Abstract
Background/aimmmune checkpoint inhibition (CPI) has an increasing impact in the multimodal treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Increasing evidence suggests treatment outcome depending on tumor cell PD-L1 expression. The purpose of this retrospective study was to investigate the prognostic value of PD-L1 expression on tumor cells in combination with CD8+ tumor stroma-infiltrating lymphocyte (TIL) density in inoperable LA-NSCLC treated with concurrent chemoradiotherapy (CRT).Patients and methodWe retrospectively assessed clinical characteristics and initial tumor biopsy samples of 31 inoperable LA-NSCLC patients treated with concurrent CRT. Prognostic impact of tumor cell PD-L1 expression (0% versus ≥1%) and CD8+ TIL density (0–40% vs. 41–100%) for local control, progression-free (PFS) and overall survival (OS) as well as correlations with clinicopathological features were evaluated.ResultsMedian OS was 14 months (range: 3–167 months). The OS rates at 1- and 2 years were 68 and 20%. Local control of the entire cohort at 1 and 2 years were 74 and 61%. Median PFS, 1-year and 2-year PFS were 13 ± 1.4 months, 58 and 19%. PD-L1 expression < 1% on tumor cells was associated with improved OS, PFS and local control in patients treated with concurrent CRT. Univariate analysis showed a trend towards improved OS and local control in patients with low CD8+ TIL density. Evaluation of Tumor Immunity in the MicroEnvironment (TIME) appears to be an independent prognostic factor for local control, PFS and OS. The longest and shortest OS were achieved in patients with type I (PD-L1neg/CD8low) and type IV (PD-L1pos/CD8low) tumors (median OS: 57 ± 37 vs. 10 ± 5 months, p = 0.05), respectively.ConclusionAssessment of PD-L1 expression on tumor cells in combination with CD8+ TIL density can be a predictive biomarker in patients with inoperable LA-NSCLC treated with concurrent CRT.
Highlights
Lung cancer remains the leading cause of cancer-related mortality worldwide [1,2,3]
programmed cell death 1 ligand 1 (PD-L1) expression < 1% on tumor cells was associated with improved overall survival (OS), progression-free survival (PFS) and local control in patients treated with concurrent CRT
Assessment of PD-L1 expression on tumor cells in combination with CD8+ tumor stroma-infiltrating lymphocyte (TIL) density can be a predictive biomarker in patients with inoperable LA-NSCLC treated with concurrent CRT
Summary
Lung cancer remains the leading cause of cancer-related mortality worldwide [1,2,3]. Locally-advanced non-small cell lung cancer (LA-NSCLC) represents as a heterogeneous disease including large tumor volume, extensive lymph node involvement, tumor-related atelectasis and infiltration of the thoracic wall, mediastinum and spine [4,5,6]. In 2015, the first programmed cell death protein 1 (PD-1) inhibitor (nivolumab) was approved by the Food and Drug Administration (FDA) for advanced or metastatic NSCLC in the second-line setting following progression during or after platinum-based chemotherapy [13, 14]. In 2016, the FDA approved monotherapy with the PD-1 inhibitor pembrolizumab in the first-line setting for patients with metastatic NSCLC with programmed cell death 1 ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥ 50% and expanded the indication in April 2019 based on the results of the KEYNOTE-042 trial for the firstline treatment of patients with stage III patients who are not candidates for surgical resection or definitive CRT or metastatic NSCLC with TPS ≥ 1% determined by an FDAapproved test. Patients’ tumors had no Epidermal Growth Factor Receptor (EGFR) or Anaplastic lymphoma kinase (ALK) genomic aberrations [15, 16]
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