ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicNew Challenges in Cancer Immunotherapy: Mechanisms, Translational Approaches, and Pan-Tumor StrategiesView all 11 articles
Prognostic Significance of Baseline Systemic Inflammation Markers in PD-L1-Negative Advanced Non-Small Cell Lung Cancer Patients Treated with the BRICS Sequential Regimen
Provisionally accepted
- 1Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
- 2900th Hospital of the People's Liberation Army Joint Logistic Support Force, Fuzhou, China
- 3The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
- 4People's Hospital of Quzhou, Quzhou, China
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Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality, with PD-L1-negative tumors exhibiting poor response to immune checkpoint inhibitors (ICIs) and chemotherapy. The multimodal BRICS regimen-integrating stereotactic body radiotherapy (SBRT), Bifidobacterium supplementation, low-dose chemotherapy, and PD-1 blockade—offers a promising approach for this high-risk subgroup. This study evaluates the prognostic role of baseline systemic inflammation markers in this context. Methods: A retrospective analysis included 23 PD-L1-negative (TPS <1%), EGFR/ALK wild-type advanced NSCLC patients treated with BRICS (2018–2024). Pretreatment markers (e.g., CLR, LDH) were assessed from blood samples. The sequential regimen involved: (1) SBRT (24 Gy/3 fractions); (2) oral probiotics (6 g/day); (3) nab-paclitaxel (200 mg); and (4) anti-PD-1 antibody over six 21-day cycles. Primary endpoints were progression-free survival (PFS) and overall survival (OS), analyzed via Cox regression and Kaplan-Meier curves. Results: Efficacy outcomes were robust: objective response rate 74.0%, disease control rate 95.7%, median PFS 16.0 months (95% CI: 9.11–22.89), and median OS 32.7 months (95% CI: 11.53–53.87). Univariate analysis showed elevated CLR predicted increased progression risk (HR=2.907, p=0.04) and death risk (HR=2.995, p=0.049), while high LDH correlated with worse PFS (HR=3.448, p=0.013) and OS (HR=3.016, p=0.041). Subgroup stratification confirmed shorter median PFS (7.10 vs. 20.0 months, p=0.008) and OS (9.20 vs. 36.20 months, p=0.031) for high LDH (≥250 U/L), and reduced PFS (14.20 vs. 19.10 months, p=0.032) and OS (17.70 vs. 36.20 months, p=0.038) for high CLR (≥10). Conclusion: Baseline CLR and LDH are independent prognostic biomarkers for PD-L1-negative NSCLC patients receiving BRICS, reflecting systemic inflammation that may limit efficacy. These markers could optimize patient stratification and guide personalized therapy.
Keywords: Non-small cell lung cancer, C-reactive protein-to-lymphocyte ratio, Lactate dehydrogenase, Prognostic biomarkers, systemic inflammation markers
Received: 15 Aug 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Chen, Lin, Wang, Wang, Peng and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jian Wang
Zongyang Yu
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