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Prognostic impact of EGFR/ALK alterations in leptomeningeal metastasis from lung adenocarcinoma treated with whole-brain radiotherapy

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Abstract

The prognosis and prognostic factors of patients receiving whole-brain radiotherapy (WBRT) for leptomeningeal metastasis (LM) from lung adenocarcinoma have not been established. Particularly, the impact of EGFR mutations and ALK rearrangements on survival remains unclear. This retrospective study evaluated the prognosis and prognostic factors of patients receiving WBRT for LM. We evaluated overall survival (OS) from WBRT initiation and clinical variables in 80 consecutive patients receiving WBRT for LM from lung adenocarcinoma at our institution between June 2013 and June 2021. After a median follow-up of 5.2 (range 0.5–56.5) months, the median OS was 6.2 months (95% CI 4.4–12.4). Of the 80 patients, 51 were classified as EGFR/ALK mutant (EGFR: 44; ALK: 6; both: 1) and 29 as wild-type. The median OS was 10.4 (95% CI 5.9–20.9) versus 3.8 (95% CI 2.5–7.7) months in the EGFR/ALK-mutant versus wild-type patients (HR = 0.49, P = 0.0063). Multivariate analysis indicated that EGFR/ALK alterations (HR = 0.54, P = 0.021) and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1 (HR = 0.25, P < 0.001) were independent factors associated with favorable OS. Among the patients who underwent brain MRI before and after WBRT, intracranial progression-free survival was longer in the 26 EGFR/ALK-mutant than 13 wild-type patients (HR = 0.31, P = 0.0039). Although the prognosis of patients receiving WBRT for LM remains poor, EGFR/ALK alterations and good ECOG PS may positively impact OS in those eligible for WBRT.

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Data availability

All data generated or analyzed for this study are included in this published article.

Abbreviations

ALK:

Anaplastic lymphoma kinase

CSF:

Cerebrospinal fluid

ECOG PS:

Eastern Cooperative Oncology Group performance status

EGFR:

Epidermal growth factor receptor

LANO:

Leptomeningeal Assessment in Neuro-Oncology

LM:

Leptomeningeal metastasis

MRI:

Magnetic resonance imaging

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PFS:

Progression-free survival

TKI:

Tyrosine kinase inhibitor

WBRT:

Whole-brain radiotherapy

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Funding

This work was supported in part by the National Cancer Center Research and Development Fund (2021-A-8) and The Yasuda Medical Foundation.

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Authors and Affiliations

  1. Department of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Hidekazu Oyoshi, Hidenari Hirata, Yasuhiro Hirano, Sadamoto Zenda, Yuzheng Zhou, Kento Tomizawa, Takeshi Fujisawa, Masaki Nakamura, Hidehiro Hojo, Atsushi Motegi, Shun-Ichiro Kageyama & Tetsuo Akimoto

  2. Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Hidekazu Oyoshi, Shunichi Ishihara & Shinji Naganawa

  3. Division of Radiation Oncology and Particle Therapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan

    Hidenari Hirata, Sadamoto Zenda, Masaki Nakamura, Hidehiro Hojo, Atsushi Motegi, Shun-Ichiro Kageyama & Tetsuo Akimoto

  4. Department of Radiology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan

    Yasuhiro Hirano

  5. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Yoshitaka Zenke & Koichi Goto

Authors
  1. Hidekazu Oyoshi
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  2. Hidenari Hirata
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  4. Sadamoto Zenda
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  8. Masaki Nakamura
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  9. Hidehiro Hojo
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  11. Shun-Ichiro Kageyama
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  13. Koichi Goto
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  14. Shunichi Ishihara
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  15. Shinji Naganawa
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  16. Tetsuo Akimoto
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Contributions

Study conception and design: HO, H. Hirata, YH. Formal analysis: HO, H. Hirata. Data curation: HO, YH. Resources: Y. Zhou, KT, TF, MN, H. Hojo, AM, SIK. Writing original-draft: HO, H. Hirata. Writing-review and editing: SZ, Y. Zenke, KG, SI, SN, TA. Project administration: H. Hirata, TA. Supervision: TA. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hidenari Hirata.

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Conflict of interest

All authors declare no competing interests.

Ethical approval

This retrospective study was approved by the National Cancer Center Hospital East Institutional Review Board (Protocol Number 2017-440).

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Supplementary Information

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10585_2023_10225_MOESM1_ESM.pdf

Supplementary file1 (PDF 409 kb) Supplementary Fig. 1 Kaplan–Meier survival curves showing differences in the overall survival of patients with EGFR-mutant (n = 44) versus ALK-rearranged (n = 6) leptomeningeal metastasis treated with WBRT. One patient with lung adenocarcinoma harboring both EGFR and ALK alterations was excluded from the analysis. OS overall survival, WBRT whole-brain radiotherapy

10585_2023_10225_MOESM2_ESM.pdf

Supplementary file2 (PDF 426 kb) Supplementary Fig. 2 Overall survival of patients with EGFR/ALK-mutant leptomeningeal metastasis who received WBRT with versus without concurrent TKI therapy. TKI tyrosine kinase inhibitor, OS overall survival, WBRT whole-brain radiotherapy

Supplementary file3 (DOCX 21 kb)

Supplementary file4 (DOCX 24 kb)

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Oyoshi, H., Hirata, H., Hirano, Y. et al. Prognostic impact of EGFR/ALK alterations in leptomeningeal metastasis from lung adenocarcinoma treated with whole-brain radiotherapy. Clin Exp Metastasis 40, 407–413 (2023). https://doi.org/10.1007/s10585-023-10225-7

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  • DOI: https://doi.org/10.1007/s10585-023-10225-7

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