### Abstract

Purpose: Multifraction (MF) stereotactic radiosurgery (SRS) purportedly reduces radionecrosis risk over single-fraction (SF) SRS in the treatment of large brain metastases. The purpose of the current work is to compare local control (LC) and radionecrosis rates of SF-SRS and MF-SRS in the definitive (SF-SRS_{D} and MF-SRS_{D}) and postoperative (SF-SRS_{P} and MF-SRS_{P}) settings. Methods and Materials: Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were used to select articles in which patients had “large” brain metastases (Group A: 4-14 cm^{3}, or about 2-3 cm in diameter; Group B: >14 cm^{3}, or about >3 cm in diameter); 1-year LC and/or rates of radionecrosis were reported; radiosurgery was administered definitively or postoperatively. Random effects meta-analyses using fractionation scheme and size as covariates were conducted. Meta-regression and Wald-type tests were used to determine the effect of increasing tumor size and fractionation on the summary estimate, where the null hypothesis was rejected for P <.05. Results: Twenty-four studies were included, published between 2008 and 2017, with 1887 brain metastases. LC random effects estimate at 1 year was 77.6% for Group A/SF-SRS_{D} and 92.9% for Group A/MF-SRS_{D} (P =.18). LC random effects estimate at 1 year was 77.1% for Group B/SF-SRS_{D} and 79.2% for Group B/MF-SRS_{D} (P =.76). LC random effects estimate at 1 year was 62.4% for Group B/SF-SRS_{P} and 85.7% for Group B/MF-SRS_{P} (P =.13). Radionecrosis incidence random effects estimate was 23.1% for Group A/SF-SRS_{D} and 7.3% for Group A/MF-SRS_{D} (P =.003). Radionecrosis incidence random effects estimate was 11.7% for Group B/SF-SRS_{D} and 6.5% for Group B/MF-SRS_{D} (P =.29). Radionecrosis incidence random effects estimate was 7.3% for Group B/SF-SRS_{P} and 7.5% for Group B/MF-SRS_{P} (P =.85). Metaregression assessing 1-year LC and radionecrosis as a continuous function of increasing tumor volume was not statistically significant. Conclusions: Treatment for large brain metastases with MF-SRS regimens may offer a relative reduction of radionecrosis while maintaining or improving relative rates of 1-year LC compared with SF-SRS. These findings are hypothesis-generating and require validation by ongoing and planned prospective clinical trials.

Original language | English (US) |
---|---|

Pages (from-to) | 618-630 |

Number of pages | 13 |

Journal | International Journal of Radiation Oncology Biology Physics |

Volume | 103 |

Issue number | 3 |

DOIs | |

State | Published - Mar 1 2019 |

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### All Science Journal Classification (ASJC) codes

- Radiation
- Oncology
- Radiology Nuclear Medicine and imaging
- Cancer Research

### Cite this

*International Journal of Radiation Oncology Biology Physics*,

*103*(3), 618-630. https://doi.org/10.1016/j.ijrobp.2018.10.038

}

*International Journal of Radiation Oncology Biology Physics*, vol. 103, no. 3, pp. 618-630. https://doi.org/10.1016/j.ijrobp.2018.10.038

**Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases : An International Meta-analysis of 24 Trials.** / Lehrer, Eric J.; Peterson, Jennifer L.; Zaorsky, Nicholas; Brown, Paul D.; Sahgal, Arjun; Chiang, Veronica L.; Chao, Samuel T.; Sheehan, Jason P.; Trifiletti, Daniel M.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases

T2 - An International Meta-analysis of 24 Trials

AU - Lehrer, Eric J.

AU - Peterson, Jennifer L.

AU - Zaorsky, Nicholas

AU - Brown, Paul D.

AU - Sahgal, Arjun

AU - Chiang, Veronica L.

AU - Chao, Samuel T.

AU - Sheehan, Jason P.

AU - Trifiletti, Daniel M.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Purpose: Multifraction (MF) stereotactic radiosurgery (SRS) purportedly reduces radionecrosis risk over single-fraction (SF) SRS in the treatment of large brain metastases. The purpose of the current work is to compare local control (LC) and radionecrosis rates of SF-SRS and MF-SRS in the definitive (SF-SRSD and MF-SRSD) and postoperative (SF-SRSP and MF-SRSP) settings. Methods and Materials: Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were used to select articles in which patients had “large” brain metastases (Group A: 4-14 cm3, or about 2-3 cm in diameter; Group B: >14 cm3, or about >3 cm in diameter); 1-year LC and/or rates of radionecrosis were reported; radiosurgery was administered definitively or postoperatively. Random effects meta-analyses using fractionation scheme and size as covariates were conducted. Meta-regression and Wald-type tests were used to determine the effect of increasing tumor size and fractionation on the summary estimate, where the null hypothesis was rejected for P <.05. Results: Twenty-four studies were included, published between 2008 and 2017, with 1887 brain metastases. LC random effects estimate at 1 year was 77.6% for Group A/SF-SRSD and 92.9% for Group A/MF-SRSD (P =.18). LC random effects estimate at 1 year was 77.1% for Group B/SF-SRSD and 79.2% for Group B/MF-SRSD (P =.76). LC random effects estimate at 1 year was 62.4% for Group B/SF-SRSP and 85.7% for Group B/MF-SRSP (P =.13). Radionecrosis incidence random effects estimate was 23.1% for Group A/SF-SRSD and 7.3% for Group A/MF-SRSD (P =.003). Radionecrosis incidence random effects estimate was 11.7% for Group B/SF-SRSD and 6.5% for Group B/MF-SRSD (P =.29). Radionecrosis incidence random effects estimate was 7.3% for Group B/SF-SRSP and 7.5% for Group B/MF-SRSP (P =.85). Metaregression assessing 1-year LC and radionecrosis as a continuous function of increasing tumor volume was not statistically significant. Conclusions: Treatment for large brain metastases with MF-SRS regimens may offer a relative reduction of radionecrosis while maintaining or improving relative rates of 1-year LC compared with SF-SRS. These findings are hypothesis-generating and require validation by ongoing and planned prospective clinical trials.

AB - Purpose: Multifraction (MF) stereotactic radiosurgery (SRS) purportedly reduces radionecrosis risk over single-fraction (SF) SRS in the treatment of large brain metastases. The purpose of the current work is to compare local control (LC) and radionecrosis rates of SF-SRS and MF-SRS in the definitive (SF-SRSD and MF-SRSD) and postoperative (SF-SRSP and MF-SRSP) settings. Methods and Materials: Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were used to select articles in which patients had “large” brain metastases (Group A: 4-14 cm3, or about 2-3 cm in diameter; Group B: >14 cm3, or about >3 cm in diameter); 1-year LC and/or rates of radionecrosis were reported; radiosurgery was administered definitively or postoperatively. Random effects meta-analyses using fractionation scheme and size as covariates were conducted. Meta-regression and Wald-type tests were used to determine the effect of increasing tumor size and fractionation on the summary estimate, where the null hypothesis was rejected for P <.05. Results: Twenty-four studies were included, published between 2008 and 2017, with 1887 brain metastases. LC random effects estimate at 1 year was 77.6% for Group A/SF-SRSD and 92.9% for Group A/MF-SRSD (P =.18). LC random effects estimate at 1 year was 77.1% for Group B/SF-SRSD and 79.2% for Group B/MF-SRSD (P =.76). LC random effects estimate at 1 year was 62.4% for Group B/SF-SRSP and 85.7% for Group B/MF-SRSP (P =.13). Radionecrosis incidence random effects estimate was 23.1% for Group A/SF-SRSD and 7.3% for Group A/MF-SRSD (P =.003). Radionecrosis incidence random effects estimate was 11.7% for Group B/SF-SRSD and 6.5% for Group B/MF-SRSD (P =.29). Radionecrosis incidence random effects estimate was 7.3% for Group B/SF-SRSP and 7.5% for Group B/MF-SRSP (P =.85). Metaregression assessing 1-year LC and radionecrosis as a continuous function of increasing tumor volume was not statistically significant. Conclusions: Treatment for large brain metastases with MF-SRS regimens may offer a relative reduction of radionecrosis while maintaining or improving relative rates of 1-year LC compared with SF-SRS. These findings are hypothesis-generating and require validation by ongoing and planned prospective clinical trials.

UR - http://www.scopus.com/inward/record.url?scp=85060478182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060478182&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2018.10.038

DO - 10.1016/j.ijrobp.2018.10.038

M3 - Article

VL - 103

SP - 618

EP - 630

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 3

ER -