Pairwise analysis of plasma cell-free DNA before and after palliative second-line paclitaxel plus ramucirumab treatment in patients with metastatic gastric cancer

• DOI: 10.1007/s10120-025-01604-y
• Publication Date: 2025-03-30T14:12:50Z
• Authors: Ji-Won Kim; Dong Soo Kyung; Won Yeong Ko; Hwang-Phill Kim; Sung-Hyun Hwang; Kui-Jin Kim; Ju Hyun Lee; Jeongmin Seo; Minsu Kang; Eun Hee Jung; Koung Jin Suh; Se Hyun Kim; Jin Won Kim; Yu Jung Kim; Jee Hyun Kim; Keun-Wook Lee
• Keywords: Ramucirumab; Cell-free fetal DNA; Surgical oncology

This study compared plasma cell-free DNA (cfDNA) and tumor tissue (ttDNA) to explore the clinical applicability of cfDNA in patients with metastatic gastric cancer (mGC) receiving palliative second-line paclitaxel + ramucirumab treatment. Targeted sequencing 106 genes was conducted using germline at baseline (baseline-cfDNA) progressive disease (PD-cfDNA). The results were those ttDNA-based panel data. Of 76 consecutive patients, 46 (27 males; median age 57.5 [range, 32-73] years) who had all three samples included. Combined analysis ttDNA baseline-cfDNA revealed that TP53 (58.7%) most frequently mutated gene, followed by CDH1 (26.1%), KRAS (21.7%), APC (13.0%). For these genes, sensitivity positive predictive value over 71.8% 51.9%, respectively. When PD-cfDNA combined, 34 (73.9%) found have additional mutations alone. 14 novel pathogenic ten (21.7%). At baseline, a high circulating fraction concentration showed significantly shorter progression-free survival (PFS) (P = 0.016) univariable multivariable analyses. High maximal variant allele frequency (VAF) 0.022), sum VAF 0.028), 0.022) associated worse PFS analysis. Although alone cannot replace entirely, mutations. Notably, emerged during Moreover, values longer PFS.