The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지

Treatment of Liver Metastases

전이성 간암의 치료

  • Choi, Hye-Jin (Division of Oncology, Department of Internal Medicine, Yonsei University College of Medicine)
  • 최혜진 (연세대학교 의과대학 내과학교실 종양내과)
  • Published : 2011.09.01
⟨ Previous Next ⟩

Abstract

Metastatic cancer is frequently found in the liver and represents life-limiting component of dieasease. There have been significant advances in past decades to improve survival for patients with liver metastases. Surgical resection may be curative and should be considered standard therapy for liver-confined metastatic colorectal cancer. Resection showed 30-50% overall 5-year survival. Advances in systemic chemotherapy and local treatment expanded the possibility of resection. For other metastatic tumors to the liver, the role of resection remains to be defined. Several new modalities including intra-arterial chemotherapy, chemoembolization, ablation, and radiation may provide effective palliation. This review discusses the current status and progress in studies on metastatic liver cancer regarding diagnostic modalities and various treatment options.

Keywords

References

  1. Devita V, Lawrene T, Rosenberg S, et al. Devita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology 9th Edition: Chater 149.
  2. Mainenti PP, Mancini M, Mainolfi C, et al. Detection of colorectal liver metastases: prospective comparison of contrast enhanced US, multidetector CT, PET/CT, and 1.5 Tesla MR with extracellular and reticulo-endothelial cell specific contrast agents. Abdom Imaging 2010;35:511-521. https://doi.org/10.1007/s00261-009-9555-2
  3. Hussain SM, Semelka RC. Hepatic imaging: comparison of modalities. Radiol Clin North Am 2005;43:929-947. https://doi.org/10.1016/j.rcl.2005.05.006
  4. Quaia E, D'Onofrio M, Palumbo A, Rossi S, Bruni S, Cova M. Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence. Eur Radiol 2006;16:1599-1609. https://doi.org/10.1007/s00330-006-0192-7
  5. Donati OF, Hany TF, Reiner CS, et al. Value of retrospective fusion of PET and MR images in detection of hepatic metastases: comparison with 18F-FDG PET/CT and Gd-EOB-DTPA-enhanced MRI. J Nucl Med 2010;51:692-699. https://doi.org/10.2967/jnumed.109.068510
  6. Bengtsson G, Carlsson G, Hafstrom L, Jonsson PE. Natural history of patients with untreated liver metastases from colorectal cancer. Am J Surg 1981;141:586-589. https://doi.org/10.1016/0002-9610(81)90057-X
  7. de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938-2947.
  8. Coppa GF, Eng K, Ranson JH, Gouge TH, Localio SA. Hepatic resection for metastatic colon and rectal cancer: an evaluation of preoperative and postoperative factors. Ann Surg 1985;202:203-208. https://doi.org/10.1097/00000658-198508000-00010
  9. Schlag P, Hohenberger P, Herfarth C. Resection of liver metastases in colorectal-cancer: competitive analysis of treatment results in synchronous versus metachronous metastases. Eur J Surg Oncol 1990;16:360-365.
  10. Wei AC, Greig PD, Grant D, Taylor B, Langer B, Gallinger S. Survival after hepatic resection for colorectal metastases: a 10-year experience. Ann Surg Oncol 2006;13:668-676. https://doi.org/10.1245/ASO.2006.05.039
  11. Fernandez FG, Drebin JA, Linehan DC, Dehdashti F, Siegel BA, Strasberg SM. 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;240:438-447; discussion 447-450. https://doi.org/10.1097/01.sla.0000138076.72547.b1
  12. Tomlinson JS, Jarnagin WR, DeMatteo RP, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 2007;25:4575-4580. https://doi.org/10.1200/JCO.2007.11.0833
  13. Are C, Gonen M, Zazzali K, et al. The impact of margins on outcome after hepatic resection for colorectal metastasis. Ann Surg 2007;246:295-300. https://doi.org/10.1097/SLA.0b013e31811ea962
  14. Kornprat P, Jarnagin WR, Gonen M, et al. Outcome after hepatectomy for multiple (four or more) colorectal metastases in the era of effective chemotherapy. Ann Surg Oncol 2007;14:1151-1160. https://doi.org/10.1245/s10434-006-9068-y
  15. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230:309-318; discussion 318-321. https://doi.org/10.1097/00000658-199909000-00004
  16. Nordlinger B, Vaillant JC, Guiguet M, et al. Survival benefit of repeat liver resections for recurrent colorectal metastases: 143 cases: Association Francaise de Chirurgie. J Clin Oncol 1994;12:1491-1496.
  17. Frilling A, Sotiropoulos GC, Li J, Kornasiewicz O, Plockinger U. Multimodal management of neuroendocrine liver metastases. HPB (Oxford) 2010;12:361-379. https://doi.org/10.1111/j.1477-2574.2010.00175.x
  18. Harrison LE, Brennan MF, Newman E, et al. Hepatic resection for noncolorectal, nonneuroendocrine metastases: a fifteen-year experience with ninety-six patients. Surgery 1997;121:625-632. https://doi.org/10.1016/S0039-6060(97)90050-7
  19. Weitz J, Blumgart LH, Fong Y, et al. Partial hepatectomy for metastases from noncolorectal, nonneuroendocrine carcinoma. Ann Surg 2005;241:269-276. https://doi.org/10.1097/01.sla.0000150244.72285.ad
  20. Curley SA. Outcomes after surgical treatment of colorectal cancer liver metastases. Semin Oncol 2005;32(6 Suppl 9):S109-S111.
  21. Portier G, Elias D, Bouche O, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol 2006;24:4976-4982. https://doi.org/10.1200/JCO.2006.06.8353
  22. Langer B, Bleiberg H, Labianca R, et al. Fluorouracil (FU) plus l-leucovorin (l-LV) versus observation after potentially curative resection of liver or lung metastases from colorectal cancer (CRC): results of the ENG (EORTC/NCIC CTG/GIVIO) randomized trial. Proc Am Soc Clin Oncol 2002;21:149a. (abstr 592)
  23. Mitry E, Fields AL, Bleiberg H, et al. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 2008;26:4906-4911. https://doi.org/10.1200/JCO.2008.17.3781
  24. Ychou M, Hohenberger W, Thezenas S, et al. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol 2009;20:1964-1970. https://doi.org/10.1093/annonc/mdp236
  25. Ensminger WD, Rosowsky A, Raso V, et al. A clinical-pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2'-deoxyuridine and 5-fluorouracil. Cancer Res 1978;38:3784-3792.
  26. Maindrault-Goebel F, Tournigand C, Andre T, et al. Oxaliplatin reintroduction in patients previously treated with leucovorin, fluorouracil and oxaliplatin for metastatic colorectal cancer. Ann Oncol 2004;15:1210-1214. https://doi.org/10.1093/annonc/mdh305
  27. Kemeny N, Huang Y, Cohen AM, et al. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 1999;341:2039-2048. https://doi.org/10.1056/NEJM199912303412702
  28. Kemeny NE, Gonen M. Hepatic arterial infusion after liver resection. N Engl J Med 2005;352:734-735. https://doi.org/10.1056/NEJM200502173520723
  29. Nordlinger B, Sorbye H, Glimelius B, 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;371:1007-1016. https://doi.org/10.1016/S0140-6736(08)60455-9
  30. Aloia T, Sebagh M, Plasse M, et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol 2006;24:4983-4990. https://doi.org/10.1200/JCO.2006.05.8156
  31. Kooby DA, Fong Y, Suriawinata A, et al. Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg 2003;7:1034-1044. https://doi.org/10.1016/j.gassur.2003.09.012
  32. Power DG, Kemeny NE. Role of adjuvant therapy after resection of colorectal cancer liver metastases. J Clin Oncol 2010;28:2300-2309. https://doi.org/10.1200/JCO.2009.26.9340
  33. Giacchetti S, Perpoint B, Zidani R, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18:136-147.
  34. Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22:229-237.
  35. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009;360:1408-1417. https://doi.org/10.1056/NEJMoa0805019
  36. Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008;26:2013-2019. https://doi.org/10.1200/JCO.2007.14.9930
  37. Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 2007;25:1670-1676. https://doi.org/10.1200/JCO.2006.09.0928
  38. Folprecht G, Gruenberger T, Bechstein WO, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomized phase 2 trial. Lancet Oncol 2010;11:38-47. https://doi.org/10.1016/S1470-2045(09)70330-4
  39. Mocellin S, Pilati P, Lise M, et al. Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era? J Clin Oncol 2007;25:5649-5654. https://doi.org/10.1200/JCO.2007.12.1764
  40. 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;24:1395-1403. https://doi.org/10.1200/JCO.2005.03.8166
  41. Leyvraz S, Spataro V, Bauer J, et al. Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy. J Clin Oncol 1997;15:2589-2595.
  42. Marrache F, Vullierme MP, Roy C, et al. Arterial phase enhancement and body mass index are predictors of response to chemoembolisation for liver metastases of endocrine tumours. Br J Cancer 2007;96:49-55 https://doi.org/10.1038/sj.bjc.6603526
  43. Bloomston M, Al-Saif O, Klemanski D, et al. Hepatic artery chemoembolization in 122 patients with metastatic carcinoid tumor: lessons learned. J Gastrointest Surg 2007;11:264-271 https://doi.org/10.1007/s11605-007-0089-z
  44. Salman HS, Cynamon J, Jagust M, et al. Randomized phase II trial of embolization therapy versus chemoembolization therapy in previously treated patients with colorectal carcinoma metastatic to the liver. Clin Colorectal Cancer 2002;2:173-179. https://doi.org/10.3816/CCC.2002.n.022
  45. Stang A, Fischbach R, Teichmann W, Bokemeyer C, Braumann D. A systematic review on the clinical benefit and role of radiofrequency ablation as treatment of colorectal liver metastases. Eur J Cancer 2009;45:1748-1756. https://doi.org/10.1016/j.ejca.2009.03.012
  46. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 1999;230:1-8. https://doi.org/10.1097/00000658-199907000-00001
  47. Siperstein AE, Berber E, Ballem N, Parikh RT. Survival after radiofrequency ablation of colorectal liver metastases: 10-year experience. Ann Surg 2007;246:559-565; discussion 565-557. https://doi.org/10.1097/SLA.0b013e318155a7b6
  48. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109-122.
  49. Katz AW, Carey-Sampson M, Muhs AG, Milano MT, Schell MC, Okunieff P. Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases. Int J Radiat Oncol Biol Phys 2007;67:793-798. https://doi.org/10.1016/j.ijrobp.2006.10.025
  50. Schefter TE, Kavanagh BD, Timmerman RD, Cardenes HR, Baron A, Gaspar LE. A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases. Int J Radiat Oncol Biol Phys 2005;62:1371-1378. https://doi.org/10.1016/j.ijrobp.2005.01.002
  51. Rusthoven KE, Kavanagh BD, Cardenes H, et al. Multiinstitutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 2009;27:1572-1578. https://doi.org/10.1200/JCO.2008.19.6329
  52. Ho S, Lau WY, Leung TW, et al. Tumour-to-normal uptake ratio of 90Y microspheres in hepatic cancer assessed with 99Tcm macroaggregated albumin. Br J Radiol 1997;70:823-828.
  53. Gray B, Van Hazel G, Hope M, et al. Randomized trial of SIRSpheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol 2001;12:1711-1720. https://doi.org/10.1023/A:1013569329846
  54. Kennedy AS, Coldwell D, Nutting C, et al. Resin 90Ymicrosphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys 2006;65:412-425. https://doi.org/10.1016/j.ijrobp.2005.12.051
  55. Tabernero J, Van Cutsem E, Diaz-Rubio E, et al. Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2007;25:5225-5232. https://doi.org/10.1200/JCO.2007.13.2183
  56. Kopetz S, Hoff PM, Morris JS, et al. Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol 2010;28:453-459. https://doi.org/10.1200/JCO.2009.24.8252