# Alliance N0574: radiosurgery alone versus radiosurgery plus whole-brain radiotherapy for one to three brain metastases

Source: https://onco.cc/key-papers/paper-alliance-n0574-brown-jama-2016/  
OnCo record `paper-alliance-n0574-brown-jama-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding whole-brain radiotherapy to focused radiosurgery for a few brain metastases caused more memory and thinking problems without lengthening life, so radiosurgery alone became standard for limited brain metastases.

## Summary

Phase 3 trial of 213 patients with one to three brain metastases randomised to stereotactic radiosurgery alone or radiosurgery plus whole-brain radiotherapy, with cognitive decline at three months as the primary endpoint.

Cognitive deterioration was more frequent with whole-brain radiotherapy (91.7 versus 63.5 percent) despite better intracranial control, and median overall survival did not differ (10.4 versus 7.4 months, not significant).

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: JAMA
- Year: 2016
- DOI: 10.1001/jama.2016.9839
- Authors: Brown PD, Jaeckle K, Ballman KV, et al.
- Findings: Cognitive deterioration at three months 91.7 percent vs 63.5 percent.; Intracranial control at one year better with whole-brain radiotherapy (85 vs 51 percent) without a survival difference.
- What it means: Patients with a limited number of brain metastases are treated with radiosurgery alone and surveillance, accepting more new brain lesions in return for preserved cognition.
- Caveats: Cognitive testing only assessed to three months in the primary endpoint.; Modern hippocampal-avoidance whole-brain radiotherapy was not used.

## Sources

- JAMA 2016: https://doi.org/10.1001/jama.2016.9839
- PubMed: https://pubmed.ncbi.nlm.nih.gov/27458945/

## Connected records

- cancers: [Brain metastases (secondary brain tumours)](https://onco.cc/cancers/secondary-brain-tumours/)
- trials: [Alliance N0574 (NCCTG N0574)](https://onco.cc/trials/alliance-n0574/)
- journals: [JAMA](https://onco.cc/journals/jama/)

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