KRAS (Kirsten Rat Sarcoma) Mutant CIrculating Tumor DNA for Monitoring Response to First Line Chemotherapy in Locally Advanced and Metastatic PANcreatic Cancer

With an incidence of more than 11,600 new cases per year in France and an annual number of deaths close to the incidence rate, adenocarcinoma of the pancreas is a public health problem especially since there is a significant increase in its incidence. incidence (+ 417% between 1980 and 2012).

Most often diagnosed late, pancreatic adenocarcinoma is managed at a metastatic stage in 60 to 70% of cases with a very poor prognosis (8.7 to 11.1 months median survival with current chemotherapies). The first line of chemotherapy therefore represents a major issue in the management of these unresectable patients. There are few predictive markers of response to chemotherapy in pancreatic adenocarcinoma. It is conventionally evaluated by scanner every 2 to 3 months. The response to chemotherapy is associated with a good prognosis while non-response has a poor prognosis and requires a 2nd line of treatment if the patient is able to receive it.

A KRAS mutation is present in approximately 70-90% of pancreatic adenocarcinomas. Its research on tissue sampling (fine needle aspiration or anatomo-pathological specimen) is not carried out routinely because no prognostic or predictive value of KRAS mutations has been demonstrated. New high-throughput DNA sequencing techniques have been developed and now allow a blood sample to detect and quantify circulating tumor DNA (ctDNA), including KRAS mutations.

Very few studies have investigated the change in cDNA levels during 1st line chemotherapy in unresectable pancreatic adenocarcinoma.

The aim of this study is to assess the predictive value of response to the 1st line of chemotherapy of mutated KRAS cDNA in unresectable metastatic or locally advanced pancreatic adenocarcinomas.