循环肿瘤 DNA 动态预测接受新辅助免疫疗法的 III 期黑色素瘤患者的复发。

IF 11.4 1区 医学 Q1 ONCOLOGY
Wei Yen Chan, Jenny H Lee, Ashleigh Stewart, Russell J Diefenbach, Maria Gonzalez, Alexander M Menzies, Christian Blank, Richard A Scolyer, Georgina V Long, Helen Rizos
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引用次数: 0

摘要

背景:新辅助治疗可提高可切除III期皮肤黑色素瘤患者的无复发生存率(RFS)。然而,准确预测个体复发风险仍是一项重大挑战。我们将循环肿瘤DNA(ctDNA)作为接受新辅助免疫疗法的可测量IIIB/C期黑色素瘤患者复发的生物标志物进行了研究:方法:对参加OpACIN-neo和PRADO临床试验的40名患者进行新辅助治疗前、手术前和/或手术后六周的血浆样本采集。患者在手术前接受两个周期的ipilimumab(抗CTLA-4)和nivolumab(抗PD-1)治疗。细胞游离DNA(cfDNA)经过无偏预扩增,然后使用Bio-Rad QX600 PCR系统的液滴数字聚合酶链反应(ddPCR)进行肿瘤信息突变检测:19/40(48%)名患者在治疗前可检测到ctDNA。其中,17/19(89%)例患者在手术后六周内零转化,无一例复发。无论治疗前ctDNA状态如何,手术后ctDNA阳性(N = 4)100%可预测复发(敏感性44%,特异性100%)。此外,7/9(78%)名未复发患者的ctDNA在手术前已清除,因此有必要进一步研究ctDNA指导下的手术治疗:结论:手术后ctDNA阳性和零转换高度预测复发,为辅助治疗的个性化调整提供了窗口。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy.

Background: Neoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy.

Methods: Plasma samples were collected pre-neoadjuvant treatment, pre-surgery and/or six weeks post-surgery from 40 patients enrolled in the OpACIN-neo and PRADO clinical trials. Patients received two cycles of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before surgery. Cell free DNA (cfDNA) underwent unbiased pre-amplification followed by tumour-informed mutation detection using droplet digital polymerase chain reaction (ddPCR) with the Bio-Rad QX600 PCR system.

Results: Pre-treatment ctDNA was detectable in 19/40 (48%) patients. Among these, 17/19 (89%) zero-converted within six weeks of surgery and none recurred. Positive ctDNA post-surgery (N = 4), irrespective of pre-treatment ctDNA status, was 100% predictive of recurrence (sensitivity 44%, specificity 100%). Furthermore, ctDNA cleared prior to surgery in 7/9 (78%) patients who did not recur, warranting further investigation into ctDNA-guided surgical management.

Conclusion: Post-surgery ctDNA positivity and zero-conversion are highly predictive of recurrence, offering a window for personalised modification of adjuvant therapy.

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来源期刊
CiteScore
18.20
自引率
1.80%
发文量
333
审稿时长
1 months
期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
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