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Radiation therapy-induced metastasis: radiobiology and clinical implications

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Abstract

Radiation therapy is an effective means of achieving local control in a wide range of primary tumours, with the reduction in the size of the tumour(s) thought to mediate the observed reductions in metastatic spread in clinical trials. However, there is evidence to suggest that the complex changes induced by radiation in the tumour environment can also present metastatic risks that may counteract the long-term efficacy of the treatment. More than 25 years ago, several largely theoretical mechanisms by which radiation exposure might increase metastatic risk were postulated. These include the direct release of tumour cells into the circulation, systemic effects of tumour and normal tissue irradiation and radiation-induced changes in tumour cell phenotype. Here, we review the data that has since emerged to either support or refute these putative mechanisms focusing on how the unique radiobiology underlying modern radiotherapy modalities might alter these risks.

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Abbreviations

CTC:

Circulating tumour cell

NSCLC:

Non-small cell lung cancer

3D-CRT:

3D-conformal radiotherapy

IMRT:

Intensity-modulated radiotherapy

VMAT:

Volumetric modulated arc therapy

FFF:

Flattening filter-free

MRT:

Microbeam radiotherapy

TGF-β:

Transforming growth factor-β1

MMP:

Matrix metallo-proteinase

EMT:

Epithelial-to-mesenchymal transition

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Acknowledgements

We would like to acknowledge the assistance of Ms Diane Russo in preparation of the manuscript. This work was supported by a grant from the Australian National Health and Medical Research Council (NHMRC #1104139).

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Authors and Affiliations

  1. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, 3000, Australia

    Benjamin J. Blyth, Aidan J. Cole, Michael P. MacManus & Olga A. Martin

  2. Cancer Research Division, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, 3000, Australia

    Benjamin J. Blyth & Olga A. Martin

  3. Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Lisburn Road, Belfast, BT9 7BL, UK

    Aidan J. Cole

  4. The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia

    Michael P. MacManus & Olga A. Martin

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Blyth, B.J., Cole, A.J., MacManus, M.P. et al. Radiation therapy-induced metastasis: radiobiology and clinical implications. Clin Exp Metastasis 35, 223–236 (2018). https://doi.org/10.1007/s10585-017-9867-5

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