European Radiology

, Volume 28, Issue 7, pp 2727–2734 | Cite as

Ablation of colorectal liver metastasis: Interaction of ablation margins and RAS mutation profiling on local tumour progression-free survival

  • Marco Calandri
  • Suguru Yamashita
  • Carlo Gazzera
  • Paolo Fonio
  • Andrea Veltri
  • Sara Bustreo
  • Rahul A. Sheth
  • Steven M. Yevich
  • Jean-Nicolas Vauthey
  • Bruno C. OdisioEmail author



To investigate effects of ablation margins on local tumour progression-free survival (LTPFS) according to RAS status in patients with colorectal liver metastases (CLM).


This two-institution retrospective study from 2005–2016 included 136 patients (91 male, median age 60 years) with 218 ablated CLM. LTPFS was performed using the Kaplan–Meier method and evaluated with the log-rank test. Uni/multivariate analyses were performed using Cox-regression models.


Three-year LTPFS rates for CLM with minimal ablation margin ≤10 mm were significantly worse than those with >10 mm in both mutant-RAS (29% vs. 48%, p=0.038) and wild-type RAS (70% vs. 94%, p=0.039) subgroups. Three-year LTPFS rates of mutant-RAS were significantly worse than wild-type RAS in both CLM subgroups with minimal ablation margin ≤10 mm (29% vs. 70%, p<0.001) and >10 mm (48% vs. 94%, p=0.006). Predictors of worse LTPFS were ablation margins ≤10 mm (HR: 2.17, 95% CI 1.2–4.1, p=0.007), CLM size ≥2 cm (1.80, 1.1–2.8, p=0.017) and mutant-RAS (2.85, 1.7–4.6, p<0.001).


Minimal ablation margin and RAS status interact as independent predictors of LTPFS following CLM ablation. While minimal ablation margins >10 mm should be always the procedural goal, this becomes especially critical for mutant-RAS CLM.

Key Points

RAS and ablation margins are predictors of local tumour progression-free survival.

Ablation margin >10 mm, always desirable, is crucial for mutant RAS metastases.

Interventional radiologists should be aware of RAS status to optimize LTPFS.


Colorectal neoplasms Metastasis DNA mutational analysis Interventional radiology Ablation techniques 



Colorectal liver metastases


Local tumour progression


Local tumour progression-free survival


Rat sarcoma viral oncogene



This study has received funding by the National Institutes of Health/National Cancer Institute under award number P30CA016672

Compliance with ethical standards


The scientific guarantor of this publication is Bruno Odisio.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects have been partially previously reported in one paper: Odisio BC, Yamashita S, Huang SY, et al (2017) Br J Surg 104:760–768


• retrospective

• observational

• multicentre study

Supplementary material

330_2017_5273_MOESM1_ESM.docx (28 kb)
ESM 1 (81 kb)
330_2017_5273_MOESM2_ESM.docx (25 kb)
ESM 1 (69 kb)


  1. 1.
    Shady W, Petre EN, Gonen M et al (2016) Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes--A 10-year Experience at a Single Center. Radiology 278:601–611.CrossRefPubMedGoogle Scholar
  2. 2.
    de Baere T, Tselikas L, Yevich S et al (2017) The role of image-guided therapy in the management of colorectal cancer metastatic disease. Eur J Cancer 75:231–242.CrossRefPubMedGoogle Scholar
  3. 3.
    Solbiati L, Ahmed M, Cova L et al (2012) Small liver colorectal metastases treated with percutaneous radiofrequency ablation: local response rate and long-term survival with up to 10-year follow-up. Radiology 265:958–968. CrossRefPubMedGoogle Scholar
  4. 4.
    Sofocleous CT, Petre EN, Gonen M et al (2011) CT-guided Radiofrequency Ablation as a Salvage Treatment of Colorectal Cancer Hepatic Metastases Developing after Hepatectomy. J Vasc Interv Radiol 22:755–761. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Van Cutsem E, Cervantes A, Adam R et al (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol Off J Eur Soc Med Oncol 27:1386–1422. CrossRefGoogle Scholar
  6. 6.
    Ruers T, Van Coevorden F, Punt CJA et al (2017) Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial. JNCI J Natl Cancer Inst.
  7. 7.
    Gillams AR, Lees WR (2009) Five-year survival in 309 patients with colorectal liver metastases treated with radiofrequency ablation. Eur Radiol 19:1206–1213. CrossRefPubMedGoogle Scholar
  8. 8.
    Wang X, Sofocleous CT, Erinjeri JP et al (2013) Margin size is an independent predictor of local tumor progression after ablation of colon cancer liver metastases. Cardiovasc Intervent Radiol 36:166–175. CrossRefPubMedGoogle Scholar
  9. 9.
    Veltri A, Sacchetto P, Tosetti I et al (2008) Radiofrequency Ablation of Colorectal Liver Metastases: Small Size Favorably Predicts Technique Effectiveness and Survival. Cardiovasc Intervent Radiol 31:948–956.CrossRefPubMedGoogle Scholar
  10. 10.
    Odisio BC, Yamashita S, Huang SY et al (2017) Local tumour progression after percutaneous ablation of colorectal liver metastases according to RAS mutation status. Br J Surg 104:760–768.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Amado RG, Wolf M, Peeters M et al (2008) Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer. J Clin Oncol 26:1626–1634.CrossRefPubMedGoogle Scholar
  12. 12.
    Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer. N Engl J Med 359:1757–1765. CrossRefPubMedGoogle Scholar
  13. 13.
    Pollock CB, Shirasawa S, Sasazuki T et al (2005) Oncogenic K-RAS is required to maintain changes in cytoskeletal organization, adhesion, and motility in colon cancer cells. Cancer Res 65:1244–1250. CrossRefPubMedGoogle Scholar
  14. 14.
    Brudvik KW, Mise Y, Chung MH et al (2016) RAS Mutation Predicts Positive Resection Margins and Narrower Resection Margins in Patients Undergoing Resection of Colorectal Liver Metastases. Ann Surg Oncol 23:2635–2643. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ahmed M, Solbiati L, Brace CL et al (2014) Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update. J Vasc Interv Radiol JVIR 25:1691–1705.e4. CrossRefPubMedGoogle Scholar
  16. 16.
    Knijn N, Mekenkamp LJM, Klomp M et al (2011) KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients. Br J Cancer 104:1020–1026.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Baas JM, Krens LL, Guchelaar H-J et al (2011) Concordance of Predictive Markers for EGFR Inhibitors in Primary Tumors and Metastases in Colorectal Cancer: A Review. The Oncologist 16:1239–1249.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gillams A, Goldberg N, Ahmed M et al (2015) Thermal ablation of colorectal liver metastases: a position paper by an international panel of ablation experts, the interventional oncology sans frontières meeting 2013. Eur Radiol 25:3438–3454.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Pathak S, Jones R, Tang JMF et al (2011) Ablative therapies for colorectal liver metastases: a systematic review: Ablation for colorectal liver metastases. Colorectal Dis 13:e252–e265.CrossRefPubMedGoogle Scholar
  20. 20.
    Hur H, Ko YT, Min BS et al (2009) Comparative study of resection and radiofrequency ablation in the treatment of solitary colorectal liver metastases. Am J Surg 197:728–736.CrossRefPubMedGoogle Scholar
  21. 21.
    Aloia TA (2006) Solitary Colorectal Liver Metastasis: Resection Determines Outcome. Arch Surg 141:460. CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Marco Calandri
    • 1
  • Suguru Yamashita
    • 2
  • Carlo Gazzera
    • 1
  • Paolo Fonio
    • 1
  • Andrea Veltri
    • 3
  • Sara Bustreo
    • 4
  • Rahul A. Sheth
    • 5
  • Steven M. Yevich
    • 5
  • Jean-Nicolas Vauthey
    • 2
  • Bruno C. Odisio
    • 5
    Email author
  1. 1.Radiology Institute, Department of Surgical SciencesUniversity of TurinTorinoItaly
  2. 2.Department of Surgical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Radiology Unit, Oncology Department, San Luigi Gonzaga HospitalUniversity of TurinOrbassanoItaly
  4. 4.Department of Medical Oncology 1Città della Salute e della ScienzaTorinoItaly
  5. 5.Department of Interventional RadiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations