Comparison of 2 stereotactic radiotherapy regimens for brain metastases: Is higher always better?
Abstract
Introduction.Stereotactic radiosurgery (SRS) has become a preferred treatment for brain metastases (BMs) due to its precision, minimizing neurocognitive side effects compared to whole-brain radiotherapy. However, the optimal dose-fractionation regimen for balancing local tumor control and minimizing radiation necrosis (RN) remains debated. This study compares 2 commonly used fractionated SRS regimens: 23.1Gy in 3 fractions and 27Gy in 3 fractions. Materials and Methods. This retrospective study included 1348 BMs treated with fractionated SRS between 2014 and 2023. Treatment planning used inhomogeneous dose delivery on a TrueBeam STX linac, delivering either 23.1Gy/3 fractions or 27Gy/3 fractions to the periphery (33Gy to the isocenter). Outcomes included local relapse-free survival (LRFS), RN-free survival (RNFS) and symptomatic RN-free survival (SRNFS), analyzed using Kaplan-Meier estimates. Impact of the main clinical factors (BMs volume, histology of the primary, concomitant systemic therapies and history of radiotherapy) were analyzed using univariate and multivariate Cox regression models. Results. Median follow-up was 12.0 months for LRFS and 11.0 months for RNFS. The 27Gy regimen showed a non-significant improvement in LRFS (HR: 0.66, 95% CI9: 0.43-1.01) but significantly increased the risk of both RN (HR: 2.29, 95% CI: 1.60-3.26) and symptomatic RN (HR: 3.74, 95% CI: 1.93-7.26). On multivariate analysis, choice of the SRS protocol was an independent predictor of RN. Conclusions. The 27Gy regimen offers modest improvements in local control but significantly increases the risk of both RN and symptomatic RN. These results emphasize the need for personalized SRS regimens and further exploration of dose optimization strategies to improve therapeutic outcomes.
BMs represent a significant challenge in cancer management, occurring in approximately 10%-40% of patients with systemic malignancies. 1,2 The incidence is increasing due to improved systemic therapies and enhanced and greater availability of magnetic resonance imaging (MRI). 3 Single fraction and fractionated stereotactic radiosurgery (SRS) have emerged as preferred treatment modalities for BMs, offering a non-invasive, highly conformal approach to target and deliver ablative radiation doses to the tumor while sparing surrounding healthy brain tissue. 4-6 Despite the widespread adoption of SRS, the optimal dose and fractionation for balancing tumor control and minimizing complications like RN remain a subject of ongoing debate. Higher doses may improve local control (LC) but increase the risk of RN, an inflammatory reaction characterized by tissue damage, vascular alterations and perilesional edema. 7-9 Radionecrosis remains a poorly understood diagnostic challenge. 10,11 Reported rates vary between 5 and 30% depending on the cohorts. 12 LC after SRS is influenced by tumor size and
Key Points• In a cohort of 1348 brain metastases, 27Gy and 23.1Gy rates were 55.1% and 44.9%.
• The 27Gy protocol showed a non-significant LRFS increase (HR: 0.66, P > .05).
• Radiation necrosis (RN) and symptomatic RN were significantly higher with 27Gy.
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BibTeX
@article{bourbonne2026comparison,
title = {{Comparison of 2 stereotactic radiotherapy regimens for brain metastases: Is higher always better?}},
author = {Vincent Bourbonne and Moncef Morjani and Brieg Dissaux and Marie Cabaret and Solène Querellou and Romuald Seizeur and Renaud Descourt and Olivier Pradier and Gurvan Dissaux and François Lucia},
journal = {Neuro-Oncology Advances},
year = {2026},
month = sep,
doi = {10.1093/noajnl/vdag126},
url = {https://univ-brest.hal.science/hal-05733826v1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Comparison of 2 stereotactic radiotherapy regimens for brain metastases: Is higher always better?
AU - Vincent Bourbonne
AU - Moncef Morjani
AU - Brieg Dissaux
AU - Marie Cabaret
AU - Solène Querellou
AU - Romuald Seizeur
AU - Renaud Descourt
AU - Olivier Pradier
AU - Gurvan Dissaux
AU - François Lucia
PY - 2026
DA - 2026/09/01
JO - Neuro-Oncology Advances
DO - 10.1093/noajnl/vdag126
UR - https://univ-brest.hal.science/hal-05733826v1
AB - Introduction.Stereotactic radiosurgery (SRS) has become a preferred treatment for brain metastases (BMs) due to its precision, minimizing neurocognitive side effects compared to whole-brain radiotherapy. However, the optimal dose-fractionation regimen for balancing local tumor control and minimizing radiation necrosis (RN) remains debated. This study compares 2 commonly used fractionated SRS regimens: 23.1Gy in 3 fractions and 27Gy in 3 fractions. Materials and Methods. This retrospective study included 1348 BMs treated with fractionated SRS between 2014 and 2023. Treatment planning used inhomogeneous dose delivery on a TrueBeam STX linac, delivering either 23.1Gy/3 fractions or 27Gy/3 fractions to the periphery (33Gy to the isocenter). Outcomes included local relapse-free survival (LRFS), RN-free survival (RNFS) and symptomatic RN-free survival (SRNFS), analyzed using Kaplan-Meier estimates. Impact of the main clinical factors (BMs volume, histology of the primary, concomitant systemic therapies and history of radiotherapy) were analyzed using univariate and multivariate Cox regression models. Results. Median follow-up was 12.0 months for LRFS and 11.0 months for RNFS. The 27Gy regimen showed a non-significant improvement in LRFS (HR: 0.66, 95% CI9: 0.43-1.01) but significantly increased the risk of both RN (HR: 2.29, 95% CI: 1.60-3.26) and symptomatic RN (HR: 3.74, 95% CI: 1.93-7.26). On multivariate analysis, choice of the SRS protocol was an independent predictor of RN. Conclusions. The 27Gy regimen offers modest improvements in local control but significantly increases the risk of both RN and symptomatic RN. These results emphasize the need for personalized SRS regimens and further exploration of dose optimization strategies to improve therapeutic outcomes. BMs represent a significant challenge in cancer management, occurring in approximately 10%-40% of patients with systemic malignancies. 1,2 The incidence is increasing due to improved systemic therapies and enhanced and greater availability of magnetic resonance imaging (MRI). 3 Single fraction and fractionated stereotactic radiosurgery (SRS) have emerged as preferred treatment modalities for BMs, offering a non-invasive, highly conformal approach to target and deliver ablative radiation doses to the tumor while sparing surrounding healthy brain tissue. 4-6 Despite the widespread adoption of SRS, the optimal dose and fractionation for balancing tumor control and minimizing complications like RN remain a subject of ongoing debate. Higher doses may improve local control (LC) but increase the risk of RN, an inflammatory reaction characterized by tissue damage, vascular alterations and perilesional edema. 7-9 Radionecrosis remains a poorly understood diagnostic challenge. 10,11 Reported rates vary between 5 and 30% depending on the cohorts. 12 LC after SRS is influenced by tumor size and Key Points• In a cohort of 1348 brain metastases, 27Gy and 23.1Gy rates were 55.1% and 44.9%. • The 27Gy protocol showed a non-significant LRFS increase (HR: 0.66, P > .05). • Radiation necrosis (RN) and symptomatic RN were significantly higher with 27Gy.
SN - 2632-2498
ER -