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Journal of Cancer Research and Clinical Oncology

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01-09-2019 | Metastasis | Original Article – Clinical Oncology

Synchronicity of genetic variants between primary sites and metastatic lymph nodes, and prognostic impact in nodal metastatic lung adenocarcinoma

Authors: Masaoki Ito, Yoshihiro Miyata, Shoko Hirano, Shingo Kimura, Fumiko Irisuna, Kyoko Ikeda, Kei Kushitani, Naoto Kishi, Yasuhiro Tsutani, Yukio Takeshima, Morihito Okada

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2019

Abstract

Purpose

Nodal positive lung adenocarcinoma includes wide range of survival. Several methods for the classification of nodal-positive lung cancer have been proposed. However, classification considering the impact of targetable genetic variants are lacking. The possibility of genetic variants for the better stratification of nodal positive lung adenocarcinoma was estimated.

Methods

Mutations of 36 genes between primary sites and metastatic lymph nodes (LNs) were compared using next-generation sequencing. Subsequently, mutations in EGFR and BRAF, rearrangements in ALK and ROS1 were evaluated in 69 resected pN1–2M0 adenocarcinoma cases. Recurrence-free survival (RFS), post-recurrence survival (PRS), and overall survival (OS) were evaluated with respect to targetable variants and tyrosine kinase inhibitor (TKI) therapy after recurrence.

Results

About 90% of variants were shared and allele frequencies were similar between primary and metastatic sites. In 69 pN1–2M0 cases, EGFR/ALK were positive in primary sites of 39 cases and same EGFR/ALK variants were confirmed in metastatic LNs of 96.7% tissue-available cases. Multivariate analyses indicated positive EGFR/ALK status was associated with worse RFS (HR 2.366; 95% CI 1.244–4.500; P = 0.009), and PRS was prolonged in cases receiving TKI therapy (no post-recurrence TKI therapies, HR 3.740; 95% CI 1.449–9.650; P = 0.006). OS did not differ with respect to targetable variants or TKI therapy.

Conclusions

Cases harbouring targetable genetic variants had a higher risk of recurrence, but PRS was prolonged by TKI therapy. Classification according to the targetable genetic status provides a basis for predicting recurrence and determining treatment strategies after recurrence.

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Title: Synchronicity of genetic variants between primary sites and metastatic lymph nodes, and prognostic impact in nodal metastatic lung adenocarcinoma
Authors: Masaoki Ito
Yoshihiro Miyata
Shoko Hirano
Shingo Kimura
Fumiko Irisuna
Kyoko Ikeda
Kei Kushitani
Naoto Kishi
Yasuhiro Tsutani
Yukio Takeshima
Morihito Okada
Publication date: 01-09-2019
Publisher: Springer Berlin Heidelberg
Keywords: Metastasis
Tyrosine Kinase Inhibitors
Tyrosine Kinase Inhibitors
Published in: Journal of Cancer Research and Clinical Oncology / Issue 9/2019
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02978-0

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