PO.CL02.01 · 临床研究

ctDNA状态和多部位疾病负荷对阑尾癌或结直肠癌腹膜转移患者的预后影响

Prognostic impact of ctDNA status and multi-site disease burden for patients with peritoneal metastases from appendiceal or colorectal cancer

编号 6444 展板 11 时间 4/21 02:00–05:00 区域 Section 40 主讲 Justin Bader, MD
分会场 Biostatistics in Clinical Trials / Surgical Oncology
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作者与单位 Authors & Affiliations

Justin M. Bader1, Kelsey LaBella1, Nicole Aguirre1, Kwasi Ofori1, Princy Gupta1, Anup Sharma2, Huxley Smart1, Alexander Kim1, Robert Tseng1, SANGWON YUN1, Michael Cecchini2, Raghav Sundar2, Kiran Turaga1

1Yale New Haven Hospital, New Haven, CT,2Yale School of Medicine, New Haven, CT

摘要 Abstract

中文摘要
目的:循环肿瘤DNA(ctDNA)对转移性阑尾癌和结直肠癌(CRC)患者具有预后意义,然而其对治疗考量和手术候选资格的影响尚不明确。目前的随机试验正在探索用于管理多部位寡转移疾病的局部区域治疗方法。我们研究了ctDNA指导的局部区域治疗在管理伴或不伴多部位疾病的腹膜转移(PM)中的作用。 方法:研究队列纳入了2023-2025年间因PM接受根治性手术干预的高级别阑尾癌或CRC患者,包括单部位(腹膜)或多部位转移(腹膜加肝、肺或远处淋巴结受累)。在术前和术后进行ctDNA检测。对人口统计学、病理学和ctDNA动态进行了单因素和多因素分析。使用Kaplan-Meier(KM)曲线分析总生存期(OS),以评估ctDNA状态和存在多部位疾病的预后影响。 结果:在研究的61名患者中,67%(n=41)为CRC,33%(n=20)为高级别阑尾癌。术后中位随访18个月,末次随访时82%的患者存活。术前,33%(n=17)的患者ctDNA阳性,其中13%术后最初清除了ctDNA。然而,这些患者均未维持持久的ctDNA阴性,因为所有患者在6个月内均转回ctDNA阳性。在术前ctDNA阴性的患者中,32%术后转为ctDNA阳性——其中91%在1年内转为阳性。术前ctDNA阴性的患者KM估计的2年OS为91.2%。 手术时39%(n=24)的患者有多部位疾病史,包括50%(n=12)为活动性多部位疾病,50%(n=12)为既往治疗过的疾病。无论是否存在多部位疾病受累(2年OS=83.3%)或仅腹膜转移(2年OS=95.6%),ctDNA阴性患者的KM估计2年OS均极佳。 结论:本研究分析了ctDNA状态和多部位疾病对接受局部区域治疗的CRC或阑尾癌PM患者的预后影响。ctDNA在接受根治性手术切除腹膜转移的患者中似乎具有预后意义。此外,具有多部位疾病且ctDNA阴性并接受腹膜转移手术的患者,其生存似乎与仅腹膜转移患者相当。鉴于PM和寡转移疾病患者管理方法各异且指南相互矛盾,ctDNA可能有助于增强治疗选择、手术资格和临床试验入组。
查看英文原文 English abstract
Purpose: Circulating tumor DNA (ctDNA) is prognostic for patients with metastatic appendiceal and colorectal cancer (CRC), however, its impact on therapy considerations and surgical candidacy is unclear. Current randomized trials are exploring approaches to locoregional therapy for management of multi-site oligometastatic disease. We investigate the role of ctDNA-guided locoregional therapies in the management of peritoneal metastases (PM) with or without multi-site disease. Methods: The study cohort included high-grade appendiceal or CRC patients with single site (peritoneum) or multi-site metastases (peritoneum plus liver, lung, or distant lymph node involvement) who had curative intent surgical interventions for PM between 2023-2025. ctDNA testing was performed in the pre- and post-operative setting. Univariate and multivariate analysis of demographics, pathological, and ctDNA dynamics were performed. Overall survival (OS) was analyzed using Kaplan-Meier (KM) curves to evaluate prognostic impact of ctDNA status and presence of multi-site disease. Results: Of the 61 patients in the study, 67% (n=41) had CRC and 33% (n=20) had high-grade appendiceal cancer. Median postoperative follow up was 18 months with 82% of patients alive at last follow up. Prior to surgery, 33% (n=17) of patients were ctDNA positive with 13% clearing their ctDNA postoperatively initially. However, none of these patients maintained durable negative ctDNA as all converted back to ctDNA positive within 6 months. Of those with negative ctDNA preoperatively, 32% converted to ctDNA positive postoperatively - including 91% converting to positive within 1 year. Patients with ctDNA negative status preoperatively had KM-estimated 2-year OS of 91.2%. History of multi-site disease was present in 39% (n=24) of patients at time of surgery including 50% (n=12) with active multi-site disease and 50% (n=12) with previously treated disease. KM-estimated 2-year OS was excellent for ctDNA negative patients regardless of multi-site disease involvement (2-year OS = 83.3%) or peritoneal-only metastases (2-year OS = 95.6%). Conclusion: This study analyzed the prognostic impact of ctDNA status and multi-site disease for patients with PM from CRC or appendiceal cancer who underwent locoregional therapy. ctDNA appears to be prognostic in patients undergoing curative intent surgical resection for peritoneal metastases. Furthermore, patients with multi-site disease who have negative ctDNA and undergo surgery for peritoneal metastases appear to have survival comparable to patients with peritoneal only metastases. With variable approaches and conflicting guidelines for the management of patients with PM and oligometastatic disease, ctDNA could augment treatment selection, surgical eligibility, and clinical trial enrollment.
利益披露 Disclosure
J. M. Bader, None.. K. LaBella, None.. N. Aguirre, None.. K. Ofori, None.. P. Gupta, None.. H. Smart, None.. A. Kim, None.. R. Tseng, None.

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