Baseline CT-derived tumor burden and liquid biopsy as biomarkers to predict survival in patients with metastatic solid cancer

Purpose: The purpose of this study was to evaluate baseline tumor burden from liquid biopsy (LB) and computed tomography (CT) as prognostic biomarkers and whether their combination refines stratification in metastatic solid cancers. Materials and methods: This retrospective cohort study included 1065 patients. Eligible patients underwent LB and chest-abdomen-pelvis CT examination at baseline. Radiologists outlined lesions on the largest axial slice, and total tumor volume (TTV) was approximated in three dimensions. LB Tumor fraction (TF) ≥ 10 % was considered high. To assess combined prognostic power of LB and TTV, patients were divided into three groups according to LB (circulating tumor deoxyribonucleic acid [ctDNA] detectability and TF) and each group was further divided into two subgroups using TTV thresholds determined by Youden's index. Overall survival (OS) analyses were performed using Cox proportional hazard models and Kaplan-Meier curves. Results: A total of 560 patients (290 women and 270 men; median age, 61 years) with 31,314 annotated lesions were selected. The median OS was 11.28 months, and the median TTV was 96.68 cm³. The LB groups included patients with undetectable ctDNA (n = 102), patients with detectable ctDNA and low TF (n = 251), and patients with high TF (n = 207). Integrating TTV thresholds (18.7 cm³, 44.9 cm³, and 159.94 cm³) to LB groups significantly stratified the population on OS. Patients with undetectable ctDNA and TTV ≥ 18.7 cm³ had significantly shorter OS (median OS, 24.8 months) than those with TTV < 18.7 cm³ (median OS, > 35 months). Conclusion: Combining baseline CT tumor burden with LB could be a valuable prognostic tool for stratifying patients with metastatic solid cancer.