Persistent low urinary excretion of 5-HIAA is a marker for favourable survival during follow-up in patients with disseminated midgut carcinoid tumours

Horst-Schrivers, Anouk N A van der; Post, Wendy J.; Kema, Ido P.; Links, Thera P.; Willemse, Pax H.B.; Wymenga, A.N.M.; Vries, Elisabeth G.E. de

doi:10.1016/j.ejca.2007.07.025

Cited by 55 publications

(56 citation statements)

References 42 publications

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“…Raised urinary 5-HIAA levels have been shown to correlate with poor survival with SI NETs by UVA, although in most previous studies this association lost its statistical significance in MVA, perhaps due to its known (and therefore confounding) association with CHD [23], which is usually also included as an independent variable in statistical models. Similar to our findings, another study showed by MVA that increased urinary 5-HIAA levels are an independent poor prognostic factor in SI NETs [20]. …”

Section: Discussionsupporting

confidence: 81%

Prognostic Factors for Survival among Patients with Small Bowel Neuroendocrine Tumours Associated with Mesenteric Desmoplasia

et al. 2018

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Background: Small intestinal neuroendocrine tumours (SI NETs) represent 30–50% of small bowel neoplasms and are often associated with diverse fibrotic complications. Mesenteric fibrosis is a hallmark of SI NETs which may cause substantial morbidity and is considered an adverse feature. However, survival analyses in this group of patients are lacking. Methods: The aim of this retrospective study was to determine the overall survival (OS) and factors affecting prognosis in a large cohort of 147 patients with SI NETs and radiological evidence of mesenteric desmoplasia from our centre. The severity of desmoplasia was graded radiologically and its effect on OS and long-term complications was assessed. The median follow-up period was 82 months. Results: The median OS was 8.7 years (95% CI 6.8–9.9) with an overall 5-year survival of 71%. The univariate analysis demonstrated that an age >65 years, a liver tumour burden >50% of the hepatic parenchyma, carcinoid heart disease, chromogranin A levels >10 times the upper limit of normal, and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels >5 times the upper limit of normal were poor prognosticators, while primary resection was associated with a longer OS. However, only an age >65 years and urinary 5-HIAA levels >10 times the upper limit of normal remained statistically significant after multivariate analysis. The severity of mesenteric desmoplasia did not seem to demonstrate a statistically significant relationship to OS or long-term outcomes. Conclusion: This study is the first comprehensive survival analysis of patients with SI NETs associated with mesenteric desmoplasia and has provided important and clinically relevant epidemiological data for this group of patients.

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Section: Discussionsupporting

confidence: 81%

Prognostic Factors for Survival among Patients with Small Bowel Neuroendocrine Tumours Associated with Mesenteric Desmoplasia

et al. 2018

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“…To illustrate this, two studies including 256 and 139 patients with midgut carcinoid tumors showed that while elevated 5-HIAA levels were predictive of poor outcome at univariate analysis, this did not remain significant at multivariate analysis [5, 6]. In another study examining 76 patients, those with persistent moderately increased urinary 5-HIAA levels (≤20 mmol/mol creatinine) had a more favourable outcome compared to those with greatly elevated levels [7]. A further study in a mixed tumor group including 119 patients (53 of midgut origin) interestingly found high 5-HIAA to be an independent survival factor [8].…”

Section: Standards For the Detection And Interpretation Of 5-hydroxyimentioning

confidence: 99%

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers

et al. 2009

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“…An Italian study of 156 GEP NETs (67 pancreatic endocrine tumors, 73 gastrointestinal carcinoids and 16 of unknown origin) noted that age >50 years compared to <50 years at diagnosis correlated with an increased risk of death, HR 2.33 (univariate analysis) [21]. Similarly, in a Dutch study of 76 patients with midgut carcinoid tumors, age as a continuous variable was a prognostic factor for survival with an HR of 1.043 and 1.052 per year for uni- and multivariate analyses, respectively [23]. A large European multicenter study comprising 7,693 patients with GEP NETs investigated the relative risk of death for patients ≥75 years and the age group of 55–74 years, and identified that compared to patients between 15 and 54 years these two groups exhibited HR values of 3.58 and 2.26, respectively [18].…”

Section: Resultsmentioning

confidence: 99%

“…With accurate prediction, patients at low risk for disease-specific death can be safely reassured, whereas patients at high risk can be considered for appropriate surgery and systemic therapy [2]. Several studies have identified prognostic factors in individual NETs but a rigorous and robust assimilation of the different indices used to define outcome is lacking [12,14,15,16,17,18,19,20,21,22,23]. Although assessment of a variety of parameters and knowledge thereof has utility in clinicopathological research and clinical trial design, patient-specific counseling and therapeutic strategy require formalized integration of diverse prognostic factors to establish a single patient-specific prognosis.…”

Section: Introductionmentioning

confidence: 99%

A Nomogram to Assess Small-Intestinal Neuroendocrine Tumor (‘Carcinoid’) Survival

et al. 2010

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Neuroendocrine tumors (NETs) are a heterogeneous group of cancers of which the commonest site is the small intestine (SI). Most information available to determine tumor behavior reflects univariate assessment of factors or is anecdotal or experience based. There currently exists no objective multivariate analysis of indices that defines SI NET prognosis. A key unmet need is the lack of a rigorous mathematical-based tool – a nomogram – for the assessment of parameters that define progress, determine prognosis and can guide therapy. Since prediction of NET behavior is a critical criterion in determining clinical strategy, we constructed a NET nomogram (Modlin Score) for prognosis prediction, patient group comparisons and a guide for stratification of treatment and surveillance. We used hazard ratio (HR), Cox analysis and Kaplan-Meier analysis of published data and the current Surveillance, Epidemiology and End Results (SEER) database (approx. 20,000 patients) to develop a nomogram from 15 variables demonstrated to provide significant multivariate HRs. These included age, gender, ethnicity, symptoms, urinary 5-hydroxyindoleacetic acid, plasma chromogranin A, liver function tests, tumor size, invasion, metastasis, histology, Ki-67 index, carcinoid heart disease and therapy (surgery or long-acting somatostatin analogs). Internal validation was assessed using 33 SI NET patients. A NET nomoscore (Modlin Score) was developed by HR weighting and stratification into low (<75), medium (75–95) and high risk (>95). This identified significant differences (p <0.03, Kaplan-Meier) in survival (15.5 ± 4.3, 9.7 ± 2.5 and 6.4 ± 1.1 years, respectively). The Modlin Score was significantly elevated (p <0.01) in deceased compared to alive patients. This nomogram represents an optimized construct based upon currently analyzable data, and application will facilitate accurate stratification for comparison in clinical trials. External validation and amplification by identification of additional indices, e.g. molecular biomarkers, are necessary. The development of a mathematically validated nomogram provides a platform for objective assessment of SI NET disease, a finite basis for precise prognostication and a tool to guide management strategy.

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Persistent low urinary excretion of 5-HIAA is a marker for favourable survival during follow-up in patients with disseminated midgut carcinoid tumours

Cited by 55 publications

References 42 publications

Prognostic Factors for Survival among Patients with Small Bowel Neuroendocrine Tumours Associated with Mesenteric Desmoplasia

Prognostic Factors for Survival among Patients with Small Bowel Neuroendocrine Tumours Associated with Mesenteric Desmoplasia

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers

A Nomogram to Assess Small-Intestinal Neuroendocrine Tumor (‘Carcinoid’) Survival

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