科技科学

Pre-clinical data interpretation requires clinical context

Nature作者：R. Muirhead2026年8月12日正文已收录本站

arising from: A. Piffkó et al. Nature https://doi.org/10.1038/s41586-025-08994-0 (2025).

We read with interest the article by Piffkó et al., which investigated the biological effects of stereotactic ablative body radiotherapy (SABR) on distant metastasis progression1. Using mouse models and samples from patients with different advanced solid tumours, the authors identified amphiregulin (AREG) as a gene that is increased following SABR and correlated lower levels of AREG with longer progression-free survivals (PFSs); concluding that “radiation-induced growth factors drive distant metastasis growth in SBRT-treated patients and in mouse models, which leads to shortened survival”. We highlight that prospective randomized trials show improved PFS after SABR, contrary to the proposed hypothesis. We have concerns that the use of such powerful language to describe this hypothesis may empower SABR denialists, and undo decades of work by the radiation oncology community to have SABR accepted as an integral part of metastatic disease management.

This is a preview of subscription content, access via your institution

References

  1. Piffkó, A. et al. Radiation-induced amphiregulin drives tumour metastasis. Nature 643, 810–819 (2025).

  2. Chalkidou, A. et al. Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study. Lancet Oncol. 22, 98–106 (2021).

    Article  PubMed  Google Scholar 

  3. Gomez, D. R. et al. Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer: long-term results of a multi-institutional phase II, randomized study. J. Clin. Oncol. 37, 1588–1565 (2019).

    Article  Google Scholar 

  4. Iyengar, P. et al. Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: a phase 2 randomized clinical trial. JAMA Oncol. 4, e173501 (2018).

    Article  Google Scholar 

  5. Wang, X.-S. et al. Randomized trial of first-line tyrosine kinase inhibitor with or without radiotherapy for synchronous oligometastatic EGFR-mutated non-small cell lung cancer. J. Natl Cancer Inst. 115, 742–748 (2023).

  6. Peng, P. et al. EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV non-small cell lung cancer (NSCLC): a prospective, multicenter, randomized, controlled phase II study. Radiother. Oncol. 184, 109681 (2023).

    Article  CAS  PubMed  Google Scholar 

  7. Iyengar, P. et al. NRG-LU002: randomized phase II/III trial of maintenance systemic therapy versus local consolidative therapy (LCT) plus maintenance systemic therapy for limited metastatic non-small cell lung cancer (NSCLC). J. Clin. Oncol. 42 (Suppl.), 8506 (2024).

  8. Palma, D. A. et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: Long-term results of the SABR-COMET phase II randomized trial. J. Clin. Oncol. 38, 2830–2838 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chmura, S. J. et al. NRG-BR002: a phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer (NCT02364557). J. Clin. Oncol. 40 (Suppl.), 1007 (2022).

  10. Tsai, C. J. et al. Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study. Lancet 403, 171–182 (2024).

    Article  PubMed  Google Scholar 

  11. Schellenberg, D. et al. Stereotactic ablative radiation for oligoprogressive cancers: results of the randomized phase 2 STOP trial. Int. J. Radiat. Oncol. Biol. Phys. 121, 28–38 (2025).

    Article  PubMed  Google Scholar 

  12. Spaas, M. et al. Checkpoint inhibitors in combination with stereotactic body radiotherapy in patients with advanced solid tumors: the CHEERS phase 2 randomized clinical trial. JAMA Oncol. 9, 1205–1213 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hellman, S. & Weichselbaum, R. R. Oligometastases. J. Clin. Oncol. 13, 8–10 (1995).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

A.T. is supported by a Cancer Research UK Radiation Research Centre of Excellence at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust (grant ref: A28724 and RRCOER-Jun24/100006) and a Cancer Research UK Programme Grant (ref: C33589/A28284). A.T. acknowledges NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. F.M. acknowledges NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care.

Author information

Authors and Affiliations

  1. Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

    R. Muirhead

  2. Department of Oncology, University of Oxford, Oxford, UK

    R. Muirhead

  3. Trinity St. James Cancer Institute, Trinity College Dublin, Dublin, Ireland

    G. G. Hanna

  4. St. Luke’s Radiation Oncology Network, Dublin, Ireland

    G. G. Hanna

  5. The Royal Marsden NHS Foundation Trust, London, UK

    F. McDonald & A. Tree

  6. The Institute of Cancer Research, London, UK

    F. McDonald & A. Tree

  7. Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada

    D. Palma

  8. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    S. Siva

  9. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia

    S. Siva

Authors

  1. R. Muirhead
  2. G. G. Hanna
  3. F. McDonald
  4. D. Palma
  5. S. Siva
  6. A. Tree

Contributions

R.M. conceived of the paper and wrote the initial draft of the paper. G.G.H., F.M., D.P., S.S. and A.T. edited the paper.

Corresponding author

Correspondence to R. Muirhead.

Ethics declarations

Competing interests

R.M. reports consulting fees from GlaxoSmithKline and Incyte. G.G.H. reports speaker honorarium from AstraZeneca. F.M. reports consulting fees and speaker fees from AstraZeneca. D.P. reports a Clinician-Scientist Grant from the Ontario Institute for Cancer Research, royalties from Uptodate.com and a consultant role with equity from Need, all unrelated to the current work. S.S. reports salary support from the Cancer Council Victoria Colebatch fellowship, unrelated to the current work. A.T. reports research funding from Elekta, Varian, Accuray and Artera, honoraria/travel assistance from Elekta, Accuray, Janssen, Bayer and Astellas.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Muirhead, R., Hanna, G.G., McDonald, F. et al. Pre-clinical data interpretation requires clinical context. Nature 656, E3–E4 (2026). https://doi.org/10.1038/s41586-026-10774-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41586-026-10774-3