- Matters Arising
- Published:
Nature volume 656, pages E5–E6 (2026) Cite this article
replying to: R. Muirhead et al. Nature https://doi.org/10.1038/s41586-026-10774-3 (2026).
We appreciate the opportunity to respond to the accompanying Comment by Muirhead et al.1 regarding our recent study2. We understand why a study examining systemic effects of radiotherapy might raise concerns among clinicians and patients who have come to trust stereotactic ablative body radiotherapy (SABR) as an effective therapy. Our goal is not to undermine confidence in SABR, which clearly benefits patients, but to identify opportunities for refinement that could improve outcomes, particularly in curative settings.
This is a preview of subscription content, access via your institution
Access options
Access through your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
27,99 € / 30 days
cancel any time
Subscription info for Chinese customers
We have a dedicated website for our Chinese customers. Please go to naturechina.com to subscribe to this journal.
Buy this article
- Purchase on SpringerLink
- Instant access to the full article PDF.
39,95 €
Prices may be subject to local taxes which are calculated during checkout
Subjects
References
Muirhead, R. et al. Pre-clinical data interpretation requires clinical context. Nature https://doi.org/10.1038/s41586-026-10774-3 (2026).
Piffkó, A. et al. Radiation-induced amphiregulin drives tumour metastasis. Nature 643, 810–819 (2025).
Article ADS PubMed PubMed Central Google Scholar
Palma, D. A. et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet 393, 2051–2058 (2019).
Article PubMed Google Scholar
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
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, 8506–8506 (2024).
Article Google Scholar
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, 1007–1007 (2022).
Article Google Scholar
Palma, D. A. et al. Measuring the integration of stereotactic ablative radiotherapy plus surgery for early-stage non-small cell lung cancer: a phase 2 clinical trial. JAMA Oncol. 5, 681–688 (2019).
Article PubMed PubMed Central Google Scholar
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
O’Reilly, M. S., Holmgren, L., Chen, C. & Folkman, J. Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat. Med. 2, 689–692 (1996).
Article PubMed Google Scholar
Krall, J. A. et al. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci. Transl. Med. 10, eaan3464 (2018).
Article PubMed PubMed Central Google Scholar
Zhang, J. et al. Inflammation awakens dormant cancer cells by modulating the epithelial-mesenchymal phenotypic state. Proc. Natl Acad. Sci. USA 122, e2515009122 (2025).
Article CAS PubMed PubMed Central Google Scholar
He, D. et al. Chemotherapy awakens dormant cancer cells in lung by inducing neutrophil extracellular traps. Cancer Cell 43, 1622–1636.e7 (2025).
Article CAS PubMed Google Scholar
Chia, S. B. et al. Respiratory viral infections awaken metastatic breast cancer cells in lungs. Nature 645, 496–506 (2025).
Article ADS CAS PubMed PubMed Central Google Scholar
Hellmann, S. & Weichselbaum, R. R. Oligometastases. J. Clin. Oncol. 13, 8–10 (1995).
Article Google Scholar
Salama, J. K. et al. Stereotactic body radiotherapy for multisite extracranial oligometastases: final report of a dose escalation trial in patients with 1 to 5 sites of metastatic disease. Cancer 118, 2962–2970 (2012).
Article PubMed Google Scholar
Download references
Ethics declarations
Competing interests
R.R.W. has stock and other ownership interests with Boost Therapeutics, Immvira, Reflexion Pharmaceuticals, Coordination Pharmaceuticals, Magi Therapeutics, Fuse Biotherapeutics and Oncosenescence. He has served in a consulting or advisory role for Aettis, Astrazeneca, Coordination Pharmaceuticals, Genus, Merck Serono, Nano proteagen, NKMax America and Shuttle Pharmaceuticals. He has received research grant funding from Varian and Regeneron, as well as NIH funding (R01CA262508 and U54 CA274291). He has received compensation including travel, accommodations or expense reimbursement from AstraZeneca, Boehringer Ingelhei and Merck Serono. S.P.P. has received research grant funding from the LUNGevity Foundation, Cancer Research Foundation, Falk Medical Research Trust and American Lung Association. R.R.W. and S.P.P. are co-founders of PersonaDx and have multiple patents pending. S.P.P. and R.R.W. have filed a patent on amphiregulin in the radiation response.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Pitroda, S.P., Weichselbaum, R.R. Reply to: Pre-clinical data interpretation requires clinical context. Nature 656, E5–E6 (2026). https://doi.org/10.1038/s41586-026-10773-4
Download citation
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41586-026-10773-4