Prognostic effect of tumor lymphocytic infiltration in resectable non-small-cell lung cancer

Elisabeth Brambilla, Gwénaël Le Teuff, Sophie Marguet, Sylvie Lantuejoul, Ariane Dunant, Stephen Graziano, Robert Pirker, Jean Yves Douillard, Thierry Le Chevalier, Martin Filipits, Rafael Rosell, Robert Kratzke, Helmut Popper, Jean Charles Soria, Frances A. Shepherd, Lesley Seymour, Ming Sound Tsao

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168 Scopus citations

Abstract

Purpose Tumor lymphocytic infiltration (TLI) has differing prognostic value among various cancers. The objective of this study was to assess the effect of TLI in lung cancer. Patients and Methods A discovery set (one trial, n = 824) and a validation set (three trials, n = 984) that evaluated the benefit of platinum-based adjuvant chemotherapy in non'small-cell lung cancer were used as part of the LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) study. TLI was defined as intense versus nonintense. The main end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs associated with TLI were estimated through a multivariable Cox model in both sets. TLI-histology and TLI-treatment interactions were explored in the combined set. Results Discovery and validation sets with complete data included 783 (409 deaths) and 763 (344 deaths) patients, respectively. Median follow-up was 4.8 and 6 years, respectively. TLI was intense in 11% of patients in the discovery set compared with 6% in the validation set (P < .001). The prognostic value of TLI in the discovery set (OS: HR, 0.56; 95% CI, 0.38 to 0.81; P = .002; DFS: HR, 0.59; 95% CI, 0.42 to 0.83; P = .002; SDFS: HR, 0.56; 95% CI, 0.38 to 0.82; P = .003) was confirmed in the validation set (OS: HR, 0.45; 95% CI, 0.23 to 0.85; P = .01; DFS: HR, 0.44; 95%CI, 0.24 to 0.78; P = .005; SDFS: HR, 0.42; 95% CI, 0.22 to 0.80; P = .008) with no heterogeneity across trials (P$ .38 for all end points). No significant predictive effect was observed for TLI (P ≥ .78 for all end points). Conclusion Intense lymphocytic infiltration, found in a minority of tumors, was validated as a favorable prognostic marker for survival in resected non'small-cell lung cancer.

Original languageEnglish (US)
Pages (from-to)1223-1230
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number11
DOIs
StatePublished - Apr 10 2016

Bibliographical note

Funding Information:
Supported by research grants from Ligue Nationale Contre le Cancer (France); le Programme National d'Excellence Specialis? cancer du poumon de l'Institut National du Cancer (France); National Cancer Institute (United States); Canadian Cancer Society Research Institute (Canada); an unrestricted grant from Sanofi; personal funding from the investigators; the Gustave Roussy Foundation; the Princess Margaret Cancer Foundation; and European contract EU-FP7 Curelung, Plateforme Detection Mol? culaire In Situ of Centre Hospitalier Universitaire Grenoble, D? l? gation ? la Recherche Clinique et ? l'innovation.

Publisher Copyright:
© 2016 by American Society of Clinical Oncology.

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