Performance of multiple multi-cancer detection tests using a large independent reference set (Alliance A212102)

作者：Marie Wood, Paul F. Pinsky, Paul J. Novotny, Elyse Leevan, Matthias Weiss, Dan Edelman, Mark A. Watson, Christos Patriotis, Jason D. Merker, Philip C. Prorok, Yujia Wen, Wendy S. Rubinstein, Konstantin H. Dragnev, Amanda L. Skarlupka, Hormuzd A. Katki, Selina Chow, Margaret Kemeny, Umang Gautam, Aswanth Reddy, William E. Burak, Steven Piantadosi, Lori M. Minasian · 发表于：JNCI Journal of the National Cancer Institute · 年份：2026 · DOI：10.1093/jnci/djag001 · 被引用次数：5 · 研究领域：Global Cancer Incidence and Screening、Cancer Genomics and Diagnostics、Ethics in Clinical Research

BACKGROUND: Reference sets are needed to evaluate performance of multi-cancer detection (MCD) assays. The National Cancer Institute funded the Alliance reference set study to assess MCDs for use in future trials. METHODS: Individuals with cancer and controls were recruited; blood specimens were collected prior to cancer treatment. A performance evaluation study was designed utilizing reference set samples. Companies (n = 6) were selected to participate based on review of performance data and ability to utilize the blood collection tube. Companies received samples from cancer types their assay was designed to detect ("targeted"), plus additional "non-targeted" and control samples. Companies reported positive/negative calls, risk scores, and tissue-of-origin (TOO) predictions. Sensitivity was computed for early (I-II) and late (III-IV) stage cases, based on positive/negative calls (SEPN) and at fixed 98% specificity (SE98). Specificity and TOO accuracy were computed. RESULTS: Five hundred and forty nine cases (encompassing 13 cancer types) and 413 controls from the reference set were included in the study. Companies assessed samples from median 6 (range 5-9) targeted cancer types and median 8 (range: 7-11) overall cancer types. Median (range) specificity was 92.3% (76.5%-98.5%). Median (range) SEPN was 32% (25%-42%) for early stage and 73% (48%-89%) for late stage; while median (range) SE98 was 19% (8%-35%) for early stage and 66% (13%-79%) for late stage. Median sensitivity fo...