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治疗前 18F-FDG-PET/CT 参数作为转移性黑色素瘤患者一线免疫治疗后无进展生存、最佳总体反应和总体生存的生物标志物。

Pre-treatment 18F-FDG-PET/CT parameters as biomarkers for progression free survival, best overall response and overall survival in metastatic melanoma patients undergoing first-line immunotherapy.

机构信息

Department of Diagnostic and Interventional Radiology, Eberhard Karls University, Tuebingen University Hospital, Tuebingen, Germany.

Fraunhofer MEVIS, Bremen, Germany.

出版信息

PLoS One. 2024 Jan 5;19(1):e0296253. doi: 10.1371/journal.pone.0296253. eCollection 2024.

Abstract

BACKGROUND

Checkpoint inhibitors have drastically improved the therapy of patients with advanced melanoma. 18F-FDG-PET/CT parameters might act as biomarkers for response and survival and thus can identify patients that do not benefit from immunotherapy. However, little literature exists on the association of baseline 18F-FDG-PET/CT parameters with progression free survival (PFS), best overall response (BOR), and overall survival (OS).

MATERIALS AND METHODS

Using a whole tumor volume segmentation approach, we investigated in a retrospective registry study (n = 50) whether pre-treatment 18F-FDG-PET/CT parameters of three subgroups (tumor burden, tumor glucose uptake and non-tumoral hematopoietic tissue metabolism), can act as biomarkers for the primary endpoints PFS and BOR as well as for the secondary endpoint OS.

RESULTS

Compared to the sole use of clinical parameters, baseline 18F-FDG-PET/CT parameters did not significantly improve a Cox proportional-hazard model for PFS (C-index/AIC: 0.70/225.17 and 0.68/223.54, respectively; p = 0.14). A binomial logistic regression analysis for BOR was not statistically significant (χ2(15) = 16.44, p = 0.35), with a low amount of explained variance (Nagelkerke's R2 = 0.38). Mean FDG uptake of the spleen contributed significantly to a Cox proportional-hazard model for OS (HR 3.55, p = 0.04).

CONCLUSIONS

The present study could not confirm the capability of the pre-treatment 18F-FDG-PET/CT parameters tumor burden, tumor glucose uptake and non-tumoral hematopoietic tissue metabolism to act as biomarkers for PFS and BOR in metastatic melanoma patients receiving first-line immunotherapy. The documented potential of 18F-FDG uptake by immune-mediating tissues such as the spleen to act as a biomarker for OS has been reproduced.

摘要

背景

检查点抑制剂极大地改善了晚期黑色素瘤患者的治疗效果。18F-FDG-PET/CT 参数可能作为反应和生存的生物标志物,从而可以识别出不能从免疫治疗中获益的患者。然而,关于基线 18F-FDG-PET/CT 参数与无进展生存期(PFS)、最佳总反应(BOR)和总生存期(OS)之间的相关性,文献很少。

材料和方法

使用全肿瘤体积分割方法,我们在一项回顾性登记研究(n=50)中研究了三个亚组(肿瘤负担、肿瘤葡萄糖摄取和非肿瘤性造血组织代谢)的治疗前 18F-FDG-PET/CT 参数是否可以作为主要终点 PFS 和 BOR 以及次要终点 OS 的生物标志物。

结果

与仅使用临床参数相比,基线 18F-FDG-PET/CT 参数并未显著改善 Cox 比例风险模型的 PFS(C 指数/AIC:0.70/225.17 和 0.68/223.54,分别;p=0.14)。BOR 的二项逻辑回归分析无统计学意义(χ2(15)=16.44,p=0.35),解释方差的数量较低(Nagelkerke 的 R2=0.38)。脾脏的平均 FDG 摄取量对 OS 的 Cox 比例风险模型有显著贡献(HR 3.55,p=0.04)。

结论

本研究不能证实治疗前 18F-FDG-PET/CT 参数肿瘤负担、肿瘤葡萄糖摄取和非肿瘤性造血组织代谢在接受一线免疫治疗的转移性黑色素瘤患者中作为 PFS 和 BOR 的生物标志物的能力。已经复制了免疫介导组织(如脾脏)的 18F-FDG 摄取作为 OS 生物标志物的潜在能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d6/10769042/9ad7ea956481/pone.0296253.g001.jpg

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