Serotonin Levels And 1-Year Mortality In Patients With Neuroendocrine Tumors: A Systematic Review And Meta-Analysis

Joish, Vijay N.; Shah, Sandip; Tierce, Jonothan C.; Patel, Deep; McKee, Chad M.; Lapuerta, Pablo; Zacks, Jerome

doi:10.2217/fon-2018-0960

Cited by 16 publications

(16 citation statements)

References 44 publications

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“…Taken together, the results of this review indicate that elevated levels of u5-HIAA are associated with increased probability of CHD diagnosis, disease progression, and mortality. This conclusion is supported by a recent systematic review and meta-analysis that reported a quantifiable relationship between increasing u5-HIAA levels in patients with NETs and higher risk of 1-year mortality [51]. There is a need for consistent and practical guidelines for the screening, diagnosis, and management of CHD in clinical practice.…”

Section: Discussionmentioning

confidence: 90%

Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review

et al. 2020

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Background: Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression, and mortality. Methods: MEDLINE, Embase, Cochrane databases, and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes. Results: Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3–65% and 3–42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with versus without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with versus without CHD were 266–1,381 versus 67.5–575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels: 791–2,247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase). Conclusions: Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression, and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients.

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Section: Discussionmentioning

confidence: 90%

Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review

et al. 2020

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“…[14][15][16] Elevated serotonin is associated with proliferative effects on fibroblasts in both the small bowel mesentery and cardiac valves [19][20][21] and with increased 1-year mortality for patients with CS. 22 Serotonin has further been associated with increased secretion, motility, and inflammation in the gastrointestinal tract, contributing to CS diarrhea. TE is postulated to improve these symptoms by reducing tumoral production of serotonin.…”

Section: Discussionmentioning

confidence: 99%

Changes in Carcinoid Syndrome Symptoms Among Patients Receiving Telotristat Ethyl in US Clinical Practice: Findings from the TELEPRO-II Real-World Study

Kulke¹,

Kennecke²,

Murali³

et al. 2021

CMAR

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Background Inadequately controlled symptoms incur a substantial burden on patients with neuroendocrine tumors and carcinoid syndrome (CS). The effectiveness of telotristat ethyl (TE) with a somatostatin analog for uncontrolled CS diarrhea has been demonstrated in clinical trials and observational studies. TELEPRO-II was a prospective observational study evaluating TE’s effectiveness in clinical practice over the first 3 months of treatment. Methods Patients initiating TE in 2018 participated in an optional nurse support program reporting CS symptoms during interviews at baseline and 1, 2, and 3 months after TE initiation. Eligible patients received TE for ≥3 months and reported symptom burden at baseline and ≥1 follow-up visit within the first 3 months. Daily bowel movement (BM) frequency and flushing episodes were reported as events/episodes per day. Stool consistency, nausea severity, urgency severity, and abdominal pain were reported on a severity scale (1–10). Symptom changes were evaluated using paired-sample t -tests and Wilcoxon signed-rank tests. Analysis of symptoms based on achievement of <30% or ≥30% reduction in daily BM frequency was conducted using a cumulative distribution function. Results A total of 684/1603 (43%) patients were eligible for analysis. At baseline, patients reported a mean of 6.3 BM/day, nausea severity of 8.4/10 and stool urgency of 8.2/10. Significant improvements in all CS symptoms were observed after 3 months of TE. Mean daily BMs were reduced 64% after 3 months of TE (mean reduction [SD], –3.99 [3.8]; P<0.0001). Most patients (74%, n=503) reported ≥30% reduction in daily BM frequency; these patients also reported improvements in other symptoms (76–87%). Patients with <30% reduction in daily BMs also reported improvements in nausea severity (62%, n=24), daily flushing episodes (66%, n=98), abdominal pain (50%, n=60), urgency severity (38%, n=64), and stool consistency (24%, n=44). Conclusion Patients treated with TE in a real-world setting experienced significant, clinically meaningful improvements in CS symptoms.

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“…The authors disclosed that every 10-unit increase in 5-HIAA level was associated with 11.8% (95% CI 8.9%-17.0%) increase in 12-month mortality incidence. 16 Worth remembering is the fact that serum 5-HIAA level measurement stands another option to screen for CS. The plasma 5-HIAA can serve as a surrogate for urine 5-HIAA.…”

Section: Biomarkersmentioning

confidence: 99%

“…The authors disclosed that every 10-unit increase in 5-HIAA level was associated with 11.8% (95% CI 8.9%-17.0%) increase in 12-month mortality incidence. 16 …”

Section: Diagnosismentioning

confidence: 99%

Carcinoid Heart Disease: How to Diagnose and Treat in 2020?

Bober

Saracyn

Kołodziej

et al. 2020

Clin Med Insights Cardiol

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Neuroendocrine tumors (NETs, originally termed “carcinoids”) create a relatively rare group of neoplasms with an approximate incidence rate of 2.5 to 5 cases per 100 000 persons. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome (CS), and 20% to 50% of subjects with CS are diagnosed with carcinoid heart disease (CaHD). The long-standing exposure to high serum serotonin concentration is one of the crucial factors in CaHD development. White plaque-like deposits on the endocardial surface of heart structures with valve leaflets and subvalvular apparatus thickening (fused and shortened chordae; thickened papillary muscles) are characteristic for CaHD. NT pro-BNP and 5-hydroxyindoleacetic acid are the 2 most useful screening markers. Long-acting somatostatin analogs are the standard of care in symptoms control. They are also the first-line treatment for tumor control in subjects with a metastatic somatostatin receptor avid disease. In cases refractory to somatostatin analogs, several options are available. We can increase a somatostatin analog to off-label doses, add telotristat ethyl or administer peptide receptor radionuclide therapy. Cardiac surgery, which mainly involves valve replacement, is presently the most efficient strategy in subjects with advanced CaHD and can relieve unmanageable symptoms or be partly responsible for better prognosis.

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Serotonin Levels And 1-Year Mortality In Patients With Neuroendocrine Tumors: A Systematic Review And Meta-Analysis

Cited by 16 publications

References 44 publications

Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review

Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review

Changes in Carcinoid Syndrome Symptoms Among Patients Receiving Telotristat Ethyl in US Clinical Practice: Findings from the TELEPRO-II Real-World Study

Carcinoid Heart Disease: How to Diagnose and Treat in 2020?

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