Neutrophil‑to‑lymphocyte ratio reflects lung injury in thoracic radiotherapy and immune checkpoint inhibitors combination therapy with different sequences

Tong,Anna; Wang,Zewen; Wang,Sinian; Li,Xiaoxue; Jiang,Qisheng; Li,Fengsheng; Yan,Peng

doi:10.3892/mco.2024.2718

Neutrophil‑to‑lymphocyte ratio reflects lung injury in thoracic radiotherapy and immune checkpoint inhibitors combination therapy with different sequences

Authors:
- Anna Tong
- Zewen Wang
- Sinian Wang
- Xiaoxue Li
- Qisheng Jiang
- Fengsheng Li
- Peng Yan
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Affiliations: Radiation Oncology Department, 960 Hospital of the PLA Joint Logistics Support Force, Jinan, Shandong 250031, P.R. China, Oncology Department, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, P.R. China, Department of Nuclear Radiation Injury and Monitoring, The PLA Rocket Force Characteristic Medical Center, Beijing 100032, P.R. China, Pathology Department, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, P.R. China
Published online on: January 18, 2024 https://doi.org/10.3892/mco.2024.2718
Article Number: 20
Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The combination of thoracic radiotherapy and immune checkpoint inhibitors (ICIs) has emerged as a novel treatment approach for malignant tumors. However, it is important to consider the potential exacerbation of lung injury associated with this treatment modality. The neutrophil‑to‑lymphocyte ratio (NLR), an inflammatory marker, holds promise as a non‑invasive indicator for assessing the toxicity of this combination therapy. To investigate this further, a study involving 80 patients who underwent thoracic radiotherapy in conjunction with ICIs was conducted. These patients were divided into two groups: The concurrent therapy group and the sequential therapy group. A logistic regression analysis was conducted to ascertain risk factors for grade ≥2 pneumonitis. Following propensity score matching, the NLR values were examined between the concurrent group and the sequential group to evaluate any disparity. A mouse model of radiation pneumonitis was established, and ICIs were administered at varying time points. The morphological evaluation of lung injury was conducted using H&E staining, while the NLR values of peripheral blood were detected through flow cytometry. Logistic regression analysis revealed that radiation dosimetric parameters (mean lung dose, total dose and V20), the inflammatory index NLR at the onset of pneumonitis, and treatment sequences (concurrent or sequential) were identified as independent predictors of grade ≥2 treatment‑related pneumonitis. The results of the morphological evaluation indicated that the severity of lung tissue injury was greater in cases where programmed cell death protein 1 (PD‑1) blockade was administered during thoracic radiotherapy, compared with cases where PD‑1 blockade was administered 14 days after radiotherapy. Moreover, the present study demonstrated that the non‑invasive indicator known as the NLR has the potential to accurately reflect the aforementioned injury.

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