Li B T, Drilon A, Johnson M L, Hsu M, Sima C S, McGinn C, Sugita H, Kris M G, Azzoli C G
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, USA Sydney Medical School, University of Sydney, Sydney, Australia.
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, USA.
Ann Oncol. 2016 Jan;27(1):154-9. doi: 10.1093/annonc/mdv498. Epub 2015 Oct 20.
While previous studies have reported on the prognostic value of total plasma cell-free deoxyribonucleic acid (cfDNA) in lung cancers, few have prospectively evaluated its predictive value for systemic therapy response.
We conducted a prospective study to evaluate the association between changes in total cfDNA and radiologic response to systemic therapy in patients with stage IIIB/IV non-small-cell lung cancers (NSCLCs). Paired blood collections for cfDNA and computed tomography (CT) assessments by RECIST v1.0 were performed at baseline and 6-12 weeks after therapy initiation. Total cfDNA levels were measured in plasma using quantitative real-time polymerase chain reaction. Associations between changes in cfDNA and radiologic response, progression-free survival (PFS), and overall survival (OS) were measured using Kruskal-Wallis and Kaplan-Meier estimates.
A total of 103 patients completed paired cfDNA and CT response assessments. Systemic therapy administered included cytotoxic chemotherapy in 57% (59/103), molecularly targeted therapy in 17% (17/103), and combination therapy in 26% (27/103). Median change in cfDNA from baseline to response assessment did not significantly differ by radiologic response categories of progression of disease, stable disease and partial response (P = 0.10). However, using radiologic response as continuous variable, there was a weak positive correlation between change in radiologic response and change in cfDNA (Spearman's correlation coefficient 0.21, P = 0.03). Baseline cfDNA levels were not associated with PFS [hazard ratio (HR) = 1.06, 95% confidence interval (CI) 0.93-1.20, P = 0.41] or OS (HR = 1.04, 95% CI 0.93-1.17, P = 0.51), neither were changes in cfDNA.
In this large prospective study, changes in total cfDNA over time did not significantly predict radiologic response from systemic therapy in patients with advanced NSCLC. Pretreatment levels of total cfDNA were not prognostic of survival. Total cfDNA level is not a highly specific predictive biomarker and future investigations in cfDNA should focus on tumor-specific genomic alterations using expanded capabilities of next-generation sequencing.
虽然既往研究报道了血浆游离脱氧核糖核酸（cfDNA）总量在肺癌中的预后价值，但很少有研究前瞻性评估其对全身治疗反应的预测价值。
我们进行了一项前瞻性研究，以评估IIIB/IV期非小细胞肺癌（NSCLC）患者中，cfDNA总量变化与全身治疗的放射学反应之间的关联。在基线期以及治疗开始后6至12周，采集用于cfDNA检测的配对血样，并依据RECIST v1.0标准进行计算机断层扫描（CT）评估。采用定量实时聚合酶链反应测定血浆中的cfDNA总量水平。使用Kruskal-Wallis检验和Kaplan-Meier估计法，测定cfDNA变化与放射学反应、无进展生存期（PFS）及总生存期（OS）之间的关联。
共有103例患者完成了配对的cfDNA和CT反应评估。所给予的全身治疗包括57%（59/103）的细胞毒性化疗、17%（17/103）的分子靶向治疗以及26%（27/103）的联合治疗。从基线期至反应评估时，cfDNA的中位变化在疾病进展、疾病稳定和部分缓解的放射学反应类别中并无显著差异（P = 0.10）。然而，将放射学反应作为连续变量时，放射学反应变化与cfDNA变化之间存在弱正相关（Spearman相关系数0.21，P = 0.03）。基线cfDNA水平与PFS[风险比（HR）= 1.06，95%置信区间（CI）0.93 - 1.20，P = 0.41]或OS（HR = 1.04，95% CI 0.93 - 1.17，P = 0.51）均无关联，cfDNA的变化情况也无关联。
在这项大型前瞻性研究中，晚期NSCLC患者随时间推移的cfDNA总量变化并不能显著预测全身治疗的放射学反应。cfDNA总量的预处理水平并无生存预后价值。cfDNA总量水平并非高度特异性的预测生物标志物，未来对cfDNA的研究应利用下一代测序的扩展能力，聚焦于肿瘤特异性基因组改变。
