Prospective validation study: a non-invasive circulating tumor DNA-based assay for simultaneous early detection of multiple cancers in asymptomatic adults.

IF 8.3 1区医学 Q1 MEDICINE, GENERAL & INTERNAL BMC Medicine Pub Date : 2025-02-14 DOI:10.1186/s12916-025-03929-y

Luu Hong Dang Nguyen, Thi Hue Hanh Nguyen, Van Hoi Le, Vinh Quang Bui, Lan Hieu Nguyen, Nhu Hiep Pham, Thanh Hai Phan, Huu Thinh Nguyen, Van Song Tran, Chi Viet Bui, Van Kha Vo, Pham Thanh Nhan Nguyen, Ha Huu Phuoc Dang, Van Dung Pham, Van Thinh Cao, Ngoc Minh Phan, Ba Linh Tieu, Giang Thi Huong Nguyen, Dac Ho Vo, Trung Hieu Tran, Thanh Dat Nguyen, Van Thien Chi Nguyen, Trong Hieu Nguyen, Vu Uyen Tran, Minh Phong Le, Thi Minh Thu Tran, Minh Nguyen Nguyen, Thi Tuong Vi Van, Anh Nhu Nguyen, Thi Thanh Nguyen, Nhu Nhat Tan Doan, Hoang Tan Nguyen, Phuoc Loc Doan, Le Anh Khoa Huynh, Tien Anh Nguyen, Huu Tam Phuc Nguyen, Y-Thanh Lu, Chi Thuy Tien Cao, Van Tung Nguyen, Thi Le Quyen Le, Thi Lan-Anh Luong, Thi Kim Phuong Doan, Thi Trang Dao, Canh Duy Phan, Thanh Xuan Nguyen, Nguyen Tuong Pham, Bao Toan Nguyen, Thi Thu Thuy Pham, Huu Linh Le, Cong Thanh Truong, Thanh Xuan Jasmine, Minh Chi Le, Van Bau Phan, Quang Binh Truong, Thi Huong Ly Tran, Minh Thien Huynh, Tu Quy Tran, Si Tuan Nguyen, Vu Tran, Van Khanh Tran, Huu Nguyen Nguyen, Duy Sinh Nguyen, Thi Van Phan, Thi Thanh-Thuy Do, Dinh Kiet Truong, Hung Sang Tang, Hoa Giang, Hoai-Nghia Nguyen, Minh-Duy Phan, Le Son Tran

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引用次数: 0

Abstract

Background: Non-invasive multi-cancer early detection (MCED) tests have shown promise in enhancing early cancer detection. However, their clinical utility across diverse populations remains underexplored, limiting their routine implementation. This study aims to validate the clinical utility of a multimodal non-invasive circulating tumor DNA (ctDNA)-based MCED test, SPOT-MAS (Screening for the Presence Of Tumor by DNA Methylation And Size).

Methods: We conducted a multicenter prospective study, K-DETEK (ClinicalTrials.gov identifier: NCT05227261), involving 9057 asymptomatic individuals aged 40 years or older across 75 major hospitals and one research institute in Vietnam. Participants were followed for 12 months.

Results: Of the 9024 eligible participants, 43 (0.48%) tested positive for ctDNA. Among these, 17 were confirmed with malignant lesions in various primary organs through standard-of-care (SOC) imaging and biopsy, with 9 cases matching our tissue of origin (TOO) predictions. This resulted in a positive predictive value of 39.53% (95%CI 26.37-54.42) and a TOO accuracy of 52.94% (95%CI 30.96-73.83). Among the 8981 participants (99.52%) who tested negative, 8974 were confirmed cancer-free during a 12-month period after testing, yielding a negative predictive value of 99.92% (95% CI 99.84-99.96). The test demonstrated an overall sensitivity of 70.83% (95%CI 50.83-85.09) and a specificity of 99.71% (95% CI 99.58-99.80) for detecting various cancer types, including those without SOC screening options.

Conclusions: This study presents a prospective validation of a multi-cancer early detection (MCED) test conducted in a lower middle-income country, demonstrating the potential of SPOT-MAS for early cancer detection. Our findings indicate that MCED tests could be valuable additions to national cancer screening programs, particularly in regions where such initiatives are currently limited.

Trial registration: ClinicalTrials.gov ID: NCT05227261. Date of registration: 07/02/2022.

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前瞻性验证研究：一种基于循环肿瘤dna的无创检测方法，可同时早期检测无症状成人中的多种癌症。

背景：无创多癌早期检测（MCED）在加强早期癌症检测方面显示出前景。然而，它们在不同人群中的临床应用仍未得到充分探索，限制了它们的常规应用。本研究旨在验证基于多模式非侵入性循环肿瘤DNA （ctDNA）的MCED测试SPOT-MAS（通过DNA甲基化和大小筛选肿瘤存在）的临床应用。方法：我们进行了一项多中心前瞻性研究K-DETEK (ClinicalTrials.gov识别码：NCT05227261)，涉及越南75家主要医院和一家研究机构的9057名年龄在40岁或以上的无症状个体。参与者被跟踪了12个月。结果：在9024名符合条件的参与者中，43名（0.48%）检测出ctDNA阳性。其中，17例通过标准护理（SOC）成像和活检证实有不同原发器官的恶性病变，其中9例符合我们的起源组织（TOO）预测。阳性预测值为39.53% (95%CI 26.37 ~ 54.42)， TOO准确率为52.94% （95%CI 30.96 ~ 73.83）。在检测为阴性的8981名参与者（99.52%）中，8974名在检测后的12个月内确诊无癌，阴性预测值为99.92% （95% CI 99.84-99.96）。检测各种类型的癌症，包括那些没有SOC筛查选项的癌症，该测试的总灵敏度为70.83% (95%CI 50.83-85.09)，特异性为99.71% （95%CI 99.58-99.80）。结论：本研究对在中低收入国家进行的多癌早期检测（MCED）测试进行了前瞻性验证，证明了SPOT-MAS在早期癌症检测方面的潜力。我们的研究结果表明，MCED测试可能是国家癌症筛查计划的宝贵补充，特别是在目前此类计划有限的地区。试验注册：ClinicalTrials.gov ID: NCT05227261。注册日期：2022年2月7日。

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

BMC Medicine 医学-医学：内科

CiteScore

13.10

自引率

1.10%

发文量

435

审稿时长

4-8 weeks

期刊介绍： BMC Medicine is an open access, transparent peer-reviewed general medical journal. It is the flagship journal of the BMC series and publishes outstanding and influential research in various areas including clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. In addition to research articles, the journal also publishes stimulating debates, reviews, unique forum articles, and concise tutorials. All articles published in BMC Medicine are included in various databases such as Biological Abstracts, BIOSIS, CAS, Citebase, Current contents, DOAJ, Embase, MEDLINE, PubMed, Science Citation Index Expanded, OAIster, SCImago, Scopus, SOCOLAR, and Zetoc.