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 ¹⁸F-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 ¹⁸F-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 ¹⁸F-FDG PET/CT–derived parameters were computed: maximum diameter of the primary lesion (T), of the largest lymph node (N), and of the largest metastatic lesion (M); SUV_max; SUV_mean; size-incorporated SUV_max; metabolic tumor volume; and total lesion glycolysis. All parameters were independently measured for T, N, and M. The associations among CTCs, cfDNA, and ¹⁸F-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 PET-based criteria (24 men; age, 64.5 ± 8.1 y). SUV_max 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.

我们的目的是评估未接受过化疗的初治患者的一侧循环肿瘤细胞（CTC）或无浆细胞DNA（cfDNA）与另一侧¹⁸ F-FDG PET / CT衍生参数的全面范围之间的关系。晚期非小细胞肺癌（NSCLC）。方法：从一项包括79个患者的研究中，评估了治疗前循环肿瘤标记物在未接受化疗的晚期NSCLC患者中作为预后指标的作用，我们招募了所有接受过^18周治疗的患者由于F-FDG PET / CT在我们机构中因临床原因而被纳入试验之前（因此也就在化疗之前）。对于每位患者，在基线时收集外周血样本以评估CTC和cfDNA。使用基于过滤的装置按尺寸分离四氯化碳，然后进行形态学鉴定和计数；从血浆中分离出cfDNA，并使用人端粒酶逆转录酶通过定量聚合酶链反应进行定量。计算出以下^18个F-FDG PET / CT衍生的参数：原发病变最大直径（T），最大淋巴结（N）和最大转移病变（M）；SUV_最大; SUV的_意思; 尺寸合并的SUV _max; 代谢肿瘤体积；和总病变糖酵解。所有参数均独立测量T，N和M。通过多元分析评估了CTC，cfDNA和¹⁸ F-FDG PET / CT衍生参数之间的关联。根据转移受限（M1a或M1b仅由于胸外淋巴结转移）或弥漫性转移疾病的存在将患者分为两组。还记录了每位患者的代谢活动性骨病变的存在与否，并对患者亚组进行了比较。结果：该试验招募的37例患者符合我们基于PET的标准（24名男性；年龄为64.5±8.1 y）。SUV_最大最大转移灶的“转移”是与基线cfDNA水平独立相关的唯一变量（P = 0.016）。在代谢活跃的骨病变患者亚组中检测到较高的cfDNA水平（P = 0.02），但将局限性转移性疾病患者与弥散性转移性疾病患者相比，则无明显差异。结论： cfDNA水平与肿瘤代谢相关，但与区域或远处的代谢肿瘤体积无关，这表明cfDNA可以更好地反映肿瘤的生物学行为或侵袭性，而不是转移性NSCLC中的肿瘤负担。