肿瘤信息个体化循环肿瘤DNA检测在引导结肠癌和高级阑尾癌腹膜转移病患接受治疗意图手术后预警复发中的作用。
Role of Tumor-informed Personalized ctDNA Assay in Informing Recurrence in Patients with Peritoneal Metastases from Colorectal and High-grade Appendix Cancer Undergoing Curative Intent Surgery.
发表日期:2023 Mar 30
作者:
Ankit Dhiman, Vishesh Kothary, Hunter D D Witmer, Celyn Bregio, Divya Sood, Cecilia T Ong, Blase Polite, Oliver S Eng, Ardaman Shergill, Kiran K Turaga
来源:
ANNALS OF SURGERY
摘要:
研究个性化肿瘤信息循环肿瘤DNA检测在升级手术治疗诊断性腹膜转移(PM)经结肠癌(CRC)和高级别阑尾癌(HGA)的患者中对再发的提示作用。CRC/HGA-PM患者中,超过50%在最佳CRS-HIPEC后再次发生。轴向成像和诊断生物标记物的有限灵敏度是延迟发现复发并开始进一步治疗的重要原因。血浆循环肿瘤DNA(ctDNA)在监测治疗反应和/或原发癌切除后复发方面具有很有前途的作用。研究对象为经过根治性CRS-HIPEC和术后序列ctDNA评估的CRC/HGA-PM患者。将产生术后ctDNA升高的患者与稳定、不可检测ctDNA水平的患者进行比较,主要结局指标是复发患者的百分比和无病生存率(DFS)。次要结果是总生存率(OS),ctDNA灵敏度,先导时间和与CEA相比ctDNA的表现。共有33名接受CC-0/1 CRS的患者(n = 13 CRC,n = 20 HGA),进行了130次序列术后ctDNA评估(中位数4,四分位数[ IQR],3-5),随访中位数13个月。ctDNA水平升高的19名患者中,90%再次发生,与ctDNA水平稳定的组(n = 14)中的21%相比(P <0.001)。上升ctDNA队列的中位DFS为11个月(IQR,6-12),而稳定队列中未达到中位DFS (P=0.01)。上升的ctDNA水平是与DFS最显著相关的因素(危险比:3.67,95% CI,1.06-12.66,P=0.03)。上升ctDNA水平预测复发的灵敏度和特异性分别为85%和84.6%。ctDNA先导时间的中位数是3个月(IQR 1-4)。CEA的灵敏度(50%)低于ctDNA的灵敏度。该研究支持序列ctDNA评估作为升级手术治疗诊断性CRC/HGA-PM患者复发的强预后生物标记物的临床有效性。它还为指导未来临床试验设计和进一步研究提供了希望。版权所有© 2023 Wolters Kluwer Health,Inc。保留所有权利。
To investigate the role of a personalized, tumor-informed ctDNA assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative CRS-HIPEC.Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in detection of recurrence and initiation of further therapies. Plasma circulating tumor DNA (ctDNA) has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection.Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial post-resection ctDNA assessments were included. Patients with rising post-operative ctDNA levels were compared to those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival (OS), ctDNA sensitivity, lead-time, and performance of ctDNA compared to CEA.130 serial post-resection ctDNA assessments (median 4, Interquartile range [IQR], 3-5) were performed in 33 patients (n=13 CRC, n=20 HGA) who underwent CC-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n=14, P<0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6-12) and not reached in the stable (P=0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI, 1.06-12.66, P=0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead-time was 3 months (IQR 1-4). CEA was less sensitive (50%) than ctDNA.This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.