Correlating total tumor volume on CT-Scan and liquid biopsy ctDNA in 1017 patients with metastatic cancer: A novel study

Liquid biopsy is an emerging technology capable of detecting cancer, while CT-imaging is the gold standard. We aim to correlate imaging features from CT-scans to liquid biopsy ctDNA tumor fraction (TF) and blood Tumor Mutational Burden (bTMB). This retrospective multicentric study included 1017 patients with metastatic cancer who underwent a variety of treatments. Liquid biopsy and contemporaneous CT-scans were collected. TF and bTMB values were computed using FoundationOne Liquid CDX solution by Roche, with high tumor fraction being over 10%. Two expert radiologists outlined all cancerous lesions in the largest axial diameter. Total tumor volume (TTV) was defined as the sum of estimated lesion volumes. Training set consisted of data from several imaging centers, while the validation set was single-center. Continuous value distributions by category were tested using the Mann-Whitney U-test, and a threshold was set with ROC curve analysis using Youden's Index. This cutoff defined high and low groups, and a Χ2 test of independence was used to examine the correlation. Sensitivity and specificity were reported with imaging features taken as the gold standard. Subanalyses were run on patients with liver lesions. Overall, 55294 lesions were annotated, most commonly located in the lung (n=20074), liver (n=11297) and lymph nodes (n=10222). The train and validation sets included 599 and 418 patients. Preliminary analyses were performed on the train set. Patients with low TF had significantly less TTV than those with high TF (p<0.001). ROC analysis yielded an AUC of 0.63 with a threshold of 106 cm3. Correlation was significant between TTV and TF categories (Χ2 test: p<0.001). The sensitivity and specificity were 76% and 42%. For patients with liver lesions (n=253) , TTV threshold was 108 cm3 with an AUC of 0.66. Correlation was significant between TTV and TF categories (Χ2 test: p<0.001). The sensitivity and specificity were 82% and 42%. Analysis showed significant correlation between TTV and ctDNA TF. Sensitivity was higher for patients with liver lesions, suggesting that some organs shed tumoral DNA more than others. The study of tumor heterogeneity on imaging and its correlation to bTMB is in progress.