Background Tumor fraction (TF) at liquid biopsy is a potential noninvasive marker for tumor burden, but validation is needed. Purpose To evaluate TF as a potential surrogate for tumor burden, assessed at contrast-enhanced CT across diverse metastatic cancers. Methods This retrospective monocentric study included patients with cancer and metastatic disease, with TF results and contemporaneous contrast-enhanced CT performed between January 2021 and January 2023. The total tumor volume (TTV), representing CT tumor burden, was calculated by adding all lesion volumes and was computed by using manually outlined annotations of each lesion on the largest surface of the axial slice. TF greater than 10% was considered high. A training-validation split was applied. Correlations between TF and TTV were assessed using regression models and Spearman correlation coefficients. Receiver operating characteristic curve analysis established the TTV cutoff. The metastatic site, histology type, and TTV were used to predict liquid biopsy contributory status. Results Among 1065 patients (median age, 62 years [IQR: 53, 70]; 537 female), 56 288 lesions were annotated, mostly in the lung (n = 20 334), lymph nodes (n = 11 651), and liver (n = 10 277). A total of 763 liquid biopsies were contributive, 254 were noncontributive, and 48 failed. The training and validation sets included 745 and 320 patients, respectively. TF helped predict TTV with the linear model (R² = 0.17; ρ = 0.41; P < .001). The TTV and TF categories achieved an area under the receiver operating characteristic curve (AUC) of 0.74 (95% CI: 0.71, 0.78), with an optimal cutoff of 151 cm³ for TTV and a TF cutoff of 10%. The sensitivity was 57% (204 of 359) and the specificity was 80% (525 of 658). TTV helped predict contributory status, with an AUC of 0.71 (95% CI: 0.67, 0.76) and an optimal cutoff greater than 37 cm³. Liver lesion volumes were significantly associated with a contributory liquid biopsy in the validation cohort. Conclusion While correlated, TF at liquid biopsy did not accurately represent the TTV at CT. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Koh in this issue.

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