P1.080. Dynamic ctDNA Profiling Predicts Pathological Complete Response and Identifies Pseudoprogression in ESCC Receiving Neoadjuvant Immunochemotherapy

Abstract

Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background The integration of anti-PD-1 antibody therapy with chemotherapy has shown promising results in the neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma. Conventional imaging may not fully capture immunotherapy effects due to unconventional response patterns like pseudoprogression. Methods We enrolled 23 esophageal squamous cell carcinoma patients receiving neoadjuvant immunochemotherapy and surgery. Plasma was collected pre- and post-treatment for ctDNA analysis. Baseline tumor biopsies were used to build ctDNA panels and assess tissue TMB via targeted sequencing. ctDNA positivity was defined by matched somatic variants; TMB was calculated as total coding mutations per sample. Results At baseline, ctDNA was detected in 87% of patients. The results demonstrated that the dynamic change patterns of ctDNA levels were significantly associated with pCR rates. Specifically, patients with undetectable ctDNA post-ICT had a significantly higher pCR rate compared to ctDNA-positive patients (71.4% vs. 12.5%, p<0.05). ctDNA dynamics stratified patients into distinct response groups, with those remaining ctDNA-negative throughout treatment exhibiting had a higher risk of pCR. In contrast, tissue TMB and PD-L1 expression were not significantly associated with pCR. Furthermore, ctDNA was effective in identifying pseudoprogression, where radiologic progression was contradicted by decreasing ctDNA levels and confirmed pCR postoperatively. Conclusion Our results suggest that ctDNA may serve as a potential biomarker for assessing treatment response in patients with esophageal squamous cell carcinoma undergoing neoadjuvant Immunochemotherapy. Further research could elucidate the specific ctDNA signatures that correlate with therapeutic efficacy and metastatic spread, enhancing personalized treatment strategies for esophageal squamous cell carcinoma.