Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: An international meta-analysis of individual patient data

Eric J. Lehrer, Jennifer Peterson, Paul D. Brown, Jason P. Sheehan, Alfredo Quinones-Hinojosa, Nicholas G. Zaorsky, Daniel Trifiletti

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background and purpose: While the combination of stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is becoming more widely used in the treatment of brain metastases (BM), there is a paucity of prospective data to validate both the safety and efficacy, as well as the optimal timing of these two therapies relative to one another. Methods: A PICOS/PRISMA/MOOSE selection protocol was used to identify 17 studies across 15 institutions in 3 countries. Inclusion criteria were patients: diagnosed with BMs; treated with SRS/ICI, either concurrently or non-concurrently; with at least one of the primary or secondary outcomes measures reported. Weighted random effects meta-analyses using the DerSimonian and Laird method was performed. The primary outcome was 1-year overall survival (OS). Secondary outcomes were 1-year local control (LC), 1-year regional brain control (RBC), and radionecrosis incidence. Results: A total of 534 patients with 1570 BM were included. The 1-year OS was 64.6% and 51.6% for concurrent and non-concurrent therapy, respectively (p < 0.001). Local control at 1-year was 89.2% and 67.8% for concurrent and non-concurrent therapy, respectively (p = 0.09). The RBC at 1-year was 38.1% and 12.3% for concurrent and ICI administration prior to SRS, respectively (p = 0.049). The overall incidence of radionecrosis for all studies was 5.3%. Conclusions: Concurrent administration of SRS/ICI may be associated with improved safety and efficacy versus sequential therapy. These findings, however, are hypothesis-generating and require further validation by ongoing and planned prospective trials.

Original languageEnglish (US)
JournalRadiotherapy and Oncology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Radiosurgery
Meta-Analysis
Neoplasm Metastasis
Brain
Therapeutics
Safety
Survival
Incidence
Outcome Assessment (Health Care)

Keywords

  • Immunotherapy
  • Ipilimumab
  • Nivolumab
  • Pembrolizumab
  • Radiation
  • Steroid

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors : An international meta-analysis of individual patient data. / Lehrer, Eric J.; Peterson, Jennifer; Brown, Paul D.; Sheehan, Jason P.; Quinones-Hinojosa, Alfredo; Zaorsky, Nicholas G.; Trifiletti, Daniel.

In: Radiotherapy and Oncology, 01.01.2018.

Research output: Contribution to journalArticle

@article{3a603cb8e38b435ebc2ecd48ac93d151,
title = "Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: An international meta-analysis of individual patient data",
abstract = "Background and purpose: While the combination of stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is becoming more widely used in the treatment of brain metastases (BM), there is a paucity of prospective data to validate both the safety and efficacy, as well as the optimal timing of these two therapies relative to one another. Methods: A PICOS/PRISMA/MOOSE selection protocol was used to identify 17 studies across 15 institutions in 3 countries. Inclusion criteria were patients: diagnosed with BMs; treated with SRS/ICI, either concurrently or non-concurrently; with at least one of the primary or secondary outcomes measures reported. Weighted random effects meta-analyses using the DerSimonian and Laird method was performed. The primary outcome was 1-year overall survival (OS). Secondary outcomes were 1-year local control (LC), 1-year regional brain control (RBC), and radionecrosis incidence. Results: A total of 534 patients with 1570 BM were included. The 1-year OS was 64.6{\%} and 51.6{\%} for concurrent and non-concurrent therapy, respectively (p < 0.001). Local control at 1-year was 89.2{\%} and 67.8{\%} for concurrent and non-concurrent therapy, respectively (p = 0.09). The RBC at 1-year was 38.1{\%} and 12.3{\%} for concurrent and ICI administration prior to SRS, respectively (p = 0.049). The overall incidence of radionecrosis for all studies was 5.3{\%}. Conclusions: Concurrent administration of SRS/ICI may be associated with improved safety and efficacy versus sequential therapy. These findings, however, are hypothesis-generating and require further validation by ongoing and planned prospective trials.",
keywords = "Immunotherapy, Ipilimumab, Nivolumab, Pembrolizumab, Radiation, Steroid",
author = "Lehrer, {Eric J.} and Jennifer Peterson and Brown, {Paul D.} and Sheehan, {Jason P.} and Alfredo Quinones-Hinojosa and Zaorsky, {Nicholas G.} and Daniel Trifiletti",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.radonc.2018.08.025",
language = "English (US)",
journal = "Radiotherapy and Oncology",
issn = "0167-8140",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors

T2 - An international meta-analysis of individual patient data

AU - Lehrer, Eric J.

AU - Peterson, Jennifer

AU - Brown, Paul D.

AU - Sheehan, Jason P.

AU - Quinones-Hinojosa, Alfredo

AU - Zaorsky, Nicholas G.

AU - Trifiletti, Daniel

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background and purpose: While the combination of stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is becoming more widely used in the treatment of brain metastases (BM), there is a paucity of prospective data to validate both the safety and efficacy, as well as the optimal timing of these two therapies relative to one another. Methods: A PICOS/PRISMA/MOOSE selection protocol was used to identify 17 studies across 15 institutions in 3 countries. Inclusion criteria were patients: diagnosed with BMs; treated with SRS/ICI, either concurrently or non-concurrently; with at least one of the primary or secondary outcomes measures reported. Weighted random effects meta-analyses using the DerSimonian and Laird method was performed. The primary outcome was 1-year overall survival (OS). Secondary outcomes were 1-year local control (LC), 1-year regional brain control (RBC), and radionecrosis incidence. Results: A total of 534 patients with 1570 BM were included. The 1-year OS was 64.6% and 51.6% for concurrent and non-concurrent therapy, respectively (p < 0.001). Local control at 1-year was 89.2% and 67.8% for concurrent and non-concurrent therapy, respectively (p = 0.09). The RBC at 1-year was 38.1% and 12.3% for concurrent and ICI administration prior to SRS, respectively (p = 0.049). The overall incidence of radionecrosis for all studies was 5.3%. Conclusions: Concurrent administration of SRS/ICI may be associated with improved safety and efficacy versus sequential therapy. These findings, however, are hypothesis-generating and require further validation by ongoing and planned prospective trials.

AB - Background and purpose: While the combination of stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is becoming more widely used in the treatment of brain metastases (BM), there is a paucity of prospective data to validate both the safety and efficacy, as well as the optimal timing of these two therapies relative to one another. Methods: A PICOS/PRISMA/MOOSE selection protocol was used to identify 17 studies across 15 institutions in 3 countries. Inclusion criteria were patients: diagnosed with BMs; treated with SRS/ICI, either concurrently or non-concurrently; with at least one of the primary or secondary outcomes measures reported. Weighted random effects meta-analyses using the DerSimonian and Laird method was performed. The primary outcome was 1-year overall survival (OS). Secondary outcomes were 1-year local control (LC), 1-year regional brain control (RBC), and radionecrosis incidence. Results: A total of 534 patients with 1570 BM were included. The 1-year OS was 64.6% and 51.6% for concurrent and non-concurrent therapy, respectively (p < 0.001). Local control at 1-year was 89.2% and 67.8% for concurrent and non-concurrent therapy, respectively (p = 0.09). The RBC at 1-year was 38.1% and 12.3% for concurrent and ICI administration prior to SRS, respectively (p = 0.049). The overall incidence of radionecrosis for all studies was 5.3%. Conclusions: Concurrent administration of SRS/ICI may be associated with improved safety and efficacy versus sequential therapy. These findings, however, are hypothesis-generating and require further validation by ongoing and planned prospective trials.

KW - Immunotherapy

KW - Ipilimumab

KW - Nivolumab

KW - Pembrolizumab

KW - Radiation

KW - Steroid

UR - http://www.scopus.com/inward/record.url?scp=85053728154&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053728154&partnerID=8YFLogxK

U2 - 10.1016/j.radonc.2018.08.025

DO - 10.1016/j.radonc.2018.08.025

M3 - Article

C2 - 30241791

AN - SCOPUS:85053728154

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

SN - 0167-8140

ER -