# Comparison of 3 vs 5 Fraction Single Isocenter Radiosurgery for Brain Metastases

**Authors:** Luke A. Moradi, Richard A. Popple, Roman L. Travis, Samuel R. Marcrom, Kristen O. Riley, James M. Markert, Christopher D. Willey, Michael C. Dobelbower, D. Hunter Boggs, Rodney J. Sullivan, Joel Pogue, John B. Fiveash

PMC · DOI: 10.1016/j.adro.2025.101927 · Advances in Radiation Oncology · 2025-10-23

## TL;DR

This study compares two radiation treatment regimens for brain metastases and finds that a 3-fraction regimen provides better tumor control with similar toxicity.

## Contribution

The study directly compares 3-fraction and 5-fraction radiosurgery regimens for brain metastases, identifying superior local control with the 3-fraction approach.

## Key findings

- The 3-fraction regimen showed better 1-year local control (97% vs. 91%) compared to the 5-fraction regimen.
- Tumors smaller than 2 cm had significantly better control with the 3-fraction regimen.
- Toxicity levels were comparable between the two regimens.

## Abstract

Single isocenter stereotactic radiosurgery (SRS) efficiently delivers radiation to patients with multiple brain metastases. Although several fractionated SRS (fSRS) regimens show acceptable local control and toxicity, few studies directly compare them. This retrospective study evaluates 2 common regimens—6 Gy × 5 fractions and 9 Gy × 3 fractions—for their effects on local control and toxicity.

A retrospective review was conducted of 1215 brain tumors from 251 patients receiving either 9 Gy × 3 fx or 6 Gy × 5 fx fSRS. All tumors were treated with single isocenter volumetric modulated arc therapy. Recurrent tumors and postoperative cavities were excluded from the analysis. Local tumor failure was defined as 25% increase in maximum tumor diameter (minimum 3 mm) or more than scant tumor cells at time of salvage surgery. Toxicity included CTCAE V5.0 central nervous system (CNS) grade 3 or greater events. Local tumor control and freedom from toxicity were calculated using Kaplan–Meier method and Cox regression models.

Overall local control was 93% at 1 year and 88% at 2 years. The 3-fraction regimen had superior 1-year local control compared with the 5-fraction regimen (97% vs. 91%, P = .001). Tumors <2 cm had significantly better control with 3 fractions (99% vs. 95%, P = .004), whereas tumors 2–4 cm showed no significant difference. One-year freedom from grade 3+ toxicity was similar between regimens (99% for 3-fx vs. 96% for 5-fx, P = .097).

In this study, 9 Gy × 3 fx for brain metastases had improved tumor control and comparable toxicity to 6 Gy × 5, particularly among tumors <2 cm. 9 Gy × 3 fx may be the preferred regimen when treating multiple tumors with one prescription using single isocenter radiosurgery as it improves efficiency and local control while having similar toxicity.

## Full-text entities

- **Genes:** EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}
- **Diseases:** cerebral hemorrhage (MESH:D002543), colorectal (MESH:D015179), death (MESH:D003643), brain (MESH:D001927), Metastases (MESH:D009362), Toxicity (MESH:D064420), COVID (MESH:D000086382), lymphoma (MESH:D008223), fSRS (MESH:D054144), Brain metastases (MESH:D001932), necrosis (MESH:D009336), melanoma (MESH:D008545), central nervous system (CNS) toxicity (MESH:D002493), Tumor (MESH:D009369), brain failure (MESH:D051437), hemorrhage (MESH:D006470), cerebral edema (MESH:D001929), seizures (MESH:D012640)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12936521/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936521/full.md

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Source: https://tomesphere.com/paper/PMC12936521