Yamazaki Motohiko, Watanabe Satoshi, Tominaga Masaki, Yagi Takuya, Goto Yukari, Yanagimura Naohiro, Arita Masashi, Ohtsubo Aya, Tanaka Tomohiro, Nozaki Koichiro, Saida Yu, Kondo Rie, Kikuchi Toshiaki, Ishikawa Hiroyuki
Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuouku, Niigata 951-8510, Japan.
Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuouku, Niigata 951-8510, Japan.
Acad Radiol. 2025 Feb;32(2):1026-1035. doi: 10.1016/j.acra.2024.08.043. Epub 2024 Sep 2.
Immune checkpoint inhibitors (ICIs) have improved lung cancer prognosis; however, ICI-related interstitial lung disease (ILD) is fatal and difficult to predict. Herein, we hypothesized that pre-existing lung inflammation on radiological imaging can be a potential risk factor for ILD onset. Therefore, we investigated the association between high uptake in noncancerous lung (NCL) on F- FDG-PET/CT and ICI-ILD in lung cancer.
Patients with primary lung cancer who underwent FDG-PET/CT within three months prior to ICI therapy were retrospectively included. Artificial intelligence was utilized for extracting the NCL regions (background lung) from the lung contralateral to the primary tumor. FDG uptake by the NCL was assessed via the SUVmax (NCL-SUVmax), SUVmean (NCL-SUVmean), and total glycolytic activity (NCL-TGA)defined as NCL-SUVmean×NCL volume [mL]. NCL-SUVmean and NCL-TGA were calculated using the following four SUV thresholds: 0.5, 1.0, 1.5, and 2.0.
Of the 165 patients, 28 (17.0%) developed ILD. Univariate analysis showed that high values of NCL-SUVmax, NCL-SUVmean (SUV threshold=2.0), and NCL-TGA (SUV threshold=1.0) were significantly associated with ILD onset (all p = 0.003). Multivariate analysis adjusted for age, tumor FDG uptake, and pre-existing interstitial lung abnormalities revealed that a high NCL-TGA (≥149.45) was independently associated with ILD onset (odds ratio, 6.588; p = 0.002). Two-year cumulative incidence of ILD was significantly higher in the high NCL-TGA group than in the low group (58.4% vs. 14.4%; p < 0.001).
High uptake of NCL on FDG-PET/CT is correlated with ICI-ILD development, which could serve as a risk stratification tool before ICI therapy in primary lung cancer.
免疫检查点抑制剂（ICI）改善了肺癌的预后；然而，ICI相关的间质性肺疾病（ILD）是致命的且难以预测。在此，我们假设放射影像学上预先存在的肺部炎症可能是ILD发病的潜在危险因素。因此，我们研究了肺癌患者中，F-FDG-PET/CT上非癌性肺组织（NCL）的高摄取与ICI-ILD之间的关联。
回顾性纳入在ICI治疗前三个月内接受FDG-PET/CT检查的原发性肺癌患者。利用人工智能从原发肿瘤对侧的肺中提取NCL区域（背景肺组织）。通过SUVmax（NCL-SUVmax）、SUVmean（NCL-SUVmean）和总糖酵解活性（NCL-TGA，定义为NCL-SUVmean×NCL体积[mL]）评估NCL的FDG摄取情况。NCL-SUVmean和NCL-TGA使用以下四个SUV阈值计算：0.5、1.0、1.5和2.0。
165例患者中，28例（17.0%）发生了ILD。单因素分析显示，NCL-SUVmax、NCL-SUVmean（SUV阈值=2.0）和NCL-TGA（SUV阈值=1.0）的高值与ILD发病显著相关（所有p=0.003）。在对年龄、肿瘤FDG摄取和预先存在的间质性肺异常进行校正的多因素分析中，高NCL-TGA（≥149.45）与ILD发病独立相关（比值比，6.588；p=0.002）。高NCL-TGA组的ILD两年累积发病率显著高于低NCL-TGA组（58.4%对14.4%；p<0.001）。
FDG-PET/CT上NCL的高摄取与ICI-ILD的发生相关，这可作为原发性肺癌ICI治疗前的风险分层工具。
