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Abstract：
The serial analysis of cell-free DNA (cfDNA) enables minimally invasive monitoring of tumor evolution, providing continuous genetic information. PERSEIDA was an observational, prospective study assessing the cfDNA RAS (KRAS/NRAS) mutational status evolution in first-line, metastatic CRC, RAS wild-type (according to baseline tumor tissue biopsy) patients. Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. One hundred and nineteen patients were included (102 received panitumumab and chemotherapy as first-line treatment-panitumumab subpopulation). Fifteen (12.6%) patients presented baseline cfDNA RAS mutations (n = 14 [13.7%], panitumumab subpopulation) (mutant allele fraction ≥0.02 for all results). No patients presented emergent mutations (cfDNA RAS mutations not present at baseline) at 20 weeks. At disease progression, 11 patients (n = 9; panitumumab subpopulation) presented emergent mutations (RAS conversion rate: 19.0% [11/58]; 17.7% [9/51], panitumumab subpopulation). In contrast, three (5.2%) patients presenting baseline cfDNA RAS mutations were RAS wild-type at disease progression. No significant associations were observed between overall response rate or progression-free survival and cfDNA RAS mutational status in the total panitumumab subpopulation. Although, in patients with left-sided tumors, a significantly longer progression-free survival was observed in cfDNA RAS wild-type patients compared to those presenting cfDNA RAS mutations at any time. Continuous evaluation of RAS mutations may provide valuable insights on tumor molecular dynamics that can help clinical practice.
摘要：
无细胞DNA（cfDNA）的系列分析可实现对肿瘤演变的微创监测，提供持续的遗传信息。PERSEIDA是一个观察，前瞻性研究评估cfDNARAS（KRAS/NRAS）突变状态的一线进化，转移性CRC,RAS野生型(根据基线肿瘤组织活检)患者。在一线治疗前收集血浆样本，20±2周后，在疾病进展中。纳入119例患者（102例接受帕尼单抗和化疗作为一线治疗-帕尼单抗亚群）。15例（12.6%）患者出现基线cfDNARAS突变（n=14[13.7%]，帕尼单抗亚群)(所有结果的突变等位基因分数≥0.02)。在20周时，没有患者出现紧急突变（基线时不存在cfDNARAS突变）。在疾病进展时，11例患者（n=9；帕尼单抗亚群）出现紧急突变（RAS转化率：19.0%[11/58]；17.7%[9/51]，帕尼单抗亚群）。相比之下,3例(5.2%)出现基线cfDNARAS突变的患者在疾病进展时是RAS野生型.在总的帕尼单抗亚群中，总的反应率或无进展生存期和cfDNARAS突变状态之间没有观察到显著的关联。虽然,在左侧肿瘤患者中，与任何时间出现cfDNARAS突变的患者相比,cfDNARAS野生型患者的无进展生存期显著延长.对RAS突变的持续评估可能为肿瘤分子动力学提供有价值的见解，可以帮助临床实践。
