The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set
Open accessAbstract
BACKGROUND: A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was a prospective, case-controlled, observational study and demonstrated that a blood-based MCED test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin (CSO) with high accuracy. The objective of this third and final CCGA substudy was to validate an MCED test version further refined for use as a screening tool. PATIENTS AND METHODS: This pre-specified substudy included 4077 participants in an independent validation set (cancer: n = 2823; non-cancer: n = 1254, non-cancer status confirmed at year-one follow-up). Specificity, sensitivity, and CSO prediction accuracy were measured. RESULTS: Specificity for cancer signal detection was 99.5% [95% confidence interval (CI): 99.0% to 99.8%]. Overall sensitivity for cancer signal detection was 51.5% (49.6% to 53.3%); sensitivity increased with stage [stage I: 16.8% (14.5% to 19.5%), stage II: 40.4% (36.8% to 44.1%), stage III: 77.0% (73.4% to 80.3%), stage IV: 90.1% (87.5% to 92.2%)]. Stage I-III sensitivity was 67.6% (64.4% to 70.6%) in 12 pre-specified cancers that account for approximately two-thirds of annual USA cancer deaths and was 40.7% (38.7% to 42.9%) in all cancers. Cancer signals were detected across >50 cancer types. Overall accuracy of CSO prediction in true positives was 88.7% (87.0% to 90.2%). CONCLUSION: In this pre-specified, large-scale, clinical validation substudy, the MCED test demonstrated high specificity and accuracy of CSO prediction and detected cancer signals across a wide diversity of cancers. These results support the feasibility of this blood-based MCED test as a complement to existing single-cancer screening tests. CLINICAL TRIAL NUMBER: NCT02889978.
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Detection and localization of surgically resectable cancers with a multi-analyte blood test
Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A. A., Wong, F., Mattox, A., et al. (2018) · Science · doi:10.1126/science.aar3247 · Cited by 2,783
Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement
US Preventive Services Task Force, Bibbins-Domingo, K., Grossman, D. C., Curry, S. J., Davidson, K. W., Epling, J. W., García, F. A. R., Gillman, M. W., Harper, D. M., Kemper, A. R., et al. (2016) · JAMA · doi:10.1001/jama.2016.5989 · Cited by 2,509
Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement
Siu, A. L., & on behalf of the U.S. Preventive Services Task Force (2016) · Annals of Internal Medicine · doi:10.7326/m15-2886 · Cited by 2,094
Liu, M. C., Oxnard, G. R., Klein, E. A., Swanton, C., Seiden, M. V., Liu, M. C., Oxnard, G. R., Klein, E. A., Smith, D., Richards, D., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.02.011 · Cited by 1,495
Self-citationSensitive tumour detection and classification using plasma cell-free DNA methylomes
Shen, S. Y., Singhania, R., Fehringer, G., Chakravarthy, A., Roehrl, M. H. A., Chadwick, D., Zuzarte, P. C., Borgida, A., Wang, T. T., Li, T., et al. (2018) · Nature · doi:10.1038/s41586-018-0703-0 · Cited by 983
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Pascual, J., Attard, G., Bidard, F.-C., Curigliano, G., De Mattos-Arruda, L., Diehn, M., Italiano, A., Lindberg, J., Merker, J. D., Montagut, C., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.05.520 · Cited by 783
A DNA methylation atlas of normal human cell types
Loyfer, N., Magenheim, J., Peretz, A., Cann, G., Bredno, J., Klochendler, A., Fox-Fisher, I., Shabi-Porat, S., Hecht, M., Pelet, T., et al. (2023) · Nature · doi:10.1038/s41586-022-05580-6 · Cited by 656
Self-citationCurrent and future colorectal cancer screening strategies
Shaukat, A., & Levin, T. R. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00612-y · Cited by 516
Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets
Zhang, S., Xiao, X., Yi, Y., Wang, X., Zhu, L., Shen, Y., Lin, D., & Wu, C. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01848-7 · Cited by 399
Large-scale pancreatic cancer detection via non-contrast CT and deep learning
Cao, K., Xia, Y., Yao, J., Han, X., Lambert, L., Zhang, T., Tang, W., Jin, G., Jiang, H., Fang, X., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02640-w · Cited by 358
Metadata
- Authors
- Klein, E. A., Richards, D., Cohn, A., Tummala, M., Lapham, R., Cosgrove, D., Chung, G., Clement, J., Gao, J., Hunkapiller, N., Jamshidi, A., Kurtzman, K. N., Seiden, M. V., Swanton, C., & Liu, M. C.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 32
- Issue
- 9
- Pages
- 1167-1177
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W3174187171
- Cited by
- 995
- References
- 5
- FWCI
- 48.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Klein, E. A., Richards, D., Cohn, A., Tummala, M., Lapham, R., Cosgrove, D., Chung, G., Clement, J., Gao, J., Hunkapiller, N., Jamshidi, A., Kurtzman, K. N., Seiden, M. V., Swanton, C., & Liu, M. C. (2021). Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Annals of Oncology. https://doi.org/10.1016/j.annonc.2021.05.806
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