Liquid biopsy tumour fraction, total tumour volume, and automated whole-body CT body composition for survival stratification in metastatic cancer: A temporally validated pan-cancer cohort study.

BACKGROUND

CT-derived total tumour volume (TTV) and liquid biopsy (LB) tumour fraction (TF) are emerging prognostic biomarkers with potential to transform survival stratification in metastatic cancer. We aimed to characterise their interplay with automated 3D body composition and their combined prognostic contribution to overall survival (OS) in a pan-cancer metastatic cohort.

PATIENTS AND

METHODS

This retrospective study included consecutive patients with metastatic solid cancers initiating a new line of systemic treatment within the STING precision medicine program (NCT04932525) at Gustave Roussy (Villejuif, France) (2021-2023). Baseline contrast-enhanced CT and LB were required within 60 days of treatment initiation. All tumour lesions were manually segmented to derive TTV. Muscular body mass (MBM), visceral and subcutaneous adipose tissue (SAT) were automatically extracted using Anthropometer3DNet. Patients were divided into training (n = 570) and temporally separated test cohort (n = 149). Prognostic models were developed using Cox regression and random survival forests, and evaluated using C-indices.

RESULTS

719 patients were included (368 women, median age: 61 years), with 38,283 segmented lesions. In training, 28.2% of patients had TF= 0% despite measurable tumour burden (median TTV 43.6 cm³). On multivariable analysis, TF, TTV, sex, MBM, and SAT were independently associated with OS. In the test cohort, body composition did not improve discrimination beyond TF, TTV, and clinical variables. The model combining TF, TTV, and clinical variables achieved a C-index of 0.678, outperforming TF-only (0.634, p = 0.04) and clinical-only models (0.563, p = 0.004). Risk stratification yielded markedly distinct survival outcomes (median OS 8.3 versus >25 months; p < 0.001), including among patients with TF= 0%.

CONCLUSION

The combination of TF and TTV significantly improves survival stratification in metastatic cancer, including in patients with undetectable ctDNA. Body composition parameters, while significantly associated with OS, provided no incremental discriminatory value beyond tumour burden biomarkers.