Liquid Biopsy for ctDNA in Peritoneal Lavage and Blood in Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

Pancreatic cancer (PC) is a deadly disease and surgical resection of the tumor is the only hope of cure. Approximately 20-25% of the PC patients are candidates for intended curative resection, but despite microscopically radical resection the majority of patients will have recurrent disease within 2 years. This indicates that most patients will harbour non-detected (i.e. occult) cancer cells at the time of resection. Studies suggest that free tumor cells in the peritoneum and in the blood are part of this occult disease burden, and that patients with such findings should not be operated but treated as having metastatic disease. However, the exact incidence of these tumor cells in an unselected cohort of patients undergoing pancreatic resection is unknown, and the potential impact on postoperative survival is also uncertain. In recent years, molecular biomarkers are increasingly being regarded as both predictive and prognostic tools for cancer patients. This study will use the most optimal available methods to investigate the incidence of biomarkers for tumor cells in the peritoneum and blood in PC patients, and to relate these findings to the final outcome of the resected patients. This project has become highly relevant since new treatment methods (i.e. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)) may be used to eradicate free tumor cells. A recent systematic review and meta-analysis demonstrated that PC patients with positive peritoneal cytology (Cy+) had a significant poorer survival than patients with negative peritoneal cytology (Cy-) (HR 3.18), and the authors concluded that Cy+ patients should not undergo surgery. This conclusion was supported by a significant lower overall survival and a higher peritoneal recurrence rate after resection of Cy+ patients when compared to Cy- patients. Agreement that Cy+ in resectable PDAC is a negative predictor of prognosis came from another recent meta-analysis and systematic review. However, this study also indicated that the median OS was worse in patients without than in those with resection among patients with Cy+, thereby emphasizing need of further careful assessment of indications for radical resection in Cy+ patients. KRAS mutations have been detected in circulating tumor DNA (ctDNA) in the blood (liquid biopsies) from patients with metastatic PC, and ctDNA is considered a marker of poor prognosis. Similar, KRAS mutations were found in the plasma of one-third of patients with a resectable …

Detailed description public domain (ClinicalTrials.gov)

1. Introduction Approximately 1.000 new cases of pancreatic cancer (PC) are diagnosed each year in Denmark. Ductal adenocarcinoma is by far the most frequent histological subtype of cancer in the pancreas and accounts for more than 90% of all cases \[1\]. Thus, in this protocol the term PC refers to pancreatic ductal adenocarcinoma. PC is a devastating disease with an overall 5-year survival of 3-7% \[2\]. Less than one in four patients are candidates for intended curative resection, but even after microscopically radical resection (R0 resection) the majority of patients will have recurrent disease within 2 years \[3\]. The discrepancy between pathological assessment and clinical outcome indicates that most patients will harbour non-detected (i.e. occult) cancer cells at the time of resection. It is of utmost importance to improve our ability for prognostication and prediction of PC, aiming at a tailored and personalized approach for treatment decisions regarding this aggressive type of cancer. This project aims to take an important step in this direction, by a 2-tiered approach: 1) Examination of the peripheral blood (detection of circulating tumor DNA), and 2) the peritoneal lavage fluid (detection of tumor DNA in the peritoneal space). 2. Background PC is a deadly disease and surgical resection of the tumor is the only hope of cure. Approximately 20-25% of the PC patients are candidates for intended curative resection at the time of diagnosis, but despite microscopically radical resection the majority of patients will have recurrent disease within 2 years \[3\]. This indicates that most patients will harbour non-detected (i.e. occult) cancer cells at the time of resection. Studies suggest that free tumor cells in the peritoneum and in the blood are part of this occult disease burden, and that patients with such findings should not be operated but treated as having metastatic disease. However, the exact incidence of these tumor cells in an unselected cohort of patients undergoing pancreatic resection is unknown, and the potential impact on postoperative survival is also uncertain. In recent years, molecular biomarkers are increasingly being regarded as both predictive and prognostic tools for cancer patients. This study will use the most optimal available methods to investigate the incidence of tumor cells in the peritoneum and blood in PC patients, and to relate these findings to the final outcome of the resected patients. This project has become …

Primary outcome public domain (ClinicalTrials.gov)

Relative frequency of ctDNA in peritoneal lavage and peripheral blood. Percentage Time frame: 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Prognostic value of ctDNA in peritoneal lavage and peripheral blood. Time frame: 2 years.

Eligibility public domain (ClinicalTrials.gov)

* Inclusion criteria: Patients diagnosed with pancreatic cancer (adenocarcinoma) on a pancreatic resection specimen Age \> 18 years Exclusion Criteria: * Duodenal carcinoma, ampullary carcinoma, bile duct cancer * Benign surgical diagnosis * Pregnancy

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 80 participants (actual).