Peritoneal Tumor Dna in a Multimodal Treatment Setting of Locally Advanced Gastric Cancer – A Novel Study Design

Abstract Background Gastric cancer is a leading cause of death from malignant diseases and has been characterized on a molecular level in recent years. In a context of precision medicine, the proposed study aims to describe the three major compartments harboring tumor cells in patients requiring multimodal therapy: peripheral blood, the abdominal cavity, and the local tumor. Unlike tumor tissues and liquid biopsies, the peritoneal space (in terms of ascites and metastatic tumor seeds) is not regularly considered in molecular diagnostics due to difficult access. This study aims to determine circulating tumor DNA in the peritoneum (ptDNA) and in the plasma (ctDNA). It will then be investigated to what extent the detection of ptDNA before and after neoadjuvant therapy correlates with ctDNA. The main goal is to evaluate the relative changes in ptDNA and ctDNA levels after systemic treatment in patients with locally advanced gastric cancer. Hypothesis: We hypothesize that ptDNA in the abdominal cavity reacts differently to chemotherapy than ctDNA in peripheral blood and therefore, peritoneal disease cannot be adequately represented by ctDNA. Patients with elevated initial ptDNA levels, especially those who do not respond to neoadjuvant therapy, might have an increased risk of peritoneal carcinomatosis and consequently require intensified systemic or local (i.e. HIPEC) treatments. Study design: ptDNA and ctDNA will be analyzed at the time of cancer diagnosis (during exploratory laparoscopy according to diagnostics guidelines) and after neoadjuvant therapy (during tumor resection). Subsequently, the determination of ptDNA in gastric cancer patients could allow the identification of a subgroup that will benefit from intensified local treatment options for peritoneal tumor seeding. Finally, the study will attempt to establish the peritoneal space as another compartment for future precision oncology diagnostics and multimodality therapy.