Abstract
BackgroundThe patient prognosis after complete resection for pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) remains a significant concern. The clinical relevance of the host immune response to NSCLC has yet to be established. We aimed to investigate the prognostic value of tumor-infiltrating lymphocytes (TILs) in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC.MethodsFrom 2005 to 2012, consecutive patients with pathologic stage IIIA(N2) NSCLC who underwent complete resection at our institution were reviewed. For each case, full-face hematoxylin and eosin-stained sections from surgical specimens were evaluated for the TIL density. A published, recommended TIL scoring scale was followed. The patients were stratified into the TIL− or TIL+ group based on pathologic evaluation.ResultsData from 320 patients were included in the analysis. Based on a median follow-up duration of 30.8 months, a higher density of TILs was associated with an improved postoperative survival time (P = 0.06). Subgroup analyses indicated that this positive effect was the greatest for patients with squamous cell carcinoma (SCC; P = 0.03). Among those with SCC, the TIL+ patients experienced a significantly increased 3-year distant metastasis-free survival (DMFS) compared to the TIL− patients (60.6% versus 42.7%, P = 0.02). Multivariate analyses of the 93 patients with SCC tumors confirmed that TIL+ was an independent prognostic factor for an increased DMFS (HR = 0.39, 95%CI 0.17–0.87, P = 0.02) and a prolonged overall survival (OS; HR = 0.47, 95%CI 0.22–1.00, P = 0.05).ConclusionsOur data suggest a potential role of TILs in predicting the survival of patients with completely resected stage IIIA(N2) NSCLC. The beneficial effects of TILs were more pronounced in the prediction of the DMFS and the OS in patients with SCC. This parameter should be considered for prospective inclusion in clinical trials.
Highlights
Stage IIIA(N2) non-small cell lung cancer (NSCLC) consists a heterogeneous group of patients with distinct clinical subsets that can be classified as follows:1) stageIIIA-1/IIIA-2, incidental mediastinal nodal involvement, found either intraoperatively in a single station or in the final pathological examination of the surgical specimen; 2) stage IIIA-3, clinical single station or multistation N2 node(s) involvement documented by computed www.impactjournals.com/oncotarget tomography (CT) and/or positron emission tomography (PET)/CT imaging; and 3) stage IIIA-4, bulky or fixed cN2 involvement identified at imaging [1]
The international guidelines recommend that patients with occult-positive N2 nodes that are discovered at the time of pulmonary resection should continue with the planned resection along with formal mediastinal lymph node dissection and that patients with minimal N2 disease could be considered for a multimodality approach that includes surgical resection [1,2,3]
We evaluated patients with occult N2 identified after complete resection (IIIA-1, IIIA-2) and minimal N2 disease identified by CT or PET/CT imaging (IIIA-3)
Summary
Stage IIIA(N2) non-small cell lung cancer (NSCLC) consists a heterogeneous group of patients with distinct clinical subsets that can be classified as follows:1) stageIIIA-1/IIIA-2, incidental mediastinal nodal involvement, found either intraoperatively in a single station or in the final pathological examination of the surgical specimen; 2) stage IIIA-3, clinical single station or multistation N2 node(s) involvement documented by computed www.impactjournals.com/oncotarget tomography (CT) and/or positron emission tomography (PET)/CT imaging; and 3) stage IIIA-4, bulky or fixed cN2 involvement identified at imaging [1]. The postoperative radiotherapy (PORT) meta-analysis [6] described a relative increase in the risk of death with the addition of PORT for completely resected NSCLC This detrimental effect was evident among patients who had no mediastinal involvement, whereas in patients with stage III and pN2 disease, a slight increase in survival was detected, the difference was not statistically significant. Patients with completely resected stage IIIA(N2) NSCLC had a 5-year OS rate of 32.8%; and even after complete resection and POCT, a significant proportion of these patients developed distant metastasis [15, 16] These findings provided the impetus for identifying patients who are at high risk of recurrence and exploring novel therapeutic approaches for improving patient survival. We aimed to investigate the prognostic value of tumor-infiltrating lymphocytes (TILs) in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC
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