Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY.
Stanford Cancer Institute, Stanford University, Stanford, CA.
JCO Precis Oncol. 2024 Sep;8:e2400216. doi: 10.1200/PO.24.00216.
Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity.
Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions. Tumor-informed plasma analysis was carried out using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). The mean variant allele frequency (VAF) of all pretreatment mutations was tracked in subsequent blood draws and correlated with radiologic response.
ctDNA kinetics were assessed in 122 samples from 21 patients. Pretreatment VAF did not differ significantly between patients who did and did not respond to chemotherapy (mean 22.5% 4.6%, = .17). A slight increase in ctDNA on cycle 1, day 1 immediately post-treatment was seen in six of the seven patients with available draws (fold change from baseline: 1.01-1.44), half of whom achieved a response. All patients who responded had a >2-fold decrease in mean VAF on cycle 2 day 1 (C2D1). Progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with a >2-fold decrease in mean VAF after one treatment cycle (6.8 2.6 months, log-rank = .0004 and 21.7 6.4 months, log rank = .04, respectively).
A >2-fold decrease in ctDNA concentration was observed by C2D1 in all patients who were sensitive to platinum-based therapy and was associated with longer PFS and OS.
小细胞肺癌（SCLC）的特征是在铂类耐药后迅速进展。治疗早期循环肿瘤（ctDNA）的动态变化可能有助于确定铂类敏感性。
对接受铂类化疗的 SCLC 患者在第 1 周期的第 1 天和随后周期的第 1 天采集连续的血浆样本，在输注前后采集配对样本。使用基于癌症个体化分析的深度测序（CAncer Personalized Profiling by deep Sequencing，CAPP-Seq）进行肿瘤信息血浆分析。在随后的血液采集样本中跟踪所有预处理突变的平均变异等位基因频率（Variant Allele Frequency，VAF），并与影像学反应相关。
在 21 名患者的 122 个样本中评估了 ctDNA 动力学。化疗反应良好和反应不佳的患者的预处理 VAF 无显著差异（平均值 22.5% 4.6%， =.17）。在 7 名可获得样本的患者中，有 6 名患者在第 1 周期第 1 天治疗后立即出现 ctDNA 轻度增加（与基线相比的倍数变化：1.01-1.44），其中一半患者有反应。所有对治疗有反应的患者在第 2 周期第 1 天（Cycle 2 Day 1，C2D1）的平均 VAF 下降>2 倍。在一个治疗周期后平均 VAF 下降>2 倍的患者的无进展生存期（Progression-free survival，PFS）和总生存期（Overall survival，OS）显著更长（6.8 2.6 个月，对数秩检验 =.0004 和 21.7 6.4 个月，对数秩检验 =.04）。
在所有对铂类治疗敏感的患者中，C2D1 观察到 ctDNA 浓度下降>2 倍，与更长的 PFS 和 OS 相关。
