使用中性粒细胞与淋巴细胞比值（NLR）和CT总体肿瘤体积预测微卫星高度不稳定（MSI）肿瘤患者的免疫治疗结果。
Predicting immunotherapy outcomes in patients with MSI tumors using NLR and CT global tumor volume.
作者信息
Belkouchi Younes, Nebot-Bral Laetitia, Lawrance Littisha, Kind Michele, David Clémence, Ammari Samy, Cournède Paul-Henry, Talbot Hugues, Vuagnat Perrine, Smolenschi Cristina, Kannouche Patricia L, Chaput Nathalie, Lassau Nathalie, Hollebecque Antoine
机构信息
Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay (BIOMAPS), UMR 1281, Université Paris-Saclay, Inserm, CNRS, CEA, Villejuif, France.
OPtimisation Imagerie et Santé (OPIS), Inria, CentraleSupélec, Université Paris-Saclay, Gif-Sur-Yvette, France.
出版信息
Front Oncol. 2022 Oct 25;12:982790. doi: 10.3389/fonc.2022.982790. eCollection 2022.
BACKGROUND
Anti-PD-(L)1 treatment is indicated for patients with mismatch repair-deficient (MMRD) tumors, regardless of tumor origin. However, the response rate is highly heterogeneous across MMRD tumors. The objective of the study is to find a score that predicts anti-PD-(L)1 response in patients with MMRD tumors.
METHODS
Sixty-one patients with various origin of MMRD tumors and treated with anti-PD-(L)1 were retrospectively included in this study. An expert radiologist annotated all tumors present at the baseline and first evaluation CT-scans for all the patients by circumscribing them on their largest axial axis (single slice), allowing us to compute an approximation of their tumor volume. In total, 2120 lesions were annotated, which led to the computation of the total tumor volume for each patient. The RECIST sum of target lesions' diameters and neutrophile-to-lymphocyte (NLR) were also reported at both examinations. These parameters were determined at baseline and first evaluation and the variation between the first evaluation and baseline was calculated, to determine a comprehensive score for overall survival (OS) and progression-free survival (PFS).
RESULTS
Total tumor volume at baseline was found to be significantly correlated to the OS (p-value: 0.005) and to the PFS (p-value:<0.001). The variation of the RECIST sum of target lesions' diameters, total tumor volume and NLR were found to be significantly associated to the OS (p-values:<0.001, 0.006,<0.001 respectively) and to the PFS (<0.001,<0.001, 0.007 respectively). The concordance score combining total tumor volume and NLR variation was better at stratifying patients compared to the tumor volume or NLR taken individually according to the OS (pairwise log-rank test p-values: 0.033,<0.001, 0.002) and PFS (pairwise log-rank test p-values: 0.041,<0.001, 0.003).
CONCLUSION
Total tumor volume appears to be a prognostic biomarker of anti-PD-(L)1 response to immunotherapy in metastatic patients with MMRD tumors. Combining tumor volume and NLR with a simple concordance score stratifies patients well according to their survival and offers a good predictive measure of response to immunotherapy.
背景
无论肿瘤起源如何，错配修复缺陷（MMRD）肿瘤患者均适用抗PD-(L)1治疗。然而，MMRD肿瘤的缓解率高度异质性。本研究的目的是找到一个能预测MMRD肿瘤患者抗PD-(L)1反应的评分。
方法
本研究回顾性纳入了61例不同起源的MMRD肿瘤且接受抗PD-(L)1治疗的患者。一位专家放射科医生通过在所有患者的基线和首次评估CT扫描上勾勒出最大轴位（单层）的肿瘤轮廓，对所有肿瘤进行标注，从而使我们能够计算出其肿瘤体积的近似值。总共标注了2120个病灶，由此计算出每位患者的总肿瘤体积。两次检查时还报告了靶病灶直径的RECIST总和以及中性粒细胞与淋巴细胞比值（NLR）。这些参数在基线和首次评估时确定，并计算首次评估与基线之间的变化，以确定总生存期（OS）和无进展生存期（PFS）的综合评分。
结果
发现基线时的总肿瘤体积与OS（p值：0.005）和PFS（p值：< 0.001）显著相关。发现靶病灶直径的RECIST总和、总肿瘤体积和NLR的变化与OS（p值分别为：< 0.001、0.006、< 0.001）和PFS（分别为< 0.001、< 0.001、0.007）显著相关。与单独根据OS（两两对数秩检验p值：0.033、< 0.001、0.002）和PFS（两两对数秩检验p值：0.041、< 0.001、0.003）采用肿瘤体积或NLR相比，将总肿瘤体积和NLR变化相结合的一致性评分在对患者进行分层方面表现更好。
结论
总肿瘤体积似乎是MMRD肿瘤转移性患者抗PD-(L)1免疫治疗反应的预后生物标志物。将肿瘤体积和NLR与一个简单的一致性评分相结合，能根据患者的生存情况很好地对患者进行分层，并为免疫治疗反应提供良好的预测指标。
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