Prognostic value of tumor-infiltrating lymphocytes for patients with completely resected stage IIIA(N2) non-small cell lung cancer
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Wen Feng1,2,*, Yuan Li3,*, Lei Shen3, Xu-Wei Cai1, Zheng-Fei Zhu2, Jian-Hua Chang4, Jia-Qing Xiang5, Ya-Wei Zhang5, Hai-Quan Chen5, Xiao-Long Fu1,2
1Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
2Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
4Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
5Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
*These authors contributed equally to this work
Xiao-Long Fu, e-mail: firstname.lastname@example.org
Keywords: lymphocytic infiltration, non-small cell lung cancer, prognosis, survival, tumor-infiltrating lymphocytes
Received: August 09, 2015 Accepted: January 01, 2016 Published: January 22, 2016
Background: The 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.
Methods: From 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.
Results: Data 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).
Conclusions: Our 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.
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