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Neuroendocrine neoplasms (NEN) are a heterogeneous group of tumors, which can be histologically separated by primary location, proliferation rate and differentiation of tumor cells. The therapeutic options and outcome depend on grading, staging and resectability of the tumor. Established treatment options of neuroendocrine tumors (NET) and carcinomas (NEC) are based especially on surgery, tumor specific medical treatments, peptide guided radioreceptor therapy (PRRT) and locoregional therapies. We report about a patient diagnosed with a pancreatic, non-functional NET/NEC G2/3 with a proliferation rate of 20% at initial immunohistochemical diagnosis. During the course of the disease, the proliferation rate increased up to more than 50% over a period of 5 years. Due to loss of response to established therapies (i.e. systemic chemotherapy, targeted therapy and brachytherapy), an off-label immunotherapy with the PD-1 antibody pembrolizumab was initiated based on a 30% PD-L1 expression in tumor cells. This report is the first demonstrating a partial remission of a pancreatic NEN using pembrolizumab monotherapy with a hepatic tumor volume reduction of at least 66%, combined with an improvement of the Karnofsky score rising from 60% to 100%. This case offers insight into the potential role of immunotherapy in a subgroup of neuroendocrine neoplasms.

Sustained partial remission of a metastatic NEN using off-label immunotherapy with pembrolizumab