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.
Highlights
Lung adenocarcinoma (LUAD) is the most common histologic subtype of non-small cell lung cancer (NSCLC)[1] and is associated with a higher risk of occult lymph node (LN) metastasis than other NSCLC tumors[2,3]
The ability to better predict pathologic LN metastasis would allow the identification of subgroups of patients who may benefit from neoadjuvant therapy before tumor resection
We found that, of 362 patients with cN0 disease, 15% (n = 54) had pathologic LN metastasis at the time of surgery
Summary
Lung adenocarcinoma (LUAD) is the most common histologic subtype of non-small cell lung cancer (NSCLC)[1] and is associated with a higher risk of occult lymph node (LN) metastasis than other NSCLC tumors[2,3]. These include centrally located tumors, large tumor size, high primary tumor maximum standardized uptake value (SUVmax), positive N1 nodes on PET/CT, and micropapillary histologic pattern[8,9,14,15]. It is unknown whether this information could potentially guide the order of first line therapy (i.e., systemic vs local) in the future. To bridge this knowledge gap, we examined tumor genomic factors in patients with clinically N2-negative (cN0-1) LUAD and assessed their association with pathologic LN metastasis identified at surgery
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