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


Authors: Caso, R.; Connolly, J. G.; Zhou, J.; Tan, K. S.; Choi, J. J.; Jones, G. D.; Mastrogiacomo, B.; Sanchez-Vega, F.; Nguyen, B.; Rocco, G.; Molena, D.; Sihag, S.; Adusumilli, P. S.; Bott, M. J.; Jones, D. R.
Article Title: 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-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. © 2021, The Author(s).
Journal Title: npj Precision Oncology
Volume: 5
Issue: 1
ISSN: 2397-768X
Publisher: Springer Nature  
Date Published: 2021-07-21
Start Page: 70
Language: English
DOI: 10.1038/s41698-021-00210-2
PROVIDER: scopus
PMCID: PMC8295366
PUBMED: 34290393
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Matthew Bott
    136 Bott
  2. David Randolph Jones
    418 Jones
  3. Daniela   Molena
    277 Molena
  4. Kay See   Tan
    244 Tan
  5. Smita Sihag
    98 Sihag
  6. Gregory Jones
    22 Jones
  7. Raul Caso Jr
    25 Caso Jr
  8. Gaetano Rocco
    132 Rocco
  9. Jian Zhou
    6 Zhou
  10. Bastien Nguyen
    31 Nguyen
  11. James J Choi
    4 Choi