Background

Genomic mutations identified from circulating tumor DNA (ctDNA) have been shown to correlate positively with clinical disease status. EGFR and intracellular cell progression and proliferation pathways involving BRCA1/2 and TP53 genes drive high ctDNA load in progressive cancer patients. Circulating tumor cells (CTCs) indicate cellular residual disease (CRD). Together, ctDNA and CTCs as dual biomarkers offer predictive insights into tumor progression and metastasis, which may be valuable for early detection and treatment modifications.

Methods

In a retrospective study, 96 cancer patients (including lung, colorectal, breast, stomach, and other cancers) who had recently undergone treatment were investigated for the presence of CTCs and genomic mutations from ctDNA using the OncoMonitor test. Libraries were prepared using a hybridization-capture method covering 1000 targets with a mean sequencing depth of 5000× on the Illumina NextSeq 2000 platform. The test detected genomic alterations including single nucleotide variations (SNVs), small insertions and deletions (INDELs), copy number variations (CNVs), and translocations (fusions) using a 96-gene panel. CTCs were isolated using the OncoDiscover platform and identified as CK18+, PD-L1+, CD45- cells in 1.5 ml of blood.

Results

Among the 96 pan-cancer patients, 15.6% (n = 15) were identified with localized progressive disease without metastasis based on radiological findings, of which 60% (n = 9) showed at least one genomic alteration detected from ctDNA. Additionally, 12.5% (n = 12) patients were identified with metastatic disease from radiological findings, of which 58.3% (n = 7) showed the presence of at least one CTC. Among these, 33.3% (n = 4) patients had two CTCs, while five patients had no detectable CTCs. Furthermore, metastatic patients showed ctDNA load in 66.6% (n = 8) of cases with at least one genomic finding.

In the metastatic disease cohort, CTC enumeration showed a concordance of 58.3% (n = 7) with metastatic radiological findings, while genomic findings from ctDNA showed a concordance of 66.6% (n = 8) with metastatic radiological findings. Among 23.9% (n = 23) patients identified radiologically with stable or treatment-responsive disease, 73.9% (n = 17) had no detectable genomic mutations from ctDNA, and 26.0% (n = 6) were CTC-negative, consistent with radiological findings. However, 26.0% (n = 6) patients had at least one genomic finding, contributing to discordance with radiological findings.

Overall, genomic findings from the dual biomarkers showed concordance with radiological findings in 26.6% (n = 4) patients with progressive disease, 41.6% (n = 5) patients with metastatic disease, and 17.3% (n = 4) patients with stable or treatment-responsive disease.

Conclusions

Patients with progressive and metastatic disease identified through radiological findings showed concordance with dual ctDNA and CTC biomarkers. The concordance of ctDNA in progressive disease and CTC detection in metastatic disease highlights the individual significance of these biomarkers and supports their combined use for monitoring disease status and guiding treatment decisions.