Département d'imagerie Médicale, Gustave Roussy, Université Paris-Saclay, 94800, Villejuif, France.
Department of Medicine, Division of Hematology Oncology, New York-Presbyterian Hospital/Columbia University Medical Center, New York, NY, USA.
Eur J Nucl Med Mol Imaging. 2019 Oct;46(11):2298-2310. doi: 10.1007/s00259-019-04411-7. Epub 2019 Jul 25.
An imaging-based stratification tool is needed to identify melanoma patients who will benefit from anti Programmed Death-1 antibody (anti-PD1). We aimed at identifying biomarkers for survival and response evaluated in lymphoid tissue metabolism in spleen and bone marrow before initiation of therapy.
This retrospective study included 55 patients from two institutions who underwent 18F-FDG PET/CT before anti-PD1. Parameters extracted were SUVmax, SUVmean, HISUV (SUV-based Heterogeneity Index), TMTV (total metabolic tumor volume), TLG (total lesion glycolysis), BLR (Bone marrow-to-Liver SUVmax ratio), and SLR (Spleen-to-Liver SUVmax ratio). Each parameter was dichotomized using the median as a threshold. Association with survival, best overall response (BOR), and transcriptomic analyses (NanoString assay) were evaluated using Cox prediction models, Wilcoxon tests, and Spearman's correlation, respectively.
At 20.7 months median follow-up, 33 patients had responded, and 29 patients died. Median PFS and OS were 11.4 (95%CI 2.7-20.2) and 28.5 (95%CI 13.4-43.8) months. TMTV (>25cm), SLR (>0.77), and BLR (>0.79) correlated with shorter survival. High TMTV (>25 cm3), SLR (>0.77), and BLR (>0.79) correlated with shorter survival, with TMTV (HR PFS 2.2, p = 0.02, and HR OS 2.5, p = 0.02) and BLR (HR OS 2.3, p = 0.04) remaining significant in a multivariable analysis. Low TMTV and TLG correlated with BOR (p = 0.03). Increased glucose metabolism in bone marrow (BLR) was associated with transcriptomic profiles including regulatory T cell markers (p < 0.05).
Low tumor burden correlates with survival and objective response while hematopoietic tissue metabolism correlates inversely with survival. These biomarkers should be further evaluated for potential clinical application.
需要一种基于影像学的分层工具来识别那些将从抗程序性死亡-1 抗体（抗 PD-1）治疗中获益的黑色素瘤患者。我们旨在确定在开始治疗之前，脾脏和骨髓中淋巴组织代谢的生存和反应评估的生物标志物。
本回顾性研究纳入了来自两个机构的 55 名接受抗 PD-1 治疗前 18F-FDG PET/CT 的患者。提取的参数包括 SUVmax、SUVmean、HISUV（基于 SUV 的异质性指数）、TMTV（总代谢肿瘤体积）、TLG（总肿瘤糖酵解）、BLR（骨髓-肝脏 SUVmax 比）和 SLR（脾脏-肝脏 SUVmax 比）。使用中位数作为阈值将每个参数分为两组。使用 Cox 预测模型、Wilcoxon 检验和 Spearman 相关分别评估与生存、最佳总反应（BOR）和转录组分析（NanoString 检测）的相关性。
在 20.7 个月的中位随访期内，33 名患者有反应，29 名患者死亡。中位 PFS 和 OS 分别为 11.4（95%CI 2.7-20.2）和 28.5（95%CI 13.4-43.8）个月。TMTV（>25cm）、SLR（>0.77）和 BLR（>0.79）与较短的生存相关。高 TMTV（>25cm3）、SLR（>0.77）和 BLR（>0.79）与较短的生存相关，TMTV（PFS 的 HR 为 2.2，p=0.02，OS 的 HR 为 2.5，p=0.02）和 BLR（OS 的 HR 为 2.3，p=0.04）在多变量分析中仍然具有显著性。低 TMTV 和 TLG 与 BOR 相关（p=0.03）。骨髓中葡萄糖代谢增加（BLR）与包括调节性 T 细胞标志物在内的转录组谱相关（p<0.05）。
低肿瘤负荷与生存和客观反应相关，而造血组织代谢与生存呈负相关。这些生物标志物应进一步评估其在临床应用中的潜力。
