Clinical characteristics and treatment patterns of patients with gastroenteropancreatic neuroendocrine neoplasia in Germany receiving peptide receptor radionuclide therapy: A real-world data registry-based study

Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare malignancies deriving from the endocrine system in the gastrointestinal tract including the pancreas. Prognosis is greatly heterogenous due to its dependency on various factors, most importantly stage and differentiation. Several studies report an alarming rise in incidence in the past decade. Despite there being some therapeutical options, best therapy sequence still needs to be defined, particularly for unresectable and/or intermediate and high-grade NENs. Peptide receptor radionuclide therapy (PRRT) was approved in Europe and USA in 2017 and 2018, respectively. Studies with real-world systematic data on characteristics and treatment patterns of PRRT-receiving patients was non-existent at the time of this writing. In this retrospective study, we identified within the German NET-Registry 203 patients diagnosed with GEP-NEN having received PRRT from 1995 to 2023. We assessed general clinical patient characteristics, disease-specific characteristics, treatments and outcomes. To obtain a more up-to-date picture of treatment modalities and outcomes, a subgroup of the study population was allocated to the "therapy cohort," defined by patients with date of first diagnosis between 2010 and 2023 (open cohort). Mean age of the study population was 58 years (SD 12 years) with 51.7% being men. Most patients had a WHO performance score of 0 to 1 (41.4% and 50.5%, respectively). Most NEN cases were of small intestine/pancreatic origin (46.3% and 45.3%, respectively) and displayed well/moderate differentiation (55.3%). Ki-67 was generally within the 3% to 20% range (57.92%). Most patients presented with metastasis at diagnosis (73.9%). Somatostatin analogs (SSAs), chemotherapy and surgery were the most common non-PRRT therapy options (65.3%, 60.2%, and 50.0%, respectively). PRRT was most often applied as third- or second-line therapy (42.3% and 36.6%, respectively), usually after surgery and/or SSA treatment. As PRRT had been administered using different regimens, tumor response evaluation showed mixed responses. Given the low sample size and considerable amount of missing response data, no correlation analysis between PRRT sequencing and tumor response could be performed. Overall, the clinical characteristics and treatment patterns tend to follow trends observed in other studies or medical guidelines. Finally, this study presents real-world data that more accurately describes GEP-NEN disease in Germany and treatment modalities after PRRT's approval.

Trial registration: ClinicalTrials.gov NCT06016855.