Smith Jarrod T, Balar Aneri, Lakhani Dhairya A, Kluwe Christien, Zhao Zhiguo, Kopparapu Prasad, Almodovar Karinna, Muterspaugh Anel, Yan Yingjun, York Sally, Horn Leora, Antic Sanja, Bertucci Caterina, Shaffer Tristan, Hodsdon Lauren, Garg Kavita, Hosseini Seyed Ali, Lim Lee, Osmundson Evan, Massion Pierre P, Lovly Christine M, Iams Wade
Department of Medicine, School of Medicine, Vanderbilt University, Nashville, Tennessee.
Division of Allergy, Pulmonary and Critical Care, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
JTO Clin Res Rep. 2020 Oct 20;2(3):100110. doi: 10.1016/j.jtocrr.2020.100110. eCollection 2021 Mar.
Blood-based next-generation sequencing assays of circulating tumor DNA (ctDNA) have the ability to detect tumor-associated mutations in patients with SCLC. We sought to characterize the relationship between ctDNA mean variant allele frequency (VAF) and radiographic total-body tumor volume (TV) in patients with SCLC.
We identified matched blood draws and computed tomography (CT) or positron emission tomography (PET) scans within a prospective SCLC blood banking cohort. We sequenced plasma using our previously developed 14-gene SCLC-specific ctDNA assay. Three-dimensional TV was determined from PET and CT scans using MIM software and reviewed by radiation oncologists. Univariate association and multivariate regression analyses were performed to evaluate the association between mean VAF and total-body TV.
We analyzed 75 matched blood draws and CT or PET scans from 25 unique patients with SCLC. Univariate analysis revealed a positive association between mean VAF and total-body TV (Spearman's ρ = 0.292, < 0.01), and when considering only treatment-naive and pretreatment patients (n = 11), there was an increase in the magnitude of association (ρ = 0.618, = 0.048). The relationship remained significant when adjusting for treatment status and bone metastases ( = 0.046). In the subgroup of patients with variants, univariate analysis revealed a significant association (ρ = 0.762, = 0.037) only when considering treatment-naive and pretreatment patients (n = 8).
We observed a positive association between mean VAF and total-body TV in patients with SCLC, suggesting mean VAF may represent a dynamic biomarker of tumor burden that could be followed to monitor disease status.
基于血液的循环肿瘤DNA（ctDNA）下一代测序检测能够在小细胞肺癌（SCLC）患者中检测到肿瘤相关突变。我们试图描述SCLC患者ctDNA平均变异等位基因频率（VAF）与影像学全身肿瘤体积（TV）之间的关系。
我们在一个前瞻性SCLC血库队列中确定了匹配的血液样本以及计算机断层扫描（CT）或正电子发射断层扫描（PET）扫描。我们使用之前开发的14基因SCLC特异性ctDNA检测方法对血浆进行测序。使用MIM软件从PET和CT扫描中确定三维TV，并由放射肿瘤学家进行审核。进行单变量关联分析和多变量回归分析以评估平均VAF与全身TV之间的关联。
我们分析了来自25例独特SCLC患者的75对匹配的血液样本以及CT或PET扫描。单变量分析显示平均VAF与全身TV之间存在正相关（Spearman's ρ = 0.292，P < 0.01），并且仅考虑未接受过治疗和治疗前的患者（n = 11）时，关联程度有所增加（ρ = 0.618，P = 0.048）。在调整治疗状态和骨转移后，这种关系仍然显著（P = 0.046）。在有变异的患者亚组中，单变量分析仅在考虑未接受过治疗和治疗前的患者（n = 8）时显示出显著关联（ρ = 0.762，P = 0.037）。
我们观察到SCLC患者的平均VAF与全身TV之间存在正相关，这表明平均VAF可能代表肿瘤负荷的动态生物标志物，可用于监测疾病状态。
