Evaluation of ctDNA in Predicting Response to Neoadjuvant Therapy and Analysis of Residual Disease in Local Advanced Gastric Cancer: Protocol of A Single-Arm Multicenter Prospective Observational Study

Abstract Background In gastric cancer, there is a controversial finding regarding the high recurrence rate after neoadjuvant therapy. The use of ctDNA detection for minimal residual disease (MRD) with plasma genotyping has shown higher sensitivity and specificity compared to imaging and serum markers for predicting recurrence. Therefore, we aim to investigate the perioperative dynamic changes in ctDNA in surgical II-III GS patients and assess the efficacy of neoadjuvant chemotherapy. Methods In detail, we will collect blood samples from each patient before neoadjuvant chemotherapy (NAC), after NAC, and one month after surgery. We will also collect tumor tissue before and after NAC. Gene mutations will be detected using a 733-gene NGS panel, and DNA concentrations will be measured. To evaluate the effectiveness of the treatment, we will use RECIST Version 1.1 (RECIST 1.1). Discussion This study aims to assess the correlation between perioperative changes in ctDNA levels and the response to chemotherapy in patients with gastric cancer. It will provide evidence that perioperative ctDNA detection may predict early recurrence, highlighting the potential clinical utility of ctDNA in guiding therapeutic decision-making. Compared to tumor tissue biopsy, ctDNA can non-invasively detect more comprehensive genomic information from a limited amount of plasma. Trial registration: Registered prospectively in the Chinese Clinical Trials Registry with registration number ChiCTR2200060842 on June 12st, 2022.