Author:
Nguyen Luu Hong Dang,Nguyen Thi Hue Hanh,Le Van Hoi,Bui Vinh Quang,Nguyen Lan Hieu,Pham Nhu Hiep,Phan Thanh Hai,Nguyen Huu Thinh,Tran Van Song,Bui Chi Viet,Vo Van Kha,Nguyen Pham Thanh Nhan,Dang Ha Huu Phuoc,Pham Van Dung,Cao Van Thinh,Phan Ngoc Minh,Tieu Ba Linh,Nguyen Giang Thi Huong,Vo Dac Ho,Tran Trung Hieu,Nguyen Thanh Dat,Nguyen Van Thien Chi,Nguyen Trong Hieu,Tran Vu Uyen,Le Minh Phong,Tran Thi Minh Thu,Nguyen Minh Nguyen,Van Thi Tuong Vi,Nguyen Anh Nhu,Nguyen Thi Thanh,Doan Nhu Nhat Tan,Nguyen Hoang Tan,Doan Phuoc Loc,Huynh Le Anh Khoa,Nguyen Tien An,Nguyen Huu Tam Phuc,Lu Y-Thanh,Cao Chi Thuy Tien,Nguyen Van Tung,Le Thi Le Quyen,Luong Thi Lan-Anh,Doan Thi Kim Phuong,Dao Thi Trang,Phan Canh Duy,Nguyen Thanh Xuan,Pham Nguyen Tuong,Nguyen Bao Toan,Pham Thi Thu Thuy,Le Huu Linh,Truong Cong Thanh,Jasmine Thanh Xuan,Le Minh Chi,Phan Van Bau,Truong Quang Binh,Tran Thi Huong Ly,Huynh Minh Thien,Tran Tu Quy,Nguyen Si Tuan,Tran Vu,Tran Van Khanh,Nguyen Huu Nguyen,Nguyen Duy Sinh,Phan Thi Van,Do Thi Thanh-Thuy,Truong Dinh Kiet,Tang Hung Sang,Giang Hoa,Nguyen Hoai-Nghia,Phan Minh-Duy,Tran Le Son
Abstract
ABSTRACTThe development of multi-cancer early detection (MCED) through a single blood test has emerged as a promising method for improving the efficiency of early cancer detection and benefiting population health. However, the lack of analytical validation and clinical evidence for their utility in diverse populations have prevented their use in clinical practice. To address these challenges, we conducted a comprehensive analytical and clinical validation for an MCED test, SPOT-MAS (Screening for the Presence Of Tumor by DNA Methylation And Size). The analytical validation was to establish the limit of detection, reproducibility of test results and assess the impact of potential interferents on test performance. Specifically, SPOT-MAS could detect at least 50% of cancer samples at a specificity of 98% if the samples have tumor fraction ≥0.049 (95% CI: 0.043-0.059). The results were consistently reproduced for both intra- and inter-batch analysis. Moreover, our test remained robust at hemoglobin contamination of 500 mg/dl and genomic DNA contamination of up to 100%. To validate the performance of SPOT-MAS test in clinical settings, we launched a multi-center prospective trial, named K-DETEK, of 10,027 asymptomatic participants in Vietnam. Our assay achieved a positive predictive value of 58.14% (95%CI: 43.33-71.62) with 84.00% (95%CI: 65.35-93.60) accuracy in predicting tumor location and a negative predictive value of 99.92% (95%CI: 99.83-99.96). To our knowledge, this is the first and largest prospective validation study in Asia supporting the utility of SPOT-MAS as a multi-cancer blood test for early detection in a low- and middle-income country, where a nationwide cancer screening program is urgently needed but currently not available.
Publisher
Cold Spring Harbor Laboratory