Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma

Abstract While next-generation sequencing (NGS) is used to guide therapy in patients with metastatic lung adenocarcinoma (LUAD), use of NGS to determine pathologic LN metastasis prior to surgery has not been assessed. To bridge this knowledge gap, we performed NGS using MSK-IMPACT in 426 treatment-n...

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Autores principales:	Raul Caso, James G. Connolly, Jian Zhou, Kay See Tan, James J. Choi, Gregory D. Jones, Brooke Mastrogiacomo, Francisco Sanchez-Vega, Bastien Nguyen, Gaetano Rocco, Daniela Molena, Smita Sihag, Prasad S. Adusumilli, Matthew J. Bott, David R. Jones
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/20e2c3f365ef4a4b89f96ace034d68c1
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spelling	oai:doaj.org-article:20e2c3f365ef4a4b89f96ace034d68c12021-12-02T16:17:16ZPreoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma10.1038/s41698-021-00210-22397-768Xhttps://doaj.org/article/20e2c3f365ef4a4b89f96ace034d68c12021-07-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00210-2https://doaj.org/toc/2397-768XAbstract While next-generation sequencing (NGS) is used to guide therapy in patients with metastatic lung adenocarcinoma (LUAD), use of NGS to determine pathologic LN metastasis prior to surgery has not been assessed. To bridge this knowledge gap, we performed NGS using MSK-IMPACT in 426 treatment-naive patients with clinical N2-negative LUAD. A multivariable logistic regression model that considered preoperative clinical and genomic variables was constructed. Most patients had cN0 disease (85%) with pN0, pN1, and pN2 rates of 80%, 11%, and 9%, respectively. Genes altered at higher rates in pN-positive than in pN-negative tumors were STK11 (p = 0.024), SMARCA4 (p = 0.006), and SMAD4 (p = 0.011). Fraction of genome altered (p = 0.037), copy number amplifications (p = 0.001), and whole-genome doubling (p = 0.028) were higher in pN-positive tumors. Multivariable analysis revealed solid tumor morphology, tumor SUVmax, clinical stage, SMARCA4 and SMAD4 alterations were independently associated with pathologic LN metastasis. Incorporation of clinical and tumor genomic features can identify patients at risk of pathologic LN metastasis; this may guide therapy decisions before surgical resection.Raul CasoJames G. ConnollyJian ZhouKay See TanJames J. ChoiGregory D. JonesBrooke MastrogiacomoFrancisco Sanchez-VegaBastien NguyenGaetano RoccoDaniela MolenaSmita SihagPrasad S. AdusumilliMatthew J. BottDavid R. JonesNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Raul Caso James G. Connolly Jian Zhou Kay See Tan James J. Choi Gregory D. Jones Brooke Mastrogiacomo Francisco Sanchez-Vega Bastien Nguyen Gaetano Rocco Daniela Molena Smita Sihag Prasad S. Adusumilli Matthew J. Bott David R. Jones Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma
description	Abstract While next-generation sequencing (NGS) is used to guide therapy in patients with metastatic lung adenocarcinoma (LUAD), use of NGS to determine pathologic LN metastasis prior to surgery has not been assessed. To bridge this knowledge gap, we performed NGS using MSK-IMPACT in 426 treatment-naive patients with clinical N2-negative LUAD. A multivariable logistic regression model that considered preoperative clinical and genomic variables was constructed. Most patients had cN0 disease (85%) with pN0, pN1, and pN2 rates of 80%, 11%, and 9%, respectively. Genes altered at higher rates in pN-positive than in pN-negative tumors were STK11 (p = 0.024), SMARCA4 (p = 0.006), and SMAD4 (p = 0.011). Fraction of genome altered (p = 0.037), copy number amplifications (p = 0.001), and whole-genome doubling (p = 0.028) were higher in pN-positive tumors. Multivariable analysis revealed solid tumor morphology, tumor SUVmax, clinical stage, SMARCA4 and SMAD4 alterations were independently associated with pathologic LN metastasis. Incorporation of clinical and tumor genomic features can identify patients at risk of pathologic LN metastasis; this may guide therapy decisions before surgical resection.
format	article
author	Raul Caso James G. Connolly Jian Zhou Kay See Tan James J. Choi Gregory D. Jones Brooke Mastrogiacomo Francisco Sanchez-Vega Bastien Nguyen Gaetano Rocco Daniela Molena Smita Sihag Prasad S. Adusumilli Matthew J. Bott David R. Jones
author_facet	Raul Caso James G. Connolly Jian Zhou Kay See Tan James J. Choi Gregory D. Jones Brooke Mastrogiacomo Francisco Sanchez-Vega Bastien Nguyen Gaetano Rocco Daniela Molena Smita Sihag Prasad S. Adusumilli Matthew J. Bott David R. Jones
author_sort	Raul Caso
title	Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma
title_short	Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma
title_full	Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma
title_fullStr	Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma
title_full_unstemmed	Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma
title_sort	preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage i and ii lung adenocarcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/20e2c3f365ef4a4b89f96ace034d68c1
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Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma

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