1149MO - Carcinoid heart disease in patients with advanced small-intestinal neuroendocrine tumours and carcinoid syndrome: A retrospective experience of two centers of excellence

Background

Up to 50% of patients (pts) with carcinoid syndrome (CS) associated with neuroendocrine tumors (NETs) develop carcinoid heart disease (CHD). Since CS is most commonly combined with metastatic small intestinal (SI) NETs we here report the large experience of two international NET-referral centers on CHD in this clinical context. Aims: to describe frequency, clinical features and prognostic impact of CHD in pts with advanced SI-NET and CS.

Methods

We reviewed clinical records of 165 pts with advanced SI-NETs and CS, presented at the multidisciplinary team (MDT) from 2015 to 2021 at European Institute of Oncology in Milan and Department of Endocrine Oncology of Uppsala University, both ENETS and EURACAN NEN Centers of Excellence (CoEs). The CHD diagnosis was echocardiography-based. Overall survival (OS) was estimated since the diagnosis of metastatic NET using the Kaplan-Meier method. The cumulative incidence function (CIF) of CHD was estimated according to method described by Kalbfleisch and Prentice. Relationship between clinical parameters and OS was studied using Cox proportional hazards regression models.

Results

The frequency of CHD was 24.8% and 5-years (y) CIF was 24.3%. Diagnosis of CHD occurred later than that of CS in 56.1% of pts. At CHD diagnosis, 39% of pts were symptomatic due to right heart failure, 36.6% had >300 μmol/24h urinary 5-Hydroxyindoleacetic Acid, and 53.7% had > 260 pg mL-1 Plasma N-terminal pro-brain natriuretic peptide. A moderate-to-severe tricuspid insufficiency (TI) was observed in 90.2% of pts, whereas pulmonary (P) I in 31.7%. In 58% of pts left-sided valves were also involved. 46.3% of CHD pts underwent thoracic surgery mostly receiving T + P valve replacement. Prognosis was significantly impaired by CHD (HR 2.85, p < 0.001). The mOS of CHD pts was 4.5 years, with a 5-y survival rate of 34.4%.

Conclusions

This study suggests that CHD has relevant prognostic role in metastatic SI-NET pts with CS, and that u5-HIAA and NT-proBNP combined with echocardiogram should be performed at CS baseline preferably in NET-referral centers. Our analysis generated some solid hypotheses to be specifically investigated in prospective homogeneous clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Spada: Financial Interests, Personal, Invited Speaker: Advanced Accelerator Applications, Sas Spa; Financial Interests, Personal, Writing Engagement: Ipsen, Merck, Advanced Accelerator Applications; Non-Financial Interests, Project Lead, Coordinator of neuroendocrine neoplasms guidelines: AIOM (Italian Association Of Medical Oncology); Non-Financial Interests, Leadership Role, I am member of Scientific Board and lead of neuroendocrine Neoplasms Guidelines: ITANET (Italian Association Of Medical Oncology). D. Cardinale: Financial Interests, Personal, Speaker, Consultant, Advisor: Siemens Healthineers, Ipsen SpA, Gilead Sciences, Inc. G. Badalamenti: Financial Interests, Personal, Speaker, Consultant, Advisor: Boehringer Ingelheim, PharmaMar, GSK, Novartis. S. Welin: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD. N. Fazio: Financial Interests, Personal, Other, Steering committee: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Merck, MSD, Novartis, Ipsen; Financial Interests, Institutional, Local PI: Astellas, MSD, Beigene, Nucana, Ipsen, Fibrogen, ITM, Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Ipsen, Novartis, Merck; Non-Financial Interests, Other, Steering committee: SPARC Europe; Non-Financial Interests, Member of Board of Directors: ENETS; Non-Financial Interests, Other, Member of the NET Faculty: ESMO; Non-Financial Interests, Other, Internal reviewer of NET guidelines: AIOM. All other authors have declared no conflicts of interest.