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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Acknowledgements
This work was partially conducted at the Analysis Center of Life Science, Natural Science Center for Basic Research and Development, Hiroshima University (Hiroshima, Japan). The authors would like to thank Editage (http://www.editage.jp) for English language editing.
Funding
This work was supported by the Japan Society for the Promotion of Science (JSPS KAKENHI Grant number 15K19938) and ESTS-ACECP travelling fellowship 2013.
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Ito, M., Miyata, Y., Hirano, S. et al. Synchronicity of genetic variants between primary sites and metastatic lymph nodes, and prognostic impact in nodal metastatic lung adenocarcinoma. J Cancer Res Clin Oncol 145, 2325–2333 (2019). https://doi.org/10.1007/s00432-019-02978-0
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DOI: https://doi.org/10.1007/s00432-019-02978-0