Gao Xiao, Xiong Jie, Huang Xin-Yun, Yang Hao-Xu, Zhong Hui-Juan, Cheng Shu, Jiang Xu-Feng, Zhao Wei-Li
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Department of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Oncologist. 2025 Jun 4;30(6). doi: 10.1093/oncolo/oyaf164.
The post-treatment Deauville scale (DS) and circulating Epstein-Barr virus (EBV)-DNA were used for prediction of long-term remission in natural killer/T-cell lymphoma (NKTCL). However, the baseline biomarkers still remain lacking for clinical application. Here, we hypothesized that 18F-FDG PET/CT, as a measure of total tumor burden, would be a baseline biomarker to identify high-risk NKTCL patients.
We analyzed PET/CT data in early-stage NKTCL patients (n = 192) receiving pegaspargase-based regimens from 2 independent clinical trials. The prognostic values of radiomic markers including total lesion glycolysis (TLG), standardized uptake value, and metabolic tumor volume were evaluated in the training (n = 127) and validation cohorts (n = 65) with a median follow-up of 37 months.
Total lesion glycolysis was a prognosticator of progression-free survival (PFS) and overall survival (OS), with 86.11% and 91.30% sensitivity and 55.77% and 53.25% specificity, respectively, which outperformed the risk model based on posttreatment DS and circulating EBV-DNA (sensitivity 53.85% and specificity 54.24% for PFS, sensitivity 43.75% and specificity 52.34% for OS). Five-year PFS and OS were 92.19% and 96.82% in the low TLG group (<75 g), versus 69.46% and 77.24% in the high TLG group (≥75 g). ScRNA-seq (n = 10) and bulk RNA-seq (n = 65) data from patients in the trials both revealed that inflammatory dendritic cells, as immunosuppressive signature, were significantly infiltrated in patients with high TLG compared with patients with low TLG.
Baseline TLG reflected an immunosuppressive microenvironment and was an effective radiomic marker for long-term remission in patients with early-stage NKTCL.
治疗后多维尔量表（DS）和循环中的爱泼斯坦-巴尔病毒（EBV）-DNA用于预测自然杀伤/T细胞淋巴瘤（NKTCL）的长期缓解情况。然而，临床应用中仍缺乏基线生物标志物。在此，我们假设18F-FDG PET/CT作为总肿瘤负荷的一种测量方法，将是识别高危NKTCL患者的基线生物标志物。
我们分析了来自2项独立临床试验的接受聚乙二醇天冬酰胺酶方案治疗的早期NKTCL患者（n = 192）的PET/CT数据。在中位随访37个月的训练队列（n = 127）和验证队列（n = 65）中评估了包括总病变糖酵解（TLG）、标准化摄取值和代谢肿瘤体积在内的放射组学标志物的预后价值。
总病变糖酵解是无进展生存期（PFS）和总生存期（OS）的预后指标，敏感性分别为86.11%和91.30%，特异性分别为55.77%和53.25%，优于基于治疗后DS和循环EBV-DNA的风险模型（PFS的敏感性为53.85%，特异性为54.24%；OS的敏感性为43.75%，特异性为52.34%）。低TLG组（<75 g）的5年PFS和OS分别为92.19%和96.82%，而高TLG组（≥75 g）分别为69.46%和77.24%。试验中患者的单细胞RNA测序（n = 10）和批量RNA测序（n = 65）数据均显示，与低TLG患者相比，高TLG患者中作为免疫抑制特征的炎性树突状细胞显著浸润。
基线TLG反映了免疫抑制微环境，是早期NKTCL患者长期缓解的有效放射组学标志物。
