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A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors

INTRODUCTION: Brain metastases (BM) are associated with dismal prognosis, and there is a dearth of effective systemic therapy. In this study, patients with BM from multiple solid tumors were identified from TriNetX databases, their clinicopathological features were evaluated, and the effects of immu...

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Autores principales: Du, Wei, Sirbu, Cristian, Lucas, B. Daniel, Jubelirer, Steven J., Khalid, Ahmed, Mei, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429930/
https://www.ncbi.nlm.nih.gov/pubmed/34513666
http://dx.doi.org/10.3389/fonc.2021.667847
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author Du, Wei
Sirbu, Cristian
Lucas, B. Daniel
Jubelirer, Steven J.
Khalid, Ahmed
Mei, Lin
author_facet Du, Wei
Sirbu, Cristian
Lucas, B. Daniel
Jubelirer, Steven J.
Khalid, Ahmed
Mei, Lin
author_sort Du, Wei
collection PubMed
description INTRODUCTION: Brain metastases (BM) are associated with dismal prognosis, and there is a dearth of effective systemic therapy. In this study, patients with BM from multiple solid tumors were identified from TriNetX databases, their clinicopathological features were evaluated, and the effects of immune checkpoint inhibitor (ICI) therapy were assessed. METHODS: Variables, including median overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status, primary diagnosis, and date of diagnosis, were retrieved from TriNetX, a real-world database. Kaplan-Meier plots and log-rank tests were applied to assess significance of differences in survival. Hazard ratio (HR) and 95% confidence interval (CI) values were calculated. All patient data were deidentified. RESULTS: A total of 227,255 patients with BM were identified in the TriNetX database; median OS was 12.3 months from initial cancer diagnosis and 7.1 months from development of BM. OS of BM from nonsmall-cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), melanoma, and renal cell carcinoma (RCC) were 8.7, 14.7, 17.8, and 15.6 months, respectively. After matching patient baseline characteristics, OS of cohorts with or without exposure to ICIs was evaluated. For all types of cancer, median OS durations for the ICI and no-ICI cohorts were 14.0 and 7.9 months, respectively (HR: 0.88; 95% CI: 0.85–0.91). More specifically, OS was remarkably prolonged in patients with NSCLC (14.4 vs. 8.2 months; HR: 0.86; 95% CI: 0.82–0.90), TNBC (23.9 vs. 11.6 months; HR: 0.87; 95% CI: 0.82–0.92), and melanoma (27.6 vs. 16.8 months; HR: 0.80; 95% CI: 0.73–0.88) if patients had exposure to ICIs. In contrast, there was no significant difference in OS of patients with RCC treated with and without ICIs (16.7 vs. 14.0 months; HR: 0.96; 95% CI: 0.86–1.10). CONCLUSIONS: Overall, BM indicates poor patient outcome. Treatment with ICIs improves survival of patients with NSCLC, TNBC, and melanoma and BM; however, no significant improvement was observed in RCC. Investigations to identify prognostic features, oncogenomic profiles, and predictive biomarkers are warranted.
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spelling pubmed-84299302021-09-11 A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors Du, Wei Sirbu, Cristian Lucas, B. Daniel Jubelirer, Steven J. Khalid, Ahmed Mei, Lin Front Oncol Oncology INTRODUCTION: Brain metastases (BM) are associated with dismal prognosis, and there is a dearth of effective systemic therapy. In this study, patients with BM from multiple solid tumors were identified from TriNetX databases, their clinicopathological features were evaluated, and the effects of immune checkpoint inhibitor (ICI) therapy were assessed. METHODS: Variables, including median overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status, primary diagnosis, and date of diagnosis, were retrieved from TriNetX, a real-world database. Kaplan-Meier plots and log-rank tests were applied to assess significance of differences in survival. Hazard ratio (HR) and 95% confidence interval (CI) values were calculated. All patient data were deidentified. RESULTS: A total of 227,255 patients with BM were identified in the TriNetX database; median OS was 12.3 months from initial cancer diagnosis and 7.1 months from development of BM. OS of BM from nonsmall-cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), melanoma, and renal cell carcinoma (RCC) were 8.7, 14.7, 17.8, and 15.6 months, respectively. After matching patient baseline characteristics, OS of cohorts with or without exposure to ICIs was evaluated. For all types of cancer, median OS durations for the ICI and no-ICI cohorts were 14.0 and 7.9 months, respectively (HR: 0.88; 95% CI: 0.85–0.91). More specifically, OS was remarkably prolonged in patients with NSCLC (14.4 vs. 8.2 months; HR: 0.86; 95% CI: 0.82–0.90), TNBC (23.9 vs. 11.6 months; HR: 0.87; 95% CI: 0.82–0.92), and melanoma (27.6 vs. 16.8 months; HR: 0.80; 95% CI: 0.73–0.88) if patients had exposure to ICIs. In contrast, there was no significant difference in OS of patients with RCC treated with and without ICIs (16.7 vs. 14.0 months; HR: 0.96; 95% CI: 0.86–1.10). CONCLUSIONS: Overall, BM indicates poor patient outcome. Treatment with ICIs improves survival of patients with NSCLC, TNBC, and melanoma and BM; however, no significant improvement was observed in RCC. Investigations to identify prognostic features, oncogenomic profiles, and predictive biomarkers are warranted. Frontiers Media S.A. 2021-08-27 /pmc/articles/PMC8429930/ /pubmed/34513666 http://dx.doi.org/10.3389/fonc.2021.667847 Text en Copyright © 2021 Du, Sirbu, Lucas, Jubelirer, Khalid and Mei https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Du, Wei
Sirbu, Cristian
Lucas, B. Daniel
Jubelirer, Steven J.
Khalid, Ahmed
Mei, Lin
A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors
title A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors
title_full A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors
title_fullStr A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors
title_full_unstemmed A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors
title_short A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors
title_sort retrospective study of brain metastases from solid malignancies: the effect of immune checkpoint inhibitors
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429930/
https://www.ncbi.nlm.nih.gov/pubmed/34513666
http://dx.doi.org/10.3389/fonc.2021.667847
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