Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysis

Abstract Background Patients with non-small cell lung cancer (NSCLC) are prone to developing brain metastases (BMs), particularly those with epidermal growth factor receptor (EGFR) mutations. In clinical practice, treatment-naïve EGFR-mutant NSCLC patients with asymptomatic BMs tend to choose EGFR-t...

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Main Authors: Mingfeng He, Xue Wu, Li Li, Guangming Yi, Yitian Wang, Hengqiu He, Ying Ye, Ruiqin Zhou, Zaicheng Xu, Zhenzhou Yang
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Radiation Oncology
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Online Access:https://doi.org/10.1186/s13014-024-02578-4
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author Mingfeng He
Xue Wu
Li Li
Guangming Yi
Yitian Wang
Hengqiu He
Ying Ye
Ruiqin Zhou
Zaicheng Xu
Zhenzhou Yang
author_facet Mingfeng He
Xue Wu
Li Li
Guangming Yi
Yitian Wang
Hengqiu He
Ying Ye
Ruiqin Zhou
Zaicheng Xu
Zhenzhou Yang
author_sort Mingfeng He
collection DOAJ
description Abstract Background Patients with non-small cell lung cancer (NSCLC) are prone to developing brain metastases (BMs), particularly those with epidermal growth factor receptor (EGFR) mutations. In clinical practice, treatment-naïve EGFR-mutant NSCLC patients with asymptomatic BMs tend to choose EGFR-tyrosine kinase inhibitors (TKIs) as first-line therapy and defer intracranial radiotherapy (RT). However, the effectiveness of upfront intracranial RT remains unclear. Methods This was a retrospective study including 217 patients from two institutions between January 2018 and December 2022. Clinical data of NSCLC patients with BMs who received EGFR-TKIs were collected. The patients were assigned to one of the three groups according to the therapeutic modality used: the upfront TKI + stereotactic radiosurgery (SRS) / fractionated stereotactic radiotherapy (fSRS) group (upfront TKI + SRS/fSRS ), the upfront TKI + whole-brain radiotherapy (WBRT) group (upfront TKI + WBRT) and the upfront TKI group. Results As of March 8, 2023, the median follow-up duration was 37.3 months (95% CI, 32.5–42.1). The median overall survival (OS) for the upfront TKI + SRS/fSRS, upfront TKI + WBRT, and upfront TKI groups were 37.8, 20.7, and 24.1 months, respectively (p = 0.015). In subgroup analysis, the upfront TKI + SRS/fSRS group demonstrated longer OS compared to the upfront TKI + WBRT and upfront TKI groups in patients treated with first or second-generation EGFR-TKIs (p = 0.021) and patients with L858R mutation (p = 0.017), whereas no survival benefit was observed in three-generation EGFR-TKIs or 19del subgroup. In the multivariable analysis, metachronous BMs, EGFR L858R mutation and nonclassic EGFR mutation were identified as independent risk factors for OS, while a DS-GPA score of 2.0–4.0 was the only independent protective factor. Conclusions This study demonstrated that upfront addition of SRS/fSRS to EGFR-TKIs was associated with longer OS compared to upfront WBRT or upfront TKI alone in EGFR-mutant NSCLC patients with BMs. This improvement was more significant in patients with L858R mutation and those treated with first or second-generation EGFR-TKIs. Further research with a larger sample size is warranted.
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spelling doaj-art-2f601887967a4d7f80401effbd47af822025-08-20T02:35:47ZengBMCRadiation Oncology1748-717X2025-01-0120111210.1186/s13014-024-02578-4Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysisMingfeng He0Xue Wu1Li Li2Guangming Yi3Yitian Wang4Hengqiu He5Ying Ye6Ruiqin Zhou7Zaicheng Xu8Zhenzhou Yang9Department of Oncology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Oncology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiothoracic Surgery, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Oncology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Oncology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Oncology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiothoracic Surgery, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Oncology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Oncology, The Second Affiliated Hospital of Chongqing Medical UniversityAbstract Background Patients with non-small cell lung cancer (NSCLC) are prone to developing brain metastases (BMs), particularly those with epidermal growth factor receptor (EGFR) mutations. In clinical practice, treatment-naïve EGFR-mutant NSCLC patients with asymptomatic BMs tend to choose EGFR-tyrosine kinase inhibitors (TKIs) as first-line therapy and defer intracranial radiotherapy (RT). However, the effectiveness of upfront intracranial RT remains unclear. Methods This was a retrospective study including 217 patients from two institutions between January 2018 and December 2022. Clinical data of NSCLC patients with BMs who received EGFR-TKIs were collected. The patients were assigned to one of the three groups according to the therapeutic modality used: the upfront TKI + stereotactic radiosurgery (SRS) / fractionated stereotactic radiotherapy (fSRS) group (upfront TKI + SRS/fSRS ), the upfront TKI + whole-brain radiotherapy (WBRT) group (upfront TKI + WBRT) and the upfront TKI group. Results As of March 8, 2023, the median follow-up duration was 37.3 months (95% CI, 32.5–42.1). The median overall survival (OS) for the upfront TKI + SRS/fSRS, upfront TKI + WBRT, and upfront TKI groups were 37.8, 20.7, and 24.1 months, respectively (p = 0.015). In subgroup analysis, the upfront TKI + SRS/fSRS group demonstrated longer OS compared to the upfront TKI + WBRT and upfront TKI groups in patients treated with first or second-generation EGFR-TKIs (p = 0.021) and patients with L858R mutation (p = 0.017), whereas no survival benefit was observed in three-generation EGFR-TKIs or 19del subgroup. In the multivariable analysis, metachronous BMs, EGFR L858R mutation and nonclassic EGFR mutation were identified as independent risk factors for OS, while a DS-GPA score of 2.0–4.0 was the only independent protective factor. Conclusions This study demonstrated that upfront addition of SRS/fSRS to EGFR-TKIs was associated with longer OS compared to upfront WBRT or upfront TKI alone in EGFR-mutant NSCLC patients with BMs. This improvement was more significant in patients with L858R mutation and those treated with first or second-generation EGFR-TKIs. Further research with a larger sample size is warranted.https://doi.org/10.1186/s13014-024-02578-4Non-small-cell lung cancerBrain metastasesEGFR-TKIIntracranial radiotherapyOverall survival
spellingShingle Mingfeng He
Xue Wu
Li Li
Guangming Yi
Yitian Wang
Hengqiu He
Ying Ye
Ruiqin Zhou
Zaicheng Xu
Zhenzhou Yang
Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysis
Radiation Oncology
Non-small-cell lung cancer
Brain metastases
EGFR-TKI
Intracranial radiotherapy
Overall survival
title Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysis
title_full Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysis
title_fullStr Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysis
title_full_unstemmed Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysis
title_short Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysis
title_sort effects of egfr tkis combined with intracranial radiotherapy in egfr mutant non small cell lung cancer patients with brain metastases a retrospective multi institutional analysis
topic Non-small-cell lung cancer
Brain metastases
EGFR-TKI
Intracranial radiotherapy
Overall survival
url https://doi.org/10.1186/s13014-024-02578-4
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