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首页> 外文期刊>The Journal of Nuclear Medicine >Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden in Chemotherapy-Naive Patients with Advanced Non-Small Cell Lung Cancer: F-18-FDG PET/CT Study
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Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden in Chemotherapy-Naive Patients with Advanced Non-Small Cell Lung Cancer: F-18-FDG PET/CT Study

机译:循环肿瘤DNA反映肿瘤代谢而不是化疗 - 幼稚患者的肿瘤负担,具有晚期非小细胞肺癌:F-18-FDG PET / CT研究

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摘要

We aimed to evaluate the relationships between circulating tumor cells (CTCs) or plasma cell-free DNA (cfDNA) on one side and a comprehensive range of F-18-FDG PET/CT-derived parameters on the other side in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Methods: From a group of 79 patients included in a trial evaluating the role of pretreatment circulating tumor markers as predictors of prognosis in chemotherapy-naive patients with advanced NSCLC, we recruited all those who underwent F-18-FDG PET/CT for clinical reasons at our institution before inclusion in the trial (and thus just before chemotherapy). For each patient, a peripheral blood sample was collected at baseline for the evaluation of CTCs and cfDNA. CTCs were isolated by size using a filtration-based device and then morphologically identified and enumerated; cfDNA was isolated from plasma and quantified by a quantitative polymerase chain reaction using human telomerase reverse transcriptase. The following F-18-FDG PET/CTderived parameters were computed: maximum diameter of the primary lesion (T), of the largest lymph node (N), and of the largest metastatic lesion (M); SUVmax; SUVmean; size-incorporated SUVmax; metabolic tumor volume; and total lesion glycolysis. All parameters were independently measured for T, N, and M. The associations among CTCs, cfDNA, and F-18-FDG PET/CT-derived parameters were evaluated by multivariate-analysis. Patients were divided into 2 groups according to the presence of either limited metastatic involvement (M1a or M1b due to extrathoracic lymph nodes only) or disseminated metastatic disease. The presence or absence of metabolically active bone lesions was also recorded for each patient, and patient subgroups were compared. Results: Thirty-seven patients recruited in the trial matched our PETbased criteria (24 men; age, 64.5 +/- 8.1 y). SUVmax for the largest metastatic lesion was the only variable independently associated with baseline cfDNA levels (P = 0.016). Higher levels of cfDNA were detected in the subgroup of patients with metabolically active bone lesions (P = 0.02), but no difference was highlighted when patients with more limited metastatic disease were compared with patients with disseminated metastatic disease. Conclusion: The correlation of cfDNA levels with tumor metabolism, but not with metabolic tumor volume at regional or distant levels, suggests that cfDNA may better reflect tumor biologic behavior or aggressiveness rather than tumor burden in metastatic NSCLC.
机译:我们旨在评估循环肿瘤细胞(CTCS)或无菌细胞DNA(CFDNA)在一侧的循环肿瘤细胞(CTCS)和综合系列的综合系列的F-18-FDG PET / CT-衍生参数在化疗 - 幼稚患者的一侧具有先进的非小细胞肺癌(NSCLC)。方法:从试验中包含的一组79名患者评估预处理循环肿瘤标志物的作用作为化疗 - 天真患者先进的NSCLC患者预后的预测因素,我们招募了所有接受F-18-FDG PET / CT的人的临床原因在纳入审判之前在我们的机构(因此在化疗之前)。对于每位患者,在基线中收集外周血样品,用于评估CTC和CFDNA。使用过滤的装置通过尺寸分离CTC,然后形态学地鉴定和列举;使用人端粒酶逆转录酶从等离子体中分离出CFDNA并通过定量聚合酶链反应量化。计算以下F-18-FDG PET / CTDERIVED参数:最大淋巴结(N)的主要病变(T)的最大直径,最大的转移性病变(M); Suvmax; Suvmean;尺寸合并的suvmax;代谢肿瘤体积;和总失因糖酵解。通过多变量分析评估所有参数,对T,N和M独立测量T,N和M.CTCS,CFDNA和F-18-FDG PET / CT衍生参数的关联。根据有限的转移性受累(仅由于脱紫外淋巴结,由于脱喉淋巴结而产生的M1A或M1B)或散发转移性疾病,患者分为2组。对于每位患者还记录了代谢活性骨病变的存在或不存在,并且比较患者亚组。结果:在审判中招募的三十七名患者符合我们的宠物标准(24名男子;年龄,64.5 +/- 8.1 y)。对于最大的转移性病变的Suvmax是唯一与基线CFDNA水平相关的唯一变量(P = 0.016)。在代谢活性骨病变的患者的亚组中检测到较高水平的CFDNA(P = 0.02),但与甲状转移疾病患者进行更有限的转移性疾病患者,没有差异。结论:CFDNA水平与肿瘤代谢的相关性,但在区域或遥远水平下的代谢肿瘤体积表明,CFDNA可能更好地反映肿瘤生物学行为或侵袭性,而不是转移性NSCLC中的肿瘤负担。

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