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Pre-clinical data interpretation requires clinical context
Nature
volume 656, pages E3–E4 (2026) Cite this article
Matters Arising to this article was published on 12 August 2026
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.
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Piffkó, A. et al. Radiation-induced amphiregulin drives tumour metastasis. Nature 643, 810–819 (2025).
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).