Endocrine Abstracts

Aim: Functional neuroendocrine tumors (NETs) represent a specific diagnostic and therapeutic challenge. Hormonal clinical syndrome can severely complicate clinical picture and affect treatment. Functional pancreatic NETs have been extensively studied. Our aim was to analyze functional lung NETs in terms of clinical characteristics and survival.

Materials and methods: We retrospectively analyzed data from 230 patients with lung NETs treated at our department from 2005 till 2022. The patients underwent standard radiological, pathohistological and hormonal evaluation. All tumors were graded according to current guidelines to typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC) and small cell lung carcinomas (SCLC). Disease stage was defined according to the ENETS/AJCC TNM staging system. Differences between functional and non-functional tumors were analyzed by non-parametric tests, overall survival was analyzed by Kaplan–Meier method, and differences by Cox-regression analysis. Statistical analysis was performed by SPSS software.

Results: Functional tumors were diagnosed in 53 patients (23%): 20 serotoninomas (8.7%), 15 with ectopic Cushing’s syndrome (6.5%), 11 calcitonin secreting (4.8%), 6 with SIADH (2.8%), and 2 with ectopic acromegaly (0.9%). Sex distribution was almost equal in the entire group (female 50.4%), and in the subgroup of functional tumors (female 45.3% female). The mean age was 55.3±13.6, with no significant difference between groups (P=0.443). Majority of functional NETs were well differentiated (TC 18.4%, AC 49.0%, LCNEC 22.4%, SCLC 10.2%), and this distribution was similar to patients with nonfunctional NETs (P=0.127). There were no significant differences in primary tumor size (P=0.705), and presence of MEN1 syndrome, but metastatic disease was less frequent in functional tumors (P=0.01), and consequently functional tumors more frequently presented in lower disease stages (P=0.02). Median overall survival in the entire group was 66.0 months (95%CI 35.7–96.3), and in the group of functional NETs 36.0 months (95%CI 4.7–67.3). Survival was significantly shorter in functional NETs compared to nonfunctional (P=0.02). When groups of different tumor grades were analyzed separately, significantly shorter survival of functional NETs was confirmed in well-differentiated tumors (P=0.011 for TC, and P=0.009 for AC), while poorly-differentiated tumors of both groups had similar survival (P=0.585 for LCNEC, and P=0.632 for SCLC).

Conclusion: Almost one quarter of patients with lung NETs have some form of recognizable hormonal syndrome. Even though functional lung NETs metastasized less frequently compared to non-functional, overall survival of these patients was significantly shorter, namely in groups of well-differentiated tumors. Treatment of these patients requires improvement of therapeutic strategies.