Combined Analyses of Circulating Tumor DNA and Immunoscore in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the PRODIGE-GERCOR IDEA-France/HORG-IDEA-Greece Trials.

IF 42.1 1区 医学 Q1 ONCOLOGY
Journal of Clinical Oncology Pub Date : 2025-05-01 Epub Date: 2025-02-04 DOI:10.1200/JCO.24.00648
Julien Taieb, John Souglakos, Ioannis Boukovinas, Antoine Falcoz, Franck Pages, Ippokratis Messaritakis, Jaafar Bennouna, Pascal Artru, Christophe Louvet, Celine Lepere, Jean Francois Emile, Olivier Bouche, Thibault Mazard, Dewi Vernerey, Konstantinos Vogiatzoglou, Maria Tzardi, Shruti Sharma, Minetta C Liu, Himanshu Sethi, Thierry André, Jérome Galon, Pierre Laurent-Puig
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引用次数: 0

Abstract

Purpose: Immunoscore (IS) and circulating tumor DNA (ctDNA) are two emerging technologies in improving prognostication and tailoring adjuvant treatments in patients resected from a stage III colon cancer (CC). Here, we analyzed the prognostic value of the two biomarkers in patients who participated in the randomized phase III IDEA-France and HORG trials.

Methods: Plasma samples were collected after surgery and before adjuvant chemotherapy. ctDNA analysis was performed using a clinically validated, personalized, tumor-informed 16-plex protein chain reaction assay. Multivariable analyses for time to recurrence (TTR; patients without recurrence or death due to CC) and overall survival (OS) were performed using ctDNA and IS results, along with other parameters including treatment duration and disease risk group.

Results: Of the 554 patients with available ctDNA results, 445 were ctDNA-negative (80.3%) and 109 were ctDNA-positive (19.7%); baseline characteristics showed more T4/N2 and venous embolism/lymphatic invasion/perineural invasion+ in ctDNA-positive patients. With a median follow-up of 6.7 years, the 2-year TTR rate was 43.5% (95% CI, 34.1 to 52.6) for ctDNA-positive patients and 88.1% (95% CI, 84.7 to 90.8) for ctDNA-negative patients (P < .0001). ctDNA was confirmed as an independent prognostic marker for both TTR (adjusted hazard ratio [adjHR], 5.21 [95% CI, 3.59 to 7.58]; P < .001) and OS (adjHR, 4.84 [95% CI, 3.40 to 6.89]; P < .001). ctDNA remained the most significant prognostic factor irrespective of disease stage, treatment duration, and IS results. IS was not prognostic in ctDNA-positive patients but remained a significant prognostic tool for ctDNA-negative patients.

Conclusion: In this combined analysis of two adjuvant trials dedicated to patients with stage III CC after surgery, ctDNA was detectable in 19.7% of the patients and was confirmed as a major independent prognostic biomarker. IS seems to bring additional prognostic information in the 80.3% of patients who are ctDNA-negative.

合并分析 III 期结肠癌患者的循环肿瘤 DNA 和免疫评分:PRODIGE-GERCOR IDEA-France/HORG-IDEA-Greece 试验的事后分析。
目的:免疫评分(IS)和循环肿瘤DNA (ctDNA)是改善III期结肠癌(CC)切除患者预后和定制辅助治疗的两种新兴技术。在这里,我们分析了这两种生物标志物在参加随机III期IDEA-France和HORG试验的患者中的预后价值。方法:术后及辅助化疗前血浆标本采集。ctDNA分析采用临床验证的、个性化的、肿瘤知情的16-plex蛋白链反应法进行。递归时间的多变量分析;无复发或因CC死亡的患者)和总生存期(OS)使用ctDNA和IS结果以及其他参数(包括治疗时间和疾病风险组)进行。结果:554例可获得ctDNA结果的患者中,ctDNA阴性445例(80.3%),ctDNA阳性109例(19.7%);基线特征显示ctdna阳性患者更多的T4/N2和静脉栓塞/淋巴浸润/神经周围浸润+。中位随访时间为6.7年,ctdna阳性患者的2年TTR率为43.5% (95% CI, 34.1 - 52.6), ctdna阴性患者的2年TTR率为88.1% (95% CI, 84.7 - 90.8) (P < 0.0001)。ctDNA被证实为TTR的独立预后指标(校正风险比[adjHR], 5.21 [95% CI, 3.59 ~ 7.58];P < 0.001)和OS (adjHR, 4.84 [95% CI, 3.40 ~ 6.89];P < 0.001)。无论疾病分期、治疗时间和IS结果如何,ctDNA仍然是最重要的预后因素。IS对ctdna阳性患者没有预后影响,但对ctdna阴性患者仍然是一个重要的预后工具。结论:在这项针对III期CC术后患者的两项辅助试验的联合分析中,19.7%的患者可检测到ctDNA,并被证实为主要的独立预后生物标志物。在80.3%的ctdna阴性患者中,IS似乎带来了额外的预后信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Clinical Oncology
Journal of Clinical Oncology 医学-肿瘤学
CiteScore
41.20
自引率
2.20%
发文量
8215
审稿时长
2 months
期刊介绍: The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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