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Molecular Diagnostics

Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation

British Journal of Cancer volume 128, pages 130–136 (2023)Cite this article

Subjects

Abstract

Background

Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood.

Methods

In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM.

Results

A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFβ pathway were associated with increased risk of development of new intrahepatic tumours (hazard ratio [HR], 2.75, 95% confidence interval [95% CI] 1.39–5.45, P = 0.004); and alterations in the Wnt pathway were associated with increased probability of receiving salvage LRT for any intrahepatic progression (HR, 5.8, 95% CI 1.94–19.5, P = 0.003).

Conclusions

Our findings indicate that genomic alterations in cancer-related signalling pathways can predict different progression patterns and the likelihood of receiving salvage LRT following percutaneous thermal ablation of CLM.

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Fig. 1: Directed acyclic graph of postulated causal relationships with OS after thermal ablation of CLM.
Fig. 2: Patient selection for progression pattern analysis and sub-analyses of genomic mutations.
Fig. 3: Frequency of alterations in seven cancer-related signalling pathways. Alterations in the signalling pathways and mutations in the predominant member gene in each of these pathways among the 101 patients included in the mutation analysis.
Fig. 4: Overall survival by intrahepatic progression and salvage LRT.
Fig. 5: Cumulative incidence of development of new tumours following initial ablation of CLM stratified by TGFβ alteration.

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Data availability

The datasets generated during and/or analysed during the current study are not publicly available because of human subjects' privacy concerns and institutional policies. Anonymized data are available from the corresponding author upon reasonable request.

Code availability

The complete R code for the statistical analysis is available in the supplementary materials.

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Acknowledgements

We thank Stephanie Deming, Research Medical Library, MD Anderson Cancer Center, for editing the manuscript.

Funding

IP is funded by a PostDoc Mobility Fellowship from the Swiss National Science Foundation under project number P2BEP3_195444. Research reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health under award numbers R01CA235564 and P30CA016672 and by the Image Guided Cancer Therapy Research Program at The University of Texas MD Anderson Cancer Center.

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Authors and Affiliations

  1. Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Iwan Paolucci, Yuan-Mao Lin & Bruno C. Odisio

  2. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Yoshikuni Kawaguchi, Harufumi Maki, Timothy E. Newhook & Jean-Nicolas Vauthey

  3. Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    A. Kyle Jones & Kristy K. Brock

  4. Radiology Institute, Department of Surgical Sciences, University of Turin, Città della Salute e della Scienza, Via Genova 3, 10126, Torino, Italy

    Marco Calandri

  5. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Scott Kopetz

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  1. Iwan Paolucci
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Contributions

IP, BCO and JNV: study design; IP, YML and BCO: writing and editing; IP, YML, BCO, YK and HM: data collection and data review; IP: statistical analysis; IP, YML, YK, HM, AKJ, MC, SK, TN, KKB and BCO: critical review and editing; BCO: supervision of the project. All authors have read and agreed to this version of the manuscript.

Corresponding author

Correspondence to Bruno C. Odisio.

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The authors declare no competing interests.

Ethics approval and consent to participate

This retrospective study was approved by The University of Texas MD Anderson Cancer Center Institutional Review Board (Nr: 2021-0340) and conducted in accordance with the Declaration of Helsinki. The requirement for written informed consent was waived.

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Paolucci, I., Lin, YM., Kawaguchi, Y. et al. Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation. Br J Cancer 128, 130–136 (2023). https://doi.org/10.1038/s41416-022-02030-y

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