ, Ibrahim SM, et al. Radioembolization of colorectal hepatic metastases using yttrium-90 microspheres. Cancer. 2009;115(9):1849–58.

    Article  PubMed  Google Scholar 

  48. Sato KT, Lewandowski RJ, Mulcahy MF, et al. Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres–safety, efficacy, and survival. Radiology. 2008;247(2):507–15.

    Article  PubMed  Google Scholar 

  49. Gray B, Van Hazel G, Hope M, et al. Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol. 2001;12(12):1711–20.

    Article  PubMed  CAS  Google Scholar 

  50. Kennedy AS, Coldwell D, Nutting C, et al. Resin (90)Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys. 2006;65(2):412–25.

    Article  PubMed  CAS  Google Scholar 

  51. Jakobs TF, Hoffmann RT, Dehm K, et al. Hepatic yttrium-90 radioembolization of chemotherapy-refractory colorectal cancer liver metastases. J Vasc Interv Radiol. 2008;19(8):1187–95.

    Article  PubMed  Google Scholar 

  52. Sharma RA, Van Hazel GA, Morgan B, et al. Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol. 2007;25(9):1099–106.

    Article  PubMed  CAS  Google Scholar 

  53. Hendlisz A, Van den Eynde M, Peeters M, et al. 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. 2010;28(23):3687–94. This study compared intravenous fluorouracil infusion alone and its combination with radioembolization in a phase III trial in patients with hepatic colorectal metastases. The results demonstrated significant improvement in time to tumor progression and time to liver progression in patients treated with the combination.

    Article  PubMed  CAS  Google Scholar 

  54. Coldwell D, Nutting C, Kennedy AK. Treatment of hepatic metastases from breast cancer with yttrium-90 SIR-Spheres radioembolization. Paper presented at: Society of Interventional Radiology Annual Meeting; March 31-April 5, 2005; New Orleans, LA.

  55. Bangash AK, Atassi B, Kaklamani V, et al. 90Y radioembolization of metastatic breast cancer to the liver: toxicity, imaging response, survival. J Vasc Interv Radiol. 2007;18(5):621–8.

    Article  PubMed  Google Scholar 

  56. Coldwell D, Nutting C, Kennedy AK. Use of yttrium-90 SirSpheres to treat metastatic unresectable neuroendorcine tumors to the liver. Paper presented at: World Congress of Gastrointestinal Cancer; June 27-30, 2005; Barcelona, Spain.

  57. Rhee TK, Lewandowski RJ, Liu DM, et al. 90Y radioembolization for metastatic neuroendocrine liver tumors: preliminary results from a multi-institutional experience. Ann Surg. 2008;247(6):1029–35.

    Article  PubMed  Google Scholar 

  58. Memon K, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for neuroendocrine liver metastases: safety, imaging, and long-term outcomes. Int J Radiat Oncol Biol Phys. 2012;83(3):887-94. Epub 2011 Dec 2. This study analyzed the role of radioembolization in 40 patients with unresectable hepatic neuroendocrine metastases with imaging-confirmed progressive disease refractory to systemic therapy and demonstrated encouraging outcomes in terms of toxicity, response, and survival.

    Google Scholar 

  59. Gonsalves CF, Eschelman DJ, Sullivan KL, Anne PR, Doyle L, Sato T. Radioembolization as salvage therapy for hepatic metastasis of uveal melanoma: a single-institution experience. AJR Am J Roentgenol. 2011;196(2):468–73. This is one of the very few studies analyzing the role of radioembolization in patients with hepatic metastases from uveal melanoma.

    Article  PubMed  Google Scholar 

  60. Abdelmaksoud MHK, Louie JD, Hwang GL, Kothary N, Minor DR, Sze DY. Yttrium-90 radioembolization of renal cell carcinoma metastatic to the liver. J Vasc Interv Radiol. 2012;23(3):323–30.e321.

    Article  PubMed  Google Scholar 

  61. Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol. 2005;16(12):1627–39.

    Article  PubMed  Google Scholar 

  62. Murthy R, Xiong H, Nunez R, et al. Yttrium 90 resin microspheres for the treatment of unresectable colorectal hepatic metastases after failure of multiple chemotherapy regimens: preliminary results. J Vasc Interv Radiol. 2005;16(7):937–45.

    Article  PubMed  Google Scholar 

  63. Sangro B, Gil-Alzugaray B, Rodriguez J, et al. Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer. 2008;112(7):1538–46.

    Article  PubMed  Google Scholar 

  64. Young JY, Rhee TK, Atassi B, et al. Radiation dose limits and liver toxicities resulting from multiple yttrium-90 radioembolization treatments for hepatocellular carcinoma. J Vasc Interv Radiol. 2007;18(11):1375–82.

    Article  PubMed  Google Scholar 

  65. Jakobs TF, Saleem S, Atassi B, et al. Fibrosis, portal hypertension, and hepatic volume changes induced by intra-arterial radiotherapy with (90)yttrium microspheres. Dig Dis Sci. 2008;53(9):2556–63.

    Article  PubMed  CAS  Google Scholar 

  66. Rhee TK, Naik NK, Deng J, et al. Tumor response after yttrium-90 radioembolization for hepatocellular carcinoma: comparison of diffusion-weighted functional MR imaging with anatomic MR imaging. J Vasc Interv Radiol. 2008;19(8):1180–6.

    Article  PubMed  Google Scholar 

  67. TheraSphere Yttrium-90 microspheres package insert, MDS Nordion, Kanata, Canada, 2004.

  68. Murthy R, Brown DB, Salem R, et al. Gastrointestinal complications associated with hepatic arterial Yttrium-90 microsphere therapy. J Vasc Interv Radiol. 2007;18(4):553–61. quiz 562.

    Article  PubMed  Google Scholar 

  69. Carretero C, Munoz-Navas M, Betes M, et al. Gastroduodenal injury after radioembolization of hepatic tumors. Am J Gastroenterol. 2007;102(6):1216–20. Epub 2007 Mar 13.

    Article  PubMed  Google Scholar 

  70. Murthy R, Eng C, Krishnan S, et al. Hepatic yttrium-90 radioembolotherapy in metastatic colorectal cancer treated with cetuximab or bevacizumab. J Vasc Interv Radiol. 2007;18(12):1588–91.

    Article  PubMed  Google Scholar 

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Acknowledgments

There was no funding provided for this monograph. RS is supported in part by NIH grant CA126809.

Disclosure

K. Memon: none; R.J. Lewandowski: consultancy for MDS Nordion; A. Riaz: none; R. Salem: consultancy for MDS Nordion and Sirtex Medical Limited.

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  1. Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA

    Khairuddin Memon MD, Robert J. Lewandowski MD, Ahsun Riaz MD & Riad Salem MD

  2. Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA

    Riad Salem MD

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  1. Khairuddin Memon MD
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Memon, K., Lewandowski, R.J., Riaz, A. et al. Chemoembolization and Radioembolization for Metastatic Disease to the Liver: Available Data and Future Studies. Curr. Treat. Options in Oncol. 13, 403–415 (2012). https://doi.org/10.1007/s11864-012-0200-x

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