Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Nonsurgical local treatment strategies for colorectal cancer liver metastases

Alan P Venook, MD
Section Editor
Kenneth K Tanabe, MD
Deputy Editor
Diane MF Savarese, MD


Surgical resection is the treatment of choice for patients with isolated colorectal cancer (CRC) liver metastases when feasible. For patients with four or fewer isolated hepatic lesions, five-year relapse-free survival rates after resection range from 24 to 58 percent, averaging 30 percent (table 1). Many of these patients are potentially cured (see "Management of potentially resectable colorectal cancer liver metastases"). However, the majority are not surgical candidates because of tumor size, location, multifocality, or inadequate hepatic reserve.

There are several nonsurgical treatment options for patients with liver-isolated CRC metastases who are not candidates for potentially curative resection. These include systemic chemotherapy, regional chemotherapy via the hepatic artery, selective internal radiation using yttrium-labeled glass or resin microspheres, and regional tumor ablation (hyperthermic or radiofrequency coagulation, intratumoral injection of ethanol or acetic acid, and cryotherapy).

Local or regional treatment approaches may be considered after the cancer has progressed on systemic therapies but remains isolated to the liver or as a means of delaying the need for systemic chemotherapy in patients who have liver-isolated metastatic disease. Whether this rationale is valid or not is unclear. Although these methods (particularly radiofrequency ablation, RFA) can provide local control in a high number of patients, whether there are any long-term survivors (ie, cures) remains uncertain. Moreover, it is unclear whether the sequential use of regional treatments followed by systemic chemotherapy at the time of progression provides better long-term benefit in terms of duration of symptom control or survival than systemic chemotherapy alone.

This topic review will focus on nonsurgical methods for local tumor ablation, regional chemotherapy into the hepatic artery, and radiation therapy. Resection and the use of pre-resection (induction) chemotherapy, as well as systemic treatment strategies for metastatic CRC, are addressed elsewhere. (See "Management of potentially resectable colorectal cancer liver metastases" and "Systemic chemotherapy for metastatic colorectal cancer: General principles" and "Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations".)


Depending on the clinical picture, biopsy may be indicated to confirm the diagnosis of metastatic disease. However, whether all patients need biopsy confirmation of suspected metastatic disease is debated. Many oncologists feel it is important to provide tissue documentation of the first site of noncurable disease, while others consider that biopsy is not necessary in a patient with a history of CRC in the preceding five years who has a new elevation of carcinoembryonic antigen (CEA) and new unresectable liver lesions on imaging that are clinically suspicious.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Apr 2017. | This topic last updated: Apr 28, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Fernandez FG, Drebin JA, Linehan DC, et al. Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET). Ann Surg 2004; 240:438.
  2. Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg 1995; 19:59.
  3. Steele G Jr, Bleday R, Mayer RJ, et al. A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group Protocol 6584. J Clin Oncol 1991; 9:1105.
  4. Wanebo HJ, Chu QD, Vezeridis MP, Soderberg C. Patient selection for hepatic resection of colorectal metastases. Arch Surg 1996; 131:322.
  5. Nordlinger B, Guiguet M, Vaillant JC, et al. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Française de Chirurgie. Cancer 1996; 77:1254.
  6. Yoon SS, Tanabe KK. Multidisciplinary management of metastatic colorectal cancer. Surg Oncol 1998; 7:197.
  7. Hughes KS, Simon R, Songhorabodi S, et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Surgery 1986; 100:278.
  8. Jamison RL, Donohue JH, Nagorney DM, et al. Hepatic resection for metastatic colorectal cancer results in cure for some patients. Arch Surg 1997; 132:505.
  9. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45:228.
  10. WHO Handbook for Reporting Results of Cancer Treatment, World Health Organization (Ed), WHO Offset Publication No. 48, Geneva, Switzerland 1979.
  11. Preketes AP, King J, Caplehorn JR, et al. CEA reduction after cryotherapy for liver metastases from colon cancer predicts survival. Aust N Z J Surg 1994; 64:612.
  12. Stang A, Fischbach R, Teichmann W, et al. A systematic review on the clinical benefit and role of radiofrequency ablation as treatment of colorectal liver metastases. Eur J Cancer 2009; 45:1748.
  13. Amersi FF, McElrath-Garza A, Ahmad A, et al. Long-term survival after radiofrequency ablation of complex unresectable liver tumors. Arch Surg 2006; 141:581.
  14. Kuvshinoff BW, Ota DM. Radiofrequency ablation of liver tumors: influence of technique and tumor size. Surgery 2002; 132:605.
  15. Hildebrand P, Kleemann M, Roblick UJ, et al. Radiofrequency-ablation of unresectable primary and secondary liver tumors: results in 88 patients. Langenbecks Arch Surg 2006; 391:118.
  16. Hildebrand P, Leibecke T, Kleemann M, et al. Influence of operator experience in radiofrequency ablation of malignant liver tumours on treatment outcome. Eur J Surg Oncol 2006; 32:430.
  17. Ahmad A, Chen SL, Kavanagh MA, et al. Radiofrequency ablation of hepatic metastases from colorectal cancer: are newer generation probes better? Am Surg 2006; 72:875.
  18. Wong SL, Mangu PB, Choti MA, et al. American Society of Clinical Oncology 2009 clinical evidence review on radiofrequency ablation of hepatic metastases from colorectal cancer. J Clin Oncol 2010; 28:493.
  19. Abitabile P, Hartl U, Lange J, Maurer CA. Radiofrequency ablation permits an effective treatment for colorectal liver metastasis. Eur J Surg Oncol 2007; 33:67.
  20. Gillams AR, Lees WR. Radio-frequency ablation of colorectal liver metastases in 167 patients. Eur Radiol 2004; 14:2261.
  21. Kosari K, Gomes M, Hunter D, et al. Local, intrahepatic, and systemic recurrence patterns after radiofrequency ablation of hepatic malignancies. J Gastrointest Surg 2002; 6:255.
  22. van Duijnhoven FH, Jansen MC, Junggeburt JM, et al. Factors influencing the local failure rate of radiofrequency ablation of colorectal liver metastases. Ann Surg Oncol 2006; 13:651.
  23. Montgomery RS, Rahal A, Dodd GD 3rd, et al. Radiofrequency ablation of hepatic tumors: variability of lesion size using a single ablation device. AJR Am J Roentgenol 2004; 182:657.
  24. Machi J, Uchida S, Sumida K, et al. Ultrasound-guided radiofrequency thermal ablation of liver tumors: percutaneous, laparoscopic, and open surgical approaches. J Gastrointest Surg 2001; 5:477.
  25. Jiang HC, Liu LX, Piao DX, et al. Clinical short-term results of radiofrequency ablation in liver cancers. World J Gastroenterol 2002; 8:624.
  26. Dodd GD 3rd, Frank MS, Aribandi M, et al. Radiofrequency thermal ablation: computer analysis of the size of the thermal injury created by overlapping ablations. AJR Am J Roentgenol 2001; 177:777.
  27. Goldberg SN, Hahn PF, Tanabe KK, et al. Percutaneous radiofrequency tissue ablation: does perfusion-mediated tissue cooling limit coagulation necrosis? J Vasc Interv Radiol 1998; 9:101.
  28. Lu DS, Raman SS, Limanond P, et al. Influence of large peritumoral vessels on outcome of radiofrequency ablation of liver tumors. J Vasc Interv Radiol 2003; 14:1267.
  29. Head HW, Dodd GD 3rd, Dalrymple NC, et al. Percutaneous radiofrequency ablation of hepatic tumors against the diaphragm: frequency of diaphragmatic injury. Radiology 2007; 243:877.
  30. Tanabe KK, Curley SA, Dodd GD, et al. Radiofrequency ablation: the experts weigh in. Cancer 2004; 100:641.
  31. Decadt B, Siriwardena AK. Radiofrequency ablation of liver tumours: systematic review. Lancet Oncol 2004; 5:550.
  32. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 1999; 230:1.
  33. Machi J, Oishi AJ, Sumida K, et al. Long-term outcome of radiofrequency ablation for unresectable liver metastases from colorectal cancer: evaluation of prognostic factors and effectiveness in first- and second-line management. Cancer J 2006; 12:318.
  34. Siperstein AE, Berber E, Ballem N, Parikh RT. Survival after radiofrequency ablation of colorectal liver metastases: 10-year experience. Ann Surg 2007; 246:559.
  35. Ruers T, Punt C, Van Coevorden F, et al. Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol 2012; 23:2619.
  36. Solbiati L, Ahmed M, Cova L, et al. Small liver colorectal metastases treated with percutaneous radiofrequency ablation: local response rate and long-term survival with up to 10-year follow-up. Radiology 2012; 265:958.
  37. Aloia TA, Vauthey JN, Loyer EM, et al. Solitary colorectal liver metastasis: resection determines outcome. Arch Surg 2006; 141:460.
  38. Abdalla EK, Vauthey JN, Ellis LM, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 2004; 239:818.
  39. Ruers TJ, Joosten JJ, Wiering B, et al. Comparison between local ablative therapy and chemotherapy for non-resectable colorectal liver metastases: a prospective study. Ann Surg Oncol 2007; 14:1161.
  40. Otto G, Düber C, Hoppe-Lotichius M, et al. Radiofrequency ablation as first-line treatment in patients with early colorectal liver metastases amenable to surgery. Ann Surg 2010; 251:796.
  41. White RR, Avital I, Sofocleous CT, et al. Rates and patterns of recurrence for percutaneous radiofrequency ablation and open wedge resection for solitary colorectal liver metastasis. J Gastrointest Surg 2007; 11:256.
  42. Lee WS, Yun SH, Chun HK, et al. Clinical outcomes of hepatic resection and radiofrequency ablation in patients with solitary colorectal liver metastasis. J Clin Gastroenterol 2008; 42:945.
  43. Gleisner AL, Choti MA, Assumpcao L, et al. Colorectal liver metastases: recurrence and survival following hepatic resection, radiofrequency ablation, and combined resection-radiofrequency ablation. Arch Surg 2008; 143:1204.
  44. Cirocchi R, Trastulli S, Boselli C, et al. Radiofrequency ablation in the treatment of liver metastases from colorectal cancer. Cochrane Database Syst Rev 2012; :CD006317.
  45. Kornprat P, Jarnagin WR, DeMatteo RP, et al. Role of intraoperative thermoablation combined with resection in the treatment of hepatic metastasis from colorectal cancer. Arch Surg 2007; 142:1087.
  46. Pearson AS, Izzo F, Fleming RY, et al. Intraoperative radiofrequency ablation or cryoablation for hepatic malignancies. Am J Surg 1999; 178:592.
  47. Elias D, Baton O, Sideris L, et al. Hepatectomy plus intraoperative radiofrequency ablation and chemotherapy to treat technically unresectable multiple colorectal liver metastases. J Surg Oncol 2005; 90:36.
  48. Pawlik TM, Izzo F, Cohen DS, et al. Combined resection and radiofrequency ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol 2003; 10:1059.
  49. Ruers T, et al. Radiofrequency ablation (RFA) combined with chemotherapy for unresectable colorectal liver metastases (CRC LM): Long-term survival results of a randomized phase II study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC) (absstr). J Clin Oncol 33, 2015 (suppl; abstr 3501). Abstract available online at http://meetinglibrary.asco.org/content/151361-156 (Accessed on July 13, 2015).
  50. de Baère T, Risse O, Kuoch V, et al. Adverse events during radiofrequency treatment of 582 hepatic tumors. AJR Am J Roentgenol 2003; 181:695.
  51. Shibata T, Niinobu T, Ogata N, Takami M. Microwave coagulation therapy for multiple hepatic metastases from colorectal carcinoma. Cancer 2000; 89:276.
  52. Liang P, Dong B, Yu X, et al. Prognostic factors for percutaneous microwave coagulation therapy of hepatic metastases. AJR Am J Roentgenol 2003; 181:1319.
  53. Martin RC, Scoggins CR, McMasters KM. Safety and efficacy of microwave ablation of hepatic tumors: a prospective review of a 5-year experience. Ann Surg Oncol 2010; 17:171.
  54. Liang P, Wang Y, Yu X, Dong B. Malignant liver tumors: treatment with percutaneous microwave ablation--complications among cohort of 1136 patients. Radiology 2009; 251:933.
  55. Muralidharan V, Christophi C. Interstitial laser thermotherapy in the treatment of colorectal liver metastases. J Surg Oncol 2001; 76:73.
  56. Pech M, Wieners G, Freund T, et al. MR-guided interstitial laser thermotherapy of colorectal liver metastases: efficiency, safety and patient survival. Eur J Med Res 2007; 12:161.
  57. Christophi C, Nikfarjam M, Malcontenti-Wilson C, Muralidharan V. Long-term survival of patients with unresectable colorectal liver metastases treated by percutaneous interstitial laser thermotherapy. World J Surg 2004; 28:987.
  58. Vogl TJ, Straub R, Eichler K, et al. Colorectal carcinoma metastases in liver: laser-induced interstitial thermotherapy--local tumor control rate and survival data. Radiology 2004; 230:450.
  59. Giorgio A, Tarantino L, Mariniello N, et al. [Ultrasonography-guided percutaneous ethanol injection in large an/or multiple liver metastasis]. Radiol Med 1998; 96:238.
  60. Giovannini M, Seitz JF. Ultrasound-guided percutaneous alcohol injection of small liver metastases. Results in 40 patients. Cancer 1994; 73:294.
  61. Ruan DT, Warren RS. Liver-directed therapies in colorectal cancer. Semin Oncol 2005; 32:85.
  62. Amin Z, Bown SG, Lees WR. Local treatment of colorectal liver metastases: a comparison of interstitial laser photocoagulation (ILP) and percutaneous alcohol injection (PAI). Clin Radiol 1993; 48:166.
  63. Riemsma RP, Bala MM, Wolff R, Kleijnen J. Percutaneous ethanol injection for liver metastases. Cochrane Database Syst Rev 2013; :CD008717.
  64. Bala MM, Riemsma RP, Wolff R, Kleijnen J. Cryotherapy for liver metastases. Cochrane Database Syst Rev 2013; :CD009058.
  65. BREEDIS C, YOUNG G. The blood supply of neoplasms in the liver. Am J Pathol 1954; 30:969.
  66. Collins JM. Pharmacologic rationale for regional drug delivery. J Clin Oncol 1984; 2:498.
  67. Aliberti C, Tilli M, Benea G, Fiorentini G. Trans-arterial chemoembolization (TACE) of liver metastases from colorectal cancer using irinotecan-eluting beads: preliminary results. Anticancer Res 2006; 26:3793.
  68. Poggi G, Quaretti P, Minoia C, et al. Transhepatic arterial chemoembolization with oxaliplatin-eluting microspheres (OEM-TACE) for unresectable hepatic tumors. Anticancer Res 2008; 28:3835.
  69. Martin RC, Robbins K, Tomalty D, et al. Transarterial chemoembolisation (TACE) using irinotecan-loaded beads for the treatment of unresectable metastases to the liver in patients with colorectal cancer: an interim report. World J Surg Oncol 2009; 7:80.
  70. Albert M, Kiefer MV, Sun W, et al. Chemoembolization of colorectal liver metastases with cisplatin, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol. Cancer 2011; 117:343.
  71. Vogl TJ, Zangos S, Eichler K, et al. Colorectal liver metastases: regional chemotherapy via transarterial chemoembolization (TACE) and hepatic chemoperfusion: an update. Eur Radiol 2007; 17:1025.
  72. Sanz-Altamira PM, Spence LD, Huberman MS, et al. Selective chemoembolization in the management of hepatic metastases in refractory colorectal carcinoma: a phase II trial. Dis Colon Rectum 1997; 40:770.
  73. Bavisotto LM, Patel NH, Althaus SJ, et al. Hepatic transcatheter arterial chemoembolization alternating with systemic protracted continuous infusion 5-fluorouracil for gastrointestinal malignancies metastatic to liver: a phase II trial of the Puget Sound Oncology Consortium (PSOC 1104). Clin Cancer Res 1999; 5:95.
  74. Martin RC, 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; 18:192.
  75. Fiorentini G, Aliberti C, Tilli M, et al. Intra-arterial infusion of irinotecan-loaded drug-eluting beads (DEBIRI) versus intravenous therapy (FOLFIRI) for hepatic metastases from colorectal cancer: final results of a phase III study. Anticancer Res 2012; 32:1387.
  76. Hunt TM, Flowerdew AD, Birch SJ, et al. Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases. Br J Surg 1990; 77:779.
  77. Bhutiani N, Akinwande O, Martin RC 2nd. Efficacy and Toxicity of Hepatic Intra-Arterial Drug-Eluting (Irinotecan) Bead (DEBIRI) Therapy in Irinotecan-Refractory Unresectable Colorectal Liver Metastases. World J Surg 2016; 40:1178.
  78. Allen-Mersh TG, Earlam S, Fordy C, et al. Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet 1994; 344:1255.
  79. Chang AE, Schneider PD, Sugarbaker PH, et al. A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. Ann Surg 1987; 206:685.
  80. Hohn DC, Stagg RJ, Friedman MA, et al. A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial. J Clin Oncol 1989; 7:1646.
  81. Kemeny N, Daly J, Reichman B, et al. Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial. Ann Intern Med 1987; 107:459.
  82. Martin JK Jr, O'Connell MJ, Wieand HS, et al. Intra-arterial floxuridine vs systemic fluorouracil for hepatic metastases from colorectal cancer. A randomized trial. Arch Surg 1990; 125:1022.
  83. Harmantas A, Rotstein LE, Langer B. Regional versus systemic chemotherapy in the treatment of colorectal carcinoma metastatic to the liver. Is there a survival difference? Meta-analysis of the published literature. Cancer 1996; 78:1639.
  84. Stagg RJ, Venook AP, Chase JL, et al. Alternating hepatic intra-arterial floxuridine and fluorouracil: a less toxic regimen for treatment of liver metastases from colorectal cancer. J Natl Cancer Inst 1991; 83:423.
  85. Hohn DC, Stagg RJ, Price DC, Lewis BJ. Avoidance of gastroduodenal toxicity in patients receiving hepatic arterial 5-fluoro-2'-deoxyuridine. J Clin Oncol 1985; 3:1257.
  86. Curley SA, Chase JL, Roh MS, Hohn DC. Technical considerations and complications associated with the placement of 180 implantable hepatic arterial infusion devices. Surgery 1993; 114:928.
  87. Ziessman HA, Thrall JH, Yang PJ, et al. Hepatic arterial perfusion scintigraphy with Tc-99m-MAA. Use of a totally implanted drug delivery system. Radiology 1984; 152:167.
  88. Kemeny N, Niedzwiecki D, Shurgot B, Oderman P. Prognostic variables in patients with hepatic metastases from colorectal cancer. Importance of medical assessment of liver involvement. Cancer 1989; 63:742.
  89. Frye JW, Venook AP, Ostroff JW, et al. Hepatic intra-arterial methylene blue injection during endoscopy: a method of detecting gastroduodenal misperfusion in patients receiving hepatic intra-arterial chemotherapy via an implanted pump. Gastrointest Endosc 1992; 38:52.
  90. Ludwig J, Kim CH, Wiesner RH, Krom RA. Floxuridine-induced sclerosing cholangitis: an ischemic cholangiopathy? Hepatology 1989; 9:215.
  91. Kemeny N, Seiter K, Niedzwiecki D, et al. A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer. Cancer 1992; 69:327.
  92. Kemeny N, Seiter K, Conti JA, et al. Hepatic arterial floxuridine and leucovorin for unresectable liver metastases from colorectal carcinoma. New dose schedules and survival update. Cancer 1994; 73:1134.
  93. Kemeny N, Conti JA, Cohen A, et al. Phase II study of hepatic arterial floxuridine, leucovorin, and dexamethasone for unresectable liver metastases from colorectal carcinoma. J Clin Oncol 1994; 12:2288.
  94. Ducreux M, Ychou M, Laplanche A, et al. Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the gastrointestinal group of the Federation Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol 2005; 23:4881.
  95. Boige V, Malka D, Elias D, et al. Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure. Ann Surg Oncol 2008; 15:219.
  96. Fiorentini G, Rossi S, Dentico P, et al. Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: a phase II clinical study. Tumori 2003; 89:382.
  97. Bouchahda M, Tanaka K, Adam R, et al. Three-drug chronotherapy via hepatic artery for patients with liver-only metastases from colorectal cancer (abstract). J Clin Oncol 2005; 23:275s.
  98. Safi F, Bittner R, Roscher R, et al. Regional chemotherapy for hepatic metastases of colorectal carcinoma (continuous intraarterial versus continuous intraarterial/intravenous therapy). Results of a controlled clinical trial. Cancer 1989; 64:379.
  99. 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.
  100. 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.
  101. de Gramont A, Bosset JF, Milan C, et al. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol 1997; 15:808.
  102. Lorenz M, Müller HH. Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma. J Clin Oncol 2000; 18:243.
  103. Kemeny NE, Niedzwiecki D, Hollis DR, et al. Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol 2006; 24:1395.
  104. Mocellin S, Pilati P, Lise M, Nitti D. Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era? J Clin Oncol 2007; 25:5649.
  105. Ben-Josef E, Normolle D, Ensminger WD, et al. Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies. J Clin Oncol 2005; 23:8739.
  106. Topkan E, Onal HC, Yavuz MN. Managing liver metastases with conformal radiation therapy. J Support Oncol 2008; 6:9.
  107. Scorsetti M, Comito T, Tozzi A, et al. Final results of a phase II trial for stereotactic body radiation therapy for patients with inoperable liver metastases from colorectal cancer. J Cancer Res Clin Oncol 2015; 141:543.
  108. Hoyer M, Roed H, Traberg Hansen A, et al. Phase II study on stereotactic body radiotherapy of colorectal metastases. Acta Oncol 2006; 45:823.
  109. van der Pool AE, Méndez Romero A, Wunderink W, et al. Stereotactic body radiation therapy for colorectal liver metastases. Br J Surg 2010; 97:377.
  110. Nag S, DeHaan M, Scruggs G, et al. Long-term follow-up of patients of intrahepatic malignancies treated with iodine-125 brachytherapy. Int J Radiat Oncol Biol Phys 2006; 64:736.
  111. Armstrong JG, Anderson LL, Harrison LB. Treatment of liver metastases from colorectal cancer with radioactive implants. Cancer 1994; 73:1800.
  112. Martinez-Monge R, Nag S, Nieroda CA, Martin EW. Iodine-125 brachytherapy in the treatment of colorectal adenocarcinoma metastatic to the liver. Cancer 1999; 85:1218.
  113. Donath D, Nori D, Turnbull A, et al. Brachytherapy in the treatment of solitary colorectal metastases to the liver. J Surg Oncol 1990; 44:55.
  114. 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; 12:1711.
  115. 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.
  116. 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; 28:3687.
  117. 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; 25:1099.
  118. van Hazel GA, Pavlakis N, Goldstein D, et al. 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 2009; 27:4089.
  119. Martin RCG, Scoggins CR, Rilling WS, et al. Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis (Abstract 174). Data presented at the 2014 ASCO Gastrointestinal Cancer Symposium, January 17, 2014. Abstract avalable online at http://meetinglibrary.asco.org/content/123058-143 (Accessed on March 20, 2014).
  120. Gibbs P. Heinermann V, Sharma NK, et al. SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 +/- bevacizumab versus mFOLFOX6 + selective internal radiation therapy (SIRT) +/- bevacizumab in patients with metastatic colorectal cancer (abstr). J Clin Oncol 33, 2015 (suppl; abstr 3502). http://meetinglibrary.asco.org/content/145884-156 (Accessed on July 13, 2015).
  121. 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.
  122. https://clinicaltrials.gov/ct2/show/NCT01721954?term=metastatic+colorectal+cancer+and+SIR-Spheres&rank=2 (Accessed on July 17, 2015).
  123. https://clinicaltrials.gov/ct2/show/NCT01895257?term=colorectal+cancer+liver+metastases+and+yttrium-90&rank=14 (Accessed on July 17, 2015).
  124. Kennedy AS, Coldwell D, Nutting C, et al. Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys 2006; 65:412.
  125. Cosimelli M, Golfieri R, Cagol PP, et al. Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases. Br J Cancer 2010; 103:324.
  126. Sato KT, Lewandowski RJ, Mulcahy MF, et al. Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival. Radiology 2008; 247:507.
  127. Bester L, Meteling B, Pocock N, et al. Radioembolization versus standard care of hepatic metastases: comparative retrospective cohort study of survival outcomes and adverse events in salvage patients. J Vasc Interv Radiol 2012; 23:96.
  128. 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 2012; 35:1066.
  129. Benson AB 3rd, Geschwind JF, Mulcahy MF, et al. Radioembolisation for liver metastases: results from a prospective 151 patient multi-institutional phase II study. Eur J Cancer 2013; 49:3122.
  130. Martin LK, Cucci A, Wei L, et al. Yttrium-90 radioembolization as salvage therapy for colorectal cancer with liver metastases. Clin Colorectal Cancer 2012; 11:195.
  131. Hickey R, Lewandowski R, Salem R. Yttrium-90 radioembolization is a viable treatment option for unresectable, chemorefractory colorectal cancer liver metastases: further evidence in support of a new treatment paradigm. Ann Surg Oncol 2015; 22:706.
  132. Saxena A, Bester L, Shan L, et al. A systematic review on the safety and efficacy of yttrium-90 radioembolization for unresectable, chemorefractory colorectal cancer liver metastases. J Cancer Res Clin Oncol 2014; 140:537.
  133. 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.
  134. Lam MG, Abdelmaksoud MH, Chang DT, et al. Safety of 90Y radioembolization in patients who have undergone previous external beam radiation therapy. Int J Radiat Oncol Biol Phys 2013; 87:323.
  135. Ruers T, Van Coevorden F, Punt CJ, et al. Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial. J Natl Cancer Inst 2017; 109.