编者按：在2026年美国妇科肿瘤学会（SGO）年会上，来自阿拉巴马大学伯明翰分校（UAB）、奥尼尔综合癌症中心的Emily E.O’Brien，MD在导师Rebecca C.Arend，MD，MSPH的指导下，口头报告了题为“Clinical Performance of a ctDNA Genome Assay to Predict Treatment Response in Patients with Advanced-Stage Ovarian Cancer Receiving Neoadjuvant Chemotherapy》（ctDNA基因组检测在接受新辅助化疗的晚期卵巢癌患者中预测治疗反应的临床性能）”的研究。本报特别采访了O’Brien医生及其导师Arend医生，就ctDNA在卵巢癌围术期管理中的临床应用前景进行了深入探讨。

 

 

既往研究表明，接受新辅助化疗的卵巢癌患者中，ctDNA阴性状态与更长的无进展生存期相关，而ctDNA阳性可识别辅助化疗结束后的早期进展。同时，在PARP抑制剂治疗的患者中，ctDNA阴性亦与延长的无进展生存期相关。本研究旨在探讨在新诊断的接受新辅助化疗的晚期卵巢癌患者中，ctDNA水平在基线及治疗全程对治疗反应和复发监测的效用。

 

研究前瞻性入组了15例接受新辅助化疗的新诊断晚期（III/IV期）卵巢癌患者，中位年龄65岁（范围46-86岁）；其中白人9例（60%），非洲裔6例（40%）；III期11例（73%），IV期4例（27%）。所有患者均接受了满意肿瘤细胞减灭术。中位随访期间，6例（40%）出现疾病复发，其中铂敏感复发1例（17%），铂耐药复发4例（66%），铂难治复发1例（17%）。

 

研究在四个关键时间节点纵向采集外周血样本：基线、新辅助化疗期间、术后及辅助化疗结束后，具体为：新辅助化疗前（基线）、新辅助化疗期间（第3周期后）、术后（间歇性肿瘤细胞减灭术后）、辅助化疗后（辅助化疗完成时）。

 

 

1.ctDNA检出率与动态变化：基线期ctDNA检出率为100%，中位ctDNA水平为165 MTM/mL。新辅助化疗后（术前）ctDNA中位水平已降至0.6 MTM/mL；辅助化疗结束后ctDNA阳性率为53%。

 

ctDNA检出率

 

2.复发风险分层：中位疾病进展时间为3.5个月（范围2.3-9.8个月），6例复发患者在辅助治疗结束后均保持ctDNA阳性，中位ctDNA水平达50 MTM/mL（范围2.2-549 MTM/mL）。未出现疾病进展的9例患者中位随访时间为17.3个月（范围10.5-26.6个月）；其中7例患者在治疗期间ctDNA转阴，且该组截至辅助治疗结束的中位ctDNA水平为0 MTM/mL（范围0-0.5 MTM/mL）。

 

3.先导预警价值：所有复发均在ctDNA检出阳性结果之后方由影像学发现；ctDNA阴性患者复发率为0%（中位随访17.3个月，自辅助治疗结束起计）。

 

综上，在6例复发患者中，无一例达到ctDNA清除；辅助治疗后ctDNA阴性患者中未观察到复发。纵向ctDNA监测可实时反映复发风险。上述发现支持在更大规模队列中前瞻性验证ctDNA清除作为铂敏感性及生存结局的生物标志物。

 

 

Emily E.O’Brien：当前的标准做法是给予三个周期新辅助化疗，然后做一次CT扫描，判断能否安全有效地切除腹腔内所有可见病灶。但问题在于，在仅依据前三个周期治疗的影像或实验室指标来预测长期结局方面，我们缺乏可靠的手段。因此，基于这两项指标（影像和实验室检查）以及目前的治疗标准，除了极端情况外（例如影像学显示病灶范围特别广泛或患者需要超过三个周期的初始化疗），我们并没有精确的方法来预判长期预后。我们这项研究的数据令人振奋，因为它提示仅通过短期的新辅助治疗就可能显示出长期应答的潜力。

 

Rebecca C.Arend：我对此稍作补充。目前我们在新辅助治疗背景下开展了越来越多探索新型药物的临床试验。例如GOG（妇科肿瘤学组）正进行的一项关于Mirvetuximab Soravtansine联合卡铂的试验，其主要终点是基于RECIST标准及CT影像的总缓解率。如果我们能利用ctDNA作为潜在的替代终点，且其对于无事件生存期或总生存期的预测效能更优，我们或许能更快获得研究结论。尤其随着抗体药物偶联物、免疫治疗和靶向治疗等新型药物逐步推进至卵巢癌的一线治疗阶段，这一点愈发重要。

 

Oncology Frontier:Now that neoadjuvant chemotherapy followed by interval debulking surgery has become an important treatment paradigm for advanced-stage ovarian cancer，what are the major challenges currently faced in evaluating the response to neoadjuvant chemotherapy?

 

Emily E.O’Brien:That is what we have done as standard.We give three cycles of chemotherapy，then do a CT scan and see if we think we can safely and effectively remove all disease that we see in the abdomen.We do not have a great way of knowing，based on any sort of imaging or lab value，what their long-term response and change will be based on just the first three cycles.

 

We do not have a great idea，based on those two things and the way we do things now，to determine what their long-term outcome will be outside of extremes—where their imaging looks really terrible，or they need more than three cycles in the upfront setting.The data we have looked at is exciting as a potential long-term response from a very short upfront course.

 

Rebecca C.Arend:I will just add to that.We are doing a lot more trials looking at novel agents in the neoadjuvant setting.One of the trials we have opened right now for the GOG is with mirvetuximab soravtansine(MIRV).It is the Carbo-MIRV regimen.One of the primary endpoints is actually overall response rate based on the RECIST criteria and CT scans.If we can use ctDNA as a surrogate endpoint，that is potentially more predictive of EFS or OS.We could get the answer sooner，especially as we are developing more and more novel agents.With all these ADCs，immunotherapies，and targeted therapies，we are seeing that move closer and closer to the upfront setting in ovarian cancer.

 

Emily E.O’Brien：仅观察四个时间点——基线期、新辅助化疗期间、手术后、以及辅助化疗后——即使是在我们较小的患者队列中，也能够识别出复发风险较高的患者。这提示在更大的队列中，这种预测能力具有潜在的应用价值。在我们的研究中，在辅助治疗结束时达到ctDNA阴性的患者没有出现复发，而那些ctDNA持续阳性的患者则出现了复发。在新辅助治疗期间前后评估ctDNA动态变化的能力，为我们提供了调整监测强度或在必要时尽早改变治疗策略的机会，因为我们能够意识到，这些患者可能预后更差，或存在常规方法无法及早发现的早期复发高风险。

 

Rebecca C.Arend：在不断汇总新出现的证据的过程中，我们最近发表了关于PARP抑制剂维持治疗期间ctDNA监测的数据。将该研究与当前数据整合分析可以发现，若患者在辅助治疗结束时仍为MRD阳性，其生物学行为可能更接近铂耐药患者。如果在PARP抑制剂治疗的最初几个月内ctDNA未清零，我们或许应考虑更换为其他治疗方案。

 

本届年会报道了多个新方案。Raludotatug Deruxtecan、KEYNOTE-B96方案（帕博利珠单抗联合紫杉醇及贝伐珠单抗）、针对高叶酸受体α表达的Mirvetuximab Soravtansine，以及针对表达水平≥25%患者的Mirvetuximab联合贝伐珠单抗，这些均是在铂耐药复发背景下新近获批的药物。未来一个有趣的研究方向是：对于正在接受PARP抑制剂维持治疗的患者，应该停用PARP抑制剂、通过联合贝伐珠单抗强化治疗，还是降阶梯更换方案？我认为ctDNA数据将帮助我们更高效地做出这类决策，并有可能避免患者接受无效治疗。

 

Oncology Frontier:Could you elaborate on the clinical utility of the Signatera genome assay in predicting response to neoadjuvant chemotherapy in advanced ovarian cancer?What are the key findings from your presentation?

 

Emily E.O’Brien:Looking at just four timepoints—baseline，during neoadjuvant chemotherapy，post-surgery，and post-adjuvant chemotherapy—we were able，even in our small cohort，to identify patients at higher risk of recurrence.This underscores the potential for larger cohorts that have that prediction capability.In our study，patients who achieved ctDNA negativity at the end of adjuvant therapy did not recur，whereas those with persistently positive ctDNA values did recur.The ability to assess ctDNA dynamics around the neoadjuvant period provides an opportunity to adjust surveillance intensity or change treatment sooner if needed，because we are aware that these patients may have worse outcomes or a heightened risk of early recurrence that we would not otherwise detect.

 

Rebecca C.Arend:Compiling the data that continues to emerge，we recently published data on ctDNA monitoring during PARP inhibitor maintenance.Integrating those findings with the current study suggests that patients who remain MRD-positive at the end of adjuvant treatment may exhibit biology more akin to platinum-resistant disease.If ctDNA fails to clear within the first few months of PARP inhibitor therapy，we should potentially contemplate a different regimen.

 

Several new regimens have been come out at this meeting.The new regimens include raludotatug deruxtecan，the KEYNOTE-B96 regimen(pembrolizumab+paclitaxel+bevacizumab)，mirvetuximab soravtansine for high folate receptor alpha expression，or mirvetuximab with bevacizumab for expression≥25%.These represent newly approved agents in the platinum-resistant setting.An intriguing area we should be looking at is:whether we should discontinue the PARP inhibitor，escalate therapy by adding bevacizumab，or de-escalate and switch treatments.I believe ctDNA data will allow us to make these decisions quicker and potentially not expose patients to ineffective treatment.

 

Emily E.O’Brien：在与罹患卵巢癌或子宫内膜癌的患者沟通时，我会指出Signatera基因检测为患者提供了一种监测复发的手段，且随着数据积累，未来或具备预测疾病进程的能力。我会告诉患者，这是一项与其肿瘤组织特异性匹配的血液检测，因而具有独一无二的个体化特征。它使我们能够以远高于常规检测的灵敏度捕捉其专属的肿瘤分子信号。这可能会改变我们的随访监测模式，例如调整影像学检查频率或决定维持治疗的时长。它有助于我们在治疗过程中更早地发现疾病进展，或比常规手段更早地识别出高复发风险。这不仅使我们在患者咨询时能提供更充分的信息，也能让那些想了解自身疾病轨迹的患者更清晰地看到未来的病程走向。

 

Rebecca C.Arend：我稍作补充。我的沟通方式侧重于强调精准医学与个体化医疗的持续进步。我一直主张尽可能多地获取信息。有些检测结果或许我们当下尚无法据其采取明确的临床行动（但信息本身仍具有价值）。例如，若我们在一线治疗时即对肿瘤进行基因测序，不仅能识别未来潜在的靶向治疗方案，还能确定患者是否符合临床试验入组条件。增加这种ctDNA检测，可以让我们通过抽血就能了解肿瘤的分子特征，并持续追踪它在血液中的变化。这一切都是为了让我们能够为患者提供更精准、更具个体化的诊疗服务。

 

Oncology Frontier:If a patient is newly diagnosed with advanced-stage ovarian cancer and about to start neoadjuvant chemotherapy，how would you explain the significance of the Signatera assay to her?

 

Emily E.O’Brien:I am talking about this.When discussing this with patients—whether they have ovarian or endometrial cancer—I explain that this test offers a method for recurrence detection and，with more data emerging，a potential ability to predict what the course of their disease is going to look like(anticipate disease trajectory).I emphasize that it is a blood test uniquely matched specifically to their tumor’s genetic signature，making it specific to them.It is something specific to the individual patient，and we cannot do the same test on anybody else.It allows us to detect their specific tumor DNA and individual cancer signature with far greater sensitivity than standard assays we have.This may influence our surveillance approach，alter the frequency of imaging，or inform whether we do maintenance and the duration of maintenance therapy.It can help us identify disease progression during treatment or signal an elevated recurrence risk sooner than conventional methods show negative information.Ultimately，it allows us to counsel patients more effectively and give them a better idea of what their disease course looks like，if that is something they want.

 

Rebecca C.Arend:To add to that，I would say my approach to patients is that we are continuing to learn so much about precision medicine and personalized medicine.I have always advocated for gathering as much information as possible.There may be things we are not certain how to act upon or what they mean(There may be findings for which we do not yet have a definitive clinical action).For instance，if we sequence a patient’s tumor upfront，we not only know what possible regimens we can use for the patient in the future，but we can also tell if the patient is eligible for a potential clinical trial.This additional ctDNA test allows us to"sequence"the tumor in a manner that permits subsequent tracking of that DNA in the bloodstream.All of this moves us toward delivering more precise and personalized care for our patients.