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Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance
BACKGROUND: Treatment paradigms for metastatic non-small cell lung cancer are increasingly based on biomarker-driven therapies, with the most common alteration being mutation in the epidermal growth factor receptor (EGFR). Change in expression of such biomarkers could have a profound impact on the c...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777541/ https://www.ncbi.nlm.nih.gov/pubmed/35201504 http://dx.doi.org/10.1007/s12672-021-00445-2 |
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author | Tonse, Raees Rubens, Muni Appel, Haley Tom, Martin C. Hall, Matthew D. Odia, Yazmin McDermott, Michael W. Ahluwalia, Manmeet S. Mehta, Minesh P. Kotecha, Rupesh |
author_facet | Tonse, Raees Rubens, Muni Appel, Haley Tom, Martin C. Hall, Matthew D. Odia, Yazmin McDermott, Michael W. Ahluwalia, Manmeet S. Mehta, Minesh P. Kotecha, Rupesh |
author_sort | Tonse, Raees |
collection | PubMed |
description | BACKGROUND: Treatment paradigms for metastatic non-small cell lung cancer are increasingly based on biomarker-driven therapies, with the most common alteration being mutation in the epidermal growth factor receptor (EGFR). Change in expression of such biomarkers could have a profound impact on the choice and efficacy of a selected targeted therapeutic, and hence the objective of this study was to analyze discordance in EGFR status in patients with lung cancer brain metastasis (LCBM). METHODS: Using PRISMA guidelines, a systematic review was performed of series in the Medline database of biopsied or resected LCBM published before May, 2020. Key words included “lung cancer” and “brain metastasis” combined with “epidermal growth factor receptor/EGFR,” and “receptor conversion/discordance or concordance.” Weighted random effects models were used to calculate pooled estimates. RESULTS: We identified 501 patients from 19 full-text articles for inclusion in this study. All patients underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. On primary/LCBM comparison, the weighted pooled estimate for overall EGFR receptor discordance was 10% (95% CI 5–17%). The weighted effects model estimated a gain of an EGFR mutation in a brain metastases in patients with negative primary tumors was 7% (95% CI 4–12%). Alternatively, the weighted effects model estimate of loss of an EGFR mutation in patients with detected mutations in the primary tumor was also 7% (95% CI 4–10%). KRAS testing was also performed on both primary tumors and LCBM in a subset of 148 patients. The weighted effects estimate of KRAS-mutation discordance among LCBM compared to primary tumors was 13% (95% CI 5–27%). The weighted effects estimated of KRAS gain and loss in LCBM was 10% (95% CI 6–18%) and 8% (95% CI 4–15%), respectively. Meta-regression analysis did not find any association with any factors that could be associated with discordances. CONCLUSIONS: EGFR and KRAS mutation status discordance between primary tumor and LCBM occurs in approximately 10% and 13% of patients, respectively. Evaluation of LCBM receptor status is key to biomarker-driven targeted therapy for intracranial disease and awareness of subtype switching is critical for those patients treated with systemic therapy alone for intracranial disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-021-00445-2. |
format | Online Article Text |
id | pubmed-8777541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-87775412022-02-03 Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance Tonse, Raees Rubens, Muni Appel, Haley Tom, Martin C. Hall, Matthew D. Odia, Yazmin McDermott, Michael W. Ahluwalia, Manmeet S. Mehta, Minesh P. Kotecha, Rupesh Discov Oncol Research BACKGROUND: Treatment paradigms for metastatic non-small cell lung cancer are increasingly based on biomarker-driven therapies, with the most common alteration being mutation in the epidermal growth factor receptor (EGFR). Change in expression of such biomarkers could have a profound impact on the choice and efficacy of a selected targeted therapeutic, and hence the objective of this study was to analyze discordance in EGFR status in patients with lung cancer brain metastasis (LCBM). METHODS: Using PRISMA guidelines, a systematic review was performed of series in the Medline database of biopsied or resected LCBM published before May, 2020. Key words included “lung cancer” and “brain metastasis” combined with “epidermal growth factor receptor/EGFR,” and “receptor conversion/discordance or concordance.” Weighted random effects models were used to calculate pooled estimates. RESULTS: We identified 501 patients from 19 full-text articles for inclusion in this study. All patients underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. On primary/LCBM comparison, the weighted pooled estimate for overall EGFR receptor discordance was 10% (95% CI 5–17%). The weighted effects model estimated a gain of an EGFR mutation in a brain metastases in patients with negative primary tumors was 7% (95% CI 4–12%). Alternatively, the weighted effects model estimate of loss of an EGFR mutation in patients with detected mutations in the primary tumor was also 7% (95% CI 4–10%). KRAS testing was also performed on both primary tumors and LCBM in a subset of 148 patients. The weighted effects estimate of KRAS-mutation discordance among LCBM compared to primary tumors was 13% (95% CI 5–27%). The weighted effects estimated of KRAS gain and loss in LCBM was 10% (95% CI 6–18%) and 8% (95% CI 4–15%), respectively. Meta-regression analysis did not find any association with any factors that could be associated with discordances. CONCLUSIONS: EGFR and KRAS mutation status discordance between primary tumor and LCBM occurs in approximately 10% and 13% of patients, respectively. Evaluation of LCBM receptor status is key to biomarker-driven targeted therapy for intracranial disease and awareness of subtype switching is critical for those patients treated with systemic therapy alone for intracranial disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-021-00445-2. Springer US 2021-11-08 /pmc/articles/PMC8777541/ /pubmed/35201504 http://dx.doi.org/10.1007/s12672-021-00445-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Tonse, Raees Rubens, Muni Appel, Haley Tom, Martin C. Hall, Matthew D. Odia, Yazmin McDermott, Michael W. Ahluwalia, Manmeet S. Mehta, Minesh P. Kotecha, Rupesh Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance |
title | Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance |
title_full | Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance |
title_fullStr | Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance |
title_full_unstemmed | Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance |
title_short | Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance |
title_sort | systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777541/ https://www.ncbi.nlm.nih.gov/pubmed/35201504 http://dx.doi.org/10.1007/s12672-021-00445-2 |
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