Background/Objectives: The surgeon’s subjective intraoperative evaluation is the standard of care to assess postoperative residual disease (RD) in advanced epithelial ovarian cancer (EOC). We investigated the feasibility of ctDNA as an objective marker for postoperative RD. Methods: This prospective study included 27 patients with advanced ovarian cancer (FIGO IIIA1–IVB) who underwent primary surgery between July 2021 and July 2022. Blood samples were analyzed preoperatively and on days 2 (d2) and 10 (d10) postoperatively. Low-coverage whole genome sequencing (WGS) was used to identify structural variants (SVs) at single-base pair resolution, single nucleotide variants (SNVs), and indels in tumor tissue to develop personalized, tumor-informed digital polymerase chain reaction (dPCR) fingerprint assays for each patient. Results: dPCR fingerprint assays were successfully developed for all patients by identifying one to eight SVs/SNVs per patient. ctDNA was detected in 96% (n= 26/27) of patients preoperatively and in 81% (n= 22/27) of patients at d10. Median ctDNA levels at d10 were significantly higher in patients with postoperative RD (median 367.38 copies (cps)/mL, 2.84% variant allele frequency; VAF) than in patients without postoperative RD (median 0.92 cps/mL, 0.017% VAF,p< 0.001). In patients with postoperative RD, ctDNA levels increased from the preoperative stage to d10 in seven out of eight patients (p= 0.016). In patients with complete tumor resection, ctDNA levels decreased from the preoperative stage to d10 in 17/19 patients (p< 0.001). Conclusions: A tumor-informed personalized ctDNA approach demonstrated feasibility, providing extremely high detection rates pre- and postoperatively. These results indicate that this approach could potentially be used for postoperative RD assessment in patients with primary advanced EOC.
背景/目的：外科医生术中主观评估是评估晚期上皮性卵巢癌术后残留病灶的标准方法。本研究探讨了循环肿瘤DNA作为术后残留病灶客观标志物的可行性。方法：这项前瞻性研究纳入了2021年7月至2022年7月期间接受初次手术的27例晚期卵巢癌患者（FIGO分期IIIA1-IVB）。分别在术前、术后第2天和第10天采集血液样本进行分析。采用低覆盖度全基因组测序技术，以单碱基对分辨率识别肿瘤组织的结构变异、单核苷酸变异和插入缺失，为每位患者建立个体化的肿瘤信息数字PCR指纹检测方法。结果：通过为每位患者识别1-8个结构变异/单核苷酸变异，成功建立了所有患者的数字PCR指纹检测方法。术前ctDNA检出率为96%（26/27），术后第10天检出率为81%（22/27）。术后存在残留病灶患者的第10天ctDNA中位水平（中位数367.38拷贝/毫升，变异等位基因频率2.84%）显著高于无残留病灶患者（中位数0.92拷贝/毫升，变异等位基因频率0.017%，p<0.001）。在术后存在残留病灶的患者中，8例中有7例从术前到术后第10天ctDNA水平呈上升趋势（p=0.016）。而在肿瘤完全切除的患者中，19例中有17例从术前到术后第10天ctDNA水平显著下降（p<0.001）。结论：基于肿瘤信息的个体化ctDNA检测方法展现出良好的可行性，术前术后均具有极高的检出率。这些结果表明该方法有望用于原发性晚期上皮性卵巢癌患者的术后残留病灶评估。
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