Skip to main content

Advertisement

Log in

Radioembolization as a Treatment Strategy for Metastatic Colorectal Cancer to the Liver: What Can We Learn from the SIRFLOX Trial?

  • Lower Gastrointestinal Cancers (AB Benson, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

In the setting of liver metastases from colorectal cancer (CRC), radioembolization with yttrium-90 has been used to treat chemotherapy refractory disease with a growing interest to establish its efficacy in prospective trials combined with first- and second-line chemotherapy. SIRFLOX is an ongoing, multi-center, phase 3 randomized trial comparing first-line chemotherapy alone or in combination with yttrium-90 radioembolization in patients with CRC who have isolated liver metastases or liver-dominant metastases. Preliminary results from SIRFLOX demonstrate that radioembolization combined with first-line chemotherapy is safe and feasible. There was no significant difference in median overall progression-free survival (PFS) between the combined radioembolization-chemotherapy and chemotherapy-only arms (10.7 versus 10.2 months). Although the trial did not meet its primary endpoint of improved median PFS, there was a significant increase in the median hepatic PFS (20.5 versus 12.6 months; p = 0.02) favoring the combination arm. Thus, combining radioembolization with chemotherapy in the first-line setting may be most effective for liver-limited metastatic CRC. Since radioembolization targets liver disease, it is plausible that the trial failed to achieve an improvement in PFS given that 40 % of the SIRFLOX population had extra-hepatic disease. It is also possible that the overall median PFS may be a poor surrogate endpoint, and other endpoints like overall survival still needs to be delineated in this setting. In addition, it is crucial to document improvement or delay in time to deterioration in quality of life symptom endpoints in this population. SIRFLOX is the first of three prospective studies that assess the efficacy of adding radioembolization to first-line chemotherapy, and the combined data from these trials will provide the necessary power for an overall survival analysis. The final results of SIRFLOX will be eagerly awaited to determine if the increased hepatic PFS in preliminary data will translate to increased overall survival benefit.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

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

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29. doi:10.3322/caac.21254.

    Article  PubMed  Google Scholar 

  2. Howlader N NA, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistic Review—colorectal cancer. In: institute Nc, editor. Bethesda, MD: National cancer institute, based on November 2014 SEER data submission, posted to the SEER web site, 2015.

  3. Lee WS, Yun SH, Chun HK, Lee WY, Yun HR, Kim J, et al. Pulmonary resection for metastases from colorectal cancer: prognostic factors and survival. Int J Color Dis. 2007;22(6):699–704. doi:10.1007/s00384-006-0218-2.

    Article  Google Scholar 

  4. Welch JP, Donaldson GA. The clinical correlation of an autopsy study of recurrent colorectal cancer. Ann Surg. 1979;189(4):496–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hayashi M, Inoue Y, Komeda K, Shimizu T, Asakuma M, Hirokawa F, et al. Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis. BMC Surg. 2010;10(1):1–12. doi:10.1186/1471-2482-10-27.

    Article  Google Scholar 

  6. Choti MA, Sitzmann JV, Tiburi MF, Sumetchotimetha W, Rangsin R, Schulicl RD, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235:759–66. doi:10.1097/00000658-200206000-00002.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240(4):644–57. discussion 57–8.

    PubMed  PubMed Central  Google Scholar 

  8. Elias D, Liberale G, Vernerey D, Pocard M, Ducreux M, Boige V, et al. Hepatic and extrahepatic colorectal metastases: when resectable, their localization does not matter, but their total number has a prognostic effect. Ann Surg Oncol. 2005;12(11):900–9. doi:10.1245/ASO.2005.01.010.

    Article  PubMed  Google Scholar 

  9. Rees M, Tekkis PP, Welsh FKS, O'Rourke T, John TG. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008;247(1):125–35. doi:10.1097/SLA.0b013e31815aa2c2.

    Article  PubMed  Google Scholar 

  10. Kanas GP, Taylor A, Primrose JN, Langeberg WJ, Kelsh MA, Mowat FS, et al. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Clin Epidemiol. 2012;4:283–301. doi:10.2147/CLEP.S34285.

    PubMed  PubMed Central  Google Scholar 

  11. Garden OJ, Rees M, Poston GJ, Mirza D, Saunders M, Ledermann J, et al. Guidelines for resection of colorectal cancer liver metastases. Gut. 2006;55 Suppl 3:iii1–8. doi:10.1136/gut.2006.098053.

    PubMed  PubMed Central  Google Scholar 

  12. Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25:4575–80. doi:10.1200/jco.2007.11.0833.

    Article  PubMed  Google Scholar 

  13. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. 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. 2008;371:1007–16. doi:10.1016/s0140-6736(08)60455-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. NGTAT Group. Expectancy or primary chemotherapy in patients with advanced asymptomatic colorectal cancer: a randomized trial. J Clin Oncol. 1992;10(6):904–11.

    Google Scholar 

  15. Scheithauer W, Rosen H, Kornek GV, Sebesta C, Depisch D. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ. 1993;306(6880):752–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bendell JC, Bekaii-Saab TS, Cohn AL, Hurwitz HI, Kozloff M, Tezcan H, et al. Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOX-bevacizumab or FOLFIRI-bevacizumab: results from ARIES, a bevacizumab observational cohort study. Oncologist. 2012;17(12):1486–95. doi:10.1634/theoncologist.2012-0190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jawed I, Wilkerson J, Prasad V, Duffy AG, Fojo T. Colorectal cancer survival gains and novel treatment regimens: a systematic review and analysis. JAMA Oncol. 2015;1(6):787–95. doi:10.1001/jamaoncol.2015.1790.

    Article  PubMed  Google Scholar 

  18. Abrams TA, Meyer G, Schrag D, Meyerhardt JA, Moloney J, Fuchs CS. Chemotherapy usage patterns in a US-wide cohort of patients with metastatic colorectal cancer. J Natl Cancer Inst. 2014;106(2):djt371. doi:10.1093/jnci/djt371.

    Article  PubMed  Google Scholar 

  19. Grothey A, Sargent D. Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used first line. J Clin Oncol. 2005;23(36):9441–2. doi:10.1200/JCO.2005.04.4792.

    Article  PubMed  Google Scholar 

  20. Grothey A, Sargent D, Goldberg RM, Schmoll HJ. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 2004;22(7):1209–14. doi:10.1200/JCO.2004.11.037.

    Article  CAS  PubMed  Google Scholar 

  21. de Gramont A, Gramont A, Figer A, Seymour M, Homerin M. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18(16):2938.

    PubMed  Google Scholar 

  22. Giacchetti S, Giacchetti S, Perpoint B, Zidani R, Bail NL. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil–leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2000;18(1):136.

    CAS  PubMed  Google Scholar 

  23. Grothey A, Buechele T, Kroening H, Ridwelski K. Phase III trial of bolus 5-fluorouracil (5-FU)/folinic acid (FA) (MAYO) vs. weekly oxaliplatin (OXA) plus high dose 24h 5-FU infusion/FA in patients with advanced colorectal cancer (CRC). Eur J Cancer. 2001;37:S257-S.

    Article  Google Scholar 

  24. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.

    Article  CAS  PubMed  Google Scholar 

  25. Heinemann V, Volker H, Ludwig Fischer von W, Thomas D, Alexander K. 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(10):1065–75.

    Article  CAS  PubMed  Google Scholar 

  26. Venook A, Niedzwiecki D, Lenz HJ, Innocenti F, Mahoney MR, O'Neil B, et al. O-0019CALGB/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. Ann Oncol. 2014;25 suppl 2:ii112–3. doi:10.1093/annonc/mdu193.19.

    Article  Google Scholar 

  27. Cutsem E, Van Eric C, Josep T, Radek L, Hans P. 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(28):3499–506.

    Article  PubMed  Google Scholar 

  28. Tabernero J, Josep T, Takayuki Y, Allen Lee C, Radka O. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16(5):499–508.

    Article  CAS  PubMed  Google Scholar 

  29. Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausova J, Macarulla T, 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(28):3499–506. doi:10.1200/JCO.2012.42.8201.

    Article  PubMed  Google Scholar 

  30. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(10):1626–34. doi:10.1200/JCO.2007.14.7116.

    Article  CAS  PubMed  Google Scholar 

  31. Li J, Jin L, Shukui Q, Ruihua X, Thomas CCY. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(6):619–29.

    Article  CAS  PubMed  Google Scholar 

  32. Grothey A, Axel G, van Eric C, Alberto S, Salvatore S. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303–12.

    Article  CAS  PubMed  Google Scholar 

  33. Martin II RG, Scoggins C, Tomalty D, Schreeder M, Metzger T, Tatum C, et al. Irinotecan drug-eluting beads in the treatment of chemo-naive unresectable colorectal liver metastasis with concomitant systemic fluorouracil and oxaliplatin: results of pharmacokinetics and phase I trial. J Gastrointest Surg. 2012;16(8):1531–8. doi:10.1007/s11605-012-1892-8.

    Article  PubMed  Google Scholar 

  34. Eichler K, Zangos S, Mack MG, Hammerstingl R, Gruber-Rouh T, Gallus C, et al. First human study in treatment of unresectable liver metastases from colorectal cancer with irinotecan-loaded beads (DEBIRI). Int J Oncol. 2012;41(4):1213–20. doi:10.3892/ijo.2012.1572.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Hunt TM, Flowerdew AD, Birch SJ, Williams JD, Mullee MA, Taylor I. 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(7):779–82.

    Article  CAS  PubMed  Google Scholar 

  36. Albert M, Kiefer MV, Sun W, Haller D, Fraker DL, Tuite CM, et al. Chemoembolization of colorectal liver metastases with cisplatin, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol. Cancer. 2011;117(2):343–52. doi:10.1002/cncr.25387.

    Article  CAS  PubMed  Google Scholar 

  37. Gruber-Rouh T, Naguib NN, Eichler K, Ackermann H, Zangos S, Trojan J, et al. Transarterial chemoembolization of unresectable systemic chemotherapy-refractory liver metastases from colorectal cancer: long-term results over a 10-year period. Int J Cancer. 2014;134(5):1225–31. doi:10.1002/ijc.28443.

    Article  CAS  PubMed  Google Scholar 

  38. Sanz-Altamira PM, Spence LD, Huberman MS, Posner MR, Steele Jr G, Perry LJ, et al. Selective chemoembolization in the management of hepatic metastases in refractory colorectal carcinoma: a phase II trial. Dis Colon Rectum. 1997;40(7):770–5.

    Article  CAS  PubMed  Google Scholar 

  39. Tellez C, Benson 3rd AB, Lyster MT, Talamonti M, Shaw J, Braun MA, 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  CAS  PubMed  Google Scholar 

  40. 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. doi:10.1148/radiol.2501080295.

    Article  PubMed  Google Scholar 

  41. Riemsma RP, Bala MM, Wolff R, Kleijnen J. Transarterial (chemo)embolisation versus no intervention or placebo intervention for liver metastases. Cochrane Database Syst Rev. 2013;4:CD009498. doi:10.1002/14651858.CD009498.pub3.

    PubMed  Google Scholar 

  42. Fiorentini G, Aliberti C, Tilli M, Mulazzani L, Graziano F, Giordani P, 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(4):1387–95.

    CAS  PubMed  Google Scholar 

  43. Martin RG, Joshi J, Robbins K, Tomalty D, Bosnjakovik P, Derner M, 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. doi:10.1245/s10434-010-1288-5.

    Article  PubMed  Google Scholar 

  44. Vogl TJ, Jost A, Nour-Eldin NA, Mack MG, Zangos S, Naguib NNN. Repeated transarterial chemoembolisation using different chemotherapeutic drug combinations followed by MR-guided laser-induced thermotherapy in patients with liver metastases of colorectal carcinoma. Br J Cancer. 2012;106(7):1274–9. doi:10.1038/bjc.2012.69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Richardson AJ, Laurence JM, Lam VWT. Transarterial chemoembolization with irinotecan beads in the treatment of colorectal liver metastases: systematic review. J Vasc Interv Radiol. 2013;24(8):1209–17. doi:10.1016/j.jvir.2013.05.055.

    Article  PubMed  Google Scholar 

  46. Akinwande O, Miller A, Hayes D, O'Hara R, Tomalty D, Martin RCG. Concomitant capecitabine with hepatic delivery of drug eluting beads in metastatic colorectal cancer. Anticancer Res. 2014;34(12):7239–45.

    CAS  PubMed  Google Scholar 

  47. Aliberti C, Fiorentini G, Muzzio PC, Pomerri F, Tilli M, Dallara S, et al. Trans-arterial chemoembolization of metastatic colorectal carcinoma to the liver adopting DC bead®, drug-eluting bead loaded with irinotecan: results of a phase II clinical study. Anticancer Res. 2011;31(12):4581–7.

    CAS  PubMed  Google Scholar 

  48. Liu DM, Thakor AS, Baerlocher M, Alshammari MT, Lim H, Kos S, et al. A review of conventional and drug-eluting chemoembolization in the treatment of colorectal liver metastases: principles and proof. Future Oncol. 2015;11(9):1421–8. doi:10.2217/fon.15.3.

    Article  CAS  PubMed  Google Scholar 

  49. Saxena A, Meteling B, Kapoor J, Golani S, Morris DL, Bester L. Is yttrium-90 radioembolization a viable treatment option for unresectable, chemorefractory colorectal cancer liver metastases? A large single-center experience of 302 patients. Ann Surg Oncol. 2015;22(3):794–802. doi:10.1245/s10434-014-4164-x. This study of 302 patients treated with Y-90 radioembolization with resin microspheres reported a median survival of 10.5 months. Factors predictoing a poorer prognosis included greater tumor volume, and number of previous lines of chemotherapy. No significant difference in survival was seen in patients with and witout extra-hepatic disease.

    Article  PubMed  Google Scholar 

  50. Kennedy AS, Coldwell D, Nutting C, Murthy R, Wertman DE, Loehr SP, et al. Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys. 2006;65(2):412–25. doi:10.1016/j.ijrobp.2005.12.051.

    Article  CAS  PubMed  Google Scholar 

  51. Kennedy AS, Ball D, Cohen SJ, Cohn M, Coldwell DM, Drooz A, et al. Multicenter evaluation of the safety and efficacy of radioembolization in patients with unresectable colorectal liver metastases selected as candidates for (90)Y resin microspheres. J Gastrointest Oncol. 2015;6(2):134–42. doi:10.3978/j.issn.2078-6891.2014.109. This multi-institutional study of 606 patients is the largest reported series to date for Y-90 radioembolization with resin microspheres. It reported a median overall survival from the first Y-90 treatment of 9.6 months. It found that predictors of better survival were performance status, tumor burder, number of chemotherapeutics, liver function and no extra-hepatic metastases.

    PubMed  PubMed Central  Google Scholar 

  52. RJ Lewandowski, K Memon, MF Mulcahy, R Hickey, K Marshall, M Williams 2014 Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: survival by era and chemotherapy. Eur J Nucl Med Mol Imaging 2014; 41(10) 1861-9 doi:10.1007/s00259-014-2799-2. This study of 214 patients treated with Y-90 radioembolization with glass microspheres reported a median survival of 10.6 months. Survival was longer in patients who received ≤2 chemotherapeutics or no biologic agent. Additional predictors of better survival were performance status, tumor burden ≤25%, and no extra-hepatic metastases

  53. Hickey R, Lewandowski RJ, Prudhomme T, Ehrenwald E, Baigorri B, Critchfield J, et al. Y90 radioembolization of colorectal hepatic metastases using glass microspheres: safety and survival outcomes from a 531-patient multicenter study. J Nucl Med. 2015. doi:10.2967/jnumed.115.166082. This multi-institutional study is the largest reported series to date for Y-90 radioembolization with glass microspheres. It reported a median overall survival from the first Y-90 treatment of 10.6 months. It found that predictors of better survival were performance status, tumor burden ≤25%, having received ≤2 chemotherapeutics, and no extra-hepatic metastases.

    Google Scholar 

  54. Cianni R, Urigo C, Notarianni E, Saltarelli A, Salvatori R, Pasqualini V, et al. Selective internal radiation therapy with SIR-spheres for the treatment of unresectable colorectal hepatic metastases. Cardiovasc Intervent Radiol. 2009;32(6):1179–86. doi:10.1007/s00270-009-9658-8.

    Article  PubMed  Google Scholar 

  55. Jakobs TF, Hoffmann R-T, Dehm K, Trumm C, Stemmler H-J, Tatsch K, et al. Hepatic yttrium-90 radioembolization of chemotherapy-refractory colorectal cancer liver metastases. J Vasc Interv Radiol. 2008;19(8):1187–95. doi:10.1016/j.jvir.2008.05.013.

    Article  PubMed  Google Scholar 

  56. Golfieri R, Mosconi C, Giampalma E, Cappelli A, Galaverni MC, Pettinato C, et al. Selective transarterial radioembolisation of unresectable liver-dominant colorectal cancer refractory to chemotherapy. Radiol Med. 2015;120(8):767–76. doi:10.1007/s11547-015-0504-6.

    Article  PubMed  Google Scholar 

  57. Cosimelli M, Golfieri R, Cagol PP, Carpanese L, Sciuto R, Maini CL, 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(3):324–31. doi:10.1038/sj.bjc.6605770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bester L, Meteling B, Pocock N, Pavlakis N, Chua TC, Saxena A, 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(1):96–105. doi:10.1016/j.jvir.2011.09.028.

    Article  PubMed  Google Scholar 

  59. Lewandowski RJ, Thurston KG, Goin JE, Wong C-YO, Gates VL, Buskirk MV, et al. 90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135–150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging. J Vasc Interv Radiol. 2005;16(12):1641–51. doi:10.1097/01.RVI.0000179815.44868.66.

    Article  PubMed  Google Scholar 

  60. Evans KA, Richardson MG, Pavlakis N, Morris DL, Liauw W, Bester L. Survival outcomes of a salvage patient population after radioembolization of hepatic metastases with yttrium-90 microspheres. J Vasc Interv Radiol. 2010;21(10):1521–6. doi:10.1016/j.jvir.2010.06.018.

    Article  PubMed  Google Scholar 

  61. Hendlisz A, Eynde MV, Peeters M, Maleux G, Lambert B, Vannoote J, 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. doi:10.1200/jco.2010.28.5643.

    Article  CAS  PubMed  Google Scholar 

  62. 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(3):706–7. doi:10.1245/s10434-014-4165-9.

    Article  PubMed  Google Scholar 

  63. Mulcahy MF, Lewandowski RJ, Ibrahim SM, Sato KT, Ryu RK, Atassi B, et al. Radioembolization of colorectal hepatic metastases using yttrium-90 microspheres. Cancer. 2009;115(9):1849–58. doi:10.1002/cncr.24224.

    Article  PubMed  Google Scholar 

  64. Saxena A, Bester L, Shan L, Perera M, Gibbs P, Meteling B, 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(4):537–47. doi:10.1007/s00432-013-1564-4. This is a systemic review of 20 studies including 979 patients treated with Y-90 radioembolization and found an overall survival of 12 months from first Y-90 treatment. Factors predicting poorer survival included the presence of extra-hepatic disease, ≥ 3 lines of chemotherapy, and extensive liver disease (≥25%).

    Article  CAS  PubMed  Google Scholar 

  65. Network NCC. Clinical practice guidelines in oncology (NCCN guidelines): colon cancer (Version 2, 2016). 2016. http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed 1 Jan 2016 2016.

  66. Van Cutsem E, Cervantes A, Nordlinger B, Arnold D. Metastatic colorectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014. doi:10.1093/annonc/mdu260.

    Google Scholar 

  67. Gray B, Van Hazel G, Hope M, Burton M, Moroz P, Anderson J, 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  CAS  PubMed  Google Scholar 

  68. Van Hazel G, Blackwell A, Anderson J, Price D, Moroz P, Bower G, 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(2):78–85. doi:10.1002/jso.20141.

    Article  PubMed  Google Scholar 

  69. Sharma RA, Van Hazel GA, Morgan B, Berry DP, Blanshard K, Price D, 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. doi:10.1200/jco.2006.08.7916.

    Article  CAS  PubMed  Google Scholar 

  70. van Hazel GA, Pavlakis N, Goldstein D, Olver IN, Tapner MJ, Price 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(25):4089–95. doi:10.1200/jco.2008.20.8116.

    Article  PubMed  Google Scholar 

  71. Hickey R, Mulcahy MF, Lewandowski RJ, Gates VL, Vouche M, Habib A, et al. Chemoradiation of hepatic malignancies: prospective, phase 1 study of full-dose capecitabine with escalating doses of yttrium-90 radioembolization. Int J Radiat Oncol Biol Phys. 2014;88(5):1025–31. doi:10.1016/j.ijrobp.2013.12.040.

    Article  PubMed  Google Scholar 

  72. 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. J Vasc Interv Radiol. 2011;22(6):780–6. doi:10.1016/j.jvir.2011.02.023.

    Article  PubMed  Google Scholar 

  73. Gibbs P, Volker H, Sharma NK, Findlay MP, Ricke J, Gebski V. SIRFLOX: randomized phase III trial comparing first-line mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 + selective internal radiation therapy (SIRT) ± bev in patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol. 2015;33:[Suppl; abstr 3502].

  74. Lim L, Gibbs P, Yip D, Shapiro JD, Dowling R, Smith D, et al. A prospective evaluation of treatment with selective internal radiation therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy. BMC Cancer. 2005;5:132. doi:10.1186/1471-2407-5-132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Chua T, Bester L, Saxena A, Morris D. Radioembolization and systemic chemotherapy improves response and survival for unresectable colorectal liver metastases. J Cancer Res Clin Oncol. 2011;137(5):865–73. doi:10.1007/s00432-010-0948-y.

    Article  CAS  PubMed  Google Scholar 

  76. Kennedy AS, McNeillie P, Dezarn WA, Nutting C, Sangro B, Wertman D, et al. Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors. Int J Radiat Oncol Biol Phys. 2009;74(5):1494–500. doi:10.1016/j.ijrobp.2008.10.005.

    Article  CAS  PubMed  Google Scholar 

  77. Carretero C, Munoz-Navas M, Betes M, Angos R, Subtil JC, Fernandez-Urien I, et al. Gastroduodenal injury after radioembolization of hepatic tumors. Am J Gastroenterol. 2007;102(6):1216–20. doi:10.1111/j.1572-0241.2007.01172.x.

    Article  PubMed  Google Scholar 

  78. Sharma RA, Wasan HS, Love SB, Dutton S, Stokes JC, Smith JL. FOXFIRE: a phase III clinical trial of chemo-radio-embolisation as first-line treatment of liver metastases in patients with colorectal cancer. Clin Oncol. 2008;20(3):261–3. doi:10.1016/j.clon.2007.12.008.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert J. Lewandowski MD.

Ethics declarations

Conflict of Interest

Bippan Singh Sangha declares that he has no conflict of interest.

Halla Nimeiri declares that she has no conflict of interest.

Ryan Hickey declares that he has no conflict of interest.

Riad Salem has received compensation from BTG for service as a consultant.

Robert J. Lewandowski has received compensation from BTG for service as a consultant.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Lower Gastrointestinal Cancers

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sangha, B.S., Nimeiri, H., Hickey, R. et al. Radioembolization as a Treatment Strategy for Metastatic Colorectal Cancer to the Liver: What Can We Learn from the SIRFLOX Trial?. Curr. Treat. Options in Oncol. 17, 26 (2016). https://doi.org/10.1007/s11864-016-0402-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-016-0402-8

Keywords

Navigation