Longitudinal Biomarker Study in Endocrine Neoplasms to Study Acquired Resistance to Alkylator Chemotherapy

What this Trial Is About

This research aims to understand how alkylating chemotherapy, especially temozolomide, may cause high tumor mutational burden (TMB) by creating mutations in the DNA mismatch repair system in endocrine neoplasms. Although hypermutation is rare in neuroendocrine tumors, about 30% of pancreatic tumors might develop high TMB after such chemotherapy, which could affect treatment response. The study is prospective and multicenter, including 94 patients from Swedish endocrine cancer centers. Participants are divided into two groups: Group A includes patients about to start alkylating chemotherapy, and Group B includes those with tumor progression after previous alkylating chemotherapy. Blood samples for liquid biopsy are taken at baseline and follow-up for Group A, with tissue biopsies collected if tumors progress. Group B patients have both liquid and tissue biopsies at inclusion, analyzed using GMS560. Participants will undergo blood draws and tissue biopsies to monitor tumor changes and hypermutation development. Researchers will study the proportion of pancreatic neuroendocrine tumor patients showing hypermutation and mismatch repair deficiency after chemotherapy over an average of two years. The study involves ongoing assessments through imaging, blood tests, and biopsies to observe tumor progression and resistance development.

Study of Acquired Resistance to Alkylator Chemotherapy in Endocrine Neoplasms