Evaluation of Pathologic Response in Lymph Nodes of Patients With Lung Cancer Receiving Neoadjuvant Chemotherapy

Abstract

Introduction: Major pathologic response (MPR), defined as residual viable tumor of less than or equal to 10%, currently serves as a surrogate end point for survival for patients with resectable NSCLC after neoadjuvant chemotherapy. However, the significance of pathologic response in lymph nodes harboring metastatic tumors in such patients remains uncertain. Therefore, we studied the effect of neoadjuvant chemotherapy on resected positive lymph nodes and determined if the degree of pathologic response in the lymph nodes alone (LN-MPR) or in combination with that of the primary tumor (PT-MPR) was able to predict the outcome.Methods: A total of 75 patients with NSCLC who underwent neoadjuvant chemotherapy and completed surgical resection were included in this study. Tissue specimens were retrospectively evaluated by two pathologists blinded to the patients' treatments and outcomes. Specimens were reviewed for the degree of pathologic response in the primary tumor and in any involved lymph nodes. The prognostic performance of LN-MPR alone or in combination with PT-MPR with respect to overall survival (OS) was evaluated using the Kaplan-Meier method and Cox regression model.Results: LN-MPR was significantly predictive of long-term OS after neoadjuvant chemotherapy. A combination of PT-MPR with LN-MPR was significantly associated with outcome and allowed stratification of patients into three prognostic groups (p ¼ 0.001).Conclusions: LN-MPR in isolation is a reliable predictor of OS in patients with NSCLC receiving neoadjuvant chemotherapy. A combination of LN-MPR with PT-MPR seems to correlate well with the outcome and can be used to predict prognosis in this patient population.

Multi-scale characterization of tumor-draining lymph nodes in resectable lung cancer treated with neoadjuvant immune checkpoint inhibitors

“…The evaluation of primary tumor response was performed as previously described: % of residual tumor = viable tumor area/total tumor bed area, whereby the total tumor bed = residual viable tumors + regression bed + necrosis. 30 , 31 …”

Pathological Response and Immune Biomarker Assessment in Non-Small-Cell Lung Carcinoma Receiving Neoadjuvant Immune Checkpoint Inhibitors

“…PR has also been evaluated in metastatic lymph nodes resected after neoadjuvant chemotherapy, and studies have shown that patients with MPR-positive lymph nodes have a better survival than those with MPR-negative lymph nodes; however, there is still no consensus on cut-offs to define MPR in lymph nodes [ 33 , 34 ]. Of note, Pater et al [ 33 ] showed that, among patients with resectable NSCLC treated with neoadjuvant chemotherapy that did not achieve MPR in primary tumors, patients with MPR-positive lymph nodes, defined as a percentage of the viable tumor <70%, have better outcomes than patients with MPR-negative lymph nodes, suggesting that this information may help to better stratify patients for prognosis. Nevertheless, the clinical impact of evaluating MPR in lymph nodes, as well as its diagnostic reproducibility among pathologists, is still under investigation [ 28 ].…”

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“…MPR is predictive of long-term survival benefit in neoadjuvant chemotherapy-treated patients with NSCLC [ 22 – 25 ] and has been implemented as candidate surrogate endpoint for evaluating novel chemotherapies and immunotherapy response, given the rare frequency of pCR following neoadjuvant chemotherapy in NSCLC (median 4%) [ 2 ].…”