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 G.
AU - Brown, Paul D.
AU - Sahgal, Arjun
AU - Chiang, Veronica L.
AU - Chao, Samuel T.
AU - Sheehan, Jason P.
AU - Trifiletti, Daniel M.
N1 - Funding Information:
Conflict of interest: P.D.B. has received honoraria from UpToDate and is a member of Novella Clinical DSMB. A.S. is a speaker for Medtronic, serves on the Elekta AB Medical Advisory Board, is a speaker for Varian Medical Systems, and received the Accuray Incorporated Research Grant from Elekta AB. S.T.C. has received honoraria from Varian. D.M.T. has received clinical research funding from Novocure.
Publisher Copyright:
© 2018
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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U2 - 10.1016/j.ijrobp.2018.10.038
DO - 10.1016/j.ijrobp.2018.10.038
M3 - Article
C2 - 30395902
AN - SCOPUS:85060478182
SN - 0360-3016
VL - 103
SP - 618
EP - 630
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 3
ER -