Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance

Abstract 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...

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Autores principales:	Raees Tonse, Muni Rubens, Haley Appel, Martin C. Tom, Matthew D. Hall, Yazmin Odia, Michael W. McDermott, Manmeet S. Ahluwalia, Minesh P. Mehta, Rupesh Kotecha
Formato:	article
Lenguaje:	EN
Publicado:	Springer 2021
Materias:	EGFR KRAS Receptor Discordance Metastasis Brain Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/31a6e2904798443fa55cf6ba79a8f326
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spelling	oai:doaj.org-article:31a6e2904798443fa55cf6ba79a8f3262021-11-14T12:44:38ZSystematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance10.1007/s12672-021-00445-22730-6011https://doaj.org/article/31a6e2904798443fa55cf6ba79a8f3262021-11-01T00:00:00Zhttps://doi.org/10.1007/s12672-021-00445-2https://doaj.org/toc/2730-6011Abstract 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.Raees TonseMuni RubensHaley AppelMartin C. TomMatthew D. HallYazmin OdiaMichael W. McDermottManmeet S. AhluwaliaMinesh P. MehtaRupesh KotechaSpringerarticleEGFRKRASReceptorDiscordanceMetastasisBrainNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENDiscover Oncology, Vol 12, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	EGFR KRAS Receptor Discordance Metastasis Brain Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	EGFR KRAS Receptor Discordance Metastasis Brain Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Raees Tonse Muni Rubens Haley Appel Martin C. Tom Matthew D. Hall Yazmin Odia Michael W. McDermott Manmeet S. Ahluwalia Minesh P. Mehta Rupesh Kotecha Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance
description	Abstract 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.
format	article
author	Raees Tonse Muni Rubens Haley Appel Martin C. Tom Matthew D. Hall Yazmin Odia Michael W. McDermott Manmeet S. Ahluwalia Minesh P. Mehta Rupesh Kotecha
author_facet	Raees Tonse Muni Rubens Haley Appel Martin C. Tom Matthew D. Hall Yazmin Odia Michael W. McDermott Manmeet S. Ahluwalia Minesh P. Mehta Rupesh Kotecha
author_sort	Raees Tonse
title	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_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_sort	systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance
publisher	Springer
publishDate	2021
url	https://doaj.org/article/31a6e2904798443fa55cf6ba79a8f326
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Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance

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