Advertisement

CardioVascular and Interventional Radiology

, Volume 40, Issue 4, pp 560–567 | Cite as

Radiofrequency Ablation Combined with Hepatic Arterial Chemoembolization Using Degradable Starch Microsphere Mixed with Mitomycin C for the Treatment of Liver Metastasis from Colorectal Cancer: A Prospective Multicenter Study

  • Koichiro YamakadoEmail author
  • Yasutaka Inaba
  • Yozo Sato
  • Taku Yasumoto
  • Sadao Hayashi
  • Takashi Yamanaka
  • Koji Nobata
  • Haruyuki Takaki
  • Atsuhiro Nakatsuka
Clinical Investigation

Abstract

Purpose

This phase II prospective study investigates possible benefits of radiofrequency ablation (RFA) combined with hepatic arterial chemoembolization using degradable starch microsphere (DSM) mixed with mitomycin C (MMC) in non-surgical candidates with colorectal liver metastases.

Materials and Methods

This study, approved by the respective institutional review board, included non-surgical candidates with 3 or fewer liver tumors of 3 cm or smaller, or a single lesion 5 cm or smaller. Percutaneous RFA was performed immediately after chemoembolization using DSM-MMC. Primary and secondary endpoints were the local tumor control rate, safety, and 2-year recurrence-free and overall survival rates.

Results

This study examined 25 patients (22 males, 3 females) with 38 tumors of mean maximum diameter of 2.2 ± 0.9 cm (standard deviation) (range 1.0–4.2 cm). Their mean age was 70.2 ± 8.2 years (range 55–82 years). Local tumor progression developed in 3 tumors (7.9%, 3/38) of 3 patients (12%, 3/25) during the mean follow-up of 34.9 ± 9.2 months (range 18.3–50.1 months). The 2-year local tumor control rates were 92.0% [95% confidence interval (CI), 81.4–100%] on a patient basis and 94.6% (95% CI, 87.3–100%) on a tumor basis. The respective 2-year overall and recurrence-free survival rates were 88.0% (95% CI, 75.3–98.5%) and 63.3% (95% CI, 44.2–82.5%), with median survival time of 48.4 months. Fever was the only adverse event requiring treatments in 2 patients (8%).

Conclusions

This combination therapy is safe, exhibiting strong anticancer effects on colorectal liver metastasis, which might contribute to patient survival.

Keywords

Colorectal cancer Liver metastasis Radiofrequency ablation Chemoembolization Local recurrence 

Notes

Acknowledgements

Funding was provided by Japan Society for the Promotion of Science (Grant No. 25461876).

Compliance with Ethical Standards

Conflict of interest

None.

Ethical Approval

This study has been approved by the institutional review board of each institution where patients were enrolled in this clinical trial.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    House MG, Ito H, Gönen M, Fong Y, Allen PJ, DeMatteo RP, Brennan MF, Blumgart LH, Jarnagin WR, D’Angelica MI. Survival after hepatic resection for metastatic colorectal cancer: trends in outcomes for 1600 patients during two decades at a single institution. J Am Coll Surg. 2010;210:744–5.CrossRefPubMedGoogle Scholar
  2. 2.
    Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, Grothey A, Vauthey JN, Nagorney DM, McWilliams RR. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27:3677–83.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, Nitti D, Torri V, Elias D, O’Callaghan C, Langer B, Martignoni G, Bouché O, Lazorthes F, Van Cutsem E, Bedenne L, Moore MJ, Rougier P. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008;26:4906–11.CrossRefPubMedGoogle Scholar
  4. 4.
    Tanis E, Nordlinger B, Mauer M, Sorbye H, van Coevorden F, Gruenberger T, Schlag PM, Punt CJ, Ledermann J, Ruers TJ. Local recurrence rates after radiofrequency ablation or resection of colorectal liver metastases. Analysis of the European Organisation for Research and Treatment of Cancer #40004 and #40983. Eur J Cancer. 2014;50:912–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Lee H, Heo JS, Cho YB, Yun SH, Kim HC, Lee WY, Choi SH, Choi DW. Hepatectomy versus radiofrequency ablation for colorectal liver metastasis: a propensity score analysis. World J Gastroenterol. 2015;21:3300–7.PubMedPubMedCentralGoogle Scholar
  6. 6.
    White RR, Avital I, Sofocleous CT, Brown KT, Brody LA, Covey A, Getrajdman GI, Jarnagin WR, Dematteo RP, Fong Y, Blumgart LH, D’Angelica M. Rates and patterns of recurrence for percutaneous radiofrequency ablation and open wedge resection for solitary colorectal liver metastasis. J Gastrointest Surg. 2007;11:256–63.CrossRefPubMedGoogle Scholar
  7. 7.
    Aloia TA, Vauthey JN, Loyer EM, et al. Solitary colorectal liver metastasis: resection determines outcome. Arch Surg. 2006;141(5):460–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as fibas-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26(12):2013–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Tol J, Koopman M, Cats A, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009;360(6):563–72.CrossRefPubMedGoogle Scholar
  10. 10.
    Van CE, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360(14):1408–17.CrossRefGoogle Scholar
  11. 11.
    Sanoff HK, Sargent DJ, Campbell ME, et al. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol. 2008;26(35):5721–7.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mulier S, Ni Y, Jamart J, Ruers T, Marchal G, Michel L. Local recurrence after hepatic radiofrequency coagulation: multivariate meta-analysis and review of contributing factors. Ann Surg. 2005;242(2):158–71.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Veltri A, Sacchetto P, Tosetti I, Pagano E, Fava C, Gandini G. Radiofrequency ablation of colorectal liver metastases: small size favorably predicts technique effectiveness and survival. Cardiovasc Intervent Radiol. 2008;31(5):948–56.CrossRefPubMedGoogle Scholar
  14. 14.
    Solbiati L, Ahmed M, Cova L, Ierace T, Brioschi M, Goldberg SN. 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(3):958–68.CrossRefPubMedGoogle Scholar
  15. 15.
    Hamada A, Yamakado K, Nakatsuka A, Uraki J, Kashima M, Takaki H, Yamanaka T, Inoue Y, Kusunoki M, Takeda K. Radiofrequency ablation for colorectal liver metastases: prognostic factors in non-surgical candidates. Jpn J Radiol. 2012;30:567–74.CrossRefPubMedGoogle Scholar
  16. 16.
    Wang X, Erinjeri JP, Jia X, Gonen M, Brown KT, Sofocleous CT, Getrajdman GI, Brody LA, Thornton RH, Maybody M, Covey AM, Siegelbaum RH, Alago W, Solomon SB. Margin size is an independent predictor of local tumor progression after ablation of colon cancer liver metastases. Cardiovasc Intervent Radiol. 2013;36:166–75.CrossRefPubMedGoogle Scholar
  17. 17.
    Abitabile P, Hartl U, Lange J, Maurer CA. Radiofrequency ablation permits an effective treatment for colorectal liver metastasis. Eur J Surg Oncol. 2007;33(1):67–71.CrossRefPubMedGoogle Scholar
  18. 18.
    Nielsen K, van Tilborg AA, Meijerink MR, Macintosh MO, Zonderhuis BM, de Lange ES, Comans EF, Meijer S, van den Tol MP. Incidence and treatment of local site recurrences following RFA of colorectal liver metastases. World J Surg. 2013;37:1340–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Wong SL, Mangu PB, Choti MA, Crocenzi TS, Dodd GD 3rd, Dorfman GS, Eng C, Fong Y, Giusti AF, Lu D, Marsland TA, Michelson R, Poston GJ, Schrag D, Seidenfeld J, Benson AB 3rd. American Society of Clinical Oncology 2009 clinical evidence review on radiofrequency ablation of hepatic metastases from colorectal cancer. J Clin Oncol. 2010;28:493–508.CrossRefPubMedGoogle Scholar
  20. 20.
    Kennedy TJ, Cassera MA, Khajanchee YS, Diwan TS, Hammill CW, Hansen PD. Laparoscopic radiofrequency ablation for the management of colorectal liver metastases: 10-year experience. J Surg Oncol. 2013;107(4):324–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Lee H, Heo JS, Cho YB, et al. Hepatectomy versus radiofrequency ablation for colorectal liver metastasis: a propensity score analysis. World J Gastroenterol. 2015;21(11):3300–7.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Ahmed M, Solbiati L, Brace CL, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria: a 10-year update. J Vasc Interv Radiol. 2014;25(11):1691–705.CrossRefPubMedGoogle Scholar
  23. 23.
    Yamakado K, Nakatsuka A, Takaki H, et al. Early stage hepatocellular carcinoma: radiofrequency ablation combined with chemoembolization versus hepatectomy. Radiology. 2008;247(1):260–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Taguchi T. Phase I study of infusion of PJ-203 (degradable starch microspheres) into hepatic artery. PJ-2S03 Clinical Study Group. Gan To Kagaku Ryoho. 1993;20(12):1817–25.PubMedGoogle Scholar
  25. 25.
    Taguchi T, Kondo M, Tanikawa K, Nakamura H, Okawa T, Ogawa N. Comparative clinical study in metastatic liver cancer between intra-arterial infusion of mitomycin C alone and intra-arterial infusion of mitomycin C combined with PJ-203 (degradable starch microspheres). Gan To Kagaku Ryoho. 1993;20(13):2027–35.PubMedGoogle Scholar
  26. 26.
    Taguchi T, Tanikawa K, Sano K, et al. Multi-center cooperative phase II study of combined infusion of PJ-203 (degradable starch microspheres) into hepatic artery in metastatic liver cancer. Gan To Kagaku Ryoho. 1993;20(13):2015–25.PubMedGoogle Scholar
  27. 27.
    Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649–55.CrossRefPubMedGoogle Scholar
  28. 28.
    Mainenti PP, Mancini M, Mainolfi C, et al. Detection of colo-rectal liver metastases: prospective comparison of contrast enhanced US, multidetector CT, PET/CT, and 1.5 Tesla MR with extracellular and reticuloendothelial cell specific contrast agents. Abdom Imaging. 2010;35:511–21.CrossRefPubMedGoogle Scholar
  29. 29.
    Common Terminology Criteria for Adverse Events v3.0 (CTCAE) The National Cancer Institute. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf.
  30. 30.
    Omary RA, Bettmann MA, Cardella JF, et al. Quality improvement guidelines for the reporting and archiving of interventional radiology procedures. J Vasc Interv Radiol. 2002;13(9 Pt 1):879–81.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2016

Authors and Affiliations

  • Koichiro Yamakado
    • 1
    • 2
    Email author
  • Yasutaka Inaba
    • 3
  • Yozo Sato
    • 3
  • Taku Yasumoto
    • 4
  • Sadao Hayashi
    • 5
  • Takashi Yamanaka
    • 2
  • Koji Nobata
    • 6
  • Haruyuki Takaki
    • 1
    • 2
  • Atsuhiro Nakatsuka
    • 2
  1. 1.Department of RadiologyHyogo College of MedicineNishinomiyaJapan
  2. 2.Department of RadiologyMie UniversityTsuJapan
  3. 3.Department of RadiologyAichi Cancer CenterChikusa-ku, NagoyaJapan
  4. 4.Department of RadiologyToyonaka Municipal HospitalToyonakaJapan
  5. 5.Department of RadiologyKagoshima UniversityKagoshimaJapan
  6. 6.Department of RadiologyKouseiren Takaoka HospitalTakaokaJapan

Personalised recommendations