Supplementary Material for: Epidemiology of Neuroendocrine Neoplasia worldwide – A Review of the Literature (2012-2022)

Background
The incidence of NENs has been rising globally; However, epidemiological studies on NENs often lack comprehensive geographical comparisons, with limited reporting on demographic variations, risk factors, and tumour site-specific trends.

Summary
This review examines the global epidemiological trends in NENs, focusing on incidence, demographic variations, risk factors, and survival outcomes across tumour sites. A literature search was conducted using PubMed, Medline, and Embase, identifying 74 eligible epidemiology-focused studies on adult NEN populations published between 2012 and October 13, 2022. Results indicate a rising incidence of NENs across multiple sites, with significant regional and demographic variations. Gastrointestinal NENs are the most prevalent, with rectal NENs experiencing the highest increase. Gastric NENs are more common in Asian countries, while appendiceal NENs are predominantly found in younger Caucasian females. Pancreatic NENs exhibit racial disparities, with Black patients diagnosed at younger ages and facing socioeconomic barriers to care. Lung NEN incidence is rising, except for small cell lung cancer, which is declining due to reduced smoking rates. Survival outcomes vary by site, with rectal and appendiceal NENs having better prognoses and gastric and colonic NENs having worse survival rates. Across all sites, advancing age is linked to poorer survival, while females generally have better outcomes. Common modifiable risk factors include obesity, type 2 diabetes, smoking, alcohol consumption, and metabolic syndrome.

Key Messages
This review provides a comprehensive global perspective on NEN epidemiology, allowing healthcare providers to identify high-risk populations to inform screening strategies and address modifiable risk factors to help mitigate the increasing incidence and improve patient outcomes worldwide.