# NRG CC001: hippocampal-avoidance whole-brain radiotherapy plus memantine for brain metastases

Source: https://onco.cc/key-papers/paper-nrg-cc001-brown-jco-2020/  
OnCo record `paper-nrg-cc001-brown-jco-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

When whole-brain radiotherapy is needed, shaping the beams to spare the hippocampus and adding memantine reduced the memory and thinking decline that the treatment causes, with no loss of tumour control.

## Summary

Phase 3 trial of 518 patients with brain metastases randomised to whole-brain radiotherapy with memantine, with or without hippocampal avoidance using intensity-modulated techniques.

Cognitive failure was less frequent with hippocampal avoidance (hazard ratio 0.74), driven by less decline in executive function and memory, with no difference in overall survival, intracranial progression or toxicity.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: Journal of Clinical Oncology
- Year: 2020
- DOI: 10.1200/JCO.19.02767
- Authors: Brown PD, Gondi V, Pugh S, et al.
- Findings: Risk of cognitive failure reduced by 26 percent with hippocampal avoidance.; No difference in survival or intracranial progression.
- What it means: Where whole-brain radiotherapy is still chosen, for many metastases or leptomeningeal disease, hippocampal avoidance with memantine is the recommended technique.
- Caveats: Excluded patients with metastases within 5 mm of the hippocampus.; Requires intensity-modulated planning capability.

## Sources

- J Clin Oncol 2020: https://doi.org/10.1200/JCO.19.02767
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32058845/

## Connected records

- cancers: [Brain metastases (secondary brain tumours)](https://onco.cc/cancers/secondary-brain-tumours/)
- trials: [NRG CC001](https://onco.cc/trials/nrg-cc001/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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