Stereotactic radiosurgery with immune checkpoint inhibitors for brain metastases: a meta-analysis study

2022 ◽  
pp. 1-11
Author(s):  
Samireh Badrigilan ◽  
Antonio Meola ◽  
Steven D. Chang ◽  
Shahab Rezaeian ◽  
Hossein Nemati ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Analysis Study

Immune checkpoint inhibitors and stereotactic radiosurgery (SRS) in melanoma brain metastases.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e21523-e21523
Author(s):  
Charlotte Fenioux ◽  
Idriss Troussier ◽  
Jean-Jacques Mazeron ◽  
Charles Henry Canova ◽  
Philippe Saiag ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Melanoma Brain Metastases

scholarly journals 72. THE COMBINED USE OF STEROIDS AND IMMUNE CHECKPOINT INHIBITORS IN BRAIN METASTASES PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii15-ii15
Author(s):  
Charissa Jessurun ◽  
Alexander Hulsbergen ◽  
Anouk de Wit ◽  
Ishaan Ramlochan Tewarie ◽  
Marike Broekman
Keyword(s):  
Systematic Review ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Tumor Type ◽  
Random Effects Models ◽  
Steroid Group

Abstract INTRODUCTION Immune checkpoint inhibitors (ICI) are increasingly being administered to cancer patients, including those with brain metastases (BMs). However, little is known about the interaction between ICI and steroids such as dexamethasone. 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 in PubMed, Embase, Web of Science, Cochrane, Academic Search Premier, and PsycINFO. Pooled effect estimates were calculated using random-effects models; analysis was performed across all included studies and stratified by tumor type. RESULTS After screening 978 abstracts, thirteen studies were included for systematic review. Ten studies reported sufficient data for meta-analysis, comprising 838 BM patients of which 335 (40%) had received steroids. In the steroid group, median OS ranged from 2.9 months to 10.2 months across studies. In the non-steroid group, median OS ranged from 4.9 to 25.1 months. Pooling results demonstrated significantly worse survival in the steroid group (HR 1.97; 95% CI 1.65–2.36); no significant heterogeneity (I2 = 0%) or publication bias (Egger’s p = 0.29) was identified. Stratified analysis showed a consistent effect across melanoma (HR 1.71, 95% CI 1.34–2.18) and non-small cell lung cancer (HR 2.26, 95% CI 1.49–3.43) subgroups. CONCLUSION Administration of steroids is associated with a significantly worse OS in BM patients receiving ICI. Further investigation on dose, timing and duration of steroids in this population is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.

scholarly journals Stereotactic Radiosurgery and Immune Checkpoint Inhibitors in the Management of Brain Metastases

2018 ◽  
Vol 19 (10) ◽  
pp. 3054 ◽  
Author(s):  
Eric Lehrer ◽  
Heather McGee ◽  
Jennifer Peterson ◽  
Laura Vallow ◽  
Henry Ruiz-Garcia ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Tumor Immunity ◽  
Clinical Data ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
High Dose ◽  
Normal Brain

Brain metastases traditionally carried a poor prognosis with an overall survival of weeks to months in the absence of treatment. Radiation therapy modalities include whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). WBRT delivers a relatively low dose of radiation, has neurocognitive sequelae, and has not been investigated for its immunostimulatory effects. Furthermore, WBRT exposes the entire intracranial tumor immune microenvironment to radiation. SRS delivers a high dose of conformal radiation with image guidance to minimize dose to surrounding normal brain tissue, and appears to promote anti-tumor immunity. In parallel with many of these discoveries, immune checkpoint inhibitors (ICIs) have demonstrated a survival advantage in multiple malignancies commonly associated with brain metastases (e.g., melanoma). Combination SRS and ICI are theorized to be synergistic in anti-tumor immunity directed to brain metastases. The purpose of this review is to explore the synergy of SRS and ICIs, including pre-clinical data, existing clinical data, and ongoing prospective trials.

scholarly journals IMMU-04. IMMUNE-RELATED ADVERSE EVENTS STRONGLY PREDICT SUPERIOR OUTCOMES IN BRAIN METASTASES PATIENTS RECEIVING LOCAL TREATMENT AND IMMUNE CHECKPOINT INHIBITORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii105-ii105
Author(s):  
Alexander Hulsbergen ◽  
Asad Lak ◽  
Yu Tung Lo ◽  
Nayan Lamba ◽  
Steven Nagtegaal ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Adverse Events ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Local Treatment ◽  
Sensitivity Analyses ◽  
Immortal Time Bias ◽  
The Brain

Abstract INTRODUCTION In several cancers treated with immune checkpoint inhibitors (ICIs), a remarkable association between the occurrence of immune-related adverse events (irAEs) and superior oncological outcomes has been reported. This effect has hitherto not been reported in the brain. This study aimed to investigate the relation between irAEs and outcomes in brain metastases (BM) patients treated with both local treatment to the brain (LT; i.e. surgery and/or radiation) and ICIs. METHODS This study is a retrospective cohort analysis of patients treated for non-small cell lung cancer (NSCLC) BMs in a tertiary institution in Boston, MA. Outcomes of interest were overall survival (OS) and intracranial progression-free survival (IC-PFS), measured from the time of LT. Sensitivity analyses were performed to account for immortal time bias (i.e., patients who live longer receive more cycles of ICIs and thus have more opportunity to develop an irAE). RESULTS A total of 184 patients were included; 62 (33.7%) were treated with neurosurgical resection and 122 (66.3%) with upfront brain radiation. irAEs occurred in 62 patients (33.7%). After adjusting for lung-Graded Prognostic Assessment, type of LT, type of ICI, newly diagnosed vs. recurrent BM, BM size and number, targetable mutations, and smoking status, irAEs were strongly associated with better OS (HR 0.33, 95% CI 0.19 – 0.58, p < 0.0001) and IC-PFS (HR 0.41; 95% CI 0.26 – 0.65; p = 0.0001). Landmark analysis including only patients who received more than 3 cycles of ICI (n = 133) demonstrated similar results for OS and IC-PFS, as did sensitivity analysis adjusting for the number of cycles administered (HR range 0.36 – 0.51, all p-values < 0.02). CONCLUSIONS After adjusting for known prognostic factors, irAEs strongly predict superior outcomes after LT in NSCLC BM patients. Sensitivity analysis suggests that this is unlikely due to immortal time bias.

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