Charissa A C Jessurun1,2,3, Alexander F C Hulsbergen1,2,3, Anouk E de Wit4, Ishaan A Tewarie1,2,3, Tom J Snijders5, Joost J C Verhoeff6, John G Phillips7, David A Reardon8,9, Rania A Mekary1,10, Marike L D Broekman1,2,3,11. 1. Computational Neuroscience Outcomes Center (CNOC), Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2. Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands. 3. Department of Neurosurgery, Haaglanden Medical Center, The Hague, the Netherlands. 4. Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 5. Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands. 6. Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands. 7. Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 8. Harvard Medical School, Boston, Massachusetts, USA. 9. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. 10. Department of Pharmaceutical Business and Administrative Sciences, School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, USA. 11. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI. METHODS: A systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies. RESULTS: After screening 1145 abstracts, 15 observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9 to 10.2 months. In the nonsteroid group, median OS ranged from 4.9 to 25.1 months. Pooled results demonstrated significantly worse OS (HR = 1.84, 95% CI 1.22-2.77) and systemic progression-free survival (PFS; HR = 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR = 1.31, 95% CI 0.42-4.07). CONCLUSIONS: Administration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.
BACKGROUND: Immune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI. METHODS: A systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies. RESULTS: After screening 1145 abstracts, 15 observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9 to 10.2 months. In the nonsteroid group, median OS ranged from 4.9 to 25.1 months. Pooled results demonstrated significantly worse OS (HR = 1.84, 95% CI 1.22-2.77) and systemic progression-free survival (PFS; HR = 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR = 1.31, 95% CI 0.42-4.07). CONCLUSIONS: Administration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.
Authors: Linda Chen; Jacqueline Douglass; Lawrence Kleinberg; Xiaobu Ye; Ariel E Marciscano; Patrick M Forde; Julie Brahmer; Evan Lipson; William Sharfman; Hans Hammers; Jarushka Naidoo; Chetan Bettegowda; Michael Lim; Kristin J Redmond Journal: Int J Radiat Oncol Biol Phys Date: 2017-12-05 Impact factor: 7.038
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Authors: Paolo Palmisciano; Ali S Haider; Chibueze D Nwagwu; Waseem Wahood; Kenny Yu; Chibawanye I Ene; Barbara J O'Brien; Salah G Aoun; Aaron A Cohen-Gadol; Tarek Y El Ahmadieh Journal: Anticancer Res Date: 2021-11 Impact factor: 2.435