Prospective validation study: a non-invasive circulating tumor DNA-based assay for simultaneous early detection of multiple cancers in asymptomatic adults.
| Title: | Prospective validation study: a non-invasive circulating tumor DNA-based assay for simultaneous early detection of multiple cancers in asymptomatic adults. |
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| Authors: | Nguyen LHD; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen THH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Le VH; National Cancer Hospital, Hanoi, Vietnam.; Bui VQ; Hanoi Oncology Hospital, Hanoi, Vietnam.; Nguyen LH; Hanoi Medical University Hospital, Hanoi Medical University, Hanoi, Vietnam.; Pham NH; Hue Central Hospital, Hue, Vietnam.; Phan TH; Medic Medical Center, Ho Chi Minh, Vietnam.; Nguyen HT; University Medical Center HCM, Ho Chi Minh, Vietnam.; Tran VS; People's Hospital 115, Ho Chi Minh, Vietnam.; Bui CV; Xuyen A General Hospital, Ho Chi Minh, Vietnam.; Vo VK; Cantho Oncology Hospital, Can Tho, Vietnam.; Nguyen PTN; Danang Oncology Hospital, Da Nang, Vietnam.; Dang HHP; Dongnai General Hospital, Bien Hoa, Vietnam.; Pham VD; Thong Nhat Dongnai General Hospital, Bien Hoa, Vietnam.; Cao VT; Le Van Thinh Hospital, Ho Chi Minh, Vietnam.; Phan NM; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tieu BL; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen GTH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Vo DH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tran TH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen TD; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen VTC; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen TH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tran VU; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Le MP; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tran TMT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen Nguyen M; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Van TTV; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen AN; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen TT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Doan NNT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen HT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Doan PL; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Huynh LAK; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen TA; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen HTP; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Lu YT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Cao CTT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen VT; National Cancer Hospital, Hanoi, Vietnam.; Le Quyen Le T; Hanoi Oncology Hospital, Hanoi, Vietnam.; Luong TL; Hanoi Medical University Hospital, Hanoi Medical University, Hanoi, Vietnam.; Doan TKP; Hanoi Medical University Hospital, Hanoi Medical University, Hanoi, Vietnam.; Dao TT; Hanoi Medical University Hospital, Hanoi Medical University, Hanoi, Vietnam.; Phan CD; Hue Central Hospital, Hue, Vietnam.; Nguyen TX; Hue Central Hospital, Hue, Vietnam.; Pham NT; Hue Central Hospital, Hue, Vietnam.; Nguyen BT; Medic Medical Center, Ho Chi Minh, Vietnam.; Pham TTT; Medic Medical Center, Ho Chi Minh, Vietnam.; Le HL; Medic Medical Center, Ho Chi Minh, Vietnam.; Truong CT; Medic Medical Center, Ho Chi Minh, Vietnam.; Jasmine TX; Medic Medical Center, Ho Chi Minh, Vietnam.; Le MC; University Medical Center HCM, Ho Chi Minh, Vietnam.; Phan VB; People's Hospital 115, Ho Chi Minh, Vietnam.; Truong QB; University Medical Center HCM, Ho Chi Minh, Vietnam.; Tran THL; Cantho Oncology Hospital, Can Tho, Vietnam.; Huynh MT; Cantho Oncology Hospital, Can Tho, Vietnam.; Tran TQ; Danang Oncology Hospital, Da Nang, Vietnam.; Nguyen ST; Thong Nhat Dongnai General Hospital, Bien Hoa, Vietnam.; Tran V; Thong Nhat Dongnai General Hospital, Bien Hoa, Vietnam.; Tran VK; Le Van Thinh Hospital, Ho Chi Minh, Vietnam.; Nguyen Nguyen H; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Gene Solutions, Ho Chi Minh, Vietnam.; Nguyen DS; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Gene Solutions, Ho Chi Minh, Vietnam.; Van Phan T; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Do TT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Truong DK; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tang HS; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Giang H; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Gene Solutions, Ho Chi Minh, Vietnam.; Nguyen HN; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Gene Solutions, Ho Chi Minh, Vietnam.; Phan MD; Medical Genetics Institute, Ho Chi Minh, Vietnam. pmduy@yahoo.com.; Gene Solutions, Ho Chi Minh, Vietnam. pmduy@yahoo.com.; Tran LS; Medical Genetics Institute, Ho Chi Minh, Vietnam. leson1808@gmail.com.; Gene Solutions, Ho Chi Minh, Vietnam. leson1808@gmail.com. |
| Source: | BMC medicine [BMC Med] 2025 Feb 14; Vol. 23 (1), pp. 90. Date of Electronic Publication: 2025 Feb 14. |
| Publication Type: | Journal Article; Multicenter Study; Observational Study; Validation Study |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 101190723 Publication Model: Electronic Cited Medium: Internet ISSN: 1741-7015 (Electronic) Linking ISSN: 17417015 NLM ISO Abbreviation: BMC Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BioMed Central, 2003- |
| MeSH Terms: | Circulating Tumor DNA*/blood ; Early Detection of Cancer*/methods ; Neoplasms*/diagnosis ; Neoplasms*/blood ; Neoplasms*/genetics; Biomarkers, Tumor/blood ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Vietnam |
| 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.; (© 2025. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: This research received approval from the Ethics Committee of the University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam (approval number: 192/HĐĐĐ-ĐHYD). Each participant provided written informed consent, adhering to the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors including LST, HNN, HG, MDP, HHN and DSN hold equity in Gene Solutions. NHN, HG, MDP and LST are inventors on the patent application (USPTO 17930705). LHDN, THHN, NMP, BLT, GTHN, DHV, THT, TDN, VTCN, THN, VUT, MPL, TMTT, MNN, TTVV, ANN, TTN, NNTD, HTN, PLD, LAKH, TAN, HTPN, YTL, CTTC, TVP, TTTD, DKT, and HST received salaries from the project funded by the Medical Genetics Institute, Ho Chi Minh City, Vietnam. We confirm that this does not alter our adherence to journal policies on sharing data and materials. VHL, VQB, LHN, NHP, THP, HTN, VST, CVB, VKV, PTNN, HHPD, VDP, VTC, BLT, TTN, HTPN, CTTC, VTN, TLQL, TLAL, TKPD, TTD, CDP, TXN, NTP, BTN, TTTP, HLL, CTT, TXJ, MCL, VBP, QBT, THLT, MTH, TQT, STN, VT, VKT declare that they have no competing interests. VHL, VQB, LHN, NHP, THP, HTN, VST, CVB, VKV, PTNN, HHPD, VDP, VTC, BLT, TTN, HTPN, CTTC, VTN, TLQL, TLAL, TKPD, TTD, CDP, TXN, NTP, BTN, TTTP, HLL, CTT, TXJ, MCL, VBP, QBT, THLT, MTH, TQT, STN, VT, and VKT declare that they have no competing interests. |
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| Contributed Indexing: | Keywords: Clinical validation; Liquid biopsy; Multicancer early detection; Multimodal analysis; Tissue of origin |
| Molecular Sequence: | ClinicalTrials.gov NCT05227261 |
| Substance Nomenclature: | 0 (Biomarkers, Tumor); 0 (Circulating Tumor DNA) |
| Entry Date(s): | Date Created: 20250213 Date Completed: 20250214 Latest Revision: 20250513 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11827191 |
| DOI: | 10.1186/s12916-025-03929-y |
| PMID: | 39948555 |
| Database: | MEDLINE |
Journal Article; Multicenter Study; Observational Study; Validation Study