137P - Clinical utility of circulating tumour DNA (ctDNA) in resectable gastric cancer (GC)

Background

Circulating tumor DNA (CtDNA) has shown its negative prognostic value in a number of studies, however, data on the role of ctDNA in resectable gastric cancer (GC) are lacking. The aim of our study was to determine the prognostic value of ctDNA at various stages of the disease using our simple and cheap test.

Methods

This prospective study included patients with diagnosis of GC who received treatment from 2017 to 2019. Tumor somatic mutations were determined by target sequencing of DNA from FFPE tumor blocks. Sequencing was performed using the custom NGS panel covering regions of frequent somatic mutations in 50 genes. Tumor-specific mutations were monitored by ddPCR in plasma samples taken before and after surgery in case of resectable GC (n=42) and before and during chemotherapy in case of advanced GC (n=13). The median time between surgery and blood sampling was 7 days (5-15 days, σ 2.3). The plasma sample was considered "positive” if the content of ctDNA was more than 0.5 copies of mutant DNA in ml plasma.

Results

Tumor-derived mutations were found in plasma with sensitivity of 74.5% (n=55): in stage IV (n=13) – 92.3%, stage III (n=24) – 70.8%, stage II (n=11) – 81.8% and in stage I (n=7) – 100%. In the group with resectable GC 24 (57.1%) pts received adjuvant or perioperative chemotherapy. Detection of ctDNA before surgery did not affect DFS (HR 0.7, 95%CI 0.04-11.5, p=0.8). In 10 (23.8%) cases ctDNA was determined after surgery. Progression of the disease was detected in 6/10 (50%) pts with ctDNA(+) and 6/32 (18.8%) - in ctDNA(-) pts (p = 0.012). One-year DFS in ctDNA(+) and ctDNA(-) pts with resectable GC after surgery were 25.4% and 73.2%, respectively. ctDNA positivity after surgery was an independent negative prognostic factor according to Cox regression model fitted to T, N, and adjuvant chemotherapy (HR 6.6, 95%CI 1.5-30, p =0.014).

Conclusions

A robust and economical assay of ctDNA detection is sensitive and demonstrates the prognostic significance of ctDNA persisting after surgery in pts with the early stage of the GC. Further clinical validation of this approach is required in trails with modifications of the perioperative treatment, in terms of escalation and de-escalation, according to the content of ctDNA.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This research is conducted under the auspices of the experimental governmental assignment of the Ministry of Health of the Russian Federation and coordinated by the FSBI “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Ministry of Health of the Russian Federation.

Disclosure

All authors have declared no conflicts of interest.