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