Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non-Small-Cell Lung Cancer

J Clin Oncol. 2016 Apr 10;34(11):1223-30. doi: 10.1200/JCO.2015.63.0970. Epub 2016 Feb 1.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Reproducibility of Results

Substances

  • Cisplatin