Impact of circulating tumor DNA genomic mutations and circulating tumor cells biomarker duo on clinical concordance in localized, progressive, and metastatic disease.
Authors: Vasudevan Aravindan , Ramesh Aarthi , Bharde Atul , D'Souza Alain , Prajapati Sangeeta , Jadhav Bhagwat , Khutale Ganesh , Patil Prathamesh , Chopra Rakesh , Deshpande Tanvi , Hariramani Kanchan , Basavalingegowda Madhura , Deshpande Richa , Jayant Sreeja , Aland Gourishankar , Kothavade Hrishita , Khandare Jayant , Shafi Gowhar 
Published: June 2024

e14546

Background: Genomic mutations have been identified from circulating tumor DNA (ctDNA) that correlates positively with clinical disease status. EGFR and intracellular cell progression/proliferation pathway-BRCA1/2 and TP53 genes drive high ctDNA load in progressive cancer patients. Circulating tumor cells (CTC) indicate Cellular Residual Disease (CRD). ctDNA and CTC as dual biomarkers offer prediction of tumor progression and metastasis implicative for early detection and treatment modifications. Methods: Retrospectively in 96 cancer patients (lung, colon-rectal, breast, stomach, etc.) who recently underwent treatment were investigated for presence of CTCs and genomic mutations from ctDNA using OncoMonitor Test. Libraries were prepared using a hybridization-capture method covering 1000 targets with mean sequencing depth 5000X on Illumina Nextseq 2000. Test detected genomic alterations from single nucleotide variation (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, with CK18+, PD-L1+, CD45- in1.5 ml of blood. Results: In 96 pan-cancer patients, 15.6% patients (n=15) were identified with localized progressive disease with no metastasis from radiological findings, of which 60% (n=9) patients showed at least 1 genomic finding from ctDNA.12.5% (n=12) patients were identified as metastatic from their radiological findings of which 58.3% (n=7) showed presence of at least 1 CTC. 33.3% (n=4) patients showed 2 CTCs and 5 patients had no CTCs. In addition, these metastatic patients showed the presence of ctDNA load in 66.6% (n=8) patients with at least 1 genomic finding. In metastatic disease cohort, CTC enumeration showed concordance of 58.3% (n=7) with metastatic radiological findings and genomic findings from ctDNA showed concordance in 66.6% (n=8) patients with metastatic radiological findings. 23.9% (n=23) patients from the cohort were radiological identified with stable/treatment responsive disease of which 73.9% (n=17) patients were not detected with genomic mutations from ctDNA and 26.0% (n=6) patients were CTC -ve, concordant with radiological findings. 26.0% (n=6) patients had at least 1 genomic finding contributing to discordance with the radiological findings. Genomic findings from duo offered concordance with radiological findings in 26.6% (n=4) patients with progressive disease, 41.6% (n=5) in metastatic disease, and 17.3% (n=4) in patients with stable/treatment responsive disease. Conclusions: Patients with progressive and metastatic disease from radiological findings showed concordance with the dual ctDNA and CTC biomarkers. Concordance of ctDNA in progressive disease and CTC in metastatic disease is indicative of individual significance.