Brain metastases from non-small cell lung cancer with EGFR or ALK mutations: A systematic review and meta-analysis of multidisciplinary approaches

Raj Singh, Eric J. Lehrer, Stephen Ko, Jennifer Peterson, Yanyan Lou, Alyx B. Porter, Rupesh Kotecha, Paul D. Brown, Nicholas G. Zaorsky, Daniel M. Trifiletti

Research output: Contribution to journalReview article

Abstract

Background and purpose: To analyze outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases harboring EGFR or ALK mutations and examine for differences between tyrosine kinase inhibitors (TKIs) alone, radiotherapy (RT) alone (either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)), or combined TKIs and RT. Materials and methods: Thirty studies were identified. Patients: with brain metastases from NSCLC. Intervention: initial TKIs alone with optional salvage RT, RT alone, or TKIs and RT. Control: wild-type NSCLC and TKIs alone for mutational and treatment analysis, respectively. Outcomes: overall survival (OS) and intracranial progression-free survival (PFS). Setting: studies with mutation information. Results: A total of 2649 patients were included. Patients with ALK and EGFR mutations had significantly higher median OS (48.5 months, p < 0.0001; and 20.9 months; p = 0.0006, respectively) compared to wild-type patients (9.9 months). Similar median OS was noted between TKIs and RT (28.3 months), RT alone (32.2 months; p = 0.22), or TKIs alone (23.9 months; p = 0.2). Patients treated with TKIs and RT had higher median PFS (18.6 months; p = 0.06) compared to TKIs alone (13.6 months) with no difference between TKIs and RT vs. RT alone (16.9 months; p = 0.72). No PFS difference was found between WBRT and TKI (23.2 months; p = 0.72) vs. WBRT alone (24 months) or SRS and TKI (16.7 months; p = 0.56) vs. SRS alone (13.6 months). Conclusion: NSCLC patients with brain metastases harboring EGFR or ALK mutations have superior OS compared to wild-type patients. No PFS or OS benefit was found with the addition of TKIs to RT.

Original languageEnglish (US)
Pages (from-to)165-179
Number of pages15
JournalRadiotherapy and Oncology
Volume144
DOIs
StatePublished - Mar 2020

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Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Meta-Analysis
Radiotherapy
Neoplasm Metastasis
Mutation
Brain
Disease-Free Survival
Radiosurgery
Survival

Keywords

  • ALK
  • Brain metastases
  • EGFR
  • Mutated
  • Radiosurgery

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Brain metastases from non-small cell lung cancer with EGFR or ALK mutations : A systematic review and meta-analysis of multidisciplinary approaches. / Singh, Raj; Lehrer, Eric J.; Ko, Stephen; Peterson, Jennifer; Lou, Yanyan; Porter, Alyx B.; Kotecha, Rupesh; Brown, Paul D.; Zaorsky, Nicholas G.; Trifiletti, Daniel M.

In: Radiotherapy and Oncology, Vol. 144, 03.2020, p. 165-179.

Research output: Contribution to journalReview article

Singh, Raj ; Lehrer, Eric J. ; Ko, Stephen ; Peterson, Jennifer ; Lou, Yanyan ; Porter, Alyx B. ; Kotecha, Rupesh ; Brown, Paul D. ; Zaorsky, Nicholas G. ; Trifiletti, Daniel M. / Brain metastases from non-small cell lung cancer with EGFR or ALK mutations : A systematic review and meta-analysis of multidisciplinary approaches. In: Radiotherapy and Oncology. 2020 ; Vol. 144. pp. 165-179.
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abstract = "Background and purpose: To analyze outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases harboring EGFR or ALK mutations and examine for differences between tyrosine kinase inhibitors (TKIs) alone, radiotherapy (RT) alone (either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)), or combined TKIs and RT. Materials and methods: Thirty studies were identified. Patients: with brain metastases from NSCLC. Intervention: initial TKIs alone with optional salvage RT, RT alone, or TKIs and RT. Control: wild-type NSCLC and TKIs alone for mutational and treatment analysis, respectively. Outcomes: overall survival (OS) and intracranial progression-free survival (PFS). Setting: studies with mutation information. Results: A total of 2649 patients were included. Patients with ALK and EGFR mutations had significantly higher median OS (48.5 months, p < 0.0001; and 20.9 months; p = 0.0006, respectively) compared to wild-type patients (9.9 months). Similar median OS was noted between TKIs and RT (28.3 months), RT alone (32.2 months; p = 0.22), or TKIs alone (23.9 months; p = 0.2). Patients treated with TKIs and RT had higher median PFS (18.6 months; p = 0.06) compared to TKIs alone (13.6 months) with no difference between TKIs and RT vs. RT alone (16.9 months; p = 0.72). No PFS difference was found between WBRT and TKI (23.2 months; p = 0.72) vs. WBRT alone (24 months) or SRS and TKI (16.7 months; p = 0.56) vs. SRS alone (13.6 months). Conclusion: NSCLC patients with brain metastases harboring EGFR or ALK mutations have superior OS compared to wild-type patients. No PFS or OS benefit was found with the addition of TKIs to RT.",
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T1 - Brain metastases from non-small cell lung cancer with EGFR or ALK mutations

T2 - A systematic review and meta-analysis of multidisciplinary approaches

AU - Singh, Raj

AU - Lehrer, Eric J.

AU - Ko, Stephen

AU - Peterson, Jennifer

AU - Lou, Yanyan

AU - Porter, Alyx B.

AU - Kotecha, Rupesh

AU - Brown, Paul D.

AU - Zaorsky, Nicholas G.

AU - Trifiletti, Daniel M.

PY - 2020/3

Y1 - 2020/3

N2 - Background and purpose: To analyze outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases harboring EGFR or ALK mutations and examine for differences between tyrosine kinase inhibitors (TKIs) alone, radiotherapy (RT) alone (either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)), or combined TKIs and RT. Materials and methods: Thirty studies were identified. Patients: with brain metastases from NSCLC. Intervention: initial TKIs alone with optional salvage RT, RT alone, or TKIs and RT. Control: wild-type NSCLC and TKIs alone for mutational and treatment analysis, respectively. Outcomes: overall survival (OS) and intracranial progression-free survival (PFS). Setting: studies with mutation information. Results: A total of 2649 patients were included. Patients with ALK and EGFR mutations had significantly higher median OS (48.5 months, p < 0.0001; and 20.9 months; p = 0.0006, respectively) compared to wild-type patients (9.9 months). Similar median OS was noted between TKIs and RT (28.3 months), RT alone (32.2 months; p = 0.22), or TKIs alone (23.9 months; p = 0.2). Patients treated with TKIs and RT had higher median PFS (18.6 months; p = 0.06) compared to TKIs alone (13.6 months) with no difference between TKIs and RT vs. RT alone (16.9 months; p = 0.72). No PFS difference was found between WBRT and TKI (23.2 months; p = 0.72) vs. WBRT alone (24 months) or SRS and TKI (16.7 months; p = 0.56) vs. SRS alone (13.6 months). Conclusion: NSCLC patients with brain metastases harboring EGFR or ALK mutations have superior OS compared to wild-type patients. No PFS or OS benefit was found with the addition of TKIs to RT.

AB - Background and purpose: To analyze outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases harboring EGFR or ALK mutations and examine for differences between tyrosine kinase inhibitors (TKIs) alone, radiotherapy (RT) alone (either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)), or combined TKIs and RT. Materials and methods: Thirty studies were identified. Patients: with brain metastases from NSCLC. Intervention: initial TKIs alone with optional salvage RT, RT alone, or TKIs and RT. Control: wild-type NSCLC and TKIs alone for mutational and treatment analysis, respectively. Outcomes: overall survival (OS) and intracranial progression-free survival (PFS). Setting: studies with mutation information. Results: A total of 2649 patients were included. Patients with ALK and EGFR mutations had significantly higher median OS (48.5 months, p < 0.0001; and 20.9 months; p = 0.0006, respectively) compared to wild-type patients (9.9 months). Similar median OS was noted between TKIs and RT (28.3 months), RT alone (32.2 months; p = 0.22), or TKIs alone (23.9 months; p = 0.2). Patients treated with TKIs and RT had higher median PFS (18.6 months; p = 0.06) compared to TKIs alone (13.6 months) with no difference between TKIs and RT vs. RT alone (16.9 months; p = 0.72). No PFS difference was found between WBRT and TKI (23.2 months; p = 0.72) vs. WBRT alone (24 months) or SRS and TKI (16.7 months; p = 0.56) vs. SRS alone (13.6 months). Conclusion: NSCLC patients with brain metastases harboring EGFR or ALK mutations have superior OS compared to wild-type patients. No PFS or OS benefit was found with the addition of TKIs to RT.

KW - ALK

KW - Brain metastases

KW - EGFR

KW - Mutated

KW - Radiosurgery

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