Abstract 497P
Background
Circulating tumor DNA (ctDNA) analysis in liquid biopsy offers a minimally invasive approach for cancer monitoring and therapeutic guidance. The optimal strategy for ctDNA detection remains under investigation, particularly for blood-based testing when tumor tissue is unavailable.
Methods
This study retrospectively evaluated the performance of a tumor-naïve ctDNA assay (K-Track™ BO, Gene Solutions) for ctDNA detection in 451 patients diagnosed with breast, colorectal, gastric, liver, lung, and ovarian cancers at either early or metastatic stage. ctDNA was analyzed by multiplex PCR and ultra-deep sequencing for approximately 500 hotspot mutations for each cancer, in combination with shallow whole genome sequencing to capture genome-wide non-mutation features including copy number and fragment length alterations.
Results
In the cohort of 202 patients at the early-stage I-III, pre-operative ctDNA detection rates using only mutations were 40.0%, 68.3%, 34.1%, 20.5%, 73.1%, and 62.5% for lung, colorectal, breast, gastric, liver, and ovarian cancer respectively. Combination of non-mutation features of ctDNA increased the above detection rates to 45.0%, 71.7%, 41.5%, 28.2%, 96.2%, and 68.8%, respectively. After 24 months of follow-up, in 21 patients experiencing cancer recurrence, post-operative ctDNA was detected in 66.7% (14 /21) of the patients using only mutations, compared with 85.7% (18/21) of the patients using the combined feature approach. The average lead time before clinical diagnosis was 4.8 months (up to 14.4 months). In the cohort of 249 patients at the metastatic stage IV, the combined feature approach detected ctDNA before treatment in 76.3%, 84.0%, 60.0%, 64.7%, 84.6%, and 72.7% of lung, colorectal, breast, gastric, liver, and ovarian cancer patients respectively. The tumor fraction was then used to monitor treatment response as demonstrated in our case studies.
Conclusions
Our tumor-naïve ctDNA assay integrating genome-wide features with hotspot mutations could reliably detect ctDNA in multiple types of cancer and demonstrated clinical utilization in residual cancer surveillance and treatment response monitoring.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Gene Solutions JSC.
Disclosure
All authors have declared no conflicts of interest.