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Improved survival and intracranial tumor control of EGFR-mutated NSCLC patients with newly developed brain metastases following stereotactic radiosurgery and EGFR-TKI: a large retrospective cohort study and meta-analyses

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Abstract

Purpose

To examine the differential effects of SRS and TKI on EGFR-mutated NSCLC patients with brain metastases (BMs) and outcomes following continuation of the same TKI agent in case of new BMs.

Methods

This study included 608 NSCLC patients (2,274 BMs) while meta-analyses included 1,651 NSCLC patients (> 3,944 BMs). Overall survival (OS) and intracranial progression free survival (iPFS) were estimated using Kaplan-Meier methods. Hazard ratios (95% CI) of prognostic factors were estimated using Cox regression models.

Results

The median OS/iPFS (95% CI) (months) for patients with wildtype EGFR/ALK, EGFR mutations, and ALK rearrangements were 17.7 (12.9–23.6)/12.1 (9.8–15.6), 28.9 (23.8–33.3)/17.7 (14.8–21.2), and 118.0 (not reached)/71.7 (15.1–not reached), respectively. In EGFR-mutated patients, meta-analyses combining our data showed significantly improved OS and iPFS of patients who received SRS and TKI (OS:35.1 months, iPFS:20.0 months) when compared to those who have SRS alone (OS:20.8 months, iPFS:11.8 months) or TKI alone (OS:24.3 months, iPFS:13.8 months). Having SRS for newly diagnosed BMs while keeping the existing TKI agent yielded OS (30.0 vs. 32.1 months, p = 0.200) non-inferior to patients who started combined SRS and TKI therapy for their newly diagnosed NSCLC with BMs. Multivariable analyses showed that good performance score and TKI therapy were associated with improved outcomes.

Conclusions

Combined SRS and TKI resulted in favorable outcomes in EGFR-mutated NSCLC patients with newly diagnosed BMs. Continuation of the same TKI agent plus SRS in case of new brain metastases yielded good clinical outcomes and may be considered a standard-of-care treatment.

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Data Availability

The study data are available from the corresponding author upon reasonable request.

Abbreviations

ALK:

Anaplastic lymphoma kinase

BMs:

Brain metastases

CI:

Confidence interval

EGFR:

Epidermal growth factor receptor

GKRS:

Gamma Knife radiosurgery

HR:

Hazard ratio

IQR:

Interquartile range

KPS:

Karnofsky performance score

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

iPFS:

Intracranial progression free survival

RT:

Radiation therapy

SRS:

Stereotactic radiosurgery

TKI:

Tyrosine kinase inhibitor

TTP:

Time to intracranial tumor progression

WBRT:

Whole brain radiation therapy

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Acknowledgements

We are thankful to the staff of Taipei Veterans General Hospital Gamma Knife group for data collection and data management.

Funding

This study was supported by Taipei Veterans General Hospital (VGHUST112-G and V110B-001). The sponsor had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan

    Ai Seon Kuan, Huai-Che Yang, David Hung-Chi Pan, Wen-Yuh Chung & Cheng-Chia Lee

  2. Institute of Public Health, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Ai Seon Kuan

  3. School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Ai Seon Kuan, Hsiu-Mei Wu, Huai-Che Yang, Chung-Jung Lin, Wan-Yuo Guo, Wen-Yuh Chung & Cheng-Chia Lee

  4. Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan

    Chi-Lu Chiang

  5. Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Chi-Lu Chiang

  6. Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Chi-Lu Chiang

  7. Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

    Hsiu-Mei Wu, Chung-Jung Lin & Wan-Yuo Guo

  8. Department of Neurosurgery, The University of Texas Health Science Center, Houston, TX, USA

    Ching-Jen Chen

  9. Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan

    David Hung-Chi Pan & Wen-Yuh Chung

  10. Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Cheng-Chia Lee

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Contributions

ASK and CCL conceived and designed the analysis. ASK conducted the statistical analysis and prepared the tables and figures. All authors helped in interpreting the findings. ASK wrote the first draft of the manuscript. All authors contributed toward subsequent revisions and approved the submitted manuscript.

Corresponding author

Correspondence to Cheng-Chia Lee.

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Ethics approval and consent to participate

Deidentified data was extracted for analysis. Written informed consent from each participant was waived and ethics approval for the study was obtained from the ethics committee of Taipei Veterans General Hospital.

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The authors declare no competing interests.

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Kuan, A.S., Chiang, CL., Wu, HM. et al. Improved survival and intracranial tumor control of EGFR-mutated NSCLC patients with newly developed brain metastases following stereotactic radiosurgery and EGFR-TKI: a large retrospective cohort study and meta-analyses. J Neurooncol 164, 729–739 (2023). https://doi.org/10.1007/s11060-023-04452-x

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