Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases

An International Meta-analysis of 24 Trials

Eric J. Lehrer, Jennifer L. Peterson, Nicholas Zaorsky, Paul D. Brown, Arjun Sahgal, Veronica L. Chiang, Samuel T. Chao, Jason P. Sheehan, Daniel M. Trifiletti

Research output: Contribution to journalArticle

3 Citations (Scopus)

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-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.

Original languageEnglish (US)
Pages (from-to)618-630
Number of pages13
JournalInternational Journal of Radiation Oncology Biology Physics
Volume103
Issue number3
DOIs
StatePublished - Mar 1 2019

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Radiosurgery
metastasis
brain
Meta-Analysis
Neoplasm Metastasis
Brain
estimates
Incidence
Population Control
incidence
Tumor Burden
fractionation
Observational Studies
Epidemiology
tumors
Outcome Assessment (Health Care)
Clinical Trials
Guidelines
epidemiology
null hypothesis

All Science Journal Classification (ASJC) codes

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

Cite this

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. / Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases : An International Meta-analysis of 24 Trials. In: International Journal of Radiation Oncology Biology Physics. 2019 ; Vol. 103, No. 3. pp. 618-630.
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title = "Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases: An International Meta-analysis of 24 Trials",
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-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.",
author = "Lehrer, {Eric J.} and Peterson, {Jennifer L.} and Nicholas Zaorsky and Brown, {Paul D.} and Arjun Sahgal and Chiang, {Veronica L.} and Chao, {Samuel T.} and Sheehan, {Jason P.} and Trifiletti, {Daniel M.}",
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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.

In: International Journal of Radiation Oncology Biology Physics, Vol. 103, No. 3, 01.03.2019, p. 618-630.

Research output: Contribution to journalArticle

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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.

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