Research Article: Lymph node volume predicts survival but not nodal clearance in Stage IIIA-IIIB NSCLC

Date Published: April 20, 2017

Publisher: Public Library of Science

Author(s): Vishesh Agrawal, Thibaud P. Coroller, Ying Hou, Stephanie W. Lee, John L. Romano, Elizabeth H. Baldini, Aileen B. Chen, David Kozono, Scott J. Swanson, Jon O. Wee, Hugo J. W. L. Aerts, Raymond H. Mak, Hyun-Sung Lee.


Locally advanced non-small cell lung cancer (LA-NSCLC) patients have poorer survival and local control with mediastinal node (N2) tumor involvement at resection. Earlier assessment of nodal burden could inform clinical decision-making prior to surgery. This study evaluated the association between clinical outcomes and lymph node volume before and after neoadjuvant therapy.

CT imaging of patients with operable LA-NSCLC treated with chemoradiation and surgical resection was assessed. Clinically involved lymph node stations were identified by FDG-PET or mediastinoscopy. Locoregional recurrence (LRR), distant metastasis (DM), progression free survival (PFS) and overall survival (OS) were analyzed by the Kaplan Meier method, concordance index and Cox regression.

73 patients with Stage IIIA-IIIB NSCLC treated with neoadjuvant chemoradiation and surgical resection were identified. The median RT dose was 54 Gy and all patients received concurrent chemotherapy. Involved lymph node volume was significantly associated with LRR and OS but not DM on univariate analysis. Additionally, lymph node volume greater than 10.6 cm3 after the completion of preoperative chemoradiation was associated with increased LRR (p<0.001) and decreased OS (p = 0.04). There was no association between nodal volumes and nodal clearance. For patients with LA-NSCLC, large volume nodal disease post-chemoradiation is associated with increased risk of locoregional recurrence and decreased survival. Nodal volume can thus be used to further stratify patients within the heterogeneous Stage IIIA-IIIB population and potentially guide clinical decision-making.

Partial Text

Lung cancer accounts for the greatest number of cancer-related deaths in the United States and has a 5 year survival rate of only 18% [1]. Lung cancer remains a challenging disease to treat, particularly for patients with advanced disease. Patients with locally advanced non–small-cell lung cancer (LA NSCLC) are composed of heterogeneous Stage III patients who are candidates for therapy with chemotherapy, radiation therapy and/or surgical resection [2]. LA NSCLC patients with mediastinal nodal involvement (N2) have decreased overall survival and local control compared to patients with hilar/peribronchial nodal disease (N1) or no nodal involvement (N0) [3]. The SWOG 8805 trial demonstrated that the strongest predictor of survival for patients with LA NSCLC treated with chemoradiation followed by resection was complete nodal clearance (defined as no evidence of disease in lymph nodes at the time of resection) [4]. Subsequent studies further validated the association between increased survival rates and patients who achieve mediastinal nodal clearance or downstaging following chemoradiation and surgical resection [5–10].

Stage III NSCLC is a broad category composed of heterogeneous tumor populations. Current TNM staging accounts for anatomic lymph node involvement but does not incorporate the significant variation in tumor burden of involved lymph nodes [22]. Multiple studies have shown that mediastinal nodal clearance is a strong predictor of OS suggesting that nodal tumor burden, in addition to anatomic involvement, is an important prognostic marker of survival [5–10]. These studies suggest a clear link between local disease control and survival. Additional methods for patient stratification by tumor burden are thus relevant for guiding clinical decision-making in patients with locally advanced NSCLC.

This study demonstrates the association between lymph node size and clinical outcomes of LRR and OS before and after neoadjuvant chemoradiation for patients undergoing trimodality therapy. This data adds to the growing body of literature underscoring the importance of patient stratification using additional imaging parameters beyond TNM staging. For patients with locally advanced NSCLC, nodal size during the course of chemoradiation should thus be incorporated along with clinical characteristics to guide clinical decision-making.




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