Cerebral small vessel disease as a possibly immune-related adverse event of immunotherapy in lung cancer patients: a retrospective study

BackgroundThis clinical study aims to investigate the incidence of cerebral small vessel disease (CSVD) in lung cancer patients treated with ICIs and to analyze its risk factors by comparing the clinical features and laboratory tests in ICIs-treated lung cancer patients with or without CSVD.MethodsT...

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Main Authors: Na Wu, Dongmei Zhou, Xiaoyu Guo, Jia Liu, Jiafan Liu, Fan Liu, Xiaonan Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1645549/full
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author Na Wu
Dongmei Zhou
Xiaoyu Guo
Jia Liu
Jiafan Liu
Fan Liu
Xiaonan Wang
author_facet Na Wu
Dongmei Zhou
Xiaoyu Guo
Jia Liu
Jiafan Liu
Fan Liu
Xiaonan Wang
author_sort Na Wu
collection DOAJ
description BackgroundThis clinical study aims to investigate the incidence of cerebral small vessel disease (CSVD) in lung cancer patients treated with ICIs and to analyze its risk factors by comparing the clinical features and laboratory tests in ICIs-treated lung cancer patients with or without CSVD.MethodsThis retrospective study included 400 hospitalized patients from January 2018 to May 2024. All patients had confirmed lung cancer, received at least one cycle of ICIs, and underwent cranial MR imaging before and after ICIs treatment. Information from the medical records, including clinical features, MR imaging findings, laboratory tests, complications, treatment, and clinical outcomes, was extracted for analysis.Results104 (26%) patients with CSVD were confirmed and 53.25% were aged≥65 years. Risk factors identified as independent predictors of CSVD included age (OR, 1.03), stage IV (OR, 2.87), and hyperlipidemia (OR, 1.02). In the CSVD group, FT4 levels decreased significantly between baseline and at the time of CSVD diagnosis, from 13.21 ± 4.56 pmol/L to 11.01 ± 2.11 pmol/L. TSH levels increased from 4.12 ± 0.46 pmol/L to 4.78 ± 1.13 pmol/L, cysteine C levels increased from 1.01 ± 0.98 mg/L to 1.29 ± 0.86 mg/L, PLR increased from 164.93 ± 27.86 to 171.27 ± 32.29 and SII rose from 774.28 ± 53.57 to 790.65 ± 68.34. All of them had no significance in the Non-CSVD group. Further Cox regression analysis showed that hypothyroidism (HR=2.38; 95% CI:1.89-5.04, P=0.005) was independent risk factors for CSVD. The incidence of hypothyroidism was 19.5% (78/400), and 43.6% (34/78) among them had CSVD. As predictors of CSVD, the cut point for FT4 was 11.84 pmol/L, and for TSH, it was 4.23 pmol/L. In Survival Analysis, CSVD did not show a significant impact on the median progression-free survival (PFS) and overall survival (OS) of lung cancer patients.ConclusionThis study found that CSVD may be a related adverse event of immunotherapy in lung cancer patients. In addition to age≥65 years, hyperlipidemia and stage IV, hypothyroidism, elevated cysteine C levels, and elevated systemic inflammatory markers such as PLR and SII were further associated with an increased risk of CSVD.
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spelling doaj-art-09edfc74066c4ffa85bd384197c7e4182025-08-26T05:28:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16455491645549Cerebral small vessel disease as a possibly immune-related adverse event of immunotherapy in lung cancer patients: a retrospective studyNa Wu0Dongmei Zhou1Xiaoyu Guo2Jia Liu3Jiafan Liu4Fan Liu5Xiaonan Wang6Department of Gerontology and Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Gerontology and Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Gerontology and Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Gerontology and Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Gerontology and Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Gerontology and Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaBackgroundThis clinical study aims to investigate the incidence of cerebral small vessel disease (CSVD) in lung cancer patients treated with ICIs and to analyze its risk factors by comparing the clinical features and laboratory tests in ICIs-treated lung cancer patients with or without CSVD.MethodsThis retrospective study included 400 hospitalized patients from January 2018 to May 2024. All patients had confirmed lung cancer, received at least one cycle of ICIs, and underwent cranial MR imaging before and after ICIs treatment. Information from the medical records, including clinical features, MR imaging findings, laboratory tests, complications, treatment, and clinical outcomes, was extracted for analysis.Results104 (26%) patients with CSVD were confirmed and 53.25% were aged≥65 years. Risk factors identified as independent predictors of CSVD included age (OR, 1.03), stage IV (OR, 2.87), and hyperlipidemia (OR, 1.02). In the CSVD group, FT4 levels decreased significantly between baseline and at the time of CSVD diagnosis, from 13.21 ± 4.56 pmol/L to 11.01 ± 2.11 pmol/L. TSH levels increased from 4.12 ± 0.46 pmol/L to 4.78 ± 1.13 pmol/L, cysteine C levels increased from 1.01 ± 0.98 mg/L to 1.29 ± 0.86 mg/L, PLR increased from 164.93 ± 27.86 to 171.27 ± 32.29 and SII rose from 774.28 ± 53.57 to 790.65 ± 68.34. All of them had no significance in the Non-CSVD group. Further Cox regression analysis showed that hypothyroidism (HR=2.38; 95% CI:1.89-5.04, P=0.005) was independent risk factors for CSVD. The incidence of hypothyroidism was 19.5% (78/400), and 43.6% (34/78) among them had CSVD. As predictors of CSVD, the cut point for FT4 was 11.84 pmol/L, and for TSH, it was 4.23 pmol/L. In Survival Analysis, CSVD did not show a significant impact on the median progression-free survival (PFS) and overall survival (OS) of lung cancer patients.ConclusionThis study found that CSVD may be a related adverse event of immunotherapy in lung cancer patients. In addition to age≥65 years, hyperlipidemia and stage IV, hypothyroidism, elevated cysteine C levels, and elevated systemic inflammatory markers such as PLR and SII were further associated with an increased risk of CSVD.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1645549/fulllung cancerimmune checkpoint inhibitorscancer immunotherapyneurological adverse eventcerebral small vessel disease
spellingShingle Na Wu
Dongmei Zhou
Xiaoyu Guo
Jia Liu
Jiafan Liu
Fan Liu
Xiaonan Wang
Cerebral small vessel disease as a possibly immune-related adverse event of immunotherapy in lung cancer patients: a retrospective study
Frontiers in Immunology
lung cancer
immune checkpoint inhibitors
cancer immunotherapy
neurological adverse event
cerebral small vessel disease
title Cerebral small vessel disease as a possibly immune-related adverse event of immunotherapy in lung cancer patients: a retrospective study
title_full Cerebral small vessel disease as a possibly immune-related adverse event of immunotherapy in lung cancer patients: a retrospective study
title_fullStr Cerebral small vessel disease as a possibly immune-related adverse event of immunotherapy in lung cancer patients: a retrospective study
title_full_unstemmed Cerebral small vessel disease as a possibly immune-related adverse event of immunotherapy in lung cancer patients: a retrospective study
title_short Cerebral small vessel disease as a possibly immune-related adverse event of immunotherapy in lung cancer patients: a retrospective study
title_sort cerebral small vessel disease as a possibly immune related adverse event of immunotherapy in lung cancer patients a retrospective study
topic lung cancer
immune checkpoint inhibitors
cancer immunotherapy
neurological adverse event
cerebral small vessel disease
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1645549/full
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