Elisabeth Brambilla1, Gwénaël Le Teuff2, Sophie Marguet2, Sylvie Lantuejoul2, Ariane Dunant2, Stephen Graziano2, Robert Pirker2, Jean-Yves Douillard2, Thierry Le Chevalier2, Martin Filipits2, Rafael Rosell2, Robert Kratzke2, Helmut Popper2, Jean-Charles Soria2, Frances A Shepherd2, Lesley Seymour2, Ming Sound Tsao2. 1. Elisabeth Brambilla and Sylvie Lantuejoul, Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale U823; and Centre Hospitalier Universitaire Albert Michallon, Grenoble; Gwénaël Le Teuff, Sophie Marguet, Ariane Dunant, Thierry Le Chevalier, and Jean-Charles Soria, Institut Gustave Roussy, Villejuif; Gwénaël Le Teuff, Sophie Marguet, Ariane Dunant, Thierry Le Chevalier, and Jean-Charles Soria, Université Paris-Sud, Orsay; Gwénaël Le Teuff, Université Paris-Saclay, Saint-Aubin; Jean-Yves Douillard, Centre René Gauducheau Institut de Cancerologie de l'Ouest, Saint-Herblain, France; Stephen Graziano, State University of New York Upstate Medical University, Syracuse, NY; Robert Pirker and Martin Filipits, Medical University of Vienna, Vienna; Helmut Popper, Medical University of Graz, Graz, Austria; Rafael Rosell, Catalan Institute of Oncology, Barcelona, Spain; Robert Kratzke, University of Minnesota, Minneapolis, MN; Frances A. Shepherd and Ming Sound Tsao, Princess Margaret Cancer Centre; Frances A. Shepherd and Ming Sound Tsao, University of Toronto, Toronto; and Lesley Seymour, Queen's University, Kingston, Ontario, Canada. ebrambilla@chu-grenoble.fr. 2. Elisabeth Brambilla and Sylvie Lantuejoul, Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale U823; and Centre Hospitalier Universitaire Albert Michallon, Grenoble; Gwénaël Le Teuff, Sophie Marguet, Ariane Dunant, Thierry Le Chevalier, and Jean-Charles Soria, Institut Gustave Roussy, Villejuif; Gwénaël Le Teuff, Sophie Marguet, Ariane Dunant, Thierry Le Chevalier, and Jean-Charles Soria, Université Paris-Sud, Orsay; Gwénaël Le Teuff, Université Paris-Saclay, Saint-Aubin; Jean-Yves Douillard, Centre René Gauducheau Institut de Cancerologie de l'Ouest, Saint-Herblain, France; Stephen Graziano, State University of New York Upstate Medical University, Syracuse, NY; Robert Pirker and Martin Filipits, Medical University of Vienna, Vienna; Helmut Popper, Medical University of Graz, Graz, Austria; Rafael Rosell, Catalan Institute of Oncology, Barcelona, Spain; Robert Kratzke, University of Minnesota, Minneapolis, MN; Frances A. Shepherd and Ming Sound Tsao, Princess Margaret Cancer Centre; Frances A. Shepherd and Ming Sound Tsao, University of Toronto, Toronto; and Lesley Seymour, Queen's University, Kingston, Ontario, Canada.
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.
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.
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