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Liver metastases from colorectal cancer: radioembolization with systemic therapy

Abstract

The majority of patients with advanced colorectal cancer die from hepatic metastases caused by disease progression; therefore, several novel technologies are in clinical development to potentially improve local control of liver disease. Radioembolization is a technique for administering radiotherapy internally to unresectable primary or secondary hepatic malignancies in a single procedure. This technique involves the injection of resin or glass microspheres that contain 90Y into the arterial supply of the liver. Clinical trials of radioembolization used with concomitant radiosensitizing chemotherapy have shown promising results in patients with metastatic colorectal cancer. Several reports suggest that radioembolization is associated with significant downsizing of liver metastases to permit subsequent surgical resection. In this article, the rationale for combining radioembolization with the cytotoxic and molecularly targeted agents licensed for the systemic treatment of colorectal cancer is outlined. Clinical data from trials of radioembolization with concomitant systemic treatment are reviewed, with an emphasis on the appropriateness of primary end points in large-scale trials and the practical aspects of surgical resection in patients whose tumors are successfully downsized by this chemoradiation approach.

Key Points

  • Radioembolization is a means of administering internal radiotherapy to unresectable hepatic malignancies by the injection of radioactive resin or glass microspheres into the arterial supply of the liver

  • Unlike local ablation techniques such as surgical resection or external-beam radiotherapy, radioembolization is not limited by the number and distribution of liver metastases

  • The safe administration and appropriate use of radioembolization depends on the experience of a multidisciplinary team, including an interventional vascular radiologist, radiation oncologist and nuclear medicine physician

  • Potential radiosensitizing effects of systemic agents used to treat metastatic colorectal cancer include cell-cycle arrest, apoptosis and direct and indirect effects on DNA bases, repair proteins and tumor vasculature

  • More than 10 prospective clinical trials of radioembolization are underway; these trials will determine whether it should be included in first-line treatment or subsequent lines of treatment

  • Hepatic artery embolization, fibrotic changes in the future liver remnant and portal hypertension raise questions as to the safety and radicality of resection following radioembolization

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Figure 1: Relationship of median PFS and baseline tumor volume in four prospective studies of radioembolization in combination with chemotherapy.
Figure 2: Integration of radioembolization clinical trials into the treatment algorithm for patients with metastatic colorectal cancer.

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Acknowledgements

This project is supported by the National Institute for Health Research Biomedical Research Centre Oxford, the Bobby Moore Fund of Cancer Research UK and the UK Medical Research Council. We thank Drs K. Vallis, D. Turner, M. Tapner and R. Adams for useful discussions and detailed comments on the manuscript.

Désirée Lie, University of California, Irvine, CA is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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Correspondence to Ricky A. Sharma.

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R. Sharma declares he is on the speakers' bureau and receives grant/research support from Sirtex Medical. The other authors, the Journal Editor Lisa Hutchinson and the CME questions author D. Lie declare no competing interests.

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Nicolay, N., Berry, D. & Sharma, R. Liver metastases from colorectal cancer: radioembolization with systemic therapy. Nat Rev Clin Oncol 6, 687–697 (2009). https://doi.org/10.1038/nrclinonc.2009.165

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