Survival analysis and pathological features of advanced non-small cell lung cancer with miliary pulmonary metastases in patients harboring epidermal growth factor receptor mutations
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Metastasis of non-small cell lung cancer (NSCLC), indicating hematogenous dissemination, is more frequent in patients harboring epidermal growth factor receptor (EGFR) mutations, who respond dramatically to EGFR–tyrosine kinase inhibitors (TKIs).
Based on the proposed association of miliary pulmonary metastasis and EGFR mutations in the previous studies, we conducted a retrospective study to assess survival of NSCLC with miliary pulmonary metastases in 223 patients harboring EGFR mutations who were treated with single agent EGFR–TKIs.
Progression-free survival (PFS) and overall survival (OS) with single agent EGFR–TKIs were 11.7 months [95% confidence interval (CI) 9.6–13.7] and 23.7 months (95% CI 20.3–26.9), respectively. Patients with and without miliary pulmonary metastases were matched using propensity scores (n = 29 per group) based on clinical characteristics. After matching, the PFS were 8.2 months (95% CI 5.2–15.0) and 14.3 months (95% CI 9.6–30.0) (p = 0.02) in patients with and without miliary pulmonary metastases, respectively. Conversely, the OS were 15.3 months (95% CI 10.6–19.4) and 27.9 months (95% CI 22.0–33.0) (p = 0.003) in patients with and without miliary pulmonary metastases, respectively. By multivariate analysis, miliary pulmonary metastasis was associated with poor prognosis (p = 0.0035).
The prognosis of patients with advanced NSCLC harboring EGFR mutations with miliary pulmonary metastasis demonstrated significantly worse outcomes compared to those without miliary pulmonary metastasis.
KeywordsEpidermal growth factor receptor mutation Lung cancer Miliary pulmonary metastasis Prognosis Tyrosine kinase inhibitor
Eastern Cooperative Oncology Group performance status
Epidermal growth factor receptor
Tyrosine kinase inhibitor
Non-small cell lung cancer
Polymerase chain reaction
Programmed death-ligand 1
The authors thank Makoto Saito, the Senior Biostatistician at the Office for Clinical Research Support in Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital for statistical advice. The authors would like to thank Enago (http://www.enago.jp) for the English language review.
This report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
There are no conflicts of interest.
The study protocol was approved by the Ethics Committee of the Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital and was conducted according to the Declaration of Helsinki.
The Ethics Committee of the Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital waive the requirement for the investigator to obtain a signed consent form for participants.
Research involving human participants and/or animals
- Lee CK et al (2015) Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol 33:1958–1965. https://doi.org/10.1200/JCO.2014.58.1736 CrossRefPubMedGoogle Scholar
- Lin C et al (2015) Programmed death-ligand 1 expression predicts tyrosine kinase inhibitor response and better prognosis in a cohort of patients with epidermal growth factor receptor mutation-positive lung adenocarcinoma. Clin Lung Cancer 16:e25–e35. https://doi.org/10.1016/j.cllc.2015.02.002 CrossRefPubMedGoogle Scholar
- Mitsudomi T et al (2010) Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11:121–128. https://doi.org/10.1016/S1470-2045(09)70364-X CrossRefPubMedGoogle Scholar
- Nagai Y et al (2005) Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp. Cancer Res 65:7276–7282. https://doi.org/10.1158/0008-5472.CAN-05-0331 CrossRefPubMedGoogle Scholar
- Rosell R et al (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13:239–246 https://doi.org/10.1016/S1470-2045(11)70393-X CrossRefPubMedGoogle Scholar
- Shim HS, Lee da H, Park EJ, Kim SH (2011) Histopathologic characteristics of lung adenocarcinomas with epidermal growth factor receptor mutations in the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification. Arch Pathol Lab Med 135:1329–1334. https://doi.org/10.5858/arpa.2010-0493-OA CrossRefPubMedGoogle Scholar
- Streicher K et al (2017) Increased CD73 and reduced IFNG signature expression in relation to response rates to anti-PD-1(L1) therapies in EGFR-mutant NSCLC. J Clin Oncol 35:11505–11505. https://doi.org/10.1200/JCO.2017.35.15_suppl.11505 CrossRefGoogle Scholar