University of Oulu

Kuusisalo, S, Tikkanen, A, Lappi-Blanco, E, et al. The prognostic and predictive roles of plasma C-reactive protein and PD-L1 in non-small cell lung cancer. Cancer Med. 2023; 12: 16087-16097. doi:10.1002/cam4.6262

The prognostic and predictive roles of plasma C-reactive protein and PD-L1 in non-small cell lung cancer

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Author: Kuusisalo, Saara1; Tikkanen, Antti1; Lappi-Blanco, Elisa2;
Organizations: 1Department of Medical Oncology and Radiotherapy and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
2Department of Pathology, Oulu University Hospital and Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
3Department of Pulmonary Medicine, Heart and Lung Center and Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
4Cancer Center, Kuopio University Hospital, Kuopio, Finland
5Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Department of Oncology, Tampere University Hospital, Tampere, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
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Language: English
Published: John Wiley & Sons, 2023
Publish Date: 2023-10-17


Background: Anti-PD-(L)1 agents have revolutionized the treatment paradigms of non-small cell lung cancer (NSCLC), while predictive biomarkers are limited. It has been previously shown that systemic inflammation, indicated by elevated C-reactive protein (CRP) level, is associated with a poor prognosis in anti-PD-(L)1 treated. The aim of the study was to analyze the prognostic and predictive value of CRP in addition to traditional prognostic and predictive markers and tumor PD-L1 score.

Methods: We identified all NSCLC patients (n = 329) who had undergone PD-L1 tumor proportion score (TPS) analysis at Oulu University Hospital 2015–22. CRP levels, treatment history, immune checkpoint inhibitor (ICI) therapy details, and survival were collected. The patients were categorized based on CRP levels (≤10 vs. >10) and PD-L1 TPS scores (<50 vs. ≥50).

Results: In the whole cohort (n = 329), CRP level of ≤10 mg/L was associated with improved survival in univariate (HR 0.30, Cl 95% 0.22–0.41) and multivariate analyzes (HR 0.44, CI 95% 0.28–0.68). With ICI treated (n = 70), both CRP of ≤10 and PD-L1 TPS of ≥50 were associated with improved progression-free survival (PFS) in univariate (HR 0.51, CI 95% 0.27–0.96; HR 0.54, CI 95% 0.28–1.02) and multivariate (HR 0.48, CI 95% 0.26–0.90; HR 0.50, CI 95% 0.26–0.95) analyzes. The combination (PD-L1 TPS ≥50 and CRP >10) carried a high negative predictive value with a median PFS of 4.11 months (CI 95% 0.00–9.63), which was similar to patients with low PD-L1 (4.11 months, CI 95% 2.61–5.60).

Conclusions: Adding plasma CRP levels to PD-L1 TPS significantly increased the predictive value of sole PD-L1. Furthermore, patients with high CRP beard little benefit from anti-PD-(L)1 therapies independent of PD-L1 score. The study highlights the combined evaluation of plasma CRP and PD-L1 TPS as a negative predictive marker for ICI therapies.

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Series: Cancer medicine
ISSN: 2045-7634
ISSN-E: 2045-7634
ISSN-L: 2045-7634
Volume: 12
Issue: 15
Pages: 16087 - 16097
DOI: 10.1002/cam4.6262
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: Study was funded by Oulu University and Finnish Cancer Society.
Copyright information: © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.