Vu Peter, Khagi Yulian, Riviere Paul, Goodman Aaron, Kurzrock Razelle
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA.
Division of Blood and Marrow Transplantation, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA.
JCO Precis Oncol. 2020 Mar 24;4. doi: 10.1200/PO.19.00204. eCollection 2020.
Studies have demonstrated an association between quantity of circulating tumor DNA (ctDNA) and poorer survival. We investigated the relationship between percent ctDNA (%ctDNA), total number of ctDNA alterations, and overall survival (OS) in liquid biopsies.
Overall, 418 patients with blood-based next-generation sequencing (54 to 73 genes) were analyzed. Eligible patients included those who had advanced/metastatic solid tumor malignancies and never received immunotherapy treatment, which may alter the survival curve in patients with high mutational burden.
Patients with a high (≥ 5%) %ctDNA had significantly shorter OS versus those with intermediate (≥ 0.4% to < 5%) or low (< 0.4%) values (median OS, 7.0 14.1 not reached [NR] months, respectively; < .0001). Patients with a high (≥ 5) total number of alterations had significantly shorter OS versus those with intermediate (≥ 1.46 to < 5), low (< 1.46), or no alterations (median OS, 4.6 11.7 21.3 NR months, respectively; < .0001). The total number of alterations correlated with %ctDNA (r = 0.85; 95% CI, 0.81 to 0.87; < .0001). However, only an intermediate to high total number of alterations (≥ 1.46) was an independent predictor of worse OS (hazard ratio, 1.96; 95% CI, 1.30 to 2.96; = .0014; multivariate analysis).
We demonstrate that the total number of alterations and %ctDNA have prognostic value and correlate with one another, but only the total number of alterations was independently associated with survival outcomes. Our findings suggest that the total number of alterations in plasma may be an indicator of more aggressive tumor biology and therefore poorer survival.
研究表明循环肿瘤DNA（ctDNA）的量与较差的生存率之间存在关联。我们调查了液体活检中ctDNA百分比（%ctDNA）、ctDNA改变的总数与总生存期（OS）之间的关系。
总体上，对418例接受基于血液的二代测序（54至73个基因）的患者进行了分析。符合条件的患者包括那些患有晚期/转移性实体瘤恶性肿瘤且从未接受过免疫治疗的患者，免疫治疗可能会改变高突变负荷患者的生存曲线。
%ctDNA高（≥5%）的患者与%ctDNA中等（≥0.4%至<5%）或低（<0.4%）的患者相比，OS显著缩短（中位OS分别为7.0、14.1和未达到[NR]个月；P<0.0001）。改变总数高（≥5）的患者与改变总数中等（≥1.46至<5）、低（<1.46）或无改变的患者相比，OS显著缩短（中位OS分别为4.6、11.7、21.3和NR个月；P<0.0001）。改变总数与%ctDNA相关（r = 0.85；95%CI，0.81至0.87；P<0.0001）。然而，只有中等至高的改变总数（≥1.46）是OS较差的独立预测因素（风险比，1.96；95%CI，1.30至2.96；P = 0.0014；多变量分析）。
我们证明改变总数和%ctDNA具有预后价值且相互关联，但只有改变总数与生存结果独立相关。我们的研究结果表明，血浆中改变的总数可能是更具侵袭性的肿瘤生物学特征的指标，因此生存率较低。
