Carcinoid Heart Disease and Decreased Overall Survival among Patients with Neuroendocrine Tumors: A Retrospective Multicenter Latin American Cohort Study

Abstract

The background to this study was that factors associated with carcinoid heart disease (CHD) and its impacts on overall survival (OS) are scantly investigated in patients (pts) with neuroendocrine tumors (NETs). In terms of materials and methods, a retrospective multicenter cohort study was conducted of factors associated with CHD in advanced NET pts with carcinoid syndrome (CS) and/or elevated urinary 5-hidroxyindole acetic acid (u5HIAA). CHD was defined as at least moderate right valve alterations. The results were the following: Among the 139 subjects included, the majority had a midgut NET (54.2%), 81.3% had CS, and 93% received somatostatin analogues. In a median follow-up of 39 months, 48 (34.5%) pts developed CHD, with a higher frequency in pts treated in public (77.2%) versus private settings (22.9%). In a multivariate logistic regression, unknown primary or colorectal NETs (Odds Ratio (OR) 4.35; p = 0.002), at least 50% liver involvement (OR 3.45; p = 0.005), and being treated in public settings (OR 4.76; p = 0.001) were associated with CHD. In a Cox multivariate regression, bone metastases (Hazard Ratio {HR} 2.8; p = 0.031), CHD (HR 2.63; p = 0.038), and a resection of the primary tumor (HR 0.33; p = 0.026) influenced the risk of death. The conclusions were the following: The incidence of CHD was higher in pts with a high hepatic tumor burden and in those treated in a public system. Delayed diagnosis and limited access to effective therapies negatively affected the lives of NET patients.

Health resource utilisation by patients with neuroendocrine tumours with or without carcinoid heart disease: a multinational study

“…The multicentric study was conducted in accordance with International Conference on Harmonisation-Guideline for Good Clinical Practice, guidelines and local laws, and the protocol was submitted and approved by local ethics committees. The sample used in this study was obtained from a database of 137 consecutive adult NET patients (19-85 years) with elevated urinary 5-HIAA to estimate the frequency and risk factors for CHD [6]. Due to the retrospective nature of this study, no formal CHD screening protocol was performed in the participating institutions; however, it is a common practice to screen patients with elevated levels of urinary 5-HIAA with echocardiograms annually or every 2 years.…”

“…The study covered the period from January 2000 to July 2018. The median follow-up time was 39 months (range: 2.7-150.6 months) [6].…”

“…Demographic data, comorbidities, tumour characteristics, cancer treatments and information on heart conditions as well as relevant medical resources used by the patients were collected and organised from patients' records by researchers at each centre as described by Uema et al [6]. Baseline characteristics were gathered from medical records at the time of carcinoid syndrome diagnosis (the date of elevated 5HIAA urinary test).…”

“…CHD has been described in up to 34.5% of patients with both NETs and CS in Latin America [6]. Delayed diagnosis and limited access to effective therapies may negatively affect the lives of patients with CHD.…”

“…Delayed diagnosis and limited access to effective therapies may negatively affect the lives of patients with CHD. Indeed, the odds of presenting CHD in Latin America were 4.76 times higher for those treated in the public setting, where availability of NET-directed therapies is limited, when compared to patients managed in a private setting [6]. Intuitively, because CHD is associated with high morbidity, it may also be linked to high health resource consumption, thus overloading health systems.…”